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Biomedical subjects

Paul Rogers

Publications and source records attributed to Paul Rogers.

18 recordsLinked to original sources
PubMed2006

The association between a self-reported history of mental health problems and a history of parasuicide in a sample of UK male prisoners.

BACKGROUND: Prisoner parasuicide is a major public and mental health concern worldwide and within the United Kingdom. OBJECTIVES: This study used a cross-sectional design to examine the association between a self-reported history of mental health problems and a history of parasuicide in male prisoners. METHODS: A total sample of 192 convicted prisoners who were about to be released from a local category "B" prison in the UK were approached and asked to complete the "Toolkit for Healthcare Needs Assessment in Prisons" which contained a range of demographic, mental and physical health questions. Unadjusted and adjusted odds ratios (with 95% confidence intervals) were determined using logistic regression. RESULTS: Fifty-one prisoners participated. The unadjusted odds ratio for having a self-reported history of mental health problems and a self-reported history of parasuicide was 15.6 (95% C.I., 2.96-82.16). Following adjustment for age, living alone, homelessness, illegal drug use and alcohol problems the odds ratio was 11.32 (95% C.I., 1.80-71.13). DISCUSSION: This study provides good evidence of an association between a history of mental health problems and a history of parasuicide in a group of UK male prisoners.

Adult↗
PubMed2006

Who has the D? How clear decision roles enhance organizational performance.

Decisions are the coin of the realm in business. But even in highly respected companies, decisions can get stuck inside the organization like loose change. As a result, the entire decision-making process can stall, usually at one of four bottlenecks: global versus local, center versus business unit, function versus function, and inside versus outside partners. Decision-making bottlenecks can occur whenever there is ambiguity or tension over who gets to decide what. For example, do marketers or product developers get to decide the features of a new product? Should a major capital investment depend on the approval of the business unit that will own it, or should headquarters make the final call? Which decisions can be delegated to an outsourcing partner, and which must be made internally? Bain consultants Paul Rogers and Marcia Blenko use an approach called RAPID (recommend, agree, perform, input, and decide) to help companies unclog their decision-making bottlenecks by explicitly defining roles and responsibilities. For example, British American Tobacco struck a new balance between global and local decision making to take advantage of the company's scale while maintaining its agility in local markets. At Wyeth Pharmaceuticals, a growth opportunity revealed the need to push more decisions down to the business units. And at the UK department-store chain John Lewis, buyers and sales staff clarified their decision roles in order to implement a new strategy for selling its salt and pepper mills. When revamping its decision-making process, a company must take some practical steps: Align decision roles with the most important sources of value, make sure that decisions are made by the right people at the right levels of the organization, and let the people who will live with the new process help design it.

Commerce↗
PubMed2005

In vitro and in vivo pharmacokinetic-pharmacodynamic relationships for the trisubstituted aminopurine cyclin-dependent kinase inhibitors olomoucine, bohemine and CYC202.

PURPOSE: To investigate pharmacokinetic-pharmacodynamic relationships for the trisubstituted aminopurine cyclin-dependent kinase inhibitors olomoucine, bohemine, and CYC202 (R-roscovitine; seliciclib) in the HCT116 human colon carcinoma model. EXPERIMENTAL DESIGN: The in vitro activity of the agents was determined in a human tumor panel using the sulforhodamine B assay. The concentration and time dependence was established in HCT116 cells. Molecular biomarkers, including RB phosphorylation and cyclin expression, were assessed by Western blotting. Pharmacokinetic properties were characterized in mice following analysis by liquid chromatography-tandem mass spectrometry. Based on these studies, a dosing regimen was developed for CYC202 that allowed therapeutic exposures in the HCT116 tumor xenograft. RESULTS: The antitumor potency of the agents in vitro was in the order olomoucine (IC50, 56 micromol/L) < bohemine (IC50, 27 micromol/L) < CYC202 (IC50, 15 micromol/L), corresponding to their activities as cyclin-dependent kinase inhibitors. Antitumor activity increased with exposure time up to 16 hours. The agents caused inhibition of RB and RNA polymerase II phosphorylation and depletion of cyclins. They exhibited relatively rapid clearance following administration to mice. CYC202 displayed the slowest clearance from plasma and the highest tumor uptake, with oral bioavailability of 86%. Oral dosing of CYC202 gave active concentrations in the tumor, modulation of pharmacodynamic markers, and inhibition of tumor growth. CONCLUSIONS: CYC202 showed therapeutic activity on human cancer cell lines in vitro and on xenografts. Pharmacodynamic markers are altered in vitro and in vivo, consistent with the inhibition of cyclin-dependent kinases. Such markers may be potentially useful in the clinical development of CYC202 and other cyclin-dependent kinase inhibitors.

Animals↗
PubMed2005

Identification of novel small molecule inhibitors of hypoxia-inducible factor-1 that differentially block hypoxia-inducible factor-1 activity and hypoxia-inducible factor-1alpha induction in response to hypoxic stress and growth factors.

Hypoxia-inducible factor-1 (HIF-1) is a transcriptional complex that is activated in response to hypoxia and growth factors. HIF-1 plays a central role in tumor progression, invasion, and metastasis. Overexpression of the HIF-1alpha subunit has been observed in many human cancers and is associated with a poor prognostic outcome with conventional treatments. Targeting HIF-1 using novel small molecule inhibitors is, therefore, an attractive strategy for therapeutic development. We have generated U2OS human osteosarcoma cells stably expressing a luciferase reporter construct under the control of a hypoxia response element (U2OS-HRE-luc). The U2OS-HRE-luc cells were robustly and reproducibly sensitive to hypoxic stress in a HIF-1-dependent manner. We developed an automated U2OS-HRE-luc cell-based assay that was used in a high-throughput screen to identify compounds that inhibited HIF-1 activity induced by treatment with the hypoxia mimetic, deferoxamine mesylate. We performed a pilot screen of the National Cancer Institute Diversity Set of 2,000 compounds. We identified eight hit compounds, six of these were also identified by Rapisarda et al. in an independent hypoxia screen. However, there were two novel hit compounds, NSC-134754 and NSC-643735, that did not significantly inhibit constitutive luciferase activity in U2OS cells (U2OS-luc). We showed that both NSC-134754 and NSC-643735 significantly inhibited HIF-1 activity and HIF-1alpha protein induced by deferoxamine mesylate. Interestingly, NSC-134754 but not NCS-643735 inhibited HIF-1 activity and HIF-1alpha protein induced by hypoxia and significantly inhibited Glut-1 expression. Finally, we showed that both NCS-134754 and NCS-643735 inhibited HIF-1alpha protein induced by insulin-like growth factor-1. Our cell-based assay approach has successfully identified novel compounds that differentially target hypoxia and/or growth factor-mediated induction of HIF-1alpha.

Antineoplastic Agents↗
PubMed2005

Intravenous ketamine sedation for painful oncology procedures.

BACKGROUND: The aim of the study was to determine the efficacy and adverse effects of intravenous (i.v.) ketamine sedation administered by nonanesthetist physicians for painful procedures. METHODS: A single-agent, procedural sedation protocol using titrated doses of ketamine i.v. (maximum 2 mg.kg(-1)) was conducted in outpatient pediatric oncology patients undergoing lumbar puncture (LP), bone marrow biopsy/aspiration (BMBx/A) or combination (LP/BMBx/A) in a tertiary care setting. The efficacy of analgesia and sedation (ability to perform the procedure), procedure duration, recovery time and the occurrence of adverse events are described. RESULTS: Fifty-eight subjects of a median age of 5 years (1-13) and median weight of 20 kg (10.5-68) underwent 119 sedations. An LP was performed in 73% of cases, a BMBx/A in 13% and LP/BMBx/A in 13%. Efficacy was 100% and the mean dose of ketamine was 1.3 mg.kg(-1) (0.4). The mean duration of the procedure was 6.6 min (4.2) and the recovery time was 11 min (4-45). Two subjects (1.7%) had a hypoxemia (SpO2 of <94%). No major airway complications occurred. The prevalence of hypertension (systolic > 20% at 5 min) was 54%. The median pain visual analogue score (VAS) for an observer was 0 (range 0-3) and caregiver was 0 (range 0-4). The median VAS for satisfaction (observer) was 10 (range 7-10) and caregiver VAS was also 10 (range 5-10). At 24 h after discharge, the incidence of bad dreams was 3.3%; vomiting, 10.8%; and abnormal behavior, 4.2%. CONCLUSION: Ketamine i.v. up to 2 mg.kg(-1) is an effective sedative for oncology procedures using a defined protocol.

Adolescent↗
PubMed2005

Isothiazolones as inhibitors of PCAF and p300 histone acetyltransferase activity.

Histone acetylation plays an important role in regulating the chromatin structure and is tightly regulated by two classes of enzyme, histone acetyltransferases (HAT) and histone deacetylases (HDAC). Deregulated HAT and HDAC activity plays a role in the development of a range of cancers. Consequently, inhibitors of these enzymes have potential as anticancer agents. Several HDAC inhibitors have been described; however, few inhibitors of HATs have been disclosed. Following a FlashPlate high-throughput screen, we identified a series of isothiazolone-based HAT inhibitors. Thirty-five N-substituted analogues inhibited both p300/cyclic AMP-responsive element binding protein-binding protein-associated factor (PCAF) and p300 (1 to >50 micromol/L, respectively) and the growth of a panel of human tumor cell lines (50% growth inhibition, 0.8 to >50 micromol/L). CCT077791 and CCT077792 decreased cellular acetylation in a time-dependent manner (2-48 hours of exposure) and a concentration-dependent manner (one to five times, 72 hours, 50% growth inhibition) in HCT116 and HT29 human colon tumor cell lines. CCT077791 reduced total acetylation of histones H3 and H4, levels of specific acetylated lysine marks, and acetylation of alpha-tubulin. Four and 24 hours of exposure to the compounds produced the same extent of growth inhibition as 72 hours of continuous exposure, suggesting that growth arrest was an early event. Chemical reactivity of these compounds, as measured by covalent protein binding and loss of HAT inhibition in the presence of DTT, indicated that reaction with thiol groups might be important in their mechanism of action. As one of the first series of small-molecule inhibitors of HAT activity, further analogue synthesis is being pursued to examine the potential scope for reducing chemical reactivity while maintaining HAT inhibition.

Acetylation↗
PubMed2005

A multidisciplinary review of nutrition considerations in the pediatric oncology population: a perspective from children's oncology group.

Over the past few decades, great progress has been made in the survival rates of childhood cancer. As survival rates have improved, there has been an increased focus on supportive care. Nutrition is a supportive-care modality that has been associated with improved tolerance to chemotherapy, improved survival, increased quality of life, and decreased risk of infection in children undergoing anticancer therapy. Guidelines and assessment criteria have been proposed for the nutrition management of a child with cancer; however, there is no consistent use of criteria among institutions treating children with cancer. This review will present the current evidence and standards of practice incorporating aspects of nutrition, nursing, pharmacology, and psychosocial challenges to consider in the nutrition management of a child with cancer. Recommendations for clinical practice are presented.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Modernising prison mental health care.

Some 90% of prisoners in England and Wales have a mental health poblem. This article outlines several initiatives, including health screening on admission and suicide prevention, to improve the care of this population.

Health Policy↗
PubMed2004

New aspects on critical care medicine training.

Recently, three fundamental changes have been introduced in medical education, all of particular importance to critical care medicine: (1) clinical teaching and medical practice now emphasize evidence-based medicine, (2) patient safety aspects are increasingly stressed, and (3) use of simulation in medical training is spreading rapidly. In 1999, the disturbingly high frequency of life-threatening or even lethal medical complications was emphasized by the Institute of Medicine in the book To Err Is Human. The Institute of Medicine recommended establishing interdisciplinary team training programs incorporating efficient methods such as simulation. Although simulation has been used by the aviation industry and the military for several decades, only during the past decade has this become a teaching method in medicine. Currently, two full-scale computerized simulators are available: METI, provided by Medical Education Technologies, Sarasota, Florida, and SimMan, manufactured by Laerdal Medical, in Stavanger, Norway. The simulation center at the University of Pittsburgh Medical Center was established in 1994 and has grown quickly to its current large facility, where, in academic year 2003 to 2004, approximately 8000 healthcare professionals were trained on the SimMan. Courses taught include clinical procedures and decision making in perioperative medicine, acute medicine, pharmacology, anesthesiology, airway management, bronchoscopy, pediatric versus adult crisis management, critical events in obstetrics, and crisis team training. Advantages of simulation training over traditional medical education methods include (1) provision of a safe environment for both patient and student during training in risky procedures, (2) unlimited exposure to rare but complicated and important clinical events, (3) the ability to plan and shape training opportunities rather than waiting for a suitable situation to arise clinically, (4) the ability to provide immediate feedback, (5) the opportunity to repeat performance, (6) the opportunity for team training, and (7) lower costs, both direct and indirect. Within the next decade, use of computerized simulators for evidence-based education and training in medicine is expected to develop considerably and spread rapidly into a very important domain of medical schools throughout the entire world.

Computer Simulation↗
PubMed2003

Pre-admission nursing assessment in a Welsh medium secure unit (1991-2000): Part 1--an analysis of practice and cost.

Pre-admission nursing assessment is a widely accepted practice in forensic mental health services, yet has never been described or evaluated. The costs and merits of this practice have not hitherto been the subject of systematic investigation. This article describes the practice of pre-admission assessments and details a method for estimating the cost of forensic nursing assessments in terms of the investment of nursing time. The method was then employed to evaluate the cost of nursing assessments to a Welsh medium secure unit over a 9-year period. The results showed that the demand for, and location, of pre-admission nursing assessment varied considerably over 9 years. Assessments were expensive in the demands that they placed on the resources of the nursing department. Due to the high investment costs, evidence is required to support such practice.

Costs and Cost Analysis↗
PubMed2003

Pre-admission nursing assessment in a Welsh Medium Secure Unit (1991-2000): Part 2--comparison of traditional nursing assessment with the HCR-20 risk assessment tool.

Pre-admission forensic nursing assessment is a tradition that has no research evidence base, little documentary support and is an expensive drain on nursing resources from clinical environments. Such an expensive practice warrants some evaluation of the quality of these nursing assessments. This study assessed the quality of nursing risk assessments through comparison with the HCR-20, a well-established and widely validated violence risk assessment instrument. There was a high degree of correspondence between nurse assessments and the contents of the HCR-20. The results offer support for forensic nurses' abilities to develop effective measures and practices based upon nursing knowledge and experience where no formal evidence base previously existed.

Forensic Psychiatry↗
PubMed2002

Quantitation and phenotypic analysis of natural killer T cells in primary biliary cirrhosis using a human CD1d tetramer.

BACKGROUND & AIMS: Natural killer T (NKT) cells are a subset of lymphocytes incriminated in playing an important role in the modulation of the innate immune response and the development of autoimmunity. However, there have been only limited studies attempting to quantitate the number of NKT cells in autoimmune disease, particularly because of difficulties associated with definition of this subpopulation. METHODS: We used a human CD1d (hCD1d) tetramer produced by a baculovirus expressing recombinant CD1d protein complexed with alpha-galactosylceramide (alpha-GalCer) and quantitated hCD1d tetramer reactive cells in blood and liver from controls and patients with primary biliary cirrhosis (PBC). RESULTS: The majority of CD1d-alphaGalCer-restricted NKT cells were positive for TCR Valpha24 and Vbeta11. There was a distinct CD4- CD8+ population within the CD1d-alphaGalCer-restricted NKT cells in addition to the CD4- CD8- and CD4+ CD8- population. The frequency of CD1d-alphaGalCer-restricted NKT cells was similar between blood and liver in healthy individuals. In contrast, the frequency of CD1d-alphaGalCer-restricted NKT cells in the liver was significantly higher than in the blood of PBC patients. The frequency of CD1d-alpha-GalCer-restricted NKT cells in the liver was also significantly higher in PBC patients than in healthy individuals. CONCLUSIONS: The frequency and function of such cells should be studied not only in blood but also in the target organ of the autoimmune disease. Selective enrichment of CD1d-alphaGalCer-restricted NKT cells at the site of inflammation is observed in PBC, suggesting a role of these cells in the development of PBC.

Antigens, CD1↗
PubMed2002

Value acceleration: lessons from private-equity masters.

The most successful private-equity firms regularly spearhead dramatic business transformations, creating exceptional returns for their investors. To understand how those firms do it, the authors studied more than 2,000 PE transactions over the past ten years and discovered that the top performers' success stems from the rigor with which they manage their businesses. This article describes the four management disciplines vital to the success of the best PE firms. First, for each business, they define an investment thesis: a brief, clear statement of how to make the business more valuable within three to five years. The thesis, which guides all actions by the company, usually focuses on growth. PE firms know that the demonstration of a path to strong growth produces the big returns on investment. Second, they don't measure too much. They zero in on a few financial indicators that most clearly reveal the business's progress in increasing its value. They watch cash more closely than earnings and tailor performance measures to each business, rather than imposing one set of measures across their entire portfolio. Third, they work their balance sheets, mining undervalued assets, turning fixed assets into sources of financing, and aggressively managing their physical capital. Last, they make the center the shareholder. Corporate staffs in PE firms make unsentimental investment decisions, buying and selling businesses when the price is right and bringing in new management when performance falters. These firms also keep their corporate centers extremely lean. By adopting these four disciplines, executives at public companies should be able to reap significantly greater returns from their own business units.

Consultants↗
PubMed1998

The Cognitive Psychology of Lottery Gambling: A Theoretical Review.

Despite the current popularity of the UK National, psychologists have tended to neglect lottery play. This review provides a summary of current research findings and outlines the main cognitive theories of gambling as related to non-pathological lottery play. A discussion of various biases and irrational thinking patterns typically found in lottery gambling will be given. These will include the misunderstanding of lottery odds, a susceptibility to the gambler's fallacy and cognitive entrapment, a belief in hot and cold numbers, unrealistic optimism, a belief in personal luck, superstitious thinking, the illusion of control, the erroneous perception of near misses, a susceptibility to prize size and rollover effects, the framing of gambling outcomes and finally, the influence of social factors on lottery play. It is concluded that the psychology of lottery play needs a more unified theory which whilst largely cognitive in emphasis, should also incorporate social motivations such as those inherent in syndicate based lottery play.

Journal Article↗
PubMedDate not supplied

The United Nations and the promotion of peace.

Despite the end of the cold war, many other conflicts persisted in the 1990s. The hope that a peace dividend would help to alleviate poverty was replaced by doubts regarding the effects of free market globalization and environmental constraints. Future concerns include the continuing aftermath of the cold war, the increased destructiveness of modern warfare, despite the increased sophistication of modern weaponry, the widening poverty gap between a wealthy elite and the majority of the world's population and developing global economic and environmental threats. The response to all this should be economic co-operation for sustainable development, including trade reform, and radical change in the environmental impact of the industrialized countries. Yet it appears that the response of the US, and to a lesser extent Europe, is to maintain the status quo in its own interests by military means, an attitude that seems to have been reinforced by the events of 11 September 2001. Nevertheless, these developments are opposed by citizen groups in the developed world and by analysts in the South. The United Nations and its agencies have been at the forefront of analysis and proposals for action in many of these fields. Its role is likely to increase in the next 30 years and it must be made as effective a global body as possible.

Environment↗
PubMedDate not supplied

The global war on terror: four years on.

The progress of the global war on terror in the four years since the 9 September 2001 attack on New York and Washington is surveyed, with particular reference to its objective of curtailing the activities of al-Qaida, the situation in Afghanistan and Iraq, and the threat to the United States from the 'axis of evil'. It is suggested that the US is unlikely to withdraw from Iraq in particular because of its dependency upon access to Middle East oil in the foreseeable future, and accordingly that the global war on terror is likely to continue for several years at least.

Afghanistan↗
PubMedDate not supplied

Assessment and management of obsessive compulsive disorder.

This article outlines the nature of obsessive compulsive disorder and sets out an evidence-based approach to assessment and treatment. The article also examines the key elements of the National Institute for Health and Clinical Excellence (2005) guideline on this condition.

Causality↗