A feasibility study on the development and integration of a teaching aid for pharmacology

Traditional methods of teaching and learning in higher education are ever-evolving. This report assesses the feasibility of developing a teaching aid for pharmacology modules. Focus groups were established to gauge student and staff opinions on the use of teaching aids and an extensive literature review was conducted. The study identifies and critically evaluates a range of possibilities that could be developed and discusses practical issues such as accessibility, inclusion and assessment, associated with these potential aids. This initial study concludes that a suitable aid could take the form of a student-led development of a wiki-type website resource that included access to case-studies giving students ‘real-life’ experience of the concepts being studied. This type of project requires considerable time and financial support; nevertheless, this idea could be extended for many drugs and could be used in any health science course.

Experimental studies of near-surface temperature cycling and surface wetting of stone and its implications for salt weathering

It has long been accepted that thermal and moisture regimes within stonework exert a major influence upon patterns of salt movement and, subsequently, the type and severity of salt-induced decay. For example, it is suggested that slow drying is more likely to bring dissolved salts to the surface, whereas rapid drying could result in the retention of some salt at or near the frequent wetting depth. In reality however, patterns of heating, cooling and surface wetting regimes that drive them – are complex and inconsistent responses to a wide range of environmental controls. As a first step to understanding the complexity of these relationships, this paper reports a series of experiments within a climatic cabinet designed to replicate the effects of short-term temperature fluctuations on the surface and sub-surface temperature regimes of a porous Jurassic limestone, and how they are influenced by surface wetting, ambient temperature and surface airflow. Preliminary results confirm the significance of very steep temperature/stress gradients within the outer centimetre or less of exposed stone under short-duration cycles of heating and cooling. This is important because this is the zone in which many stone decay processes, particularly salt weathering, operate, these processes invariably respond to temperature and moisture fluctuations, and short-term interruptions to insolation could, for example,
trigger these fluctuations on numerous occasions over a day. The data also indicate that there are complex patterns of temperature reversal with depth that are influenced in their intensity and location by surface wetting and moisture penetration, airflow across the surface and ambient air temperature. The presence of multiple temperature reversals and their variation over the course of heating and cooling phases belies previous assumtions of smooth, exponential increases and decreases in subsurface temperatures in response, for example to diurnal patterns of heating and cooling

Genetic variants influencing human aging from late-onset Alzheimer's disease (LOAD) genome-wide association studies (GWAS)

Genetics plays a crucial role in human aging with up to 30% of those living to the mid-80s being determined by genetic variation. Survival to older ages likely entails an even greater genetic contribution. There is increasing evidence that genes implicated in age-related diseases, such as cancer and neuronal disease, play a role in affecting human life span. We have selected the 10 most promising late-onset Alzheimer's disease (LOAD) susceptibility genes identified through several recent large genome-wide association studies (GWAS). These 10 LOAD genes (APOE, CLU, PICALM, CR1, BIN1, ABCA7, MS4A6A, CD33, CD2AP, and EPHA1) have been tested for association with human aging in our dataset (1385 samples with documented age at death [AAD], age range: 58-108 years; mean age at death: 80.2) using the most significant single nucleotide polymorphisms (SNPs) found in the previous studies. Apart from the APOE locus (rs2075650) which showed compelling evidence of association with risk on human life span (p = 5.27 × 10(-4)), none of the other LOAD gene loci demonstrated significant evidence of association. In addition to examining the known LOAD genes, we carried out analyses using age at death as a quantitative trait. No genome-wide significant SNPs were discovered. Increasing sample size and statistical power will be imperative to detect genuine aging-associated variants in the future. In this report, we also discuss issues relating to the analysis of genome-wide association studies data from different centers and the bioinformatic approach required to distinguish spurious genome-wide significant signals from real SNP associations.

Studies to Reduce Unnecessary Medication Use in Frail Older Adults:A Systematic Review

