Neuroprotective effects of low-dose lithium in individuals at ultra-high risk for psychosis. A longitudinal MRI/MRS study

Objectives: To investigate if low-dose lithium may counteract the microstructural and metabolic brain changes proposed to occur in individuals at ultra-high risk (UHR) for psychosis. Methods: Hippocampal T2 relaxation time (HT2RT) and proton magnetic resonance spectroscopy (1H-MRS) measurements were performed prior to initiation and following three months of treatment in 11 UHR patients receiving low-dose lithium and 10 UHR patients receiving treatment as usual (TAU). HT2RT and 1H-MRS percentage change scores between scans were compared using one-way ANOVA and correlated with behavioural change scores. Results: Low-dose lithium significantly reduced HT2RT compared to TