2,476 research outputs found

    Temporal Dynamics of Neural Computations for Stimulus Value and Effort Cost

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    We often make decisions not only based on an item’s value, but also the effort required to obtain it: e.g., using a vending machine versus walking to a café. Whereas good-based value is represented in ventromedial prefrontal cortex (vmPFC), recent data has implicated dorsomedial frontal cortex (dmFC) in integrating stimulus value with effort cost to derive net (combined) value. However, the temporal dynamics of net value computation remain unclear. Here we examined this question using event-related potentials (ERP) while hungry subjects decided whether to work at different levels of physical effort cost (low, medium, or high grip strength) for the opportunity to obtain food. Subjects’ decisions generally incorporated both stimulus value and effort cost, as indicated by significant logistic fits to their choice curves. Parametric ERP responses associated with net value were visible from 100-300 ms after stimulus onset, negatively correlated with effort cost, and from ~450-650 ms, positively correlated with stimulus value. Distributed reconstruction of stimulus-locked responses revealed significant sources in the vmPFC, but not dmFC. In contrast, response-locked signals were chiefly localized to dmFC and superior parietal sources rather than vmPFC, and largely reflected effort cost computations preceding response. Together, these data suggest that localization of net value integration to vmPFC and dmFC sources depends on whether the data is time-locked to the onset of stimulus or response. In line with a transition from good-based to action-based valuation, computations of effort cost may play an increasing role in dmFC activity in the time directly leading up to choice

    Phosphorylation of androgen receptors at serine 515 is a potential prognostic marker for triple negative breast cancer

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    1.7 million cases of breast cancer are diagnosed every year with 522,000 deaths. Molecular classifications of breast cancer have resulted in improved treatments. However, treatments for triple negative breast cancer (TNBC) are lacking. Analysis of molecular targets for TNBC is a priority. One potential candidate is androgen receptor (AR) phosphorylation. This study assessed the role of AR phosphorylation at ser81/ser515 and their two upstream effectors, cyclin-dependent kinase 1 (pCDK1) and extracellular-regulated kinase 1/2 (pERK1/2) in 332 ductal breast cancer patients by immunohistochemistry. pERK1/2 combined with AR-515 associated with improved cancer-specific survival (CSS, p = 0.038), decreased size (p = 0.001), invasive grade (p < 0.001), necrosis (p = 0.003), b-lymphocytes (p = 0.020), molecular subtype (p < 0.001) and estrogen receptor (ER)/progesterone receptor (PR)-status (p < 0.001). The cohort was therefore stratified into ER+ve and ER-ve patients. In ER+ve tumours, pERK1/2 combined with AR-515 associated with improved CSS (p = 0.038), smaller size (p = 0.004), invasive grade (p = 0.001), decreased b-lymphocytes (p = 0.013) and increased plasma cells (p = 0.048). In contrast, in TNBC patients, phosphorylation of AR-515 associated with poorer CSS (p = 0.007). pERK1/2 combined with AR-515 associated with decreased inflammation (p = 0.003), increased tumour stroma (p = 0.003) and tumour budding (p = 0.011), with trends towards decrease CSS (p = 0.065) and macrophage levels (p = 0.093). In Conclusions, AR-515 may be an important regulator of inflammation in breast cancer potential via ERK1/2 phosphorylation. AR-515 is a potential prognostic marker and therapeutic target for TNBC

    Look at Mummy: challenges in training parents to deliver a home treatment program for childhood apraxia of speech in a rural Canadian community

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    Introduction: Children requiring speech pathology services in rural and remote locations face many barriers in accessing adequate services. This has particular consequences for children who need intensive treatment for therapy to be effective, such those with childhood apraxia of speech (CAS). Parent training has been used to overcome speech pathology service delivery barriers for a range of other communication disorders. However, the effectiveness of training parents to deliver a motor-based treatment for CAS within rural and remote contexts has not been evaluated. This study examined the effectiveness and feasibility of training parents in a rural community to use the treatment approach of dynamic temporal and tactile cueing (DTTC) in order to provide more intensive treatment sessions at home. Methods: The study used an experimental single case across behaviours design and parent interviews to evaluate outcomes both quantitatively and qualitatively. The study included four parent- child dyads from a mixed socioeconomic rural community in Canada. Child participants ranged in age from 3 years to 8 years. Child treatment outcomes were measured using an improvement rate difference (IRD) calculation based on percentage of phonemes correct. Fidelity to the treatment protocol was measured using a fidelity score. Results: All parents reported challenges in carrying out the program due to social and behavioural challenges. Parents also reported benefits such as being able to spend more time with their child and learning some useful cueing techniques. Only one of the four participants had a moderate effect size for his target words (RD=57%). Conclusion: While training parents to deliver DTTC may be effective for some parent-child dyads, clinicians are advised that parent training may not be suitable for all families, and parents in rural and remote communities may face particular social circumstances that make following through with an intensive treatment program difficult

