Low intensity transcranial magnetic stimulation modulates skilled motor learning in adult mice

Repetitive transcranial magnetic stimulation (rTMS) is commonly used to modulate cortical plasticity in clinical and non-clinical populations. Clinically, rTMS is delivered to targeted regions of the cortex at high intensities (>1 T). We have previously shown that even at low intensities, rTMS induces structural and molecular plasticity in the rodent cortex. To determine whether low intensity rTMS (LI-rTMS) alters behavioural performance, daily intermittent theta burst LI-rTMS (120 mT) or sham was delivered as a priming or consolidating stimulus to mice completing 10 consecutive days of skilled reaching training. Relative to sham, priming LI-rTMS (before each training session), increased skill accuracy (~9%) but did not alter the rate of learning over time. In contrast, consolidating LI-rTMS (after each training session), resulted in a small increase in the rate of learning (an additional ~1.6% each day) but did not alter the daily skill accuracy. Changes in behaviour with LI-rTMS were not accompanied with long lasting changes in brain-derived neurotrophic factor (BDNF) expression or in the expression of plasticity markers at excitatory and inhibitory synapses for either priming or consolidation groups. These results suggest that LI-rTMS can alter specific aspects of skilled motor learning in a manner dependent on the timing of intervention

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

Welfare conditionality and social marginality: the folly of the tutelary state?

In a contemporarnb 1`vby evolution of the tutelary state, welfare reform in the United Kingdom has been characterised by moves towards greater conditionality and sanctioning. This is influenced by the attributing responsibility for poverty and unemployment to the behaviour of marginalised individuals. Mead (1992) has argued that the poor are dependants who ought to receive support on condition of certain restrictions imposed by a protective state that will incentivise engagement with support mechanisms. This article examines how the contemporary tutelary and therapeutic state has responded to new forms of social marginality. Drawing on a series of in-depth interviews conducted with welfare claimants with an offending background in England and Scotland, the article examines their encounters with the welfare system and argues that alienation, rather than engagement with support, increasingly characterises their experiences

Occupation of racial grief, loss as a resource : learning from ‘The Combahee River Collective Black Feminist Statement'

The methodology of ‘occupation’ through rereading The Combahee River Collective Black Feminist Statement (The Combahee River Collective, in: James, Sharpley-Whiting (eds) The Black Feminist Reader. Blackwell Publishers Ltd., Oxford, pp 261–270, 1977) demonstrates the necessity of temporal linkages to historical Black feminist texts and the wisdom of Black feminist situated knowers. This paper argues that racism produces grief and loss and as long as there is racism, we all remain in racial grief and loss. However, in stark contrast to the configuration of racial grief and loss as something to get over, perhaps grief and loss can be thought about differently, for example, in terms of racial grief and loss as a resource. This paper questions Western Eurocentric paternalistic responses to Black women’s ‘talk about their feelings of craziness… [under] patriarchal rule’ (The Combahee River Collective 1977: 262) and suggests alternative ways of thinking about the psychological impact of grief and loss in the context of racism. In this paper, a Black feminist occupation of racial grief and loss includes the act of residing within, and the act of working with the constituent elements of racial grief and loss. The proposal is that an occupation of racial grief and loss is a paradoxical catalyst for building a twenty-first century global intersectional Black feminist movement

A classical view on nonclassical nucleation

Understanding and controlling nucleation is important for many crystallization applications. Calcium carbonate (CaCO_{3}) is often used as a model system to investigate nucleation mechanisms. Despite its great importance in geology, biology, and many industrial applications, CaCO_{3} nucleation is still a topic of intense discussion, with new pathways for its growth from ions in solution proposed in recent years. These new pathways include the so-called nonclassical nucleation mechanism via the assembly of thermodynamically stable prenucleation clusters, as well as the formation of a dense liquid precursor phase via liquid–liquid phase separation. Here, we present results from a combined experimental and computational investigation on the precipitation of CaCO_{3} in dilute aqueous solutions. We propose that a dense liquid phase (containing 4–7 H_{2}O per CaCO_{3} unit) forms in supersaturated solutions through the association of ions and ion pairs without significant participation of larger ion clusters. This liquid acts as the precursor for the formation of solid CaCO_{3} in the form of vaterite, which grows via a net transfer of ions from solution according to z Ca^{2+} + zCO_{3}^{2−} → z CaCO_{3}. The results show that all steps in this process can be explained according to classical concepts of crystal nucleation and growth, and that long-standing physical concepts of nucleation can describe multistep, multiphase growth mechanisms

Effect of garlic on cardiovascular disorders: a review

Garlic and its preparations have been widely recognized as agents for prevention and treatment of cardiovascular and other metabolic diseases, atherosclerosis, hyperlipidemia, thrombosis, hypertension and diabetes. Effectiveness of garlic in cardiovascular diseases was more encouraging in experimental studies, which prompted several clinical trials. Though many clinical trials showed a positive effect of garlic on almost all cardiovascular conditions mentioned above, however a number of negative studies have recently cast doubt on the efficary of garlic specially its cholesterol lowering effect of garlic. It is a great challenge for scientists all over the world to make a proper use of garlic and enjoy its maximum beneficial effect as it is the cheapest way to prevent cardiovascular disease. This review has attempted to make a bridge the gap between experimental and clinical study and to discuss the possible mechanisms of such therapeutic actions of garlic

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified