The extent and reasons for compliance failure with oral treatment regimens in haematology outpatients

Focal points: Self-completion questionnaires were used to determine issues with compliance surrounding the use of oral chemotherapy in haematology patients Forty-two patients were identified of which 40 responded over a two-month period Twenty-one respondents (52.5 per cent) indicated that they experienced difficulties in taking their medication Difficulties were not apparently related to the time of dosing; the size of dose units (hydroxyurea) and foil packed agents caused particular difficulties

Eigen-Adaptation and Distributed Representation of 2-D Phase, Energy, Scale and Orientation in Spatial Vision

Distributed representations (DR) of cortical channels are pervasive in models of spatio-temporal vision. A central idea that underpins current innovations of DR stems from the extension of 1-D phase into 2-D images. Neurophysiological evidence, however, provides tenuous support for a quadrature representation in the visual cortex, since even phase visual units are associated with broader orientation tuning than odd phase visual units (J.Neurophys.,88,455–463, 2002). We demonstrate that the application of the steering theorems to a 2-D definition of phase afforded by the Riesz Transform (IEEE Trans. Sig. Proc., 49, 3136–3144), to include a Scale Transform, allows one to smoothly interpolate across 2-D phase and pass from circularly symmetric to orientation tuned visual units, and from more narrowly tuned odd symmetric units to even ones. Steering across 2-D phase and scale can be orthogonalized via a linearizing transformation. Using the tiltafter effect as an example, we argue that effects of visual adaptation can be better explained by via an orthogonal rather than channel specific representation of visual units. This is because of the ability to explicitly account for isotropic and cross-orientation adaptation effect from the orthogonal representation from which both direct and indirect tilt after-effects can be explained.

Growth of U.S. Ecotourism and Its Future in the 1990s

Ecotourism, a new term for low-impact nature travel, is receiving increasing attention. The author has researched the development of the U.S. ecotourism market from 1980-1989 in order to obtain data on the growth of this market segment. Factors involved in the growth of the U.S. ecotourism market are then examined in order to project the growth of this maeket during the 1990's.

Jane Pickens Langley with sister Patti Pickens

General note: Title and date provided by Bettye Lane.

Biomarker analysis in oesophagogastric cancer: Results from the REAL3 and TransMAGIC trials.

BACKGROUND: REAL3 (Randomised ECF for Advanced or Locally advanced oesophagogastric cancer 3) was a phase II/III trial designed to evaluate the addition of panitumumab (P) to epirubicin, oxaliplatin and capecitabine (EOC) in untreated advanced oesophagogastric adenocarcinoma, or undifferentiated carcinoma. MAGIC (MRC Adjuvant Gastric Infusional Chemotherapy) was a phase III study which demonstrated that peri-operative epirubicin, cisplatin and infused 5-fluorouracil (ECF) improved survival in early oesophagogastric adenocarcinoma. PATIENTS AND METHODS: Analysis of response rate (RR; the primary end-point of phase II) and biomarkers in the first 200 patients randomised to EOC or modified dose (m) EOC+P in REAL3 was pre-planned to determine if molecular selection for the on-going study was indicated. KRAS, BRAF and PIK3CA mutations and PTEN expression were assessed in pre-treatment biopsies and results correlated with response to mEOC+P. Association between these biomarkers and overall survival (OS) was assessed in MAGIC patients to determine any prognostic effect. RESULTS: RR was 52% to mEOC+P, 48% to EOC. Results from 175 assessable biopsies: mutations in KRAS (5.7%), BRAF (0%), PIK3CA (2.5%) and loss of PTEN expression (15.0%). None of the biomarkers evaluated predicted resistance to mEOC+P. In MAGIC, mutations in KRAS, BRAF and PIK3CA and loss of PTEN (phosphatase and tensin homolog) were found in 6.3%, 1.0%, 5.0% and 10.9%, respectively, and were not associated with survival. CONCLUSIONS: The RR of 52% in REAL3 with mEOC+P met pre-defined criteria to continue accrual to phase III. The frequency of the mutations was too low to exclude any prognostic or predictive effect.

Towards a 21st-century roadmap for biomedical research and drug discovery: consensus report and recommendations

Decades of costly failures in translating drug candidates from preclinical disease models to human therapeutic use warrant reconsideration of the priority placed on animal models in biomedical research. Following an international workshop attended by experts from academia, government institutions, research funding bodies, and the corporate and nongovernmental organisation (NGO) sectors, in this consensus report, we analyse, as case studies, five disease areas with major unmet needs for new treatments. In view of the scientifically driven transition towards a human pathway-based paradigm in toxicology, a similar paradigm shift appears to be justified in biomedical research. There is a pressing need for an approach that strategically implements advanced, human biology-based models and tools to understand disease pathways at multiple biological scales. We present recommendations to help achieve this.

A retrospective study examining the nature, contributory factors and predictors of dispensing errors in community pharmacy

Introduction: Since 2005, the workload of community pharmacists in England has increased with a concomitant increase in stress and work pressure. However, it is unclear how these factors are impacting on the ability of community pharmacists to ensure accuracy during the dispensing process. This research seeks to extend our understanding of the nature, outcome, and predictors of dispensing errors. Methodology: A retrospective analysis of a purposive sample of incident report forms (IRFs) from the database of a pharmacist indemnity insurance provider was conducted. Data collected included; type of error, degree of harm caused, pharmacy and pharmacist demographics, and possible contributory factors. Results: In total, 339 files from UK community pharmacies were retrieved from the database. The files dated from June 2006 to November 2011. Incorrect item (45.1%, n = 153/339) followed by incorrect strength (24.5%, n = 83/339) were the most common forms of error. Almost half (41.6%, n = 147/339) of the patients suffered some form of harm ranging from minor harm (26.7%, n = 87/339) to death (0.3%, n = 1/339). Insufficient staff (51.6%, n = 175/339), similar packaging (40.7%, n = 138/339) and the pharmacy being busier than normal (39.5%, n = 134/339) were identified as key contributory factors. Cross-tabular analysis against the final accuracy check variable revealed significant association between the pharmacy location (P < 0.024), dispensary layout (P < 0.025), insufficient staff (P < 0.019), and busier than normal (P < 0.005) variables. Conclusion: The results provide an overview of some of the individual, organisational and technical factors at play at the time of a dispensing error and highlight the need to examine further the relationships between these factors and dispensing error occurrence.

The roles of community pharmacists and other pharmacy staff:public perceptions

Introduction: The focus of the community pharmacist’s (CP’s) activities continues to move away from traditional dispensing activities towards the provision of health services. Current functions of CPs cover a combination of roles including prescription matters, counselling and service provision. These expanding roles, along with raised prescription volume, have increased CP workload. Therefore, it has become commonplace to delegate certain activities to other pharmacy staff (PS). This research aimed to examine public perceptions of CPs and other PS functions. Methodology: A self-completion postal questionnaire was sent to a random sample of 9769 members of the general public in England. Participants were asked to indicate which functions they believed CPs and other PS perform. Data were imported into SPSS 22 for analysis. Results: A response rate of 15.7% (n = 1537) was achieved. The roles most commonly attributed to CPs were monitoring prescription appropriateness (90.4%, n = 1390) and counselling patients on prescribed medicines (90.4%, n = 1389). The role most commonly attributed to other PS was sales transactions (92.4%, n = 1420). Similar numbers of responders agreed that the delivery of health services was the role of both CPs and other PS (58.9%, n = 906; 57.0%, n = 876). Conclusion: Despite a move towards more service based practice, the public still primarily associate the CP’s role with activities centred on dispensing. The provision of health services was seen to be equally carried out by CPs and other PS. As the CP’s service-based activities continue to develop, promotional activities may be required to ensure developments in CP functions are recognised by the public

Genomic structure and marker-derived gene networks for growth and meat quality traits of brazilian nelore beef cattle.

Nelore is the major beef cattle breed in Brazil with more than 130 million heads. Genome-wide association studies (GWAS) are often used to associate markers and genomic regions to growth and meat quality traits that can be used to assist selection programs. An alternative methodology to traditional GWAS that involves the construction of gene network interactions, derived from results of several GWAS is the AWM (Association Weight Matrices)/PCIT (Partial Correlation and Information Theory). With the aim of evaluating the genetic architecture of Brazilian Nelore cattle, we used high-density SNP genotyping data (~770,000 SNP) from 780 Nelore animals comprising 34 half-sibling families derived from highly disseminated and unrelated sires from across Brazil. The AWM/PCIT methodology was employed to evaluate the genes that participate in a series of eight phenotypes related to growth and meat quality obtained from this Nelore sample.

Pipkiiα Is Widely Expressed In Hematopoietic-derived Cells And May Play A Role In The Expression Of Alpha- And Gamma-globins In K562 Cells.

Characterized for the first time in erythrocytes, phosphatidylinositol phosphate kinases (PIP kinases) belong to a family of enzymes that generate various lipid messengers and participate in several cellular processes, including gene expression regulation. Recently, the PIPKIIα gene was found to be differentially expressed in reticulocytes from two siblings with hemoglobin H disease, suggesting a possible relationship between PIPKIIα and the production of globins. Here, we investigated PIPKIIα gene and protein expression and protein localization in hematopoietic-derived cells during their differentiation, and the effects of PIPKIIα silencing on K562 cells. PIPKIIα silencing resulted in an increase in α and γ globins and a decrease in the proliferation of K562 cells without affecting cell cycle progression and apoptosis. In conclusion, using a cell line model, we showed that PIPKIIα is widely expressed in hematopoietic-derived cells, is localized in their cytoplasm and nucleus, and is upregulated during erythroid differentiation. We also showed that PIPKIIα silencing can induce α and γ globin expression and decrease cell proliferation in K562 cells.

Obesity And Inflammation And The Effect On The Hematopoietic System.

Bone marrow is organized in specialized microenvironments known as 'marrow niches'. These are important for the maintenance of stem cells and their hematopoietic progenitors whose homeostasis also depends on other cell types present in the tissue. Extrinsic factors, such as infection and inflammatory states, may affect this system by causing cytokine dysregulation (imbalance in cytokine production) and changes in cell proliferation and self-renewal rates, and may also induce changes in the metabolism and cell cycle. Known to relate to chronic inflammation, obesity is responsible for systemic changes that are best studied in the cardiovascular system. Little is known regarding the changes in the hematopoietic system induced by the inflammatory state carried by obesity or the cell and molecular mechanisms involved. The understanding of the biological behavior of hematopoietic stem cells under obesity-induced chronic inflammation could help elucidate the pathophysiological mechanisms involved in other inflammatory processes, such as neoplastic diseases and bone marrow failure syndromes.