    Design synthesis and shape generation

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    If we are to capitalise on the potential that a design approach might bring to innovation in business and society, we need to build a better understanding of the evolving skill-sets that designers will need and the contexts within which design might operate. This demands more discourse between those involved in cutting edge practice, the researchers who help to uncover principles, codify knowledge and create theories and the educators who are nurturing future design talent. This book promotes such a discourse by reporting on the work of twenty research teams who explored different facets of future design activity as part of Phase 2 of the UK's research council supported Designing for the 21st Century Research Initiative. Each of these contributions describes the origins of the project, the research team and their project aims, the research methods used and the new knowledge and understanding generated. Editor and Initiative Director, Professor Tom Inns, provides an introductory chapter that suggests ways the reader might navigate these viewpoints. This chapter concludes with an overview of the key lessons that might be learnt from this collection of design research activity

    Understanding the impact of lumbar disc degeneration and chronic low back pain: A cross-sectional electromyographic analysis of postural strategy during predicted and unpredicted postural perturbations

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    People with chronic low back pain (LBP) exhibit changes in postural control. Stereotypical muscle activations resulting from external perturbations include anticipatory (APAs) and compensatory (CPAs) postural adjustments. The aim and objective of this study was to determine differences in postural control strategies (peak amplitude, APAs and CPAs) between symptomatic and asymptomatic adults with and without Lumbar Disc Degeneration (LDD) using surface electromyography during forward postural perturbation. Ninety-seven subjects participated in the study (mean age 50 years (SD 12)). 3T MRI was used to acquire T2 weighted images (L1-S1). LDD was determined using Pfirrmann grading. A bespoke translational platform was designed to deliver horizontal perturbations in sagittal and frontal planes. Electromyographic activity was analysed bilaterally from 8 trunk and lower limb muscles during four established APA and CPA epochs. A Kruskal-Wallis H test with Bonferroni correction for multiple comparisons was conducted. Four groups were identified: no LDD no pain (n = 19), LDD no pain (n = 38), LDD pain (n = 35) and no LDD pain (n = 5). There were no significant differences in age or gender between groups. The most significant difference between groups was observed during forward perturbation. In the APA and CPA phases of predictable forward perturbation there were significant differences ankle strategy between groups (p = 0.007-0.008); lateral gastrocnemius and tibialis anterior activity was higher in the LDD pain than the LDD no pain group. There were no significant differences in the unpredictable condition (p>0.05). These findings were different from the remaining groups, where significant differences in hip strategy were observed during both perturbation conditions (p = 0.004-0.006). Symptomatic LDD patients exhibit different electromyographic strategies to asymptomatic LDD controls. Future LBP electromyographic research should benefit from considering assessment of both lower limbs in addition to the spine. This approach could prevent underestimation of postural control deficits and guide targeted rehabilitation

    Is intrinsic lumbar spine shape associated with lumbar disc degeneration? An exploratory study

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    Acknowledgements Thank you to Lesley Honeyfield (Lead Research Radiographer, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London) for assisting with imaging optimisation and the acquisition of MR images and to all participants in this study. We also thank the University of Aberdeen Data Management Team for programming support for ‘Shape’ software. Funding JD would like to acknowledge the support of Versus Arthritis (Clinical Doctoral Fellowship award, grant number 20172) and the UKSSB and Society for Back Pain Research (Travel Fellowship award) for funding this research. Funders did not have a role in the design of the study, analysis or interpretation of the data.Peer reviewedPublisher PD

    Mobile phone app aimed at improving iron intake and bioavailability in premenopausal women: a qualitative evaluation

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    BACKGROUND: Low iron intake can lead to iron deficiency, which can result in impaired health and iron-deficiency anemia. A mobile phone app, combining successful dietary strategies to increase bioavailable iron with strategies for behavior change, such as goal setting, monitoring, feedback, and resources for knowledge acquisition, was developed with the aim to increase bioavailable iron intake in premenopausal women. OBJECTIVE: To evaluate the content, usability, and acceptability of a mobile phone app designed to improve intake of bioavailable dietary iron. METHODS: Women aged 18-50 years with an Android mobile phone were invited to participate. Over a 2-week period women were asked to interact with the app. Following this period, semistructured focus groups with participants were conducted. Focus groups were audio recorded and analyzed via an inductive open-coding method using the qualitative analysis software NVivo 10. Themes were identified and frequency of code occurrence was calculated. RESULTS: Four focus groups (n=26) were conducted (age range 19-36 years, mean 24.7, SD 5.2). Two themes about the app\u27s functionality were identified (frequency of occurrence in brackets): interface and design (134) and usability (86). Four themes about the app\u27s components were identified: goal tracker (121), facts (78), photo diary (40), and games (46). A number of suggestions to improve the interface and design of the app were provided and will inform the ongoing development of the app. CONCLUSIONS: This research indicates that participants are interested in iron and their health and are willing to use an app utilizing behavior change strategies to increase intake of bioavailable iron. The inclusion of information about the link between diet and health, monitoring and tracking of the achievement of dietary goals, and weekly reviews of goals were also seen as valuable components of the app and should be considered in mobile health apps aimed at adult women

    Associations between dietary iron and zinc intakes, and between biochemical iron and zinc status in women

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    Iron and zinc are found in similar foods and absorption of both may be affected by food compounds, thus biochemical iron and zinc status may be related. This cross-sectional study aimed to: (1) describe dietary intakes and biochemical status of iron and zinc; (2) investigate associations between dietary iron and zinc intakes; and (3) investigate associations between biochemical iron and zinc status in a sample of premenopausal women aged 18–50 years who were recruited in Melbourne and Sydney, Australia. Usual dietary intakes were assessed using a 154-item food frequency questionnaire (n = 379). Iron status was assessed using serum ferritin and hemoglobin, zinc status using serum zinc (standardized to 08:00 collection), and presence of infection/inflammation using C-reactive protein (n = 326). Associations were explored using multiple regression and logistic regression. Mean (SD) iron and zinc intakes were 10.5 (3.5) mg/day and 9.3 (3.8) mg/day, respectively. Median (interquartile range) serum ferritin was 22 (12–38) μg/L and mean serum zinc concentrations (SD) were 12.6 (1.7) μmol/L in fasting samples and 11.8 (2.0) μmol/L in nonfasting samples. For each 1 mg/day increase in dietary iron intake, zinc intake increased by 0.4 mg/day. Each 1 μmol/L increase in serum zinc corresponded to a 6% increase in serum ferritin, however women with low serum zinc concentration (AM fasting < 10.7 μmol/L; AM nonfasting < 10.1 μmol/L) were not at increased risk of depleted iron stores (serum ferritin <15 μg/L; p = 0.340). Positive associations were observed between dietary iron and zinc intakes, and between iron and zinc status, however interpreting serum ferritin concentrations was not a useful proxy for estimating the likelihood of low serum zinc concentrations and women with depleted iron stores were not at increased risk of impaired zinc status in this cohort

    Electronic Medical Record Cancer Incidence over Six Years Comparing New Users of Glargine with New Users of NPH Insulin

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    Background: Recent studies suggested that insulin glargine use could be associated with increased risk of cancer. We compared the incidence of cancer in new users of glargine versus new users of NPH in a longitudinal clinical cohort with diabetes for up to 6 years. Methods and Findings: From all patients who had been regularly followed at Massachusetts General Hospital from 1/01/2005 to 12/31/2010, 3,680 patients who had a medication record for glargine or NPH usage were obtained from the electronic medical record (EMR). From those we selected 539 new glargine users (age: 60.1±13.6 years, BMI: 32.7±7.5 kg/m2) and 343 new NPH users (61.5±14.1 years, 32.7±8.3 kg/m2) who had no prevalent cancer during 19 months prior to glargine or NPH initiation. All incident cancer cases were ascertained from the EMR requiring at least 2 ICD-9 codes within a 2 month period. Insulin exposure time and cumulative dose were validated. The statistical analysis compared the rates of cancer in new glargine vs. new NPH users while on treatment, adjusted for the propensity to receive one or the other insulin. There were 26 and 28 new cancer cases in new glargine and new NPH users for 1559 and 1126 person-years follow-up, respectively. There were no differences in the propensity-adjusted clinical characteristics between groups. The adjusted hazard ratio for the cancer incidence comparing glargine vs. NPH use was 0.65 (95% CI: 0.36–1.19). Conclusions: Insulin glargine is not associated with development of cancers when compared with NPH in this longitudinal and carefully retrieved EMR data
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