A longstanding issue in the field of nutrition is the potential inaccuracy of methods traditionally used for dietary assessment (i.e. food diaries and food frequency questionnaires). It is possible to overcome the limitations and biases of these techniques by combining them with analytical measurements in human biofluids. Metabolomic technologies are gaining popularity as nutritional tools due to their capacity to measure metabolic responses to external stimuli, such as the ingestion of certain foods. This project performed both LC-MS and 1H-NMR metabolomic profiling on serum samples collected as part of the NICOLA study (Northern Irish Cohort for the Longitudinal Study of Aging) in order to discover novel dietary biomarkers. A dietary validation cohort (NIDAS) was incorporated within NICOLA, involving 45 males and 50 females, aged 50 years and over. Participants provided detailed dietary data (4-day food diary) and blood samples at two time-points, six months apart. Serum samples were processed on two analytical platforms. 1H-NMR spectra were acquired using a Bruker 600 MHz Ascent coupled to a TCI cryoprobe and processed using Bayesil (University of Alberta, Canada). A Waters TQ-S coupled with an Acquity I-class UPLC was used in combination with a targeted commercially available kit (AbsoluteIDQ p180 kit, Biocrates). Mass spectra obtained were processed with MetIDQ and verified using MassLynx (v4.1). Data were tested for normality, and metabolite concentrations were correlated with recorded dietary intake of each food type using SPSS. Additional tests (PCA, PLS-DA, ROC Curves) were performed on MetaboAnalyst 4.0 (University of Alberta, Canada). More than 50 statistically significant (P < 0.05) food-metabolite correlations were detected, 15 of which remained significant after eliminating potential confounding from sex, age and BMI. The strongest correlations were between fruit consumption and acetic acid, and between dairy consumption and certain glycerophospholipids (e.g. LysoPC aa C20:3). Stratifying the cohort by gender yielded further correlations, including PC ae C38:2 (dairy; males), PC aa C34:4 (dairy; females), PC aa C36:4 (dairy; females) and trans-4-Hydroxyproline (meat; males). A number of potential blood-based food biomarkers were detected, many of which are gender-specific, and some are corroborated by previously published studies. However, further validation work is required. For example, biological plausibility needs to be established, and the findings need to be reproduced in other cohorts to demonstrate their applicability in larger and more diverse populations. These results contribute greatly to the ongoing efforts to discover and validate reliable nutritional biomarkers as an objective and unbiased measurement of food intake.

Agents of opportunity (AO) in academic medical centers (AMC) are defined as unregulated or lightly regulated substances used for medical research or patient care that can be used as “dual purpose” substances by terrorists to inflict damage upon populations. Most of these agents are used routinely throughout AMC either during research or for general clinical practice. To date, the lack of careful regulations for AOs creates uncertain security conditions and increased malicious potential. Using a consensus-based approach, we collected information and opinions from staff working in an AMC and 4 AMC-affiliated hospitals concerning identification of AO, AO attributes, and AMC risk and preparedness, focusing on AO security and dissemination mechanisms and likely hospital response. The goal was to develop a risk profile and framework for AO in the institution. Agents of opportunity in 4 classes were identified and an AO profile was developed, comprising 16 attributes denoting information critical to preparedness for AO misuse. Agents of opportunity found in AMC present a unique and vital gap in public health preparedness. Findings of this project may provide a foundation for a discussion and consensus efforts to determine a nationally accepted risk profile framework for AO. This foundation may further lead to the implementation of appropriate regulatory policies to improve public health preparedness. Agents of opportunity modeling of dissemination properties should be developed to better predict AO risk.

(Disaster Med Public Health Preparedness. 2010;4:318-325)

Background: Agents of opportunity (AO) are potentially harmful biological, chemical, radiological, and pharmaceutical substances commonly used for health care delivery and research. AOs are present in all academic medical centers (AMC), creating vulnerability in the health care sector; AO attributes and dissemination methods likely predict risk; and AMCs are inadequately secured against a purposeful AO dissemination, with limited budgets and competing priorities. We explored health care workers' perceptions of AMC security and the impact of those perceptions on AO risk.

Methods: Qualitative methods (survey, interviews, and workshops) were used to collect opinions from staff working in a medical school and 4 AMC-affiliated hospitals concerning AOs and the risk to hospital infrastructure associated with their uncontrolled presence. Secondary to this goal, staff perception concerning security, or opinions about security behaviors of others, were extracted, analyzed, and grouped into themes.

Results: We provide a framework for depicting the interaction of staff behavior and access control engineering, including the tendency of staff to “defeat” inconvenient access controls. In addition, 8 security themes emerged: staff security behavior is a significant source of AO risk; the wide range of opinions about “open” front-door policies among AMC staff illustrates a disparity of perceptions about the need for security; interviewees expressed profound skepticism concerning the effectiveness of front-door access controls; an AO risk assessment requires reconsideration of the security levels historically assigned to areas such as the loading dock and central distribution sites, where many AOs are delivered and may remain unattended for substantial periods of time; researchers' view of AMC security is influenced by the ongoing debate within the scientific community about the wisdom of engaging in bioterrorism research; there was no agreement about which areas of the AMC should be subject to stronger access controls; security personnel play dual roles of security and customer service, creating the negative perception that neither role is done well; and budget was described as an important factor in explaining the state of security controls.

Conclusions: We determined that AMCs seeking to reduce AO risk should assess their institutionally unique AO risks, understand staff security perceptions, and install access controls that are responsive to the staff's tendency to defeat them. The development of AO attribute fact sheets is desirable for AO risk assessment; new funding and administrative or legislative tools to improve AMC security are required; and security practices and methods that are convenient and effective should be engineered.

(Disaster Med Public Health Preparedness. 2010;4:291-299)

Several writers have suggested that there is an inverted U-curve of status or prestige across the lifespan in Western society. The old and the young are apparently accorded less status than persons in midlife, and women are seen as having less status than men.

In this study of 198 older individuals (mean age 67), the same inverted U-curve was found, but gender differences were very small. Much less extreme status ratings were given by this older sample than by the earlier samples of young adults. Also, status ratings were again mostly unaffected by respondents' characteristics such as age, sex, marital status, or social class. Older adults, therefore, seem to accept the broad cultural views of age stratification, but are slightly more egalitarian than the young.

Objectives: The objective of this study is to profile the health technology assessments (HTAs) produced in Canada and other selected countries and assess their potential to inform policy making about health systems in jurisdictions other than the ones for which they were produced, and to develop and pilot test prototypes for packaging and assessing the relevance of HTAs for health system managers and policy makers.

Methods: We compiled an inventory of all HTAs that were produced by nine HTA agencies between September 2003 and August 2006; coded the title and abstract of each HTA according to the technologies assessed, methods used, and whether or not context-specific actionable messages were provided; developed a prototype for a structured, decision-relevant HTA summary and for a relevance-assessment form; and pilot-tested the prototypes using semistructured telephone interviews with a purposive sample of Canadian healthcare managers and policy makers.

Results: Our review of the 223 HTAs identified that: (i) 44 HTAs addressed health system arrangements (20 percent); (ii) 205 incorporated a systematic review (92 percent), whereas only 12 incorporated a sociopolitical assessment using explicit methods (5 percent); and (iii) 50 contained context-specific actionable messages (22 percent). Our interviews identified significant support for both the general idea of an HTA summary and the prototype's specific elements, but mixed views about using peer assessments of relevance.

Conclusions: Those involved in supporting the use of HTAs in policy making about health systems may wish to produce structured decision-relevant summaries for their systematic review-containing HTAs to increase the prospects for their HTAs being used outside the jurisdiction for which they were produced.

A rapid technique is described for characterizing and monitoring, in single insects, the insensitivity of acetylcholinesterase (AChE) to organophosphorus and carbamate insecticides. Ninety-six insects are homogenized simultaneously in a microtitre plate and portions (e.g. 0·05 for Musca domestica L.) assayed colorimetrically with acetylthiocholine in the presence and absence of diagnostic concentrations of insecticide. Reactions are monitored by a kinetic microplate reader linked to a microcomputer that determines mean AChE activities automatically by linear regressions of absorbance-time data. Mean inhibited activity is then expressed as a percentage of uninhibited activity. Several inhibitors can be tested against the same insect to yield an ‘insensitivity profile‘ of individuals and strains. In tests on M. domestica adults of known AChE genotype, the assay clearly distinguished not only between a sensitive and two slightly (3-15-fold) insensitive AChE variants but between all six genotypic combinations of these three alleles.

The anatomy and behaviour of the oncomiracidia of Kuhnia scombri, K. sprostonae and Grubea cochlear, related mazocraeid monogeneans from the gill chamber of the mackerel, Scomber scombrus, caught off Plymouth are compared. K. sprostonae and G. cochlear are new records at Plymouth. The most important anatomical difference between these larvae is that those of Kuhnia spp. possess a pair of pigment-shielded eyes which are lacking in G. cochlear. The freshly hatched larvae of Kuhnia spp. are strongly photopositive but this response wanes after about 1 h in K. scombri and 1–5 h in K. sprostonae. No response to light was detected in larvae of G. cochlear. Most older larvae of Kuhnia spp. and of G. cochlear swim continuously upwards and downwards, even in ‘darkness’, indicating an alternation between positive and negative geotropism. The larvae of Kuhnia spp. possess angular cells (?) of unknown function close to the pharynx. The larvae of all three species contain prominent anterior glands and lipid droplets; the latter are depleted during their long free-swimming lives (up to 36 h in Kuhnia spp. at 13–14°C).

The eggs of the polyopisthocotylean monogenean Plectanocotyle gurnardi (van Beneden & Hesse, 1863) Llewellyn, 1941, from the gills of gurnards (Triglidae) develop and hatch readily when maintained in the laboratory. However, the impression was gained that some or all of this hatching might be the consequence of inadvertent shadowing or accidental mechanical disturbance of the eggs by the investigators. Since similar stimuli are known to induce hatching in some other monogeneans (see Kearn, 1982; Whittington & Kearn, 1988) and since such stimuli are likely to be generated by the activities of potential hosts, it was decided to embark on a more detailed investigation of hatching in P. gurnardi and to attempt to learn more about the behaviour of gurnards. During these investigations, the availability of freshly hatched larvae of P. gurnardi presented an opportunity to study their behaviour and to expand our knowledge of their anatomy.

Objectives and Methods: Many authors have argued that ethical, legal, and social issues (“ELSIs”) should be explicitly integrated into health technology assessment (HTA), yet doing so poses challenges. This discussion may be particularly salient for technologies viewed as ethically complex, such as genetic screening. Here we provide a brief overview of contemporary discussions of the issues from the HTA literature. We then describe key existing policy evaluation frameworks in the fields of disease screening and public health genomics. Finally, we map the insights from the HTA literature to the policy evaluation frameworks, with discussion of the implications for HTA in genetic screening.

Results and Conclusions: A critical discussion in the HTA literature considers the definition of ELSIs in HTA, highlighting the importance of thinking beyond ELSIs as impacts of technology. Existing HTA guidance on integrating ELSIs relates to three broad approaches: literature synthesis, involvement of experts, and consideration of stakeholder values. The thirteen key policy evaluation frameworks relating to disease screening and public health genomics identified a range of ELSIs relevant to genetic screening. Beyond straightforward impacts of screening, these ELSIs require consideration of factors such as the social and political context surrounding policy decisions. The three broad approaches to addressing ELSIs described above are apparent in the screening/genomics literatures. In integrating these findings we suggest that the method chosen for addressing ELSIs in HTA for genetic screening may determine which ELSIs are prioritized; and that an important challenge is the lack of guidance for evaluating such methods.

Objectives: Promoting the adoption of clinical practice guidelines is a challenging task. Research shows that adopters' beliefs about guidelines and the process of their development are important predictors of guideline use. Our objective is to report on the development and refinement of an instrument designed to measure oncologists' assessments of guidelines in oncology.

Method: A theoretically derived instrument was drafted. Oncologists were asked to complete a questionnaire for each draft guideline they were asked to review. Factor analyses and multilevel modeling techniques were undertaken to explore the properties of the instrument and refine it.

Results: A total of 488 Ontario clinicians were sent 1,494 new questionnaires regarding 34 clinical practice guidelines produced between 1999 and 2002. A refined eighteen-item questionnaire with four stable factors that predicted 60 percent of the variance emerged. The factors are interpreted as guideline quality, applicability, acceptability, and comparative value. The four factors predicted oncologists' endorsements of draft guidelines and, with the exception of quality, predicted their intentions to use the guidelines. As expected, variation in the factor scores could be attributed more to the differences among the oncologist who completed the survey than to the differences among the guidelines themselves.

Conclusions:An instrument composed of four stable and theoretically relevant factors emerged. The findings support the hypothesis that beliefs about guideline attributes and development attributes relate to oncologists' endorsement of and intentions to use guidelines. Our next step is to link the responses of the survey with actual clinical behavior.

Objective: To identify and compare clinical practice guideline appraisal instruments.

Methods: Appraisal instruments, defined as instruments intended to be used for guideline evaluation, were identified by searching MEDLINE (1966–99) using the Medical Subject Heading (MeSH) practice guidelines, reviewing bibliographies of the retrieved articles, and contacting authors of guideline appraisal instruments. Two reviewers independently examined the questions/statements from all the instruments and thematically grouped them. The 44 groupings were collapsed into 10 guideline attributes. Using the items, two reviewers independently undertook a content analysis of the instruments.

Results: Fifteen instruments were identified, and two were excluded because they were not focused on evaluation. All instruments were developed after 1992 and contained 8 to 142 questions/statements. Of the 44 items used for the content analysis, the number of items covered by each instrument ranged from 6 to 34. Only the instrument by Cluzeau and colleagues included at least one item for each of the 10 attributes, and it addressed 28 of the 44 items. This instrument and that of Shaneyfelt et al. are the only instruments that have so far been validated.

Conclusions: A comprehensive, concise, and valid instrument could help users systematically judge the quality and utility of clinical practice guidelines. The current instruments vary widely in length and comprehensiveness. There is insufficient evidence to support the exclusive use of any one instrument, although the Cluzeau instrument has received the greatest evaluation. More research is required on the reliability and validity of existing guideline appraisal instruments before any one instrument can become widely adopted.

Background: Despite the growing medical and public interest in reducing exposure to allogeneic blood, little is known about the use of alternatives to allogeneic transfusion. This study was conducted to determine the availability of these technologies in Canadian hospitals and was undertaken under the auspices of the International Study of Peri-Operative Transfusion (ISPOT), a 10-country study of the effectiveness of, attitudes toward, and practices related to the use of alternatives to allogeneic transfusion.

Methods: A cross-sectional national mail survey of Canadian hospitals with greater than 50 medical/surgical beds. Chiefs of anesthesia, surgery, and the divisions of cardiac, orthopedic, vascular, and urology were initially mailed a brief postcard asking which of seven technologies were used in their center. This was then followed up with a one-page questionnaire asking how frequently the technologies were used, their thoughts on the appropriateness of the use of the technologies, barriers to their greater use, and reasons for nonuse of the technologies.

Results: Response rates to the postcard survey ranged from 70%–98%, depending on the technology and type of surgery, and ranged from 27%–53% for the follow-up questionnaire. All technologies were used most frequently in cardiac surgery. Aprotinin, tranexamic acid, aminocaproic acid, desmopressin, and cell salvage were reported used in over 70% of cardiac surgery centers. Of these, tranexamic acid and cell salvage were the only ones used routinely in some centers. Acute normovolemic hemodilution and erythropoietin were used in 45% and 20% of cardiac centers, respectively. The drugs were used in less than 15% of orthopedic, vascular, and urologic divisions, with the exception of desmopressin in urologic and vascular surgery and aminocaproic acid in urologic surgery. The techniques of cell salvage and acute normovolemic hemodilution were used in 30%–45% of these divisions, with the exception of cell salvage, which was used in less than 15% of urology units. In more than 60% of cases, the technologies were considered to be used “about right,” although an important minority felt that they were underused.

Conclusions: In general, alternatives to perioperative allogeneic transfusion were rarely used except in cardiac surgery.