Publications by authors named "Emily Griffiths"

30 Publications

  • Page 1 of 1

Acoustic detection range and population density of Cuvier's beaked whales estimated from near-surface hydrophones.

J Acoust Soc Am 2021 01;149(1):111

Ocean Associates, Incorporated, 4007 North Abingdon Street, Arlington, Virginia 22207, USA.

The population density of Cuvier's beaked whales is estimated acoustically with drifting near-surface hydrophone recorders in the Catalina Basin. Three empirical approaches (trial-based, distance-sampling, and spatially explicit capture-recapture) are used to estimate the probability of detecting the echolocation pulses as a function of range. These detection functions are used with two point-transect methods (snapshot and dive-cue) to estimate density. Measurement errors result in a small range of density estimates (3.9-5.4 whales per 1000 km). Use of multiple approaches and methods allows comparison of the required information and assumptions of each. The distance-sampling approach with snapshot-based density estimates has the most stringent assumptions but would be the easiest to implement for large scale surveys of beaked whale density. Alternative approaches to estimating detection functions help validate this approach. The dive cue method of density estimation has promise, but additional work is needed to understand the potential bias caused by animal movement during a dive. Empirical methods are a viable alternative to the theoretical acoustic modeling approaches that have been used previously to estimate beaked whale density.
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http://dx.doi.org/10.1121/10.0002881DOI Listing
January 2021

Respiratory Health of Pacific Youth: An Observational Study of Associated Risk and Protective Factors Throughout Childhood.

JMIR Res Protoc 2020 Oct 21;9(10):e18916. Epub 2020 Oct 21.

Paediatric Department, Faculty of Medical & Health Sciences, University of Auckland, Auckland, New Zealand.

Background: Respiratory disease is the third most common cause of death in New Zealand, with Pacific people living in New Zealand bearing the greatest burden of this type of disease. Although some epidemiological outcomes are known, we lack the specifics required to formulate targeted and effective public health interventions. The Pacific Islands Families (PIF) birth cohort study is a study that provides a unique source of data to assess lung function and current respiratory health among participants entering early adulthood and to examine associations with early life events during critical periods of growth.

Objective: This paper aims to provide an overview of the design, methods, and scope of the Respiratory Health of Pacific Youth Study, which uses the overall PIF study cohort aged 18-19 years.

Methods: From 2000-2019, the PIF study has followed, from birth, the growth, and the development of 1398 Pacific children born in Auckland, New Zealand. Participants were nested within the overall PIF study (at ages 18-19 years) from June 2018, and assessments were undertaken until mid-November 2019. The assessments included respiratory and general medical histories, a general physical examination, assessment of lung function (forced expiratory volume and forced vital capacity), self-completed questionnaires (St George's Respiratory Questionnaire, European Quality of Life 5 Dimensions-3 Level, Epworth Sleepiness Scale for Children and Adolescents, and Leicester Cough Questionnaire), blood tests (eosinophils, Immunoglobulin E, Immunoglobulin G, Immunoglobulin A, Immunoglobulin M, and C-reactive protein), and chest x-rays. Noninferential analyses will be carried out on dimensionally reduced risk and protective factors and confounders.

Results: Data collection began in June 2018 and ended in November 2019, with a total of 466 participants recruited for submission of the paper. Collection and collation of chest x-ray data is still underway, and data analysis and expected results will be published by November 2020.

Conclusions: This is the first longitudinal observational study to address the burden of respiratory disease among Pacific youth by determining factors in early life that impose long-term detriments in lung function and are associated with the presence of respiratory illness. Identifying risk factors and the magnitude of their effects will help in adopting preventative measures, establishing whether any avoidable risks can be modified by later resilient behaviors, and provide baseline measurements for the development of respiratory disease in later adult life. The study results can be translated into practice guidelines and inform health strategies with immediate national and international impact.

International Registered Report Identifier (irrid): DERR1-10.2196/18916.
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http://dx.doi.org/10.2196/18916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641786PMC
October 2020

Detection and classification of narrow-band high frequency echolocation clicks from drifting recorders.

J Acoust Soc Am 2020 05;147(5):3511

Marine Mammal and Turtle Division, Southwest Fisheries Science Center, National Marine Fisheries Service, 8901 La Jolla Shores Boulevard, La Jolla, California 92037, USA.

In the California Current off the United States West Coast, there are three offshore cetacean species that produce narrow-band high frequency (NBHF) echolocation pulses: Dall's porpoise (Phocoenoides dalli) and two species of Kogia. NBHF pulses exist in a highly specialized acoustic niche thought to be outside the hearing range of killer whales and other potential mammal-eating odontocetes. Very little is known about the dwarf and pygmy sperm whales (K. sima and K. breviceps), including their NBHF pulse characteristics. This paper presents a multivariate clustering method using data from unmanned drifting acoustic recorders and visually verified porpoise recordings to discriminate between probable porpoise and Kogia clicks. Using density clustering, this study finds three distinct clusters whose geographic distributions are consistent with the known habitat range for Kogia and Dall's porpoise. A Random Forest classification model correctly assigned 97% of the clicks to their cluster. Visually verified Dall's porpoise clicks from towed hydrophones were strongly associated with one of the clusters, while a second cluster tended to be outside the geographic range of Dall's porpoise and unlike the Dall's porpoise cluster. These clicks, presumed to be made by Kogia, exhibited greater spectral variance than previous Kogia echolocation studies. It is possible that the structure of Kogia NBHF pulses may not be as stereotypical as previously described.
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http://dx.doi.org/10.1121/10.0001229DOI Listing
May 2020

Diving behavior of Cuvier's beaked whales inferred from three-dimensional acoustic localization and tracking using a nested array of drifting hydrophone recorders.

J Acoust Soc Am 2018 10;144(4):2030

Centre for Research into Ecological and Environmental Modelling, The Observatory, Buchanan Gardens, University of St. Andrews, St. Andrews, Fife, KY16 9LZ, United Kingdom.

Echolocation pulses from Cuvier's beaked whales are used to track the whales' three-dimensional diving behavior in the Catalina Basin, California. In 2016, five 2-element vertical hydrophone arrays were suspended from the surface and drifted at ∼100-m depth. Cuvier's beaked whale pulses were identified, and vertical detection angles were estimated from time-differences-of-arrival of either direct-path signals received on two hydrophones or direct-path and surface-reflected signals received on the same hydrophone. A Bayesian state-space model is developed to track the diving behavior. The model is fit to these detection angle estimates from at least four of the drifting vertical arrays. Results show that the beaked whales were producing echolocation pulses and are presumed to be foraging at a mean depth of 967 m (standard deviation = 112 m), approximately 300 m above the bottom in this basin. Some whales spent at least some time at or near the bottom. Average swim speed was 1.2 m s, but swim direction varied during a dive. The average net horizontal speed was 0.6 m s. Results are similar to those obtained from previous tagging studies of this species. These methods may allow expansion of dive studies to other whale species that are difficult to tag.
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http://dx.doi.org/10.1121/1.5055216DOI Listing
October 2018

E3 ubiquitin ligases LNX1 and LNX2 localize at neuronal gap junctions formed by connexin36 in rodent brain and molecularly interact with connexin36.

Eur J Neurosci 2018 11 2;48(9):3062-3081. Epub 2018 Nov 2.

Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Science, University of Manitoba, Winnipeg, Manitoba, Canada.

Electrical synapses in the mammalian central nervous system (CNS) are increasingly recognized as highly complex structures for mediation of neuronal communication, both with respect to their capacity for dynamic short- and long-term modification in efficacy of synaptic transmission and their multimolecular regulatory and structural components. These two characteristics are inextricably linked, such that understanding of mechanisms that contribute to electrical synaptic plasticity requires knowledge of the molecular composition of electrical synapses and the functions of proteins associated with these synapses. Here, we provide evidence that the key component of gap junctions that form the majority of electrical synapses in the mammalian CNS, namely connexin36 (Cx36), directly interacts with the related E3 ubiquitin ligase proteins Ligand of NUMB protein X1 (LNX1) and Ligand of NUMB protein X2 (LNX2). This is based on immunofluorescence colocalization of LNX1 and LNX2 with Cx36-containing gap junctions in adult mouse brain versus lack of such coassociation in LNX null mice, coimmunoprecipitation of LNX proteins with Cx36, and pull-down of Cx36 with the second PDZ domain of LNX1 and LNX2. Furthermore, cotransfection of cultured cells with Cx36 and E3 ubiquitin ligase-competent LNX1 and LNX2 isoforms led to loss of Cx36-containing gap junctions between cells, whereas these junctions persisted following transfection with isoforms of these proteins that lack ligase activity. Our results suggest that a LNX protein mediates ubiquitination of Cx36 at neuronal gap junctions, with consequent Cx36 internalization, and may thereby contribute to intracellular mechanisms that govern the recently identified modifiability of synaptic transmission at electrical synapses.
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http://dx.doi.org/10.1111/ejn.14198DOI Listing
November 2018

Dengue Fever Surveillance in India Using Text Mining in Public Media.

Am J Trop Med Hyg 2018 01;98(1):181-191

Department of Computer Science, North Carolina State University, Raleigh, North Carolina.

Despite the improvement in health conditions across the world, communicable diseases remain among the leading mortality causes in many countries. Combating communicable diseases depends on surveillance, preventive measures, outbreak investigation, and the establishment of control mechanisms. Delays in obtaining country-level data of confirmed communicable disease cases, such as dengue fever, are prompting new efforts for short- to medium-term data. News articles highlight dengue infections, and they can reveal how public health messages, expert findings, and uncertainties are communicated to the public. In this article, we analyze dengue news articles in Asian countries, with a focus in India, for each month in 2014. We investigate how the reports cluster together, and uncover how dengue cases, public health messages, and research findings are communicated in the press. Our main contributions are to 1) uncover underlying topics from news articles that discuss dengue in Asian countries in 2014; 2) construct topic evolution graphs through the year; and 3) analyze the life cycle of dengue news articles in India, then relate them to rainfall, monthly reported dengue cases, and the Breteau Index. We show that the five main topics discussed in the newspapers in Asia in 2014 correspond to 1) prevention; 2) reported dengue cases; 3) politics; 4) prevention relative to other diseases; and 5) emergency plans. We identify that rainfall has 0.92 correlation with the reported dengue cases extracted from news articles. Based on our findings, we conclude that the proposed method facilitates the effective discovery of evolutionary dengue themes and patterns.
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http://dx.doi.org/10.4269/ajtmh.17-0253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928697PMC
January 2018

Precision and bias in estimating detection distances for beaked whale echolocation clicks using a two-element vertical hydrophone array.

J Acoust Soc Am 2017 06;141(6):4388

Ocean Associates, Inc., 4007 North Abingdon Street, Arlington, Virginia 22207, USA.

Detection distances are critical for cetacean density and abundance estimation using distance sampling methods. Data from a drifting buoy system consisting of an autonomous recorder and a two-element vertical hydrophone array at ∼100-m depth are used to evaluate three methods for estimating the horizontal distance (range) to beaked whales making echolocation clicks. The precision in estimating time-differences-of-arrival (TDOA) for direct- and surface-reflected-path clicks is estimated empirically using repeated measures over short time periods. A Teager-Kaiser energy detector is used to improve estimates of TDOA for surface-reflected signals. Simulations show that array tilt in the direction of the source cannot be reliably estimated given this array geometry and these measurements of TDOA error, which means that range cannot be reliably estimated. If array tilt can be reduced to less than 0.5°, range can be reliably estimated up to ∼3000 m. If array depth is increased to 200 m and array tilt is less than 1°, range can be reliably estimated up to ∼5000 m. Prior information on the depth of vocalizing beaked whales and estimates of declination angle can be used to precisely estimate range, but different analytical methods are required to avoid bias and to treat distributions of depth probabilistically.
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http://dx.doi.org/10.1121/1.4985109DOI Listing
June 2017

Neuropsychiatric symptoms following metal-on-metal implant failure with cobalt and chromium toxicity.

BMC Psychiatry 2017 01 24;17(1):33. Epub 2017 Jan 24.

The Institute of Medicine, University of Chester and University Centre Shrewsbury, Bache Hall, Countess Way, Chester, Cheshire, CH2 1JR, UK.

Background: There were at least 31,171 metal-on-metal (MoM) hip implants in the UK between 2003 and 2011. Some of these were subject to failure and widescale recalls and revisions followed.

Method: This is a presentation of ten cases (mean age 60 years) where we evaluated neuropsychiatric morbidity following metal-on-metal hip implant failure and revision. Implants were ASR total hip replacement (acetabular implant, taper sleeve adaptor and unipolar femoral implants) performed between 2005 and 2009. This case series describes, for the first time, neuropsychiatric complications after revision where there has been cobalt and chromium toxicity.

Results: Pre-revision surgery, nine patients had toxic levels of chromium and cobalt (mean level chromium 338 nmol/l, mean cobalt 669.4 nmol/l). Depression assessment showed 9 of 9 respondents fulfilled the BDI criteria for depression and 3 of these were being treated. 7 of 9 patients showing short term memory deficit with mean mini mental state examination score of 24.2. The normal population mean MMSE for this group would be expected to be 28 with <25 indicating possible dementia.

Conclusions: We found neurocognitive and depressive deficits after cobalt and chromium metallosis following MoM implant failure. Larger studies of neurocognitive effects are indicated in this group. There may be implications for public health.
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http://dx.doi.org/10.1186/s12888-016-1174-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259873PMC
January 2017

Cetacean acoustic detections from free-floating vertical hydrophone arrays in the southern California Current.

J Acoust Soc Am 2016 11;140(5):EL399

Marine Mammal and Turtle Division, Southwest Fisheries Science Center, National Marine Fisheries Service, 8901 La Jolla Shores Drive, La Jolla, California 92037, USA

Drifting acoustic recorders were deployed in the southern California Current during Fall 2014. Two hydrophones configured as a 2-m vertical array at 100 m depth recorded using a 192 kHz sample rate on a 10% duty cycle (2 min/20 min). Beaked whales were detected in 33 of 8618 two-minute recordings. Sperm whales were detected in 185 recordings, and dolphins in 2291 recordings. Many beaked whales detected were over an abyssal plain and not associated with slope or seamount features. Results show the feasibility of using free-floating recording systems to detect a variety of cetacean species over periods of several months.
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http://dx.doi.org/10.1121/1.4967012DOI Listing
November 2016

Can Nocturnal Flight Calls of the Migrating Songbird, American Redstart, Encode Sexual Dimorphism and Individual Identity?

PLoS One 2016 10;11(6):e0156578. Epub 2016 Jun 10.

Information Science, Cornell Laboratory of Ornithology, Cornell University, Ithaca, New York, United States of America.

Bird species often use flight calls to engage in social behavior, for instance maintain group cohesion and to signal individual identity, kin or social associations, or breeding status of the caller. Additional uses also exist, in particular among migrating songbirds for communication during nocturnal migration. However, our understanding of the information that these vocalizations convey is incomplete, especially in nocturnal scenarios. To examine whether information about signaler traits could be encoded in flight calls we quantified several acoustic characteristics from calls of a nocturnally migrating songbird, the American Redstart. We recorded calls from temporarily captured wild specimens during mist-netting at the Powdermill Avian Research Center in Rector, PA. We measured call similarity among and within individuals, genders, and age groups. Calls from the same individual were significantly more similar to one another than to the calls of other individuals, and calls were significantly more similar among individuals of the same sex than between sexes. Flight calls from hatching-year and after hatching-year individuals were not significantly different. Our results suggest that American Redstart flight calls may carry identifiers of gender and individual identity. To our knowledge, this is the first evidence of individuality or sexual dimorphism in the flight calls of a migratory songbird. Furthermore, our results suggest that flight calls may have more explicit functions beyond simple group contact and cohesion. Nocturnal migration may require coordination among numerous individuals, and the use of flight calls to transmit information among intra- and conspecifics could be advantageous. Applying approaches that account for such individual and gender information may enable more advanced research using acoustic monitoring.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0156578PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902225PMC
July 2017

Improving the post-meal experience of hospitalised patients with eating disorders using visuospatial, verbal and somatic activities.

