Publications by authors named "Lisa Taylor"

79 Publications

Predicting Infection Risk in Multiple Sclerosis Patients Treated with Ocrelizumab: A Retrospective Cohort Study.

CNS Drugs 2021 Apr 13. Epub 2021 Apr 13.

Department of Neurology, Melbourne MS Centre, Royal Melbourne Hospital, Parkville, VIC, 3050, Australia.

Background: Ocrelizumab safety outcomes have been well evaluated in clinical trials and open-label extension (OLE) studies. However, risk factors for infection in patients with multiple sclerosis (MS) receiving ocrelizumab have not been extensively studied in the real-world setting.

Objective: The aim of this study was to examine factors determining risk of self-reported infections and antimicrobial use in patients receiving ocrelizumab for MS.

Methods: A retrospective, observational cohort study was conducted in patients receiving ocrelizumab at the Royal Melbourne Hospital. Infection type and number were reported by patients, and the associations of potential clinical and laboratory risk factors with self-reported infection and antimicrobial use were estimated using univariate and multivariable logistic regression models.

Results: A total of 185 patients were included in the study; a total of 176 infections were reported in 89 patients (46.1%), and antimicrobial use was identified in 47 patients (25.3%). In univariate analyses, a higher serum IgA was associated with reduced odds of infection (OR 0.44, 95% CI 0.25-0.76). In multivariable analyses, older age (OR 0.94, 95% CI 0.88-0.99), higher serum IgA (OR 0.37, 95% CI 0.17-0.80) and higher serum IgG (OR 0.81, 95% CI 0.67-0.99) were associated with reduced odds of infection. Older age (OR 0.85, 95% CI 0.75-0.96) and higher serum IgA (OR 0.23, 95% CI 0.07-0.79) were associated with reduced odds of antimicrobial use, whilst longer MS disease duration (OR 1.22, 95% CI 1.06-1.41) and higher Expanded Disability Status Scale (EDSS) score (OR 1.99, 95% CI 1.02-3.86) were associated with increased odds of antimicrobial use.

Conclusions: Higher serum IgA and IgG and older age were associated with reduced odds of infection. Our findings highlight that infection risk is not uniform in patients with MS receiving ocrelizumab and substantiate the need to monitor immunoglobulin levels pre-treatment and whilst on therapy.
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http://dx.doi.org/10.1007/s40263-021-00810-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042832PMC
April 2021

Barriers impacting the POINT pragmatic trial: the unavoidable overlap between research and intervention procedures in "real-world" research.

Trials 2021 Feb 4;22(1):114. Epub 2021 Feb 4.

Department of Psychology, Indiana University Purdue University Indianapolis, 402 N. Blackford St., Indianapolis, IN, 46202, USA.

Background: This manuscript provides a research update to the ongoing pragmatic trial of Project POINT (Planned Outreach, Intervention, Naloxone, and Treatment), an emergency department-based peer recovery coaching intervention for linking patients with opioid use disorder to evidence-based treatment. The research team has encountered a number of challenges related to the "real-world" study setting since the trial began. Using an implementation science lens, we sought to identify and describe barriers impacting both the intervention and research protocols of the POINT study, which are often intertwined in pragmatic trials due to the focus on external validity.

Method: Qualitative data were collected from 3 peer recovery coaches, 2 peer recovery coach supervisors, and 3 members of the research team. Questions and deductive qualitative analysis were guided by the Consolidated Framework for Implementation Research (CFIR).

Results: Nine unique barriers were noted, with 5 of these barriers impacting intervention and research protocol implementation simultaneously. These simultaneous barriers were timing of intervention delivery, ineffective communication with emergency department staff, lack of privacy in the emergency department, the fast-paced emergency department setting, and patient's limited resources. Together, these barriers represent the intervention characteristics, inner setting, and outer setting domains of the CFIR.

Conclusion: Results highlight the utility of employing an implementation science framework to assess implementation issues in pragmatic trials and how this approach might be used as a quality assurance mechanism given the considerable overlap that exists between research and intervention protocols in real-world trial settings. Previously undocumented changes to the trial design that have been made as a result of the identified barriers are discussed.
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http://dx.doi.org/10.1186/s13063-021-05065-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859893PMC
February 2021

Ethical climate in contemporary paediatric intensive care.

J Med Ethics 2021 Jan 11. Epub 2021 Jan 11.

School of Medicine, University of Queensland, Brisbane, Queensland, Australia.

Ethical climate (EC) has been broadly described as how well institutions respond to ethical issues. Developing a tool to study and evaluate EC that aims to achieve sustained improvements requires a contemporary framework with identified relevant drivers. An extensive literature review was performed, reviewing existing EC definitions, tools and areas where EC has been studied; ethical challenges and relevance of EC in contemporary paediatric intensive care (PIC); and relevant ethical theories. We surmised that existing EC definitions and tools designed to measure it fail to capture nuances of the PIC environment, and sought to address existing gaps by developing an EC framework for PIC founded on ethical theory. In this article, we propose a Paediatric Intensive Care Ethical Climate (PICEC) conceptual framework and four measurable domains to be captured by an assessment tool. We define PICEC as the collective felt experience of interdisciplinary team members arising from those factors that enable or constrain their ability to navigate ethical aspects of their work. PICEC both results from and is influenced by how well ethical issues are understood, identified, explored, reflected on, responded to and addressed in the workplace. PICEC encompasses four, core inter-related domains representing drivers of EC including: (1) organisational culture and leadership; (2) interdisciplinary team relationships and dynamics; (3) integrated child and family-centred care; and (4) ethics literacy. Future directions involve developing a PICEC measurement tool, with implications for benchmarking as well as guidance for, and evaluation of, targeted interventions to foster a healthy EC.
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http://dx.doi.org/10.1136/medethics-2020-106818DOI Listing
January 2021

Fast and safe: Optimising multiple sclerosis infusions during COVID-19 pandemic.

Mult Scler Relat Disord 2021 Jan 1;47:102642. Epub 2020 Dec 1.

Alfred Health, Clinical Neurosciences, Melbourne, Australia; Department of Neuroscience, Central Clinical School, Monash University, Melbourne Australia.

Background: The COVID-19 pandemic challenges multiple sclerosis services to be innovative in delivering infusible therapies. To reduce time in clinical settings, and potential staff or space losses, we implemented rapid infusion protocols for selected patients.

Objective: To analyse the rate of infusion related reactions and patient experience of rapid infusions of natalizumab and ocrelizumab. To document time reduction patients spent in clinical settings during the COVID-19 pandemic.

Methods: Patients with prior exposure to at least three natalizumab or two 300mg ocrelizumab infusions were approved for rapid protocols. A retrospective audit and survey were completed.

Results: We analysed 269 rapid natalizumab infusions and 100 rapid ocrelizumab infusions. Infusion related reactions during the natalizumab or ocrelizumab infusions occurred in two patients (1.52%) and eight patients (8%), respectively. All infusion related reactions were mild to moderate and did not require infusion discontinuation. No infusion reactions occurred during the post-infusion observation. Patient experience was positive.

Conclusion: Frequency or severity of infusion related reactions in rapid infusions were no different compared to published data. In the setting of COVID-19, pandemic rapid infusion protocols could potentially save hospital resources and limit patient exposure to a high-risk clinical setting while still maintaining ongoing treatment of multiple sclerosis.
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http://dx.doi.org/10.1016/j.msard.2020.102642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955770PMC
January 2021

Hemipteran defensive odors trigger predictable color biases in jumping spider predators.

Sci Rep 2020 12 14;10(1):21898. Epub 2020 Dec 14.

Entomology and Nematology Department, University of Florida, 1881 Natural Area Drive, Gainesville, FL, 32611, USA.

Multimodal warning displays often pair one signal modality (odor) with a second modality (color) to avoid predation. Experiments with bird predators suggest these signal components interact synergistically, with aversive odors triggering otherwise hidden aversions to particular prey colors. In a recent study, this phenomenon was found in a jumping spider (Habronattus trimaculatus), with the defensive odor from a coreid bug (Acanthocephala femorata) triggering an aversion to red. Here, we explore how generalizable this phenomenon is by giving H. trimaculatus the choice between red or black prey in the presence or absence of defensive odors secreted from (1) eastern leaf-footed bugs (Leptoglossus phyllopus, Hemiptera), (2) grass stinkbugs (Mormidea pama, Hemiptera), (3) Asian ladybird beetles (Harmonia axyridis, Coleoptera), and (4) eastern lubber grasshoppers (Romalea microptera, Orthoptera). As expected, in the presence of the hemipteran odors, spiders were less likely to attack red prey (compared to no odor). Unexpectedly, the beetle and grasshopper odors did not bias spiders away from red. Our results with the hemipteran odors were unique to red; follow-up experiments indicated that these odors did not affect biases for/against green prey. We discuss our findings in the context of generalized predator foraging behavior and the functions of multimodal warning displays.
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http://dx.doi.org/10.1038/s41598-020-78952-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736339PMC
December 2020

Brain amyloid and the transition to dementia in Down syndrome.

Alzheimers Dement (Amst) 2020 11;12(1):e12126. Epub 2020 Nov 11.

Department of Pediatrics Irvine Medical Center University of California Orange California USA.

Introduction: Down syndrome (DS) is associated with elevated risk for Alzheimer's disease (AD) due to amyloid beta (Aβ) lifelong accumulation. We hypothesized that the spatial distribution of brain Aβ predicts future dementia conversion in individuals with DS.

Methods: We acquired F-florbetapir positron emission tomography scans from 19 nondemented individuals with DS at baseline and monitored them for 4 years, with five individuals transitioning to dementia. Machine learning classification using an independent test set determined features on F-florbetapir standardized uptake value ratio maps that predicted transition.

Results: In addition to "AD signature" regions including the inferior parietal cortex, temporal lobes, and the cingulum, we found that Aβ cortical binding in the prefrontal and superior frontal cortices distinguished subjects who transitioned to dementia. Classification did well in predicting transitioners.

Discussion: Our study suggests that specific regional profiles of brain amyloid in older adults with DS may predict cognitive decline and are informative in evaluating the risk for dementia.
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http://dx.doi.org/10.1002/dad2.12126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656170PMC
November 2020

Association of Pregnancy With the Onset of Clinically Isolated Syndrome.

JAMA Neurol 2020 Dec;77(12):1496-1503

Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia.

Importance: Multiple sclerosis (MS) is usually diagnosed in women during their childbearing years. Currently, no consensus exists on whether pregnancy can delay the first episode of demyelination or clinically isolated syndrome (CIS).

Objective: To investigate the association of pregnancy with time to CIS onset.

Design, Setting, And Participants: This multicenter cohort study collected reproductive history (duration of each pregnancy, date of delivery, length of breastfeeding) on all participants between September 1, 2016, and June 25, 2019. Adult women being treated at the MS outpatient clinics of 4 tertiary hospitals in 2 countries (Charles University and General University Hospital in Prague, Czech Republic; Royal Melbourne Hospital in Melbourne, Australia; Alfred Hospital in Melbourne, Australia; and John Hunter Hospital in Newcastle, Australia) were recruited to participate in the study. Preexisting data (date of CIS onset, date of birth, sex, date of clinical onset, and Expanded Disability Status Scale result) were collected from MSBase, an international registry of long-term prospectively collected data on patients with MS. Data analyses were performed from June 1, 2019, to February 3, 2020.

Exposures: Gravida (defined as any pregnancy, including pregnancy that ended in miscarriage and induced abortion) and parity (defined as childbirth after gestational age of more than 20 weeks, including livebirth and stillbirth) before CIS onset.

Main Outcomes And Measures: Time to CIS onset. The following were assessed: (1) whether women with previous pregnancies and childbirths had a delayed onset of CIS compared with those who had never been pregnant and those who had never given birth, and (2) whether a dose response existed, whereby a higher number of gravidity and parity was associated with a later onset of CIS.

Results: Of the 2557 women included in the study, the mean (SD) age at CIS onset was 31.5 (9.7) years. Of these women, before CIS onset, 1188 (46%) had at least 1 pregnancy and 1100 (43%) had at least 1 childbirth. The mean (SD) age at first pregnancy was 23.3 (4.5) years and at first childbirth was 23.8 (4.5) years. Women with previous pregnancies and childbirths had a later onset of CIS compared with those who had never been pregnant (HR, 0.68; 95% CI, 0.62-0.75; P < .001), with a median delay of 3.3 (95% CI, 2.5-4.1) years. Women who had given birth also had a later CIS onset compared with women who had never given birth (HR 0.68; 95% CI, 0.61-0.75; P < .001), with a similar median delay of 3.4 (95% CI, 1.6-5.2) years. A higher gravidity and parity number was not associated with delay in CIS onset.

Conclusions And Relevance: This study suggests an association between previous pregnancies and childbirths and timing of CIS onset, but having more pregnancies or childbirths did not appear to be associated with a later CIS onset. Further studies are needed to help explain the mechanisms behind the associations between pregnancy and onset of multiple sclerosis.
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http://dx.doi.org/10.1001/jamaneurol.2020.3324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490748PMC
December 2020

Down syndrome: Distribution of brain amyloid in mild cognitive impairment.

Alzheimers Dement (Amst) 2020 17;12(1):e12013. Epub 2020 Apr 17.

Department of Pediatrics University of California Irvine Medical Center Orange California.

Introduction: Down syndrome (DS) is associated with a higher risk of dementia. We hypothesize that amyloid beta (Aβ) in specific brain regions differentiates mild cognitive impairment in DS (MCI-DS) and test these hypotheses using cross-sectional and longitudinal data.

Methods: 18F-AV-45 (florbetapir) positron emission tomography (PET) data were collected to analyze amyloid burden in 58 participants clinically classified as cognitively stable (CS) or MCI-DS and 12 longitudinal CS participants.

Results: The study confirmed our hypotheses of increased amyloid in inferior parietal, lateral occipital, and superior frontal regions as the main effects differentiating MCI-DS from the CS groups. The largest annualized amyloid increases in longitudinal CS data were in the rostral middle frontal, superior frontal, superior/middle temporal, and posterior cingulate cortices.

Discussion: This study helps us to understand amyloid in the MCI-DS transitional state between cognitively stable aging and frank dementia in DS. The spatial distribution of Aβ may be a reliable indicator of MCI-DS in DS.
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http://dx.doi.org/10.1002/dad2.12013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233421PMC
April 2020

Methods for independently manipulating palatability and color in small insect prey.

PLoS One 2020 7;15(4):e0231205. Epub 2020 Apr 7.

Entomology and Nematology Department, University of Florida, Gainesville, FL, United States of America.

Understanding how the psychology of predators shapes the defenses of colorful aposematic prey has been a rich area of inquiry, with emphasis on hypothesis-driven experiments that independently manipulate color and palatability in prey to examine predator responses. Most of these studies focus on avian predators, despite calls to consider more taxonomically diverse predators. This taxonomic bias leaves gaps in our knowledge about the generalizability of current theory. Here we have adapted tools that have been successfully used with bird predators and scaled them down and tested them with smaller predators (Habronattus jumping spiders) and small insect prey (termites, milkweed bug nymphs, pinhead crickets, fruit flies). Specifically, we test (1) the application of denatonium benzoate (DB) to the surface of live termites, crickets, and fruit flies, and (2) the effectiveness of manipulating the palatability of milkweed bug nymphs through diet. We also test the effectiveness of combining these palatability manipulations with various color manipulations. Across several experiments, we confirm that our palatability manipulations are not detectable to the spiders before they attack (i.e., they do not produce aversive odors that spiders avoid), and show that unpalatable prey are indeed quickly rejected and spiders do not habituate to the taste with experience. We also investigate limitations of these techniques by assessing possible unintended effects on prey behavior and the risk of contact contamination when using DB-treated prey in experiments. While similar tools have been used to manipulate color and palatability with avian predators and relatively large insect prey, we show how these techniques can be effectively adapted for use with small invertebrate predators and prey.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231205PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138310PMC
July 2020

Toward a Molecular Understanding of the Impact of Crystal Size and Shape on Punch Sticking.

Mol Pharm 2020 04 5;17(4):1148-1158. Epub 2020 Mar 5.

Pharmaceutical Materials Science and Engineering Laboratory, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, 9-127B Weaver-Densford Hall, 308 Harvard Street S.E., Minneapolis, Minnesota 55455, United States.

Punch sticking during tablet manufacturing is a common problem facing the pharmaceutical industry. Using several model compounds, effects of crystal size and shape of active pharmaceutical ingredients (API) on punch sticking propensity were systematically investigated in this work to provide molecular insights into the punch-sticking phenomenon. In contrast to the common belief that smaller API particles aggravate punch sticking, results show that particle size reduction can either reduce or enhance API punch sticking, depending on the complex interplay among the particle surface area, plasticity, cohesive strength, and specific surface functional groups. Therefore, other factors, such as crystal mechanical properties, surface chemistry of crystal facets exposed to the punch face, and choice of excipients in a formulation, should be considered for a more reliable prediction of the initiation and progression of punch sticking. The exposure of strong electronegative groups to the punch face facilitates the onset of sticking, while higher plasticity and cohesive strength aggravate sticking.
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http://dx.doi.org/10.1021/acs.molpharmaceut.9b01185DOI Listing
April 2020

Influence of seeing a red face during the male-male encounters of mosquito-specialist spiders.

Learn Behav 2020 03;48(1):104-112

Entomology and Nematology Department, University of Florida, P.O. Box 110620, Gainesville, FL, 32611-0620, USA.

Males of Evarcha culicivora, an East African jumping spider (Salticidae), have bright red faces. Here, we investigated how seeing a red face might influence a male's behaviour during encounters with another male. We applied black eyeliner to conceal the red on a male's face and measured the spectral properties of male faces with and without the eyeliner. Only the faces without eyeliner reflected in the long-wavelength range corresponding to red. In experiments over 2 days, where eyeliner was absent on the first day and present on the second, we compared how two groups of males responded to their mirror images. Face Group: eyeliner concealed their faces. Head Group: eyeliner was applied to the tops of the males' heads instead of on their faces. The males from both groups displayed to their mirror image as if it were a living same-sex conspecific. However, when they could see a red face, males in the face group escalated to higher levels of aggression to their mirror image and initiated displaying from farther away than when the red had been concealed. We also found that the influence of eyeliner was stronger for the face group than for the head group. These findings suggest that, when seeing a red face, E. culicivora males become more confident that the individual in view is another male.
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http://dx.doi.org/10.3758/s13420-020-00411-yDOI Listing
March 2020

Comparison of the effectiveness of a tailored cognitive behavioural therapy with a supportive listening intervention for depression in those newly diagnosed with multiple sclerosis (the ACTION-MS trial): protocol of an assessor-blinded, active comparator, randomised controlled trial.

Trials 2020 01 20;21(1):100. Epub 2020 Jan 20.

Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.

Background: Multiple sclerosis (MS) is an unpredictable, chronic neurological disease accompanied with high rates of depression and anxiety, particularly in the early stages of diagnosis. There is evidence to suggest that cognitive behavioural therapy (CBT) is effective for the treatment of depression amongst individuals with MS; however, there is a paucity of tailored CBT interventions designed to be offered in the newly diagnosed period. This trial is the first to assess the effectiveness and cost-effectiveness of a tailored CBT intervention compared to a supportive listening (SL) intervention amongst individuals with MS who are depressed.

Methods: ACTION-MS is a two-arm parallel group, assessor-blinded, active comparator, randomised controlled trial which will test whether a tailored CBT-based intervention compared to an SL intervention can reduce depression and related factors such as anxiety, fatigue, pain and sleep problems in those newly diagnosed with MS. Sixty participants who are within 5 years of having received a diagnosis of MS and scored within the mild to moderate range of depression on the Beck Depression Inventory (BDI-II) will be recruited from MS clinics located across three hospital sites in Melbourne, Australia. The primary outcome is depression severity using the BDI-II at post-assessment. Intervention satisfaction and acceptability will be assessed. A cost-effectiveness analysis will also be conducted. Data will be analysed on an intention-to-treat basis.

Discussion: There is a scarcity of psychological interventions for depression targeting the newly diagnosed period. However, interventions during this time point have the potential to have a major impact on the mental and physical wellbeing of those newly diagnosed with MS. The current trial will provide data on the effectiveness of a tailored CBT intervention for the treatment of depression in those newly diagnosed with MS. Findings will also provide effect size estimates that can be used to power a later-stage multi-centre trial of treatment efficacy, and will provide information on the mechanisms underlying any treatment effects and cost-effectiveness data for delivering this intervention in outpatient MS clinics.

Trial Registration: ISRCTN trials registry, ISRCTN63987586. Current controlled trials. Retrospectively registered on 20 October 2017.
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http://dx.doi.org/10.1186/s13063-019-4018-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971867PMC
January 2020

Variation in activity rates may explain sex-specific dorsal color patterns in Habronattus jumping spiders.

PLoS One 2019 16;14(10):e0223015. Epub 2019 Oct 16.

School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America.

In many animals, color pattern and behavior interact to deceive predators. For mimics, such deception can range from precise (near-perfect mimicry) to only subtle resemblance (imperfect mimicry) and such strategies often differ by sex because of differing ecological selection pressures. In this field study, we examine variation in behavior and ecology that may be linked with sex differences in dorsal color pattern in three sympatric species of Habronattus jumping spiders (H. clypeatus, H. hallani, H. pyrrithrix). Males of these species have conspicuous dorsal patterning that is subtly reminiscent of the general color patterns of wasps and bees, while females are cryptic. We show that, compared with females, these conspicuous males exhibited increased leg-waving behavior outside of the context of courtship; such behavior is common in jumping spiders that mimic wasps and bees presumably because a mimic's waving legs resemble antennae. Males of a fourth sympatric species (H. hirsutus) without conspicuous dorsal patterning did not exhibit increased leg-waving. These results are consistent with and offer preliminary support for the idea that male color and behavior may work together to deceive predators. We also examined whether higher movement rates of males (who must wander to find females) and/or different use of the microhabitat by the sexes could explain sexual dichromatism. We found that microhabitat use was similar for males and females, but males of all three conspicuously-colored species spent more time actively moving than females. To our knowledge, this is the first study to speculate that conspicuous male dorsal coloration in Habronattus may have a deceptive function, and to explore why dorsal coloration differs between the sexes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223015PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795386PMC
March 2020

Phase 1/2a clinical trial of gene-corrected autologous cell therapy for recessive dystrophic epidermolysis bullosa.

JCI Insight 2019 10 3;4(19). Epub 2019 Oct 3.

Stanford University School of Medicine, Department of Dermatology, Redwood City, California, USA.

BACKGROUNDRecessive dystrophic epidermolysis bullosa (RDEB) patients have mutations in the COL7A1 gene and thus lack functional type VII collagen (C7) protein; they have marked skin fragility and blistering. This single-center phase 1/2a open-label study evaluated the long-term efficacy, safety, and patient-reported outcomes in RDEB patients treated with gene-corrected autologous cell therapy.METHODSAutologous keratinocytes were isolated from participant skin biopsies. Epidermal sheets were prepared from cells transduced with a retrovirus carrying the full-length human COL7A1 gene. These gene-corrected autologous epidermal sheets measured 5 × 7 cm (35 cm2) and were transplanted onto 6 wound sites in each of 7 adult participants (n = 42 sites total) from 2013 to 2017. Participants were followed for 2 to 5 years.RESULTSNo participants experienced any serious related adverse events. Wound healing of 50% or greater by Investigator Global Assessment was present in 95% (36 of 38) of treated wounds versus 0% (0 of 6) of untreated control wounds at 6 months (P < 0.0001). At year 1, 68% (26 of 38) of treated wounds had 50% or greater healing compared with 17% (1 of 6) of control wounds (P = 0.025). At year 2, 71% (27 of 38) of treated wounds had 50% or greater healing compared with 17% (1 of 6) of control wounds (P = 0.019).CONCLUSIONC7 expression persisted up to 2 years after treatment in 2 participants. Treated wounds with 50% or greater healing demonstrated improvement in patient-reported pain, itch, and wound durability. This study provides additional data to support the clinically meaningful benefit of treating chronic RDEB wounds with ex vivo, C7 gene-corrected autologous cell therapy. This approach was safe and promoted wound healing that was associated with improved patient-reported outcomes.TRIAL REGISTRATIONClinicaltrials.gov identifier: NCT01263379.FUNDINGEpidermolysis Bullosa Research Partnership, Epidermolysis Bullosa Medical Research Foundation, NIH R01 AR055914, Office of Research and Development at the Palo Alto Veteran's Affairs Medical Center, and the Dermatology Foundation.
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http://dx.doi.org/10.1172/jci.insight.130554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795403PMC
October 2019

Manipulation of Color Patterns in Jumping Spiders for Use in Behavioral Experiments.

J Vis Exp 2019 05 21(147). Epub 2019 May 21.

Department of Entomology and Nematology, University of Florida; Florida Museum of Natural History, University of Florida.

In the field of behavioral ecology, many experiments are designed to investigate the evolutionary purposes of colorful traits in the context of sexual selection and predation. Methods are various but mostly consist of modifying the color patterns of individuals with diverse colorants. Such techniques have been used across many vertebrate taxa, particularly in birds, but have remained underdeveloped for invertebrates because of the difficulty of effectively manipulating color in small organisms. Instead, to manipulate the appearance of invertebrates, scientists have usually modified the lighting environment to filter out certain wavelengths. However, such a method affects not only the phenotypic trait of interest but the entire appearance of the individual and its surrounding. Here, scaling down the techniques previously used on colorful birds, we present ways of manipulating the colors of small arthropods, using equally emblematic but understudied species: the colorful jumping spiders.
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http://dx.doi.org/10.3791/59824DOI Listing
May 2019

Odor alters color preference in a foraging jumping spider.

Behav Ecol 2018 Jul-Aug;29(4):833-839. Epub 2018 May 23.

Entomology and Nematology Department, University of Florida, Gainesville, FL, USA.

In many prey taxa with aposematic coloration, prey defenses also involve signals in other modalities (odors, sounds, etc.), yet the selective forces that have driven multimodality in warning displays are not well understood. One potential hypothesis that has recently received support in the avian literature (but has yet to be examined in invertebrates) is that different signal components may interact synergistically, such that one component of a signal (odor) may trigger a predator's aversion to another component of a signal (color). Here, we gave jumping spiders () the choice between red or black prey (artificially colored termites) in either the presence or absence of odor from the chemically defended coreid bug (). When the odor was present, spiders were more likely to avoid the color red compared with when the odor was absent. Interestingly, this pattern only held up when the odor was novel; subsequent exposure to the odor had no effect on color preference. Moreover, this pattern only held for the color red (a color typically used as a warning color and often paired with odor). We replicated this experiment giving spiders the choice between green or black prey, and found that the presence of the odor had no effect on the spiders' responses to the color green. We discuss these findings in the context of predator psychology and the evolution of prey coloration.
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http://dx.doi.org/10.1093/beheco/ary068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041943PMC
May 2018

Specialists and generalists coexist within a population of spider-hunting mud dauber wasps.

Behav Ecol 2017 May-Jun;28(3):890-898. Epub 2017 Apr 1.

Entomology and Nematology Department, University of Florida, 1881 Natural Area Drive, Gainesville, FL 32611, USA.

Individual foraging specialization describes the phenomenon where conspecifics within a population of generalists exhibit differences in foraging behavior, each specializing on different prey types. Individual specialization is widespread in animals, yet is understudied in invertebrates, despite potential impacts to food web and population dynamics (Hymenoptera: Sphecidae) is an excellent system to examine individual specialization. Females of these mud dauber wasps capture and paralyze spiders which they store in mud nests to provision their offspring. Individuals may make hundreds of prey choices in their short lifespan and fully intact prey items can be easily excavated from their mud nests, where each distinct nest cell represents a discrete foraging bout. Using data collected from a single population of (where all individuals had access to the same resources), we found evidence of strong individual specialization; individuals utilized different resources (with respect to prey taxa, prey ecological guild, and prey size) to provision their nests. The extent of individual specialization differed widely within the population with some females displaying extreme specialization (taking only prey from a single species) while others were generalists (taking prey from up to 6 spider families). We also found evidence of temporal consistency in individual specialization over multiple foraging events. We discuss these findings broadly in the context of search images, responses to changing prey availability, and intraspecific competition pressure.
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http://dx.doi.org/10.1093/beheco/arx050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5873241PMC
April 2017

Dependence of Punch Sticking on Compaction Pressure-Roles of Particle Deformability and Tablet Tensile Strength.

J Pharm Sci 2017 08 4;106(8):2060-2067. Epub 2017 May 4.

Department of Pharmaceutics, Pharmaceutical Materials Science and Engineering Laboratory, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455. Electronic address:

Punch sticking is a complex phenomenon influenced primarily by particle size, tooling surface roughness, tooling design, and tooling construction material. When particle and environmental factors are controlled, compaction pressure has a distinct effect on punch sticking behavior for a given active pharmaceutical ingredient (API). This research focuses on the effect of compaction pressure on punch sticking using 5 compounds with different sticking propensities. The results collectively show that sticking tends to be more problematic under higher compaction pressures and for more ductile compounds. This is attributed to the greater punch surface coverage by the API and the stronger cohesion of API to the existing API layer on the punch.
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http://dx.doi.org/10.1016/j.xphs.2017.04.059DOI Listing
August 2017

Frequent misdirected courtship in a natural community of colorful Habronattus jumping spiders.

PLoS One 2017 5;12(4):e0173156. Epub 2017 Apr 5.

School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America.

Male courtship display is common in many animals; in some cases, males engage in courtship indiscriminately, spending significant time and energy courting heterospecifics with whom they have no chance of mating or producing viable offspring. Due to high costs and few if any benefits, we might expect mechanisms to evolve to reduce such misdirected courtship (or 'reproductive interference'). In Habronattus jumping spiders, males frequently court heterospecifics with whom they do not mate or hybridize; females are larger and are voracious predators, posing a severe risk to males who court indiscriminately. In this study, we examined patterns of misdirected courtship in a natural community of four sympatric Habronattus species (H. clypeatus, H. hallani, H. hirsutus, and H. pyrrithrix). We used direct field observations to weigh support for two hypotheses (differential microhabitat use and species recognition signaling) to explain how these species reduce the costs associated with misdirected courtship. We show that, while the four species of Habronattus do show some differences in microhabitat use, all four species still overlap substantially, and in three of the four species individuals equally encountered heterospecifics and conspecifics. Males courted females at every opportunity, regardless of species, and in some cases, this led to aggression and predation by the female. These results suggest that, while differences in microhabitat use might reduce misdirected courtship to some extent, co-existence of these four species may be possible due to complex communication (i.e. species-specific elements of a male's courtship display). This study is the first to examine misdirected courtship in jumping spiders. Studies of misdirected courtship and its consequences in the field are limited and may broaden our understanding of how biodiversity is maintained within a community.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0173156PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381776PMC
August 2017

Powder properties and compaction parameters that influence punch sticking propensity of pharmaceuticals.

Int J Pharm 2017 Apr 21;521(1-2):374-383. Epub 2017 Feb 21.

Pharmaceutical Materials Science and Engineering Laboratory, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, 9-127 B Weaver-Densford Hall,308 Harvard Street S.E., Minneapolis, MN 55455, United States. Electronic address:

Punch sticking is a frequently occurring problem that challenges successful tablet manufacturing. A mechanistic understanding of the punch sticking phenomenon facilitates the design of effective strategies to solve punch sticking problems of a drug. The first step in this effort is to identify process parameters and particle properties that can profoundly affect sticking performance. This work was aimed at elucidating the key material properties and compaction parameters that influence punch sticking by statistically analyzing punch sticking data of 24 chemically diverse compounds obtained using a set of tooling with removable upper punch tip. Partial least square (PLS) analysis of the data revealed that particle surface area and tablet tensile strength are the most significant factors attributed to punch sticking. Die-wall pressure, ejection force, and take-off force also correlate with sticking, but to a lesser extent.
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http://dx.doi.org/10.1016/j.ijpharm.2017.02.053DOI Listing
April 2017

Interlaboratory validation of organism recovery for use in 42-day sediment toxicity tests with Hyalella azteca.

Environ Toxicol Chem 2017 04 7;36(4):1085-1089. Epub 2016 Nov 7.

AquaTox Testing & Consulting, Guelph, Ontario, Canada.

Environment and Climate Change Canada has developed a 42-d sediment toxicity test that includes a reproduction endpoint with the freshwater amphipod Hyalella azteca. The new methodology conducts the entire exposure in sediment, in contrast to existing standardized methods whereby adults are transferred to a water-only exposure before release of their first brood at day 28. This midtest transfer to clean water was because of the results of a juvenile H. azteca recovery trial conducted in the 1990s concluding that reproductive endpoints could be biased because of low recovery of young amphipods from sediment. Using a new procedure and reduced volume of sediment, an interlaboratory recovery trial was conducted using 2-d to 5-d old H. azteca added to control sediment. A total of 29 technicians from 8 laboratories participated in the present study. The average recovery for all laboratories and all technicians was 76% (coefficient of variation [CV] = 30%). Based on an initial target recovery of at least 80%, 19 of 29 (66%) technicians met this criterion, with an average recovery for this group of 88% (CV = 8.3%). Factors that reduced recovery success included: not using a light table, technicians with minimal sediment testing experience, and the use of imported young amphipods with limited acclimation. Excluding those results, the overall average recovery, which included 17 participating technicians, increased from 76% to 88% and lowered the CV from 30% to 8.6%. Based on these results, Environment and Climate Change Canada will recommend ≥85% average recovery of young in control sediment and require ≥80% as a technician performance criterion in its new test design for the reproduction methodology. Environ Toxicol Chem 2017;36:1085-1089. © 2016 Crown in the right of Canada. Published by Wiley Periodicals Inc. on behalf of SETAC.
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http://dx.doi.org/10.1002/etc.3638DOI Listing
April 2017

Mechanism and Kinetics of Punch Sticking of Pharmaceuticals.

J Pharm Sci 2017 01 17;106(1):151-158. Epub 2016 Sep 17.

Pharmaceutical Materials Science and Engineering Laboratory, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455. Electronic address:

Adherence of powder onto tablet tooling, known as punch sticking, is one of the tablet manufacturing problems that need to be resolved. An important step toward the resolution of this problem is to quantify sticking propensity of different active pharmaceutical ingredients (APIs) and understand physicochemical factors that influence sticking propensity. In this study, mass of adhered material onto a removable upper punch tip as a function of number of compression is used to monitor sticking kinetics of 24 chemically diverse compounds. We have identified a mathematical model suitable for describing punch sticking kinetics of a wide range of compounds. Chemical analyses have revealed significant enrichment of API content in the adhered mass. Based on this large set of data, we have successfully developed a new punch sticking model based on a consideration of the interplay of interaction strength among API, excipient, and punch surface. The model correctly describes the general shape of sticking profile, that is, initial rise in accumulated mass followed by gradual increase to a plateau. It also explains why sometimes sticking is arrested after monolayer coverage of punch surface by API (punch filming), while in other cases, API buildup is observed beyond monolayer coverage.
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http://dx.doi.org/10.1016/j.xphs.2016.07.015DOI Listing
January 2017

Don't go with the 'FLO' - a student mobile texting service to enhance nursing student retention.

Nurse Educ Today 2016 Oct 28;45:80-6. Epub 2016 Jun 28.

Simple Shared Healthcare, Unit A 3 Longbow Close, Harlescott Lane, Shrewsbury, Shropshire SY1 3GZ, United Kingdom. Electronic address:

Background: The review undertaken revealed that there is an abundance of literature concerning retention and the high levels of attrition among undergraduate students and of relevance here, nurse education. The study undertaken evaluated the use of mobile phone automated texts designed to provide information, support and reassurance to help alleviate the stress and anxieties that some undergraduate nursing students experience during the early phase of their studies and which can lead to some students leaving their programme.

Objective: The objective of the study was to evaluate how use of automated mobile phone texts, using a system known as FLO, could usefully supplement pastoral support, as an intervention to reduce attrition among undergraduate nursing students.

Design: A qualitative and quantitative evaluation was conducted using an open-ended questionnaire designed specifically for the study.

Participants: The sample were two cohorts of undergraduate first year student nurses (n=178). Of these 123 (69%) signed up to FLO and 77 (63%) completed the evaluation form.

Methods: The evaluation form that was administered in a classroom situation one week after use of FLO had ceased. Data were analysed through use of a descriptive statistics and thematic analysis approaches.

Results: A range of key themes emerged from the analysis including that text messages were helpful and supportive, increased a sense of belonging to the University and encouraged retention. There were some unresolved issues concerning the costs incurred by participants when sending reply text messages.

Conclusions: It is concluded that FLO or use of similar mobile phone protocols can be a useful addition to approaches to improve undergraduate nursing student retention rates.
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http://dx.doi.org/10.1016/j.nedt.2016.06.019DOI Listing
October 2016

Validation of a new standardized test method for the freshwater amphipod Hyalella azteca: Determining the chronic effects of silver in sediment.

Environ Toxicol Chem 2016 10 7;35(10):2430-2438. Epub 2016 Jul 7.

Environment Canada, Ottawa, Ontario, Canada.

Environment Canada has developed a new 42-d sediment toxicity test method that includes a reproduction test endpoint with the freshwater amphipod Hyalella azteca. Because of concerns that existing standard methodologies, whereby adults are transferred to a water-only exposure before release of their first brood at day 28, will lead to internal contaminant depuration and loss of sensitivity, the Environment Canada methodology conducts the entire exposure in sediment. To demonstrate applicability of the method for assessing the toxicity of chemical-spiked sediment, H. azteca were exposed for 42 d to sediment amended with silver nitrate (AgNO ). Mortality was significantly higher at the highest sediment concentration of Ag (2088 mg/kg dry wt); however, there was no significant reduction in biomass or reproduction as a result of Ag exposure despite significant bioaccumulation. Based on Ag measurements and speciation modeling, the principle route of Ag exposure was likely through the ingestion of complexed colloidal or particulate Ag. The techniques used to recover young amphipods from sediment were critical, and although this effort can be labor intensive (20-45 min/replicate), the technicians demonstrated 91% recovery in blind trials. For the first time, Environment Canada will require laboratories to report their recovery proficiency for the 42-d test-without this information, data will not be accepted. Overall, the reproduction test will be more applicable when only a few chemical concentrations need to be evaluated in laboratory-amended sediments or for field-collected contaminated site assessments (i.e., contaminated site vs reference site comparisons). Environ Toxicol Chem 2016;35:2430-2438. © 2016 SETAC.
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http://dx.doi.org/10.1002/etc.3453DOI Listing
October 2016

Using an interlaboratory study to revise methods for conducting 10-d to 42-d water or sediment toxicity tests with Hyalella azteca.

Environ Toxicol Chem 2016 10 21;35(10):2439-2447. Epub 2016 Jun 21.

Environment Canada, Ottawa, Ontario, Canada.

Studies have been conducted to refine US Environmental Protection Agency, ASTM International, and Environment Canada standard methods for conducting 42-d reproduction tests with Hyalella azteca in water or in sediment. Modifications to the H. azteca method include better-defined ionic composition requirements for exposure water (i.e., >15 mg/L of chloride and >0.02 mg/L of bromide) and improved survival, growth, and reproduction with alternate diets provided as increased rations over time in water-only or whole-sediment toxicity tests. A total of 24 laboratories volunteered to participate in the present interlaboratory study evaluating the performance of H. azteca in 42-d studies in control sand or control sediment using the refined methods. Improved growth and reproduction of H. azteca was observed with 2 alternate diets of 1) ramped diatoms (Thalassiosira weissflogii) + ramped Tetramin or 2) yeast-cerophyll-trout chow (YCT) + ramped Tetramin, especially when compared with results from the traditional diet of 1.8 mg YCT/d. Laboratories were able to meet proposed test acceptability criteria and in most cases had lower variation in growth or reproduction compared with previous interlaboratory studies using the traditional YCT diet. Laboratory success in conducting 42-d H. azteca exposures benefited from adherence to several key requirements of the detailed testing, culturing, and handling methods. Results from the present interlaboratory study are being used to help revise standard methods for conducting 10-d to 42-d water or sediment toxicity exposures with H. azteca. Environ Toxicol Chem 2016;35:2439-2447. © 2016 SETAC.
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http://dx.doi.org/10.1002/etc.3417DOI Listing
October 2016

Real-time product attribute control to manufacture antibodies with defined N-linked glycan levels.

Biotechnol Prog 2015 Sep-Oct;31(5):1433-41. Epub 2015 Jul 27.

Product and Process Development, Amgen Inc., 1201 Amgen Court West, Seattle, WA, 98119.

Pressures for cost-effective new therapies and an increased emphasis on emerging markets require technological advancements and a flexible future manufacturing network for the production of biologic medicines. The safety and efficacy of a product is crucial, and consistent product quality is an essential feature of any therapeutic manufacturing process. The active control of product quality in a typical biologic process is challenging because of measurement lags and nonlinearities present in the system. The current study uses nonlinear model predictive control to maintain a critical product quality attribute at a predetermined value during pilot scale manufacturing operations. This approach to product quality control ensures a more consistent product for patients, enables greater manufacturing efficiency, and eliminates the need for extensive process characterization by providing direct measures of critical product quality attributes for real time release of drug product.
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http://dx.doi.org/10.1002/btpr.2136DOI Listing
August 2016

Spectral filtering enables trichromatic vision in colorful jumping spiders.

Curr Biol 2015 May;25(10):R403-4

Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA. Electronic address:

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http://dx.doi.org/10.1016/j.cub.2015.03.033DOI Listing
May 2015

A new era for clinical quality measurement data.

J AHIMA 2013 Oct;84(10):66-7

AHIMA.

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October 2013

Show me the data: From data exchange to data aggregation, HIM has role to play.

J AHIMA 2013 Sep;84(9):60-1

AHIMA.

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September 2013