BACKGROUND: Overuse of unnecessary medications in frail older adults with limited life expectancy remains an understudied challenge. OBJECTIVE: To identify intervention studies that reduced use of unnecessary medications in frail older adults. A secondary goal was to identify and review studies focusing on patients approaching end of life. We examined criteria for identifying unnecessary medications, intervention processes for medication reduction, and intervention effectiveness. METHODS: A systematic review of English articles using MEDLINE, EMBASE, and International Pharmaceutical Abstracts from January 1966 to September 2012. Additional studies were identified by searching bibliographies. Search terms included prescription drugs, drug utilization, hospice or palliative care, and appropriate or inappropriate. A manual review of 971 identified abstracts for the inclusion criteria (study included an intervention to reduce chronic medication use; at least 5 participants; population included patients aged at least 65 years, hospice enrollment, or indication of frailty or risk of functional decline-including assisted living or nursing home residence, inpatient hospitalization) yielded 60 articles for full review by 3 investigators. After exclusion of review articles, interventions targeting acute medications, or studies exclusively in the intensive care unit, 36 articles were retained (including 13 identified by bibliography review). Articles were extracted for study design, study setting, intervention description, criteria for identifying unnecessary medication use, and intervention outcomes. RESULTS: The studies included 15 randomized controlled trials, 4 non-randomized trials, 6 pre-post studies, and 11 case series. Control groups were used in over half of the studies (n = 20). Study populations varied and included residents of nursing homes and assisted living facilities (n = 16), hospitalized patients (n = 14), hospice/palliative care patients (n = 3), home care patients (n = 2), and frail or disabled community-dwelling patients (n = 1). The majority of studies (n = 21) used implicit criteria to identify unnecessary medications (including drugs without indication, unnecessary duplication, and lack of effectiveness); only one study incorporated patient preference into prescribing criteria. Most (25) interventions were led by or involved pharmacists, 4 used academic detailing, 2 used audit and feedback reports targeting prescribers, and 5 involved physician-led medication reviews. Overall intervention effect sizes could not be determined due to heterogeneity of study designs, samples, and measures. CONCLUSIONS: Very little rigorous research has been conducted on reducing unnecessary medications in frail older adults or patients approaching end of life.

Stress processes in caring for an end-of-life family member:Application of a theoretical model

Objectives: Family caregivers play a vital role in maintaining the lives of individuals with advanced illness living in the community. However, the responsibility of caregiving for an end-of-life family member can have profound consequences on the psychological, physical and financial well-being of the caregiver. While the literature has identified caregiver stress or strain as a complex process with multiple contributing factors, few comprehensive studies exist. This study examined a wide range of theory-driven variables contributing to family caregiver stress. Method: Data variables from interviews with primary family caregivers were mapped onto the factors within the Stress Process Model theoretical framework. A hierarchical multiple linear regression analysis was used to determine the strongest predictors of caregiver strain as measured by a validated composite index, the Caregiver Strain Index. Results: The study included 132 family caregivers across south-central/western Ontario, Canada. About half of these caregivers experienced high strain, the extent of which was predicted by lower perceived program accessibility, lower functional social support, greater weekly amount of time caregivers committed to the care recipient, younger caregiver age and poorer caregiver self-perceived health. Conclusion: This study examined the influence of a multitude of factors in the Stress Process Model on family caregiver strain, finding stress to be a multidimensional construct. Perceived program accessibility was the strongest predictor of caregiver strain, more so than intensity of care, highlighting the importance of the availability of community resources to support the family caregiving role.

Educating families about end-of-life care in advanced dementia:Acceptability of a Canadian family booklet to nurses from Canada, France, and Japan

Background: The families of people with late-stage dementia need to be informed about the course of the dementia and the comfort/ palliative care option. A booklet was written for that purpose and can be provided to family members by physicians and nurses. Methods: The acceptability of the booklet for nurses was tested in Canada (French and English version), France (French Canadian version) and Japan (translated and adapted version). Results: Overall, 188 nurses completed a survey questionnaire. The booklet was accepted best in Canada and less so in France and Japan. Despite regional variation, the majority of the nurses perceived the booklet as useful for families. The French and Japanese nurses also reported a greater need for palliative care education in advanced dementia. Conclusion: The booklet may help nurses educate families about end-of-life issues in dementia palliative care, but local adaptation of the booklet content and physician engagement are necessary.

Optimizing Research on End-of-Life Care for Seniors:The Collective New Emerging Team on End of Life Care for Seniors University of Ottawa, Institute of Palliative Care

Background: End-of-life care for seniors is an important and neglected area of research. The University of Ottawa Institute of Palliative Care has expanded its research capacity by developing a Canadian Institutes of Health Research (CIHR) funded new emerging team on end-of-life care for seniors. This initiative brings together an interdisciplinary team of researchers from palliative care and geriatrics to develop a comprehensive program of research. Methods: 1) A variety of investigators from the fields of palliative care and geriatrics and disciplines of epidemiology, medicine, nursing, psychology and social work will collaborate on the development of a research agenda focussed on end-of-life care for seniors. 2) The conceptual model for the research program consists of 4 broad interrelated domains that are congruent with the CIHR themes of health services, clinical issues, population health and psychosocial, cultural, spiritual and ethical issues; this framework will guide the research program and all studies emanating from the program. 3) Research studies will focus on 5 areas of inquiry that are central to end-of-life care for seniors: palliative end-of-life care for rural seniors, care settings, burden, role of volunteers, and delirium. Results: This new team has the potential to obtain peer-reviewed funding, recruit and train a new generation of researchers, and build a network of concerned researchers. Conclusions: The new team should ultimately contribute to an improved quality of care for seniors who are approaching death.

The spark of life:The role of electric fields in regulating cell behaviour using the eye as a model system

Endogenous electric fields (EF) have long been known to influence cell behaviour during development, neural cell tropism, wound healing and cell behaviour generally. The effect is based on short circuiting of electrical potential differences across cell and tissue boundaries generated by ionic segregation. Recent in vitro and in vivo studies have shown that EF regulate not only cell movement but orientation of cells during mitosis, an effect which may underlie shaping of tissues and organs. The molecular basis of this effect is founded on receptor-mediated cell signalling events and alterations in cytoskeletal function as revealed in studies of gene deficient cells. Remarkably, not all cells respond directionally to EF in the same way and this has consequences, for instance, for lens development and vascular remodelling. The physical basis of EF effect may be related to changes induced in 'bound water' at the cell surface, whose organisation in association with trans-membrane proteins (e.g. receptors) is disrupted when EF are generated. Copyright © 2007 S. Karger AG.

The Role of Arg228 in the phosphorylation of galactokinase: The mechanism of GHMP kinases by QM/MM studies

GHMP kinases are a group of structurally-related small molecule kinases. They have been found in all kingdoms of life and are mostly responsible for catalysing the ATP-dependent phosphorylation of intermediary metabolites. Although the GHMP kinases are of clinical, pharmaceutical and biotechnological importance, the mechanism of GHMP-kinases is controversial. A catalytic base mechanism was suggested for mevalonate kinase that has a structural feature of the ?-phosphate of ATP close to an aspartate residue; however, for one GHMP member, homoserine kinase, where the residue acting as general base is absent, a direct phosphorylation mechanism was suggested. Furthermore, it has been proposed by some authors that all the GHMP kinases function via the direct phosphorylation mechanism. This controversy in mechanism has limited our ability to exploit these enzymes as drug targets and in biotechnology. Here the phosphorylation reaction mechanism of the human galactokinase, a member of GHMP kinase was investigated using molecular dynamics simulations and density functional theory-based QM/MM calculations (B3LYP-D/AMBER99). The reaction coordinates were localized by potential energy scan using adiabatic mapping method. Our results indicate that a highly conserved Glu174 captures Arg105 to the proximity of the a-phosphate of ATP forming a H-bond network, therefore the mobility of ATP in the large oxyanion hole is restricted. Arg228 functions to stabilize the negative charge developed at the ß,?-bridging oxygen of the ATP during bond cleavage. The reaction occurs via direct phosphorylation mechanism and the Asp186 in proximity of ATP does not directly participate in the reaction pathway. Since Arg228 is not conserved among GHMP kinases, reagents which form interactions with Arg228, and therefore can interrupt its function in phosphorylation may be developed into potential selective inhibitors for galactokinase.

The overlap between war and crime: unpacking Foucault and Agamben’s studies within the context of the war on terror

This article will consider the current convergence between war and crime by unpacking Foucault’s analysis of power and Agamben’s elaboration on the conjunction between the banning of a life and the constitution of the polity. It will show that these perspectives link together crime and war as mechanisms that contribute to the governance of the population by legitimating authority and their use of force through the military and the police while excluding part of the population. It will expose how these convergences highlight the problem of the political in the constitution of the social order at the global level. In the current contingency, crime and war are strongly implicated in the crucial political function of calling people to share their similarities and differences, and yet are not the best mechanisms for dealing with the sharing of a world in common.

Modern-day clinical course of type 1 diabetes mellitus after 30 years' duration:the diabetes control and complications trial/epidemiology of diabetes interventions and complications and Pittsburgh epidemiology of diabetes complications experience (1983-2005)

Clinical treatment goals of type 1 diabetes mellitus (T1DM) have changed since the Diabetes Control and Complications Trial (DCCT) demonstrated reduced long-term complications with intensive diabetes therapy. There have been few longitudinal studies to describe the clinical course of T1DM in the age of intensive therapy. Our objective was to describe the current-day clinical course of T1DM.

General Nurses’ Experiences of End-Of-Life Care in the Acute Hospital Setting

Approximately 90% of the UK population spend some time in hospital in their final year of life, and more than half of the population die in hospital. This review aims to explore the experiences of general nurses when providing end-of-life care to patients in the acute hospital setting. Nine studies were identified through a literature search, and each was then analysed and evaluated until themes emerged. Six themes were drawn from the literature: lack of education and knowledge, lack of time with patients, barriers arising in the culture of the health-care setting, communication barriers, symptom management, and nurses' personal issues. The themes cause concern about the quality of end-of-life care being provided in the acute care setting. The literature appears to be consistent in the view that terminally ill patients are best cared for in specialised care settings, such as palliative care units and hospices. However, increasing demands on health services will result in greater numbers of dying patients being admitted to the acute hospital setting. It is therefore paramount that general nurses' educational needs are met to ensure they develop clinical competence to provide high-quality holistic end-of-life care.

Lung stereotactic body radiation therapy (SBRT) delivered over 4 or 11days: A comparison of acute toxicity and quality of life.

Abstract
PURPOSE:
The optimal duration over which lung SBRT should be delivered is unknown. We conducted a randomized pilot study in patients treated with four fractions of lung SBRT delivered over 4 or over 11days.
METHODS:
Patients with a peripheral solitary lung tumor (NSCLC or pulmonary metastasis) ?5cm were eligible. For NSCLC lung tumors ?3cm, a dose of 48Gy in 4 fractions was used, otherwise 52Gy in 4 fractions was delivered. Patients were randomized to receive treatment over 4 consecutive days or over 11days. The primary end-point was acute grade ?2 toxicity. Secondary end-points included quality of life (QOL) assessed using the EORTC QLQ-C30 and QLQ-LC13 questionnaires.
RESULTS:
Fifty four patients were enrolled. More patients in the 11day group had respiratory symptoms at baseline. 55.6% patients treated over 4days and 33.3% of patients treated over 11days experienced acute grade ?2 toxicity (p=0.085). Dyspnea, fatigue and coughing domains were worse in the 11day group at baseline. At 1 and 4months, more patients in the 4day group experienced a clinically meaningful worsening in the dyspnea QOL domain compared to the 11day group (44.5% vs 15.4%, p=0.02; 38.5% vs 12.0%, p=0.03, respectively). However, raw QOL scores were not different at these time-points between treatment groups.
CONCLUSIONS:
Grade 2 or higher acute toxicity was more common in the 4day group, approaching statistical significance. More patients treated on 4 consecutive days reported a clinically meaningful increase in dyspnea, although interpretation of these results is challenging due to baseline imbalance between treatment groups. Larger studies are required to validate these results.

Differential expression of liver fluke β-tubulin isotypes at selected life cycle stages

We have shown that Fasciola hepatica expresses at least six ß-tubulins in the adult stage of its life cycle, designated F.hep-ß-tub1-6 (Ryan et al., 2008). Here we show that different complements of tubulin isotypes are expressed in different tissues and at different life cycle stages; this information may inform the search for novel anthelmintics. The predominant (as judged by quantitative PCR) isotype transcribed at the adult stage was F.hep-ß-tub1 and immunolocalisation studies revealed that this isotype occurred mainly in mature spermatozoa and vitelline follicles. Quantitative PCR indicated that changes occurred in the transcription levels of ß-tubulin isotypes at certain life cycle stages and may be of importance in the efficacy of benzimidazole-based anthelmintic drugs, but there were no significant differences between the triclabendazole (TCBZ)-susceptible Leon isolate and the TCBZ-resistant Oberon isolate in the transcription levels of each of the isotypes. When three well-characterised isolates with differing susceptibilities to TCBZ were compared, only one amino acid change resulting from a homozygous coding sequence difference (Gly269Ser) in isotype 4 was observed. However, this change was not predicted to alter the overall structure of the protein. In conclusion, these findings indicate that there is tissue-specific expression of tubulin isotypes in the liver fluke but the development of resistance to TCBZ is not associated with changes in its presumed target molecule.

Wear analysis and prediction of the life of a riveting die used in the automotive industry

Knowledge on the life span of the riveting dies used in the automotive industry is sparse. It is often the case that only when faulty products are produced are workers aware that their tool needs to be changed. This is of course costly both in terms of time and money. Responding to this challenge, this paper proposes a methodology which integrates wear and stress analysis to quantify the life of a riveting die. Experiments are carried out to measure the applied load required to split a rivet. The obtained results (i.e. force curves) are used to validate the wear mechanisms of the die observed using scanning electron microscopy. Sliding, impact, and adhesive wears are observed on the riveting die after a certain number of riveting cycles. The stress distribution on the die during riveting is simulated using a finite element (FE) approach. In order to confirm the accuracy of the FE model, the experimental force results are compared with the ones produced from FE simulation. The maximum and minimum von Mises' stresses generated from the FE model are input into a Goodman diagram and an S-N curve to compute the life of the riveting die. It is found that the riveting die is predicted to run for 4 980 000 cycles before failure.