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1.
PLoS Biol ; 21(7): e3002184, 2023 07.
Article in English | MEDLINE | ID: mdl-37463136

ABSTRACT

The use of English as the common language of science represents a major impediment to maximising the contribution of non-native English speakers to science. Yet few studies have quantified the consequences of language barriers on the career development of researchers who are non-native English speakers. By surveying 908 researchers in environmental sciences, this study estimates and compares the amount of effort required to conduct scientific activities in English between researchers from different countries and, thus, different linguistic and economic backgrounds. Our survey demonstrates that non-native English speakers, especially early in their careers, spend more effort than native English speakers in conducting scientific activities, from reading and writing papers and preparing presentations in English, to disseminating research in multiple languages. Language barriers can also cause them not to attend, or give oral presentations at, international conferences conducted in English. We urge scientific communities to recognise and tackle these disadvantages to release the untapped potential of non-native English speakers in science. This study also proposes potential solutions that can be implemented today by individuals, institutions, journals, funders, and conferences. Please see the Supporting information files (S2-S6 Text) for Alternative Language Abstracts and Figs 5 and 6.


Subject(s)
Language , Linguistics , Humans , Surveys and Questionnaires
2.
Annu Rev Biomed Eng ; 26(1): 119-139, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38316063

ABSTRACT

Recent advances in single-cell and multicellular microfluidics technology have provided powerful tools for studying cancer biology and immunology. The ability to create controlled microenvironments, perform high-throughput screenings, and monitor cellular interactions at the single-cell level has significantly advanced our understanding of tumor biology and immune responses. We discuss cutting-edge multicellular and single-cell microfluidic technologies and methodologies utilized to investigate cancer-immune cell interactions and assess the effectiveness of immunotherapies. We explore the advantages and limitations of the wide range of 3D spheroid and single-cell microfluidic models recently developed, highlighting the various approaches in device generation and applications in immunotherapy screening for potential opportunities for point-of-care approaches.


Subject(s)
Microfluidics , Neoplasms , Point-of-Care Systems , Single-Cell Analysis , Humans , Single-Cell Analysis/methods , Microfluidics/methods , Tumor Microenvironment , Immunotherapy/methods , Spheroids, Cellular , Microfluidic Analytical Techniques/instrumentation , Microfluidic Analytical Techniques/methods , Cell Communication , Animals , Lab-On-A-Chip Devices
3.
Eur J Neurosci ; 59(12): 3337-3352, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38654472

ABSTRACT

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is caused by a loss-of-function mutation in CDKL5 gene, encoding a serine-threonine kinase highly expressed in the brain. CDD manifests with early-onset epilepsy, autism, motor impairment and severe intellectual disability. While there are no known treatments for CDD, the use of cannabidiol has recently been introduced into clinical practice for neurodevelopmental disorders. Given the increased clinical utilization of cannabidiol, we examined its efficacy in the CDKL5R59X knock-in (R59X) mice, a CDD model based on a human mutation that exhibits both lifelong seizure susceptibility and behavioural deficits. We found that cannabidiol pre-treatment rescued the increased seizure susceptibility in response to the chemoconvulsant pentylenetetrazol (PTZ), attenuated working memory and long-term memory impairments, and rescued social deficits in adult R59X mice. To elucidate a potential mechanism, we compared the developmental hippocampal and cortical expression of common endocannabinoid (eCB) targets in R59X mice and their wild-type littermates, including cannabinoid type 1 receptor (CB1R), transient receptor potential vanilloid type 1 (TRPV1) and 2 (TRPV2), G-coupled protein receptor 55 (GPR55) and adenosine receptor 1 (A1R). Many of these eCB targets were developmentally regulated in both R59X and wild-type mice. In addition, adult R59X mice demonstrated significantly decreased expression of CB1R and TRPV1 in the hippocampus, and TRPV2 in the cortex, while TRPV1 was increased in the cortex. These findings support the potential for dysregulation of eCB signalling as a plausible mechanism and therapeutic target in CDD, given the efficacy of cannabidiol to attenuate hyperexcitability and behavioural deficits in this disorder.


Subject(s)
Cannabidiol , Protein Serine-Threonine Kinases , Seizures , Animals , Cannabidiol/pharmacology , Seizures/drug therapy , Seizures/genetics , Seizures/metabolism , Mice , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Receptor, Cannabinoid, CB1/genetics , Receptor, Cannabinoid, CB1/metabolism , Epileptic Syndromes/genetics , Epileptic Syndromes/drug therapy , Pentylenetetrazole , Hippocampus/metabolism , Hippocampus/drug effects , Disease Models, Animal , Gene Knock-In Techniques/methods , Male , TRPV Cation Channels/genetics , TRPV Cation Channels/metabolism , Endocannabinoids/metabolism , Behavior, Animal/drug effects , Mice, Inbred C57BL , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Spasms, Infantile , Receptors, Cannabinoid
4.
J Card Fail ; 30(1): 64-77, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38065308

ABSTRACT

Given the numerous opportunities and the wide knowledge gaps in pediatric heart failure, an international group of pediatric heart failure experts with diverse backgrounds were invited and tasked with identifying research gaps in each pediatric heart failure domain that scientists and funding agencies need to focus on over the next decade.


Subject(s)
Heart Failure , Humans , Child , Heart Failure/diagnosis , Heart Failure/therapy , Evidence Gaps
5.
Lancet ; 399(10319): 36-49, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34883053

ABSTRACT

BACKGROUND: Given the importance of flexible use of different COVID-19 vaccines within the same schedule to facilitate rapid deployment, we studied mixed priming schedules incorporating an adenoviral-vectored vaccine (ChAdOx1 nCoV-19 [ChAd], AstraZeneca), two mRNA vaccines (BNT162b2 [BNT], Pfizer-BioNTech, and mRNA-1273 [m1273], Moderna) and a nanoparticle vaccine containing SARS-CoV-2 spike glycoprotein and Matrix-M adjuvant (NVX-CoV2373 [NVX], Novavax). METHODS: Com-COV2 is a single-blind, randomised, non-inferiority trial in which adults aged 50 years and older, previously immunised with a single dose of ChAd or BNT in the community, were randomly assigned (in random blocks of three and six) within these cohorts in a 1:1:1 ratio to receive a second dose intramuscularly (8-12 weeks after the first dose) with the homologous vaccine, m1273, or NVX. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentrations measured by ELISA in heterologous versus homologous schedules at 28 days after the second dose, with a non-inferiority criterion of the GMR above 0·63 for the one-sided 98·75% CI. The primary analysis was on the per-protocol population, who were seronegative at baseline. Safety analyses were done for all participants who received a dose of study vaccine. The trial is registered with ISRCTN, number 27841311. FINDINGS: Between April 19 and May 14, 2021, 1072 participants were enrolled at a median of 9·4 weeks after receipt of a single dose of ChAd (n=540, 47% female) or BNT (n=532, 40% female). In ChAd-primed participants, geometric mean concentration (GMC) 28 days after a boost of SARS-CoV-2 anti-spike IgG in recipients of ChAd/m1273 (20 114 ELISA laboratory units [ELU]/mL [95% CI 18 160 to 22 279]) and ChAd/NVX (5597 ELU/mL [4756 to 6586]) was non-inferior to that of ChAd/ChAd recipients (1971 ELU/mL [1718 to 2262]) with a GMR of 10·2 (one-sided 98·75% CI 8·4 to ∞) for ChAd/m1273 and 2·8 (2·2 to ∞) for ChAd/NVX, compared with ChAd/ChAd. In BNT-primed participants, non-inferiority was shown for BNT/m1273 (GMC 22 978 ELU/mL [95% CI 20 597 to 25 636]) but not for BNT/NVX (8874 ELU/mL [7391 to 10 654]), compared with BNT/BNT (16 929 ELU/mL [15 025 to 19 075]) with a GMR of 1·3 (one-sided 98·75% CI 1·1 to ∞) for BNT/m1273 and 0·5 (0·4 to ∞) for BNT/NVX, compared with BNT/BNT; however, NVX still induced an 18-fold rise in GMC 28 days after vaccination. There were 15 serious adverse events, none considered related to immunisation. INTERPRETATION: Heterologous second dosing with m1273, but not NVX, increased transient systemic reactogenicity compared with homologous schedules. Multiple vaccines are appropriate to complete primary immunisation following priming with BNT or ChAd, facilitating rapid vaccine deployment globally and supporting recognition of such schedules for vaccine certification. FUNDING: UK Vaccine Task Force, Coalition for Epidemic Preparedness Innovations (CEPI), and National Institute for Health Research. NVX vaccine was supplied for use in the trial by Novavax.


Subject(s)
Adjuvants, Vaccine/administration & dosage , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Immunization, Secondary/adverse effects , Immunization, Secondary/methods , Immunogenicity, Vaccine , mRNA Vaccines/administration & dosage , 2019-nCoV Vaccine mRNA-1273/administration & dosage , 2019-nCoV Vaccine mRNA-1273/immunology , Aged , BNT162 Vaccine/administration & dosage , BNT162 Vaccine/immunology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , ChAdOx1 nCoV-19/administration & dosage , ChAdOx1 nCoV-19/immunology , Female , Humans , Male , Middle Aged , Single-Blind Method , United Kingdom , Vaccination/adverse effects , Vaccination/methods , mRNA Vaccines/immunology
6.
Public Health Nutr ; 26(12): 3088-3099, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37727877

ABSTRACT

OBJECTIVE: To evaluate the impact of increased availability of healthier options on purchasing of different types of vending snack products sold in English leisure (sports) centres. DESIGN: An evaluation of an intervention using pre-post methods and interrupted time series analysis. Products within the vending machines were altered over three phases to increase the availability of healthier options, using agreed nutrition criteria - Government Buying Standards for Food and Catering Services (GBSF) for England - as a guide, as well as product availability. The primary outcome was the change in mean weekly purchased energy between the first and third phase. Secondary outcomes included changes by phase and by week in weekly number of purchases, fats, sugars and salt for all products combined and by individual product categories. SETTING: Fifteen sports centres in the city of Leeds, West Yorkshire, UK. PARTICIPANTS: Snack products sold in eighteen vending machines. RESULTS: Energy purchased reduced from baseline to phase 2, for all product categories combined, by 47·25 MJ (95 % CI (-61·22, -33·27)) per machine and by 279 kJ, (95 % CI (-325, -266)) per product unit. There were reductions in most nutrients purchased in all individual product categories except chocolate confectionery. Nutrients per product unit decreased for all product categories except saturated fat in chocolate confectionery. Minimal underlying trends in the baseline phase were identified, indicating changes in outcomes were likely to be due to the intervention. CONCLUSIONS: Introducing standards to increase availability of healthier snack products in vending machines is feasible without substantially affecting sales.


Subject(s)
Food Preferences , Snacks , Humans , Nutritional Status , Commerce , England , Food Dispensers, Automatic , Beverages , Nutritive Value
7.
Lancet ; 398(10303): 856-869, 2021 09 04.
Article in English | MEDLINE | ID: mdl-34370971

