Spacelab Life Sciences-1

This report provides an historical overview of the Spacelab Life Sciences-1 (SLS-1) mission along with the resultant biomaintenance data and investigators' findings. Only the nonhuman elements, developed by Ames Research Center (ARC) researchers, are addressed herein. The STS-40 flight of SLS-1, in June 1991, was the first spacelab flown after 'return to orbit', it was also the first spacelab mission specifically designated as a Life Sciences Spacelab. The experiments performed provided baseline data for both hardware and rodents used in succeeding missions

Consultative Total Parenteral Nutrition Teams: The Effect on the Incidence of Total Parenteral Nutrition‐Related Complications

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141387/1/jpen0146.pd

Eccentricity Evolution in Simulated Galaxy Clusters

Strong cluster eccentricity evolution for $z \le 0.13$ has appeared in a variety of observational data sets. We examine the evolution of eccentricity in simulated galaxy clusters using a variety of simulation methodologies, amplitude normalizations, and background cosmologies. We do not find find such evolution for $z < 0.1$ in any of our simulation ensembles. We suggest a systematic error in the form of a redshift-dependent selection effect in cluster catalogs or missing physics in cluster simulations important enough to modify the cluster morphology.Comment: Revised version to be published in ApJ. Moderate revisions, including additional N-body simulations with varying amplitude normalization and background matter density within OCDM and $\lambda$CDM scenarios reinforce our conclusion that observed clusters have recently relaxed much more rapidly than simulated one

Actin dynamics tune the integrated stress response by regulating eukaryotic initiation factor 2α dephosphorylation.

Four stress-sensing kinases phosphorylate the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α) to activate the integrated stress response (ISR). In animals, the ISR is antagonised by selective eIF2α phosphatases comprising a catalytic protein phosphatase 1 (PP1) subunit in complex with a PPP1R15-type regulatory subunit. An unbiased search for additional conserved components of the PPP1R15-PP1 phosphatase identified monomeric G-actin. Like PP1, G-actin associated with the functional core of PPP1R15 family members and G-actin depletion, by the marine toxin jasplakinolide, destabilised the endogenous PPP1R15A-PP1 complex. The abundance of the ternary PPP1R15-PP1-G-actin complex was responsive to global changes in the polymeric status of actin, as was its eIF2α-directed phosphatase activity, while localised G-actin depletion at sites enriched for PPP1R15 enhanced eIF2α phosphorylation and the downstream ISR. G-actin's role as a stabilizer of the PPP1R15-containing holophosphatase provides a mechanism for integrating signals regulating actin dynamics with stresses that trigger the ISR.This work was funded by the Medical Research Council (UK) (MRC Ref G1002610) and a Wellcome Trust Strategic Award for core facilities to the Cambridge Institute for Medical Research (CIMR, Wellcome 100140). SJM holds a Senior Clinical Research Fellowship from the Medical Research Council (MRC Ref G1002610). DR is a Wellcome Trust Principal Research Fellow (Wellcome 084812/Z/08/Z). The June Hancock Mesothelioma Research Fund funded LED (JH09-2); the British Lung Foundation funded HJC (APHD11-4); CD is a member of the CIMR PhD programme funded by the Wellcome Trust; and VP holds a Diabetes UK Arthur and Sadie Pethybridge PhD Studentship.This is the final published version. It first appeared at http://elifesciences.org/content/4/e04872

Insulin Intensification for People with Type 2 Diabetes

BackgroundType 2 diabetes is a progressive disorder and with time, it is appropriate for insulin therapy to be initiated in the majority of people. Insulin is commonly initiated with once-daily basal insulin. However, when glycaemic control becomes unsatisfactory despite the introduction of basal insulin, no clear guidelines exist for intensifying the insulin regimen. In this article we aim to provide a clinician’s approach to both the optimisation of the basal insulin dose, and strategies to intensify insulin therapy.MethodsAn expert consensus panel, consisting of the authors, was convened to review the current practice of insulin intensification in people with type 2 diabetes and to develop a pragmatic algorithm for clinicians. The panel reviewed the published literature on the use of insulin in clinical practice, the evidence for different intensification strategies, and the potential impact of patient-related factors on insulin choices. ResultsInsulin intensification should only be considered after the basal insulin dose has been optimised. This is achieved by taking into account basal and prandial (pre and post) blood glucose levels, individualised target HbA1c, and dietary factors. If optimal basal insulin together with oral medications is not sufficient to reach glycaemic targets, the next step is to introduce a basal plus 1 regimen or switch to twice-daily premixed insulin. Each has advantages and disadvantages and existing guidelines do not emphasise or support any particular regimen. Therefore, it is important to individualise the choice according to the individual’s needs. A practical algorithm has been developed to help clinicians choose an appropriate second-line regimen.ConclusionAs beta-cell failure progresses in people with type 2 diabetes, basal insulin regimens need to be optimised and then intensified when necessary to maintain agreed glycaemic targets

Pharmacogenomics is the future of prescribing inpsychiatry

NoPatients' pharmacogenetic data could be used to improve adherence to antipsychotic medication by increasing the likelihood of therapeutic response and reducing the prevalence of adverse drug reactions

Proportion of Antipsychotics with CYP2D6 Pharmacogenetic (PGx) Associations Prescribed in an Early Intervention in Psychosis (EIP) Cohort: A Cross-Sectional Study

YesBackground: Prescribing drugs for psychosis (antipsychotics) is challenging due to high rates of poor treatment outcomes, which are in part explained by an individual’s genetics. Pharmacogenomic (PGx) testing can help clinicians tailor the choice or dose of psychosis drugs to an individual’s genetics, particularly psychosis drugs with known variable response due to CYP2D6 gene variants (‘CYP2D6-PGx antipsychotics’). Aims: This study aims to investigate differences between demographic groups prescribed ‘CYP2D6-PGx antipsychotics’ and estimate the proportion of patients eligible for PGx testing based on current pharmacogenomics guidance. Methods: A cross-sectional study took place extracting data from 243 patients’ medical records to explore psychosis drug prescribing, including drug transitions. Demographic data such as age, sex, ethnicity, and clinical sub-team were collected and summarised. Descriptive statistics explored the proportion of ‘CYP2D6-PGx antipsychotic’ prescribing and the nature of transitions. We used logistic regression analysis to investigate associations between demographic variables and prescription of ‘CYP2D6-PGx antipsychotic’ versus ‘non-CYP2D6-PGx antipsychotic’. Results: Two-thirds (164) of patients had been prescribed a ‘CYP2D6-PGx antipsychotic’ (aripiprazole, risperidone, haloperidol or zuclopenthixol). Over a fifth (23%) of patients would have met the suggested criteria for PGx testing, following two psychosis drug trials. There were no statistically significant differences between age, sex, or ethnicity in the likelihood of being prescribed a ‘CYP2D6-PGx antipsychotic’. Conclusions: This study demonstrated high rates of prescribing ‘CYP2D6-PGx-antipsychotics’ in an EIP cohort, providingThis research was supported by the National Institute for Health and Care Research (NIHR) Yorkshire and Humber Patient Safety Translational Research Centre (NIHR Yorkshire and Humber PSTRC). This research has been funded through a scholarship from the Bradford District Care NHS Foundation Trust in partnership with the University of Bradford

The Role of the External Auditor in UK Bank Regulation and Supervision

ABSTRACT The role of the external auditor in the supervisory process requires standards such as independence, objectivity and integrity to be achieved. Even though the regulator and external auditor perform similar functions, namely the verification of financial statements, they serve particular interests. The regulator works towards safeguarding financial stability and investor interests. On the other hand, the external auditor serves the private interests of the shareholders of a company. The financial audit remains an important aspect of corporate governance that makes management accountable to shareholders for its stewardship of a company. The debate surrounding the role of external auditors focusses in particular on auditor independence. A survey by the magazine “Financial Director” shows that the fees derived from audit clients in terms of non-audit services are significant in comparison with fees generated through auditing. Accounting firms sometimes engage in a practice called “low balling” whereby they set audit fees at less than the market rate and make up for the deficit by providing non audit services. As a result, some audit firms have commercial interests to protect too. There is concern that the auditor's interests to protect shareholders of a company and his commercial interests do not conflict with each other. Sufficient measures need to be in place to ensure that the external auditor's independence is not affected. As well as considering threats to auditor independence and safeguards to protect against such threats, this paper focuses on how the external auditor can assist the FSA through two of its principal regulatory tools in the FSA's response to risk, namely supervision and enforcement. A lot of work and improvements on audit independence have been carried out over the years and there should be an ongoing process of review and further efforts aimed at improvement. Key words: Supervision, Enforcement, Independenc

Proportion of Antipsychotics with CYP2D6 Pharmacogenetic (PGx) Associations Prescribed in an Early Intervention in Psychosis (EIP) Cohort: A Cross-Sectional Study

Background:: Prescribing drugs for psychosis (antipsychotics) is challenging due to high rates of poor treatment outcomes, which are in part explained by an individual’s genetics. Pharmacogenomic (PGx) testing can help clinicians tailor the choice or dose of psychosis drugs to an individual’s genetics, particularly psychosis drugs with known variable response due to CYP2D6 gene variants (‘CYP2D6-PGx antipsychotics’). Aims:: This study aims to investigate differences between demographic groups prescribed ‘CYP2D6-PGx antipsychotics’ and estimate the proportion of patients eligible for PGx testing based on current pharmacogenomics guidance. Methods:: A cross-sectional study took place extracting data from 243 patients’ medical records to explore psychosis drug prescribing, including drug transitions. Demographic data such as age, sex, ethnicity, and clinical sub-team were collected and summarised. Descriptive statistics explored the proportion of ‘CYP2D6-PGx antipsychotic’ prescribing and the nature of transitions. We used logistic regression analysis to investigate associations between demographic variables and prescription of ‘CYP2D6-PGx antipsychotic’ versus ‘non-CYP2D6-PGx antipsychotic’. Results:: Two-thirds (164) of patients had been prescribed a ‘CYP2D6-PGx antipsychotic’ (aripiprazole, risperidone, haloperidol or zuclopenthixol). Over a fifth (23%) of patients would have met the suggested criteria for PGx testing, following two psychosis drug trials. There were no statistically significant differences between age, sex, or ethnicity in the likelihood of being prescribed a ‘CYP2D6-PGx antipsychotic’. Conclusions:: This study demonstrated high rates of prescribing ‘CYP2D6-PGx-antipsychotics’ in an EIP cohort, providing a rationale for further exploration of how PGx testing can be implemented in EIP services to personalise the prescribing of drugs for psychosis