J Eat Disord 2016 11;4. Epub 2016 Mar 11.

University College London, Clinical, Educational & Health Psychology, 1-19 Torrington Place, London, WC1E 7HB UK ; Eating Disorders Service, North East London NHS Foundation Trust, London, UK.

Background: This study compares the effects of different cognitive tasks on post-meal negative affect, positive affect, intrusive thoughts and intrusive images of hospitalised patients with eating disorders.

Methods: Twenty-five participants were recruited from an eating disorder service. Using a within-subjects design, participants performed one of the following tasks for 15 min: the game 'Tetris' (visuospatial), a general knowledge 'Quiz' (verbal), 'Braille' translation (somatic) and 'Sitting Quietly' (control). In total, participants completed each task on three occasions.

Results: The visuospatial, verbal and somatic tasks had beneficial effects on all positive and negative indicators, when compared with 'Sitting Quietly'. Visuospatial and somatic tasks were more effective at reducing intrusive imagery than the verbal task.

Conclusions: The results suggest that certain engaging activities can help hospitalised patients with eating disorders manage the difficult post-meal period.
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http://dx.doi.org/10.1186/s40337-016-0098-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788931PMC
March 2016

Erratum to: 'The potential impact of coinfection on antimicrobial chemotherapy and drug resistance'.

Trends Microbiol 2015 Nov 1;23(11):742. Epub 2015 Oct 1.

Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA; Fogarty International Center, National Institutes of Health, Bethesda, MD, USA.

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http://dx.doi.org/10.1016/j.tim.2015.09.001DOI Listing
November 2015

Bottom-up regulation of malaria population dynamics in mice co-infected with lung-migratory nematodes.

Ecol Lett 2015 Dec 18;18(12):1387-96. Epub 2015 Oct 18.

Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, 08544, USA.

When and how populations are regulated by bottom up vs. top down processes, and how those processes are affected by co-occurring species, are poorly characterised across much of ecology. We are especially interested in the community ecology of parasites that must share a host. Here, we quantify how resources and immunity affect parasite propagation in experiments in near-replicate 'mesocosms'' - i.e. mice infected with malaria (Plasmodium chabaudi) and nematodes (Nippostrongylus brasiliensis). Nematodes suppressed immune responses against malaria, and yet malaria populations were smaller in co-infected hosts. Further analyses of within-host epidemiology revealed that nematode co-infection altered malaria propagation by suppressing target cell availability. This is the first demonstration that bottom-up resource regulation may have earlier and stronger effects than top-down immune mechanisms on within-host community dynamics. Our findings demonstrate the potential power of experimental ecology to disentangle mechanisms of population regulation in complex communities.
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http://dx.doi.org/10.1111/ele.12534DOI Listing
December 2015

The potential impact of coinfection on antimicrobial chemotherapy and drug resistance.

Trends Microbiol 2015 Sep 29;23(9):537-544. Epub 2015 May 29.

Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA.

Across a range of pathogens, resistance to chemotherapy is a growing problem in both public health and animal health. Despite the ubiquity of coinfection, and its potential effects on within-host biology, the role played by coinfecting pathogens on the evolution of resistance and efficacy of antimicrobial chemotherapy is rarely considered. In this review, we provide an overview of the mechanisms of interaction of coinfecting pathogens, ranging from immune modulation and resource modulation, to drug interactions. We discuss their potential implications for the evolution of resistance, providing evidence in the rare cases where it is available. Overall, our review indicates that the impact of coinfection has the potential to be considerable, suggesting that this should be taken into account when designing antimicrobial drug treatments.
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http://dx.doi.org/10.1016/j.tim.2015.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4835347PMC
September 2015

Analysis of a summary network of co-infection in humans reveals that parasites interact most via shared resources.

Proc Biol Sci 2014 May 11;281(1782):20132286. Epub 2014 Mar 11.

Department of Entomology, North Carolina State University, , Raleigh, NC 27695-7613, USA, Department of Animal and Plant Sciences, University of Sheffield, , Alfred Denny Building, Western Bank, Sheffield S10 2TN, UK, Centre for Immunology, Infection and Evolution, Institute of Evolutionary Biology, School of Biological Sciences, Ashworth Labs, University of Edinburgh, , Kings Buildings, West Mains Road, Edinburgh EH9 3JT, UK, Institute of Integrative Biology, University of Liverpool, , Liverpool L69 7ZB, UK, Institute of Evolutionary Biology and Environmental Studies, University of Zürich, , Winterthurerstrasse 190, Zürich 8057, Switzerland.

Simultaneous infection by multiple parasite species (viruses, bacteria, helminths, protozoa or fungi) is commonplace. Most reports show co-infected humans to have worse health than those with single infections. However, we have little understanding of how co-infecting parasites interact within human hosts. We used data from over 300 published studies to construct a network that offers the first broad indications of how groups of co-infecting parasites tend to interact. The network had three levels comprising parasites, the resources they consume and the immune responses they elicit, connected by potential, observed and experimentally proved links. Pairs of parasite species had most potential to interact indirectly through shared resources, rather than through immune responses or other parasites. In addition, the network comprised 10 tightly knit groups, eight of which were associated with particular body parts, and seven of which were dominated by parasite-resource links. Reported co-infection in humans is therefore structured by physical location within the body, with bottom-up, resource-mediated processes most often influencing how, where and which co-infecting parasites interact. The many indirect interactions show how treating an infection could affect other infections in co-infected patients, but the compartmentalized structure of the network will limit how far these indirect effects are likely to spread.
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http://dx.doi.org/10.1098/rspb.2013.2286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3973251PMC
May 2014

Birth order and post-traumatic stress disorder.

Psychol Health Med 2014 11;19(1):24-32. Epub 2013 Mar 11.

a Faculty of Health and Social Care , University of Chester , Chester , UK .

Objective: To compare the birth order of patients with post-traumatic stress disorder (PTSD) and adjustment disorder (AD) with population norms.

Method: 83 PTSD patients and 104 AD control patients from a psychiatric trauma clinic were diagnosed according to DCR-10 guidelines. A family history was taken as to number of siblings, and their birth order. We compared the distribution of birth order for each patient group against birth order distributions expected by chance for the same years of birth using UK population-level birth order from the Office for National Statistics.

Results: Psychiatric patients with PTSD were more likely to be from a large family, specifically to be the fifth child or later (OR 4.78, p < .001) and less likely to be the eldest child (OR .65, p < .001) than the general population in England and Wales. There were no differences for birth order between AD patients and the general population.

Conclusion: People with PTSD are more likely to be the youngest children from large families than expected from a random sample of people born in the same years. This association with birth order was not found for another psychiatric diagnosis AD from the same clinic. We discuss possible psychosocial and biological causes, and implications for further research.
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http://dx.doi.org/10.1080/13548506.2013.774432DOI Listing
May 2014

Biochemical and computational analysis of LNX1 interacting proteins.

PLoS One 2011 8;6(11):e26248. Epub 2011 Nov 8.

Department of Medical Biophysics, University of Toronto, Toronto, Canada.

PDZ (Post-synaptic density, 95 kDa, Discs large, Zona Occludens-1) domains are protein interaction domains that bind to the carboxy-terminal amino acids of binding partners, heterodimerize with other PDZ domains, and also bind phosphoinositides. PDZ domain containing proteins are frequently involved in the assembly of multi-protein complexes and clustering of transmembrane proteins. LNX1 (Ligand of Numb, protein X 1) is a RING (Really Interesting New Gene) domain-containing E3 ubiquitin ligase that also includes four PDZ domains suggesting it functions as a scaffold for a multi-protein complex. Here we use a human protein array to identify direct LNX1 PDZ domain binding partners. Screening of 8,000 human proteins with isolated PDZ domains identified 53 potential LNX1 binding partners. We combined this set with LNX1 interacting proteins identified by other methods to assemble a list of 220 LNX1 interacting proteins. Bioinformatic analysis of this protein list was used to select interactions of interest for future studies. Using this approach we identify and confirm six novel LNX1 binding partners: KCNA4, PAK6, PLEKHG5, PKC-alpha1, TYK2 and PBK, and suggest that LNX1 functions as a signalling scaffold.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0026248PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3210812PMC
May 2012

Beating Bipolar: exploratory trial of a novel Internet-based psychoeducational treatment for bipolar disorder.

Bipolar Disord 2011 Aug-Sep;13(5-6):571-7

Department of Psychological Medicine and Neurology, Cardiff University School of Medicine, Heath Park, Cardiff, UK.

Objectives:   Psychoeducational approaches are promising interventions for the long-term management of bipolar disorder. In consultation with professionals, patients, and their families we have developed a novel web-based psychoeducational intervention for bipolar disorder called Beating Bipolar. We undertook a preliminary exploratory randomized trial to examine efficacy, feasibility and acceptability.

Methods:   This was an exploratory randomized controlled trial of Beating Bipolar (current controlled trials registration number: ISRCTN81375447). The control arm was treatment-as-usual and the a priori primary outcome measure was quality of life [measured by the brief World Health Organization Quality of Life (WHOQOL-BREF) scale]. Secondary outcomes included psychosocial functioning, insight, depressive and manic symptoms and relapse, and use of healthcare resources. Fifty participants were randomized to either the Beating Bipolar intervention plus treatment-as-usual or just treatment-as-usual. The intervention was delivered over a four-month period and outcomes were assessed six months later.

Results:   There was no significant difference between the intervention and control groups on the primary outcome measure (total WHOQOL-BREF score) but there was a modest improvement within the psychological subsection of the WHOQOL-BREF for the intervention group relative to the control group. There were no significant differences between the groups on any of the secondary outcome measures.

Conclusions:   Beating Bipolar is potentially a safe and engaging intervention which can be delivered remotely to large numbers of patients with bipolar disorder at relatively low cost. It may have a modest effect on psychological quality of life. Further work is required to establish the impact of this intervention on insight, knowledge, treatment adherence, self-efficacy and self-management skills.
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http://dx.doi.org/10.1111/j.1399-5618.2011.00949.xDOI Listing
February 2012

The nature and consequences of coinfection in humans.

J Infect 2011 Sep 16;63(3):200-6. Epub 2011 Jun 16.

Department of Animal and Plant Sciences, Alfred Denny Building, Western Bank, University of Sheffield, Sheffield S10 2TN, UK.

Objective: Many fundamental patterns of coinfection (multi-species infections) are undescribed, including the relative frequency of coinfection by various pathogens, differences between single-species infections and coinfection, and the burden of coinfection on human health. We aimed to address the paucity of general knowledge on coinfection by systematically collating and analysing data from recent publications to understand the types of coinfection and their effects.

Methods: From an electronic search to find all publications from 2009 on coinfection and its synonyms in humans we recorded data on i) coinfecting pathogens and their effect on ii) host health and iii) intensity of infection.

Results: The most commonly reported coinfections differ from infections causing highest global mortality, with a notable lack of serious childhood infections in reported coinfections. We found that coinfection is generally reported to worsen human health (76% publications) and exacerbate infections (57% publications). Reported coinfections included all kinds of pathogens, but were most likely to contain bacteria.

Conclusions: These results suggest differences between coinfected patients and those with single infections, with coinfection having serious health effects. There is a pressing need to quantify the tendency towards negative effects and to evaluate any sampling biases in the coverage of coinfection research.
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http://dx.doi.org/10.1016/j.jinf.2011.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430964PMC
September 2011

Unrecognised bipolar disorder in primary care patients with depression.

Br J Psychiatry 2011 Jul 3;199(1):49-56. Epub 2011 Feb 3.

Department of Psychological Medicine and Neurology, Cardiff University School of Medicine, University Hospital of Wales, Cardiff, UK.

Background: Bipolar disorder is complex and can be difficult to diagnose. It is often misdiagnosed as recurrent major depressive disorder.

Aims: We had three main aims. To estimate the proportion of primary care patients with a working diagnosis of unipolar depression who satisfy DSM-IV criteria for bipolar disorder. To test two screening instruments for bipolar disorder (the Hypomania Checklist (HCL-32) and Bipolar Spectrum Diagnostic Scale (BSDS)) within a primary care sample. To assess whether individuals with major depressive disorder with subthreshold manic symptoms differ from those individuals with major depressive disorder but with no or little history of manic symptoms in terms of clinical course, psychosocial functioning and quality of life.

Method: Two-phase screening study in primary care.

Results: Three estimates of the prevalence of undiagnosed bipolar disorder were obtained: 21.6%, 9.6% and 3.3%. The HCL-32 and BSDS questionnaires had quite low positive predictive values (50.0 and 30.1% respectively). Participants with major depressive disorder and with a history of subthreshold manic symptoms differed from those participants with no or little history of manic symptoms on several clinical features and on measures of both psychosocial functioning and quality of life.

Conclusions: Between 3.3 and 21.6% of primary care patients with unipolar depression may have an undiagnosed bipolar disorder. The HCL-32 and BSDS screening questionnaires may be more useful for detecting broader definitions of bipolar disorder than DSM-IV-defined bipolar disorder. Subdiagnostic features of bipolar disorder are relatively common in primary care patients with unipolar depression and are associated with a more morbid course of illness. Future classifications of recurrent depression should include dimensional measures of bipolar symptoms.
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http://dx.doi.org/10.1192/bjp.bp.110.083840DOI Listing
July 2011

Developing an online psychoeducation package for bipolar disorder.

J Ment Health 2011 Feb;20(1):21-31

Department of Psychological Medicine and Neurology, Cardiff University, Heath Park, Cardiff, UK.

Background: Medications are known to be effective for bipolar disorder but treatment non-adherence and psychosocial effects can impact adversely on long-term outcome. Psychoeducation may help address some of these issues.

Aims: This article describes the development of a novel online psychoeducation programme ( www.BeatingBipolar.org ) for patients with bipolar disorder.

Method: The programme was developed in three stages--a literature review, development of a draft outline of the programme and focus groups with mental health professionals and service users.

Results: Data highlighted the importance of presenting a supportive style of programme, realistic stories and positive role models within the programme and providing a variety of information delivery styles. Desired outcomes of the programme were an increased sense of control over bipolar disorder, reduced stigma and improved understanding for family and carers.

Conclusion: The iterative development process using focus groups with service users and mental health professionals provided important insights into users' needs and preferences as well as identifying valued outcomes. Interactive online psychoeducation materials benefit from a systematic design process which is informed by a range of viewpoints.
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http://dx.doi.org/10.3109/09638237.2010.525565DOI Listing
February 2011

Reducing the Hypomania Checklist (HCL-32) to a 16-item version.

J Affect Disord 2010 Aug 2;124(3):351-6. Epub 2010 Feb 2.

Department of Psychological Medicine, School of Medicine, Cardiff University, University Hospital of Wales, Cardiff, CF14 4XN, UK.

Background: The under-recognition of hypomanic symptoms by both clinicians and patients is a major clinical problem which contributes to misdiagnosis and diagnostic delay in patients with bipolar disorder. The recent development of validated screening instruments for hypomania, such as the Hypomania Checklist (HCL-32), may help to improve the detection of bipolar disorder. In this study, we assess whether it is possible to reduce the number of items on the HCL-32 without any loss in the screening tool's ability to reliably differentiate between bipolar disorder (BD) and major depressive disorder (MDD).

Methods: Using our large samples of patients with DSM-IV defined bipolar I disorder (BD-I) (n=230) and recurrent MDD (n=322), we performed item correlations in order to identify potentially redundant items in the HCL-32. We then tested the performance of a shortened 16-item HCL questionnaire within a separate sample of patients with BD (including BD-I, BD-II and BD-NOS) (n=59) and MDD (n=76).

Results: The structure of the 16-item HCL demonstrated two main factors similar to those identified for the HCL-32 (an 'active-elated' factor and a 'risk-taking/irritable' factor). A score of 8 or more on a shortened 16-item version of the HCL had excellent ability to distinguish between BD and MDD. The sensitivity (83%) and specificity (71%) of the 16-item version were very similar to those for the full 32-item HCL.

Limitations: The HCL-16 was derived after subjects had completed the full HCL-32. It will be important to test the validity of a 'stand-alone' 16-item HCL questionnaire.

Conclusions: A shortened 16-item HCL (the HCL-16) is potentially a useful screening tool for hypomania within busy clinical settings.
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http://dx.doi.org/10.1016/j.jad.2010.01.004DOI Listing
August 2010

The Bipolar Interactive Psychoeducation (BIPED) study: trial design and protocol.

BMC Psychiatry 2009 Aug 12;9:50. Epub 2009 Aug 12.

South East Wales Trials Unit, Department of Primary Care and Public Health, 7thfloor Neuadd Merionnydd, School of Medicine, Cardiff University, Heath Park, Cardiff, UK, CF14 4XN.

Background: Bipolar disorders affect between 3-5% of the population and are associated with considerable lifelong impairment. Since much of the morbidity associated with bipolar disorder is caused by recurrent depressive symptoms, which are often only poorly responsive to antidepressants, there is a need to develop alternative, non-pharmacological interventions. Psychoeducational interventions have emerged as promising long-term therapeutic options for bipolar disorder.

Methods/design: The study is an exploratory, individually randomised controlled trial. The intervention known as 'Beating Bipolar' is a psychoeducational programme which is delivered via a novel web-based system. We will recruit 100 patients with a diagnosis of DSM-IV bipolar disorder (including type I and type II) currently in clinical remission. The primary outcome is quality of life. This will be compared for those patients who have participated in the psychoeducational programme with those who received treatment as usual. Quality of life will be assessed immediately following the intervention as well as 10 months after randomisation. Secondary outcomes include current depressive and manic symptoms, number of episodes of depression and mania/hypomania experienced during the follow-up period, global functioning, functional impairment and insight. An assessment of costs and a process evaluation will also be conducted which will explore the feasibility and acceptability of the intervention as well as potential barriers to effectiveness.

Discussion: Bipolar disorder is common, under-recognised and often poorly managed. It is a chronic, life-long, relapsing condition which has an enormous impact on the individual and the economy. This trial will be the first to explore the effectiveness of a novel web-based psychoeducational intervention for patients with bipolar disorder which has potential to be easily rolled out to patients.

Trial Registration: Current Controlled Trials ISRCTN81375447.
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http://dx.doi.org/10.1186/1471-244X-9-50DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2734537PMC
August 2009

Genomic imprinting and the expression of affect in Angelman syndrome: what's in the smile?

J Child Psychol Psychiatry 2007 Jun;48(6):571-9

School of Psychology, University of Birmingham, UK.

Background: Kinship theory (or the genomic conflict hypothesis) proposes that the phenotypic effects of genomic imprinting arise from conflict between paternally and maternally inherited alleles. A prediction arising for social behaviour from this theory is that imbalance in this conflict resulting from a deletion of a maternally imprinted gene, as in Angelman syndrome (AS), will result in a behavioural phenotype that should evidence behaviours that increase access to maternally provided social resources (adult contact).

Method: Observation of the social behaviour of children with AS (n = 13), caused by a deletion at 15q11-q13, and a matched comparison group (n = 10) was undertaken for four hours in a socially competitive setting and the effect of adult attention on child behaviours and the effect of child smiling on adult behaviours evaluated using group comparisons and observational lag sequential analyses.

Results: The AS group smiled more than the comparison group in all settings, which had different levels of adult attention, and more when the level of adult attention was high. Smiling by children with AS evoked higher levels of adult attention, eye contact and smiling both than by chance and in comparison to other children and this effect was sustained for 30 s to 50 s. Smiling by children with AS was frequently preceded by child initiated contact toward the adult.

Discussion: The results are consistent with a kinship theory explanation of the function of heightened levels of sociability and smiling in Angelman syndrome and provide support for an emotion signalling interpretation of the mechanism by which smiling accesses social resources. Further research on other behaviours characteristic of Angelman and Prader-Willi syndromes warrant examination from this perspective.
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http://dx.doi.org/10.1111/j.1469-7610.2007.01736.xDOI Listing
June 2007

Cbl-3-deficient mice exhibit normal epithelial development.

Mol Cell Biol 2003 Nov;23(21):7708-18

Department of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada M5G 2C1.

Cbl family proteins are evolutionarily conserved ubiquitin ligases that negatively regulate signaling from tyrosine kinase-coupled receptors. The mammalian cbl family consists of c-Cbl, Cbl-b, and the recently cloned Cbl-3 (also known as Cbl-c). In this study, we describe the detailed expression pattern of murine Cbl-3 and report the generation and characterization of Cbl-3-deficient mice. Cbl-3 exhibits an expression pattern distinct from those of c-Cbl and Cbl-b, with high levels of Cbl-3 expression in epithelial cells of the gastrointestinal tract and epidermis, as well as the respiratory, urinary, and reproductive systems. Cbl-3 expression was not detected in nonepithelial cells, but within epithelial tissues, the levels of Cbl-3 expression varied from undetectable in the alveoli of the lungs to very strong in the cecum and colon. Despite this restricted expression pattern, Cbl-3-deficient mice were viable, healthy, and fertile and displayed no histological abnormalities up to 18 months of age. Proliferation of epithelial cells in the epidermises and gastrointestinal tracts was unaffected by the loss of Cbl-3. Moreover, Cbl-3 was not required for attenuation of epidermal growth factor-stimulated Erk activation in primary keratinocytes. Thus, Cbl-3 is dispensable for normal epithelial development and function.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC207562PMC
http://dx.doi.org/10.1128/mcb.23.21.7708-7718.2003DOI Listing
November 2003

The MAGUK family protein CARD11 is essential for lymphocyte activation.

Immunity 2003 Jun;18(6):763-75

Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr Gasse 7, A-1030, Vienna, Austria.

Members of the MAGUK family proteins cluster receptors and intracellular signaling molecules at the neuronal synapse. We report that genetic inactivation of the MAGUK family protein CARD11/Carma1/Bimp3 results in a complete block in T and B cell immunity. CARD11 is essential for antigen receptor- and PKC-mediated proliferation and cytokine production in T and B cells due to a selective defect in JNK and NFkappaB activation. Moreover, B cell proliferation and JNK activation were impaired upon stimulation of TLR4 with lipopolysaccharide, indicating that CARD11 is involved in both the innate and adaptive immune systems. Our results show that the same family of molecules are critical regulators of neuronal synapses and immune receptor signaling.
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http://dx.doi.org/10.1016/s1074-7613(03)00148-1DOI Listing
June 2003

Communication between the TCR and integrins: role of the molecular adapter ADAP/Fyb/Slap.

Curr Opin Immunol 2002 Jun;14(3):317-22

Amgen, Department of Medical Biophysics and Immunology, University of Toronto, 620 University Avenue, Ontario M5G 2C1, Toronto, Canada.

TCR stimulation induces integrin-mediated adhesion, facilitating stabilization of conjugates between T cells and antigen-presenting cells and thereby contributing to T cell activation. Integrin activation has been shown to require cytoskeletal reorganization; however, the molecular mechanisms mediating communication between the TCR and integrins remain unclear. Recently the adapter protein ADAP/Fyb/Slap has been shown to couple TCR stimulation to integrin activation by mediating increased integrin avidity. ADAP may also play a role in transduction of external signals by integrins. Like other adapters, ADAP is a multifunctional protein and interacts with molecules such as Fyn, Slp-76, Ena/VASP proteins, Vav1, WASP and the Arp2/3 complex.
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http://dx.doi.org/10.1016/s0952-7915(02)00334-5DOI Listing
June 2002

ADAP-ting TCR signaling to integrins.

Sci STKE 2002 Apr 9;2002(127):re3. Epub 2002 Apr 9.

Amgen, Department of Medical Biophysics, University of Toronto, 620 University Avenue, Toronto, Ontario, Canada M5G 2C1.

Adaptor proteins are essential components of T cell receptor (TCR) signaling cascades regulating gene transcription and cytoskeletal reorganization. The molecular adaptor adhesion- and degranulation-promoting adaptor protein (ADAP), also known as Fyn binding protein (FYB) or Slp-76-associated protein of 130 kilodaltons (SLAP-130), interacts with a number of signaling intermediates including Slp-76, the Src family tyrosine kinase Fyn, vasodilator-stimulated phosphoprotein (VASP), and the actin-nucleating protein WASP. Recently ADAP was shown genetically to positively regulate T cell activation, TCR-induced integrin clustering, and T cell adhesion. The mechanism by which ADAP couples TCR stimulation to integrin clustering remains unclear; however, studies of ADAP, the exchange factor Vav1, and WASP suggest that TCR and integrin clustering may be controlled by distinct signaling pathways.
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http://dx.doi.org/10.1126/stke.2002.127.re3DOI Listing
April 2002

Vav1 controls integrin clustering and MHC/peptide-specific cell adhesion to antigen-presenting cells.

Immunity 2002 Mar;16(3):331-43

Amgen Institute, 620 University Avenue, Toronto, Ontario M5G 2C1, Canada.

Integrin-mediated adhesion is essential for the formation of stable contacts between T cells and antigen-presenting cells (APCs). We show that Vav1 controls integrin-mediated adhesion of thymocytes and T cells to ECM proteins and ICAM1 following TCR stimulation. In a peptide-specific system, Vav1 is required for T cell adhesion to peptide-loaded APCs. Intriguingly, TCR-induced cell adhesion and aggregation of integrins occurs independent of WASP. Whereas LFA-1 and actin caps colocalize in wasp(-/-) T cells in response to TCR stimulation, loss of WASP uncouples TCR caps from actin patches. Our data reveal a novel role for Vav1 and WASP in the regulation of TCR-induced integrin clustering and cell adhesion and show that integrin and TCR clustering are controlled by distinct pathways.
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http://dx.doi.org/10.1016/s1074-7613(02)00291-1DOI Listing
March 2002