Learning intrinsic excitability in medium spiny neurons

We present an unsupervised, local activation-dependent learning rule for intrinsic plasticity (IP) which affects the composition of ion channel conductances for single neurons in a use-dependent way. We use a single-compartment conductance-based model for medium spiny striatal neurons in order to show the effects of parametrization of individual ion channels on the neuronal activation function. We show that parameter changes within the physiological ranges are sufficient to create an ensemble of neurons with significantly different activation functions. We emphasize that the effects of intrinsic neuronal variability on spiking behavior require a distributed mode of synaptic input and can be eliminated by strongly correlated input. We show how variability and adaptivity in ion channel conductances can be utilized to store patterns without an additional contribution by synaptic plasticity (SP). The adaptation of the spike response may result in either "positive" or "negative" pattern learning. However, read-out of stored information depends on a distributed pattern of synaptic activity to let intrinsic variability determine spike response. We briefly discuss the implications of this conditional memory on learning and addiction.Comment: 20 pages, 8 figure

Childhood vascular phenotypes have differing associations with pre- and postnatal growth

Objective: In children aged 8--9 years, we examined the associations of linear and abdominal circumference growth during critical stages of prenatal and postnatal development with six vascular measurements commonly used as early markers of atherosclerosis and later cardiovascular disease (CVD) risk. Methods: In 724 children from the UK Southampton Women's Survey mother--offspring cohort, offspring length/height and abdominal circumference measurements were collected at 10 ages between 11 weeks’ gestation and age 8--9 years. Using residual growth modelling and linear regression, we examined the independent associations between growth and detailed vascular measures made at 8--9 years. Results: Postnatal linear and abdominal circumference growth were associated with higher childhood SBP and carotid--femoral pulse wave velocity, whereas prenatal growth was not. For example, 1SD faster abdominal circumference gain between ages 3 and 6 years was associated with 2.27 [95% confidence interval (CI): 1.56--2.98] mmHg higher SBP. In contrast, faster abdominal circumference gain before 19 weeks’ gestation was associated with greater carotid intima--media thickness [0.009 mm (0.004--0.015) per 1SD larger 19-week abdominal circumference), whereas later growth was not. We found no strong associations between prenatal or postnatal growth and DBP or measures of endothelial function. Conclusion: Higher postnatal linear growth and adiposity gain are related to higher SBP and carotid--femoral pulse wave velocity in childhood. In contrast, faster growth in early gestation is associated with greater childhood carotid intima--media thickness, perhaps resulting from subtle changes in vascular structure that reflect physiological adaptations rather than subclinical atherosclerosis

Advance telephone calls ahead of reminder questionnaires increase response rate in non-responders compared to questionnaire reminders only : The RECORD phone trial

Peer reviewedPublisher PD

Feeling our way: academia, emotions and a politics of care

This paper aims to better understand the role of emotions in academia, and their part in producing, and challenging, an increasingly normalized neoliberal academy. It unfolds from two narratives that foreground emotions in and across academic spaces and practices, to critically explore how knowledges and positions are constructed and circulated. It then moves to consider these issues through the lens of care as a political stance towards being and becoming academics in neoliberal times. Our aim is to contribute to the burgeoning literature on emotional geographies, explicitly bringing this work into conversation with resurgent debates surrounding an ethic of care, as part of a politic of critiquing individualism and managerialism in (and beyond) the academy. We consider the ways in which neoliberal university structures circulate particular affects, prompting emotions such as desire and anxiety, and the internalisation of competition and audit as embodied scholars. Our narratives exemplify how attendant emotions and affect can reverberate and be further reproduced through university cultures, and diffuse across personal and professional lives. We argue that emotions in academia matter, mutually co-producing everyday social relations and practices at and across all levels. We are interested in their political implications, and how neoliberal norms can be shifted through practices of caring-with

Fabrication of CaO-NaO-SiO2/TiO2 Scaffolds for Surgical Applications

A series of titanium (Ti) based glasses were formulated (0.62 SiO2-0.14 Na2O-0.24 CaO, with 0.05 mol% TiO2 substitutions for SiO2) to develop glass/ceramic scaffolds for bone augmentation. Glasses were initially characterised using X-ray diffraction (XRD) and particle size analysis, where the starting materials were amorphous with 4.5 μm particles. Hot stage microscopy and high temperature XRD were used to determine the sintering temperature (̃700 °C) and any crystalline phases present in this region (Na2Ca3Si6O16, combeite and quartz). Hardness testing revealed that the Ti-free control (ScC- 2.4 GPa) had a significantly lower hardness than the Ti-containing materials (Sc1 and Sc2 ̃6.6 GPa). Optical microscopy determined pore sizes ranging from 544 to 955 lm. X-ray microtomography calculated porosity from 87 to 93 % and surface area measurements ranging from 2.5 to 3.3 SA/mm3. Cytotoxicity testing (using mesenchymal stem cells) revealed that all materials encouraged cell proliferation, particularly the higher Ti-containing scaffolds over 24-72 h. © Springer Science+Business Media, LLC 2012

Biocompatibility of CaO-Na2O-SiO2/TiO2 Glass Ceramic Scaffolds for Orthopaedic Applications

This work aims to determine the effect of substituting TiO2 for SiO2 in a 0.62SiO2-Na2O-0.24CaO based glass-ceramic scaffold. High temperature X-ray Diffraction (HT-XRD) was used to determine the sintering temperature (700oC). Both optical microscopy and x-ray micotomography was used to determine the average pore size (540-680ìm) of each scaffold. Cytocompatibility of each scaffold was conducted using murine mesenchymal stem cells. © 2013 IEEE

A Randomized Controlled Trial of Extended Brief Intervention for Alcohol-Dependent Patients in an Acute Hospital Setting

To determine whether alcohol-dependent patients in a hospital setting benefit from extended brief interventions (EBI) delivered by an Alcohol Specialist Nurse. Methods Alcohol-dependent patients recruited via screening at the emergency department (ED) (n = 267), whether or not admitted to hospital, were randomized to EBI (up to six counselling sessions offered) or control. At 6 months, 84.2% of patients were assessed by a researcher blinded to the intervention. The primary outcome was a fall in Severity of Alcohol Dependence Questionnaire. Results There was no difference between groups in the primary outcome [odds ratio (OR) 1.02; 95% confidence interval (CI): 0.38, 2.75, P = 0.97]. Secondary outcomes including alcohol consumption and readiness to change did not show a significant difference between groups. However, all secondary outcome measures improved, on average, in both arms. Conclusions Although EBI can be delivered in an ED or inpatient setting, it was not shown to be an advantage over screening and usual management (which included advice on alternative services), with patients in both groups showing an average improvement