ABSTRACT

BACKGROUND: Use of heterologous prime-boost COVID-19 vaccine schedules could facilitate mass COVID-19 immunisation. However, we have previously reported that heterologous schedules incorporating an adenoviral vectored vaccine (ChAdOx1 nCoV-19, AstraZeneca; hereafter referred to as ChAd) and an mRNA vaccine (BNT162b2, Pfizer-BioNTech; hereafter referred to as BNT) at a 4-week interval are more reactogenic than homologous schedules. Here, we report the safety and immunogenicity of heterologous schedules with the ChAd and BNT vaccines. METHODS: Com-COV is a participant-blinded, randomised, non-inferiority trial evaluating vaccine safety, reactogenicity, and immunogenicity. Adults aged 50 years and older with no or well controlled comorbidities and no previous SARS-CoV-2 infection by laboratory confirmation were eligible and were recruited at eight sites across the UK. The majority of eligible participants were enrolled into the general cohort (28-day or 84-day prime-boost intervals), who were randomly assigned (1:1:1:1:1:1:1:1) to receive ChAd/ChAd, ChAd/BNT, BNT/BNT, or BNT/ChAd, administered at either 28-day or 84-day prime-boost intervals. A small subset of eligible participants (n=100) were enrolled into an immunology cohort, who had additional blood tests to evaluate immune responses; these participants were randomly assigned (1:1:1:1) to the four schedules (28-day interval only). Participants were masked to the vaccine received but not to the prime-boost interval. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentration (measured by ELISA) at 28 days after boost, when comparing ChAd/BNT with ChAd/ChAd, and BNT/ChAd with BNT/BNT. The heterologous schedules were considered non-inferior to the approved homologous schedules if the lower limit of the one-sided 97·5% CI of the GMR of these comparisons was greater than 0·63. The primary analysis was done in the per-protocol population, who were seronegative at baseline. Safety analyses were done among participants receiving at least one dose of a study vaccine. The trial is registered with ISRCTN, 69254139. FINDINGS: Between Feb 11 and Feb 26, 2021, 830 participants were enrolled and randomised, including 463 participants with a 28-day prime-boost interval, for whom results are reported here. The mean age of participants was 57·8 years (SD 4·7), with 212 (46%) female participants and 117 (25%) from ethnic minorities. At day 28 post boost, the geometric mean concentration of SARS-CoV-2 anti-spike IgG in ChAd/BNT recipients (12 906 ELU/mL) was non-inferior to that in ChAd/ChAd recipients (1392 ELU/mL), with a GMR of 9·2 (one-sided 97·5% CI 7·5 to ∞). In participants primed with BNT, we did not show non-inferiority of the heterologous schedule (BNT/ChAd, 7133 ELU/mL) against the homologous schedule (BNT/BNT, 14 080 ELU/mL), with a GMR of 0·51 (one-sided 97·5% CI 0·43 to ∞). Four serious adverse events occurred across all groups, none of which were considered to be related to immunisation. INTERPRETATION: Despite the BNT/ChAd regimen not meeting non-inferiority criteria, the SARS-CoV-2 anti-spike IgG concentrations of both heterologous schedules were higher than that of a licensed vaccine schedule (ChAd/ChAd) with proven efficacy against COVID-19 disease and hospitalisation. Along with the higher immunogenicity of ChAd/BNT compared with ChAD/ChAd, these data support flexibility in the use of heterologous prime-boost vaccination using ChAd and BNT COVID-19 vaccines. FUNDING: UK Vaccine Task Force and National Institute for Health Research.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine , Aged , Antibodies, Viral/blood , BNT162 Vaccine , COVID-19 Vaccines/administration & dosage , ChAdOx1 nCoV-19 , Equivalence Trials as Topic , Female , Humans , Immunization Schedule , Immunoglobulin G/blood , Intention to Treat Analysis , Male , Middle Aged , Single-Blind Method , Spike Glycoprotein, Coronavirus/immunology
8.
Int J Colorectal Dis ; 37(4): 979-982, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35260934

ABSTRACT

AIM: Colorectal cancer (CRC) is the third most deadly and fourth most common cancer worldwide. Early detection, resection, and appropriate surveillance of precursor polyps result in better outcomes. Colonoscopy is a safe, accurate, and effective tool for surveillance and follow-up of premalignant polyps. Recommended surveillance intervals are based on polyp, procedural, and patient-related factors. The United States Multi-Society Task Force (MSTF) on CRC publishes guidelines with periodic updates on surveillance. We sought to evaluate adherence to post-polypectomy surveillance guidelines by academic gastroenterologists at a high-volume center. METHODS: One-year retrospective study evaluating compliance with post-polypectomy recommendations after average risk adult screening colonoscopies. Data was collected on number and size of polyps, quality of bowel prep, initial follow-up recommendations, polyp pathology, and follow-up recommendations. Correlation with the 2012 MSTF guidelines was also evaluated. Endoscopist experience was categorized as greater or less than 10 years of practice experience. Binomial regression was used to model the association between the providers' years of experience (<10 vs. >10) and the likelihood of agreement between initial assessment and post-pathology assessment. RESULTS: There was a greater than 85% adherence to post-polypectomy surveillance guidelines, independent of endoscopist experience. CONCLUSION: There is a high level of adherence to post-polypectomy guidelines by practicing academic gastroenterologists independent of post-fellowship clinical experience.


Subject(s)
Colonic Polyps , Colorectal Neoplasms , Gastroenterologists , Adult , Colonic Polyps/pathology , Colonoscopy , Colorectal Neoplasms/pathology , Follow-Up Studies , Humans , Retrospective Studies , United States
9.
J Exp Child Psychol ; 207: 105090, 2021 07.
Article in English | MEDLINE | ID: mdl-33684892

ABSTRACT

Fictional stories can affect many aspects of children's behavior and cognition, yet little is known about how they might help or hinder children's executive function skills. The current study investigated the role of story content (fantasy or reality) and mode of engagement with the story (pretense or a non-pretense control) on children's inhibitory control, an important component of early executive function. A total of 60 3-year-olds were randomly assigned to hear a fantastical or realistic story and were encouraged to engage in either pretense or a non-pretense activity related to the story. They then completed the Less Is More task of inhibitory control. Story content had no impact on children's inhibitory control; children performed equally well after hearing a fantastical or realistic story. However, children who engaged in story-related pretend play showed greater inhibitory control than those who engaged in a non-pretense activity. We found no interaction between story content and play engagement type. These results held when controlling for baseline inhibitory control, receptive vocabulary, age, gender, affect, and propensity toward pretense. Therefore, mode of play engagement with a story was more important in promoting children's inhibitory control skills than the degree of realism in the story.


Subject(s)
Child Development , Executive Function , Child, Preschool , Cognition , Fantasy , Humans , Thinking
10.
J Neurosci ; 39(24): 4814-4828, 2019 06 12.
Article in English | MEDLINE | ID: mdl-30952813

ABSTRACT

Pathogenic mutations in cyclin-dependent kinase-like 5 (CDKL5) result in CDKL5 deficiency disorder (CDD), a rare disease marked by early-life seizures, autistic behaviors, and intellectual disability. Although mouse models of CDD exhibit dendritic instability and alterations in synaptic scaffolding proteins, studies of glutamate receptor levels and function are limited. Here we used a novel mouse model of CDD, the Cdkl5R59X knock-in mouse (R59X), to investigate changes in synaptic glutamate receptor subunits and functional consequences. Male mice were used for all experiments to avoid the confounding effects of X-inactivation that would be present in female heterozygous mice. We showed that adult male R59X mice recapitulated the behavioral outcomes observed in other mouse models of CDD, including social deficits and memory and learning impairments, and exhibited decreased latency to seizure upon pentylenetetrazol administration. Furthermore, we observed a specific increase in GluA2-lacking α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptors (AMPARs) in the adult R59X hippocampus, which is accompanied electrophysiologically by increased rectification ratio of AMPAR EPSCs and elevated early-phase long term potentiation (LTP). Finally, we showed that acute treatment with the GluA2-lacking AMPAR blocker IEM-1460 decreased AMPAR currents, and rescued social deficits, working memory impairments, and seizure behavior latency in R59X mice.SIGNIFICANCE STATEMENT CDKL5 deficiency disorder (CDD) is a rare disease marked by autistic-like behaviors, intellectual disability, and seizures. While synaptic dysfunction has been observed in mouse models of CDD, there is limited information on how synaptic alterations contribute to behavioral and functional changes in CDD. Here we reveal elevated hippocampal GluA2-lacking AMPAR expression in a novel mouse model of CDD that is accompanied by changes in synaptic AMPAR function and plasticity. We also show, for the first time, that acutely targeting GluA2-lacking AMPAR dysregulation rescues core synaptic and neurobehavioral deficits in CDD.


Subject(s)
Epileptic Syndromes/drug therapy , Epileptic Syndromes/genetics , Protein Serine-Threonine Kinases/deficiency , Protein Serine-Threonine Kinases/genetics , Receptors, AMPA/drug effects , Spasms, Infantile/drug therapy , Spasms, Infantile/genetics , Adult , Animals , Behavior, Animal , Child, Preschool , Disease Models, Animal , Epileptic Syndromes/psychology , Excitatory Postsynaptic Potentials/genetics , Female , Gene Knock-In Techniques , Humans , Learning Disabilities/genetics , Learning Disabilities/psychology , Male , Memory Disorders/genetics , Memory Disorders/psychology , Mice , Mice, Inbred C57BL , Mice, Neurologic Mutants , Mutation/genetics , Psychomotor Performance , Receptors, AMPA/deficiency , Receptors, AMPA/genetics , Seizures/chemically induced , Seizures/physiopathology , Social Behavior , Spasms, Infantile/psychology
11.
Small ; 15(37): e1901442, 2019 09.
Article in English | MEDLINE | ID: mdl-31353802

ABSTRACT

Herein, the use of red blood cells (RBCs) as carriers of cytoplasmically interned phototherapeutic agents is described. Photolysis promotes drug release from the RBC carrier thereby providing the means to target specific diseased sites. This strategy is realized with a vitamin B12-taxane conjugate (B12-TAX), in which the drug is linked to the vitamin via a photolabile CoC bond. The conjugate is introduced into mouse RBCs (mRBCs) via a pore-forming/pore-resealing procedure and is cytoplasmically retained due to the membrane impermeability of B12. Photolysis separates the taxane from the B12 cytoplasmic anchor, enabling the drug to exit the RBC carrier. A covalently appended Cy5 antenna sensitizes the conjugate (Cy5-B12-TAX) to far red light, thereby circumventing the intense light absorbing properties of hemoglobin (350-600 nm). Microscopy and imaging flow cytometry reveal that Cy5-B12-TAX-loaded mRBCs act as drug carriers. Furthermore, intravital imaging of mice furnish a real time assessment of circulating phototherapeutic-loaded mRBCs as well as evidence of the targeted photorelease of the taxane upon photolysis. Histopathology confirms that drug release occurs in a well resolved spatiotemporal fashion. Finally, acoustic angiography is employed to assess the consequences of taxane release at the tumor site in Nu/Nu-tumor-bearing mice.


Subject(s)
Drug Carriers/chemistry , Drug Delivery Systems/methods , Erythrocytes/cytology , Animals , Bridged-Ring Compounds/chemistry , Female , Flow Cytometry , Humans , Mice , Photolysis , Prodrugs/chemistry , Taxoids/chemistry , Vitamin B 12/chemistry
12.
Proc Biol Sci ; 286(1907): 20191135, 2019 07 24.
Article in English | MEDLINE | ID: mdl-31311472

ABSTRACT

Poaching fuelled by international trade in horn caused the deaths of over 1000 African rhinoceros (Ceratotherium simum and Diceros bicornis) per year between 2013 and 2017. Deterrents, which act to establish avoidance behaviours in animals, have the potential to aid anti-poaching efforts by moving at-risk rhinos away from areas of danger (e.g. near perimeter fences). To evaluate the efficacy of deterrents, we exposed a population of southern white rhinos (C. simum simum) to acoustic- (honeybee, siren, turtle dove), olfactory- (chilli, sunflower), and drone-based stimuli on a game reserve in South Africa. We exposed rhinos to each stimulus up to four times. Stimuli were considered effective deterrents if they repeatedly elicited avoidance behaviour (locomotion away from the deterrent). Rhinos travelled significantly further in response to the siren than to the honeybee or turtle dove stimulus, and to low-altitude drone flights than to higher altitude flights. We found the drone to be superior at manipulating rhino movement than the siren owing to its longer transmission range and capability of pursuit. By contrast, the scent stimuli were ineffective at inciting avoidance behaviour. Our findings indicate that deterrents are a prospective low-cost and in situ method to manage rhino movement in game reserves.


Subject(s)
Aircraft , Avoidance Learning , Conservation of Natural Resources/methods , Noise , Perissodactyla , Animals , Smell , South Africa
14.
J Neurophysiol ; 118(5): 2806-2818, 2017 11 01.
Article in English | MEDLINE | ID: mdl-28814634

ABSTRACT

Sensory feedback influences motor circuits and/or their projection neuron inputs to adjust ongoing motor activity, but its efficacy varies. Currently, less is known about regulation of sensory feedback onto projection neurons that control downstream motor circuits than about sensory regulation of the motor circuit neurons themselves. In this study, we tested whether sensory feedback onto projection neurons is sensitive only to activation of a motor system, or also to the modulatory state underlying that activation, using the crab Cancer borealis stomatogastric nervous system. We examined how proprioceptor neurons (gastropyloric receptors, GPRs) influence the gastric mill (chewing) circuit neurons and the projection neurons (MCN1, CPN2) that drive the gastric mill rhythm. During gastric mill rhythms triggered by the mechanosensory ventral cardiac neurons (VCNs), GPR was shown previously to influence gastric mill circuit neurons, but its excitation of MCN1/CPN2 was absent. In this study, we tested whether GPR effects on MCN1/CPN2 are also absent during gastric mill rhythms triggered by the peptidergic postoesophageal commissure (POC) neurons. The VCN and POC pathways both trigger lasting MCN1/CPN2 activation, but their distinct influence on circuit feedback to these neurons produces different gastric mill motor patterns. We show that GPR excites MCN1 and CPN2 during the POC-gastric mill rhythm, altering their firing rates and activity patterns. This action changes both phases of the POC-gastric mill rhythm, whereas GPR only alters one phase of the VCN-gastric mill rhythm. Thus sensory feedback to projection neurons can be gated as a function of the modulatory state of an active motor system, not simply switched on/off with the onset of motor activity.NEW & NOTEWORTHY Sensory feedback influences motor systems (i.e., motor circuits and their projection neuron inputs). However, whether regulation of sensory feedback to these projection neurons is consistent across different versions of the same motor pattern driven by the same motor system was not known. We found that gating of sensory feedback to projection neurons is determined by the modulatory state of the motor system, and not simply by whether the system is active or inactive.


Subject(s)
Feedback, Sensory/physiology , Movement/physiology , Neurons/physiology , Sensory Gating/physiology , Action Potentials , Animals , Brachyura , Central Pattern Generators/physiology , Electric Stimulation , Ganglia, Invertebrate/physiology , Male , Mastication/physiology , Microelectrodes , Neural Pathways/physiology , Periodicity , Proprioception/physiology , Tissue Culture Techniques
15.
Child Dev ; 88(5): 1563-1571, 2017 09.
Article in English | MEDLINE | ID: mdl-27982409

ABSTRACT

This study investigated the benefits of self-distancing (i.e., taking an outsider's view of one's own situation) on young children's perseverance. Four- and 6-year-old children (N = 180) were asked to complete a repetitive task for 10 min while having the option to take breaks by playing an extremely attractive video game. Six-year-olds persevered longer than 4-year-olds. Nonetheless, across both ages, children who impersonated an exemplar other-in this case a character, such as Batman-spent the most time working, followed by children who took a third-person perspective on the self, or finally, a first-person perspective. Alternative explanations, implications, and future research directions are discussed.


Subject(s)
Attention/physiology , Child Behavior/physiology , Child Development/physiology , Executive Function/physiology , Theory of Mind/physiology , Age Factors , Child , Child, Preschool , Female , Humans , Male
16.
JAAPA ; 30(5): 23-27, 2017 May.
Article in English | MEDLINE | ID: mdl-28441669

ABSTRACT

Cystic fibrosis (CF) affects more than 30,000 people in the United States and 80,000 people worldwide. This life-threatening genetic disorder causes a buildup of thick, viscous mucus secretions in various organ systems, most commonly the gastrointestinal, pulmonary, and genitourinary systems. This article reviews the clinical manifestations, diagnosis, and monitoring of patients with CF as well as guidelines for management and emerging pharmacologic treatments.


Subject(s)
Cystic Fibrosis/physiopathology , Cystic Fibrosis/therapy , Drainage, Postural/methods , Respiration , Respiratory Therapy/methods , Chlorides/analysis , Cystic Fibrosis/diagnosis , Humans , Infant, Newborn , Neonatal Screening/methods , Prognosis , Sweating/physiology
17.
Dev Sci ; 19(3): 419-26, 2016 May.
Article in English | MEDLINE | ID: mdl-25997842

ABSTRACT

This experimental research assessed the influence of graded levels of self-distancing - psychological distancing from one's egocentric perspective - on executive function (EF) in young children. Three- (n = 48) and 5-year-old (n = 48) children were randomly assigned to one of four manipulations of distance from the self (from proximal to distal: self-immersed, control, third person, and exemplar) on a comprehensive measure of EF. Performance increased as a function of self-distancing across age groups. Follow-up analyses indicated that 5-year-olds were driving this effect. They showed significant improvements in EF with increased distance from the self, outperforming controls both when taking a third person perspective on the self and when taking the perspective of an exemplar other (e.g., Batman) through role play. Three-year-olds, however, did not show increased EF performance as a function of greater distance from the self. Preliminary results suggest that developments in theory of mind might contribute to these age-related differences in efficacy. These findings speak to the importance of psychological distancing in the expression of conscious control over thought and action from a young age and suggest a promising new avenue for early EF intervention.


Subject(s)
Adaptation, Psychological/physiology , Ego , Executive Function/physiology , Interpersonal Relations , Analysis of Variance , Child, Preschool , Female , Humans , Male , Psychological Distance , Psychology, Child/methods , Psychology, Developmental/methods , Role Playing , Self Concept
18.
J Educ Psychol ; 108(3): 329-341, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27158155

ABSTRACT

A growing body of research indicates that self-control is critical to academic success. Surprisingly little is known, however, about the diverse strategies students use to implement self-control or how well these strategies work. To address these issues, we conducted a naturalistic investigation of self-control strategies (Study 1) and two field experiments (Studies 2 and 3). In Study 1, high school students described the strategies they use to manage interpersonal conflicts, get academic work done, eat healthfully, and manage other everyday self-control challenges. The majority of strategies in these self-nominated incidents as well as in three hypothetical academic scenarios (e.g., studying instead of texting friends) were reliably classified using the process model of self-control. As predicted by the process model, students rated strategies deployed early in the impulse-generation process (situation selection, situation modification) as being dramatically more effective than strategies deployed later (attentional deployment, cognitive change, response modulation). In Study 2, high school students randomly assigned to implement situation modification were more likely to meet their academic goals during the following week than students assigned either to implement response modulation or no strategy at all. In Study 3, college students randomly assigned to implement situation modification were also more successful in meeting their academic goals, and this effect was partially mediated by decreased feelings of temptation throughout the week. Collectively, these findings suggest that students might benefit from learning to initiate self-control when their impulses are still nascent.

19.
Child Dev ; 86(4): 1272-1281, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25876213

ABSTRACT

Experiments performed primarily with adults show that self-distancing facilitates adaptive self-reflection. However, no research has investigated whether adolescents spontaneously engage in this process or whether doing so is linked to adaptive outcomes. In this study, 226 African American adolescents, aged 11-20, reflected on an anger-related interpersonal experience. As expected, spontaneous self-distancing during reflection predicted lower levels of emotional reactivity by leading adolescents to reconstrue (rather than recount) their experience and blame their partner less. Moreover, the inverse relation between self-distancing and emotional reactivity strengthened with age. These findings highlight the role that self-distancing plays in fostering adaptive self-reflection in adolescence, and begin to elucidate the role that development plays in enhancing the benefits of engaging in this process.

20.
J Couns Psychol ; 62(4): 655-69, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25751018

ABSTRACT

Breast cancer survivors represent the largest proportion of cancer survivors, and the rate of young breast cancer survivors who are diagnosed before the age of 40 is increasing. Cancer survivorship scholarship has begun to address many aspects of survivors' quality of life, yet the role of work and career issues have been understudied, particularly for young survivors. To explore the work lives and career development of young breast cancer survivors, this study used consensual qualitative research methodology (Hill, Thompson, & Williams, 1997) to analyze data from qualitative interviews with 13 young women diagnosed with breast cancer before the age of 40. The 4 career-related domains that emerged from the data were (a) cancer-related work challenges, (b) coping with cancer-related work challenges, (c) reappraisal of career development after cancer, and (d) components of career and life satisfaction after cancer. Experiencing breast cancer at a young age was viewed by participants as contributing to an increased desire for work to provide a sense of meaning as well as financial security and insurance. Cancer was further viewed as contributing to lost control over career success and work choices, treatment side effects that interfere with work self-efficacy and capabilities, and interpersonal difficulties connecting within and outside of work. Women with more extensive cancer treatment and side effects reported greater work struggles. Despite this, participants' cancer narratives were characterized by a range of coping strategies, including reframing and seeking control, and by evidence of persistence, resilience, and hope. Implications for research and practice are discussed.


Subject(s)
Breast Neoplasms/psychology , Career Mobility , Survivors/psychology , Work/psychology , Work/trends , Adaptation, Psychological , Adult , Breast Neoplasms/diagnosis , Female , Humans , Quality of Life/psychology , Young Adult
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