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Typically defined as a personality trait that is characterised by the setting of exceedingly high performance standards and overly critical self-evaluation tendencies, perfectionism has been associated with an increased risk for a variety of psychopathology, including anxiety disorders, depression, and eating disorders. However, due to the various ways in which the achievement-based construct has been defined and conceptualised in the literature, questions remain about its nature, structure, measurement, specific maintaining factors, and treatment. For example, it is unclear as to the extent to which dimensions of perfectionism are considered “functional” and “pathological” and more importantly, the nature of the relationship between the more adaptive facets of perfectionism and unfavourable performance situations (e.g., situations that imply a failure to meet performance expectations or standards). The present thesis had three broad aims. First, to investigate potential measurement issues with self-report instruments commonly used to assess multidimensional perfectionism. Second, the present research focused on broadening understanding of the cognitive, affective, and behavioural constructs that underlie both adaptive and maladaptive dimensions of perfectionism, and particularly how these are impacted during performance situations. Third, this thesis sought to gain a better understanding of the role of self-relevant constructs (i.e., self-concept and self-concept certainty) across adaptive and maladaptive dimensions of perfectionism. Findings from the present thesis contribute to a better understanding of the measurement issues associated with perfectionism measures and extend upon models of perfectionism by suggesting the role that a series of affective, cognitive (including the self-concept and self-concept certainty), and behavioural processes play in maintaining adaptive and maladaptive perfectionism

Immunosuppression is a major factor facilitating glioblastoma (GBM) progression and therapeutic resistance. We previously demonstrated that myeloid-derived suppressor cells (MDSCs) expand in GBM patients, but the mechanisms by which MDSC subsets promote tumorigenesis remain unknown. Using multiple syngeneic mouse GBM models, we show that monocytic MDSCs (mMDSCs) accumulate in tumors of males and associate with poor prognosis. Consistent with preclinical observations, males, who constitute 60% of GBM patients and have a worse prognosis than females, had significantly more tumor-infiltrating mMDSCs. In contrast, female tumor-bearing mice had a two-fold increase in circulating granulocytic MDSC (gMDSC) frequency, and a high gMDSC gene signature correlated with poor prognosis of female patients. Male-to-female bone marrow transplantation indicated that immune cell-intrinsic discrepancies drive the sex differences in GBM survival. In line with the differential MDSC localization, targeting gMDSCs with anti-Ly6G neutralizing antibodies extended the lifespan of female mice without affecting males. However, mMDSCs were protected from the anti-Ly6C depletion strategy due to their systemic and local proliferation, as indicated by ex vivo Ki-67 staining and subsequently confirmed by gene expression analysis. Drug-prediction using the differential expression profiles and subsequent pre-clinical testing established that mMDSCs can be targeted by chemotherapies, while IL-1 inhibitors are effective against gMDSCs. These findings indicate that MDSC subset variation represents an opportunity for improved immunotherapy efficacy while accounting for sex as a biological variable.

NHS providers and commissioners ended 2015/2016 with a deficit of £1.85 billion – the largest aggregate deficit in NHS history. One option is to meet this deficit is to improve productivity delivering better value care to help the NHS meet its efficiency targets.1 This is supported by the Carter Report where it stated that pharmacists and clinical pharmacy technicians to spend much more time on clinical pharmacy services than on infrastructure activities or back-office services.2AimThe aim was to improve the efficiency and cost effectiveness of the paediatric rheumatology service for methotrexate patients requiring therapeutic drug monitoring (TDM) by assigning tasks according to skill mix.MethodValue stream mapping (VSM), a lean methodology analysing the current state of a process through work flow mapping and designing a future state for the process in order to improve the process. This was used by the pharmacist and consultant to review the paediatric pharmacy rheumatology patient flow. Each step was determined then reviewed for value to patient care and assigned to the consultant, pharmacist or patient care co-ordinator (PCC) according to skill mix.3Results18 different processes were mapped for monitoring a new and current patient’s blood test results and homecare supply. For a new patient registration 5 steps were involved, 8 steps for monitoring a patient’s blood results and 5 steps for homecare supply. In addition, the pharmacist attended the rheumatology clinics when methotrexate patients were booked in. This involved approximately 2 hours every 2 weeks, taking into account that clinics usually did not run on time, to see between 1–3 patients. After VSM it was agreed the consultant would contact the pharmacist when there is a new patient or a current patient requires review. Previously the pharmacist was responsible for contacting patients/parents and carers to remind them of overdue blood tests taking around 45 min a week. With VSM the PCC was identified as the best person to do this. On a weekly basis the pharmacist will access the TDM database and update a list of patients that was overdue blood tests. This list is sent to the consultant and PCC. The PCC will contact the families and update the list with outcomes. Homecare prescriptions were previously organised by the pharmacist for the consultant to sign. The pharmacist continues to ensure the prescriptions are correct in terms of need for supply (liaison with the homecare company, medical documents and consultant for clinical need) and dosage but the PCC liaising with the consultant for administration purposes such as printing of prescriptions and returning prescriptions back to the pharmacist. A standard operating procedure was written to ensure roles and responsibilities are clear.ConclusionThis simple and quick exercise has improved the efficiency and cost effectiveness of the service as the most appropriate person now actions each step. Having access to a PCC has saved the pharmacist approximately 1 hour a week and the consultant clinic referral system approximately 2 hours twice a month equating to over 1.5 working days a month.ReferencesDunn P, McKenna H, Murray R. Deficits in the NHS 2016. The Kings Fund available at https://www.kingsfund.org.uk/sites/default/files/field/field_publication_file/Deficits_in_the_NHS_Kings_Fund_July_2016_1.pdf (Accessed 12.12.17).Lord Carter of Coles. Operational productivity and performance in English NHS acute hospitals: Unwarranted variations. Department of Health. London. Available at https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/499229/Operational_productivity_A.pdf (Accessed 12.12.17).