Professional standards support for curriculum mentors: report on the TDA funded ‘Professional Standards Support for Curriculum mentors’ at the University of Southampton

A revised framework of professional standards for teachers was published by the Training and Development Agency for Schools (TDA). These standards replaced existing teacher standards in September 2007 and form a clear, progressive framework of standards for teachers. The standards are statements of a teacher's professional attributes, knowledge and understanding, and skills. Importantly they clarify expectations at each career stage helping teachers identify how they need to develop professionally to progress in their careers.• the awards of Qualified Teacher Status (QTS) (Q)• teachers on the main scale (Core) (C)• teachers on the upper pay scale (Post Threshold Teachers) (P)• Excellent Teachers (E)• Advanced Skills Teachers (ASTs) (A)The Training and Development Agency for Schools (TDA) made funding available to help support initial teacher training (ITT) providers in meeting the revised qualified teacher status (QTS) standards which came into effect in September 2007. A Guidance to accompany the standards for Qualified Teacher Status (QTS) was also produced by the TDA<br/

Introduction to the Court of Arbitration for Sport (CAS) & the Role of National Courts in International Sports Disputes, An Symposium

The founding purpose of the Court of Arbitration for Sport (CAS) was to take international sports disputes out of national courts and provide a highly specialized forum where those disputes could be heard and decided, quickly and inexpensively, according to a flexible procedure. Since its inception, CAS has gained the recognition and trust of the international sports community and today, is the last instance of appeal for parties involved in a wide-range of sports-related disputes, including those related to all Olympic sports and many non-Olympic sports, football disputes, doping infractions and international commercial contracts. CAS has come to provide sportsmen and women, their respective governing bodies and other entities involved in the sports world with an efficient, cost effective and final resolution to their disputes. This paper will predominantly provide an introduction to the CAS (parts II - VIII); as to the role of national courts in international sports disputes and the skirmishes that can arise, part IX of this paper looks at this issue by reference to recent case law

Inflammation produces catecholamine resistance in obesity via activation of PDE3B by the protein kinases IKKε and TBK1.

Obesity produces a chronic inflammatory state involving the NFκB pathway, resulting in persistent elevation of the noncanonical IκB kinases IKKε and TBK1. In this study, we report that these kinases attenuate β-adrenergic signaling in white adipose tissue. Treatment of 3T3-L1 adipocytes with specific inhibitors of these kinases restored β-adrenergic signaling and lipolysis attenuated by TNFα and Poly (I:C). Conversely, overexpression of the kinases reduced induction of Ucp1, lipolysis, cAMP levels, and phosphorylation of hormone sensitive lipase in response to isoproterenol or forskolin. Noncanonical IKKs reduce catecholamine sensitivity by phosphorylating and activating the major adipocyte phosphodiesterase PDE3B. In vivo inhibition of these kinases by treatment of obese mice with the drug amlexanox reversed obesity-induced catecholamine resistance, and restored PKA signaling in response to injection of a β-3 adrenergic agonist. These studies suggest that by reducing production of cAMP in adipocytes, IKKε and TBK1 may contribute to the repression of energy expenditure during obesity. DOI: http://dx.doi.org/10.7554/eLife.01119.001

Audiovisual Processing is Abnormal in Parkinson\u27s Disease and Correlates with Freezing of Gait and Disease Duration

Background: Sensory and perceptual disturbances progress with disease duration in Parkinson’s disease (PD) and probably contribute to motor deficits such as bradykinesia and gait disturbances, including freezing of gait (FOG). Simple reaction time tests are ideal to explore sensory processing, as they require little cognitive processing. Multisensory integration is the ability of the brain to integrate sensory information from multiple modalities into a single coherent percept, which is crucial for complex motor tasks such as gait. 9 10 11 12 13 Objectives: The aims of this study were to: 1. Assess differences in unisensory (auditory and visual) and multisensory processing speed in people with PD and age-matched healthy controls. 2. Compare relative differences in unisensory processing in people with PD with disease duration and freezing of gait status taking into account the motor delays, which are invariably present in PD. 3. Compare relative differences in multisensory (audiovisual) processing between the PD cohort and age-matched controls. 14 15 16 17 Methods: 39 people with PD (23 with FOG) and 17 age-matched healthy controls performed a reaction time task in response to unisensory (auditory-alone, visual-alone) and multisensory (audiovisual) stimuli. 18 19 Results: The PD group were significantly slower than controls for all conditions compared with healthy controls but auditory reaction times were significantly faster than visual for the PD group only. These relative unisensory differences are correlated with disease duration and divide the PD group by FOG status, but these factors are co-dependent. Although multisensory facilitation occurs in PD, it is significantly less enhanced than in healthy controls. 20 21 22 23 Conclusion: There are significant unisensory and multisensory processing abnormalities in PD. The relative differences in unisensory processing are specific to PD progression, providing a link between these sensory abnormalities and a motor feature of PD. Sensory disturbances have previously been postulated to be central to FOG but this is the first study to predict audiovisual processing abnormalities using FOG status. The multisensory processing abnormalities are independent of disease duration and FOG status and may be a potential biomarker for the disease

A case series of premenstrual disorders presenting to the UK's National Female Hormone Clinic

Aims and method We aimed to describe the clinical characteristics of female patients presenting with premenstrual disorders to a tertiary service in the UK. We conducted a retrospective case-note review of referrals to the National Female Hormone Clinic from April 2014 to August 2020. Based on clinical assessment, we determined whether the patient met criteria for premenstrual dysphoric disorder or premenstrual exacerbation of an underlying psychiatric disorder. Results Of 146 patients seen in clinic for premenstrual disorders, an ICD-10 psychiatric diagnosis was made in 130 (89.0%); a minority 16 (11.0%) did not have a psychiatric diagnosis. Following assessment, 94 patients (64.4%) met criteria for premenstrual dysphoric disorder and 67 (45.6%) had exacerbation of a psychiatric disorder. Clinical implications Patients presenting to this specialist service had complex psychiatric comorbidity; almost half presented with exacerbation of a psychiatric disorder

Injury by knife crime amongst children is associated with socioeconomic deprivation:an observational study

PURPOSE: Children who live in areas of socioeconomic deprivation may be at higher risk of being victims of violent crime such as knife wounds. The current study investigated whether socioeconomic disparity was associated with higher risk of knife crime. METHODS: An observational study included patients aged ≤ 17 years at a UK Major Trauma Centre injured by knife trauma from 2016 to 2022. Indices of deprivation were recorded according to the zip code of residence and compared with those of all of England. These included Index of Multiple Deprivation (IMD); income; employment; education and skills; health and disability; crime; barriers to housing and services; living environment; and Income Deprivation Affecting Children Index (IDACI). RESULTS: There were 139 patients (96% male) with median age of 16 years. When compared with the whole of England, patients had worse indices of IMD (p = 0.021); income (p < 0.001); employment (p < 0.001); education and skills (p < 0.001); health and disability; and IDACI (p < 0.001). There were no significant differences in indices of crime, barriers to housing and services or living environment. CONCLUSIONS: Paediatric knife injury was associated with poor socioeconomic status in multiple domains. Focussed efforts to address socioeconomic disparities should be a priority as a public health measure for vulnerable children

Caveolin-3 Microdomain: Arrhythmia Implications for Potassium Inward Rectifier and Cardiac Sodium Channel

In human cardiac ventricular myocytes, caveolin-3 functions as a scaffolding and regulatory protein for signaling molecules and compartmentalizes ion channels. Our lab has recently explored this sub-cellular microdomain and found that potassium inward rectifier Kir2.x is found in association with caveolin-3. The three cardiac Kir2.x isoforms (Kir2.1, Kir2.2, and Kir2.3) are the molecular correlates of IK1 in the heart, of which Kir2.1 is the dominant isoform in the ventricle. Kir2.1 channels assemble with Kir2.2 and Kir2.3 forming hetero-tetramers that modulate IK1. IK1 sets the resting membrane potential and assists with terminal phase 3 ventricular repolarization. In our studies using native human ventricular tissue, Kir2.x co-localizes with caveolin-3 and significance of the association between Kir2.x and caveolin-3 is emphasized in relation to mutations in the gene which encodes caveolin-3, CAV3, associated with Long QT Syndrome 9 (LQT9). LQT9-associated CAV3 mutations cause decreased current density in Kir2.1 and Kir2.2 as homomeric and heteromeric channels, which affects repolarization and membrane potential stability. A portion of Kir2.1 cardiac localization parallels that of the cardiac sodium channel (Nav1.5). This may have implications for Long QT9 in which CAV3 mutations cause an increase in the late current of Nav1.5 (INa−L) via nNOS mediated nitrosylation of Nav1.5. In iPS-CMs, expression of LQT9 CAV3 mutations resulted in action potential duration (APD) prolongation and early-after depolarizations (EADs), supporting the arrhythmogenicity of LQT9. To evaluate the combined effect of the CAV3 mutants on INa−L and IK1, we studied both ventricular and Purkinje myocyte mathematical modeling. Interestingly, mathematical ventricular myocytes, similar to iPS-CMs, demonstrated EADs but no sustained arrhythmia. In contrast, Purkinje modeling demonstrated delayed-after depolarizations (DADs) driven mechanism for sustained arrhythmia, dependent on the combined loss of IK1 and gain of INa−L. This finding changes the overall assumed arrhythmia phenotype for LQT9. In future studies, we are exploring caveolar micro-domain disruption in heart failure and how this effects Kir2.x and Nav1.5. Here we review the caveolae cardiac microdomain of Kir2.x and Nav1.5 and explore some of the downstream effects of caveolin-3 and caveolae disruption in specific clinical scenarios

Skin-targeted inhibition of PPAR β/δ by selective antagonists to treat PPAR β/δ-mediated psoriasis-like skin disease in vivo

We have previously shown that peroxisome proliferator activating receptor ß/δ (PPAR β/δ is overexpressed in psoriasis. PPAR β/δ is not present in adult epidermis of mice. Targeted expression of PPAR β/δ and activation by a selective synthetic agonist is sufficient to induce an inflammatory skin disease resembling psoriasis. Several signalling pathways dysregulated in psoriasis are replicated in this model, suggesting that PPAR β/δ activation contributes to psoriasis pathogenesis. Thus, inhibition of PPAR β/δ might harbour therapeutical potential. Since PPAR β/δ has pleiotropic functions in metabolism, skin-targeted inhibition offer the potential of reducing systemic adverse effects. Here, we report that three selective PPAR β/δ antagonists, GSK0660, compound 3 h, and GSK3787 can be formulated for topical application to the skin and that their skin concentration can be accurately quantified using ultra-high performance liquid chromatography (UPLC)/mass spectrometry. These antagonists show efficacy in our transgenic mouse model in reducing psoriasis-like changes triggered by activation of PPAR β/δ. PPAR β/δ antagonists GSK0660 and compound 3 do not exhibit systemic drug accumulation after prolonged application to the skin, nor do they induce inflammatory or irritant changes. Significantly, the irreversible PPAR β/δ antagonist (GSK3787) retains efficacy when applied topically only three times per week which could be of practical clinical usefulness. Our data suggest that topical inhibition of PPAR β/δ to treat psoriasis may warrant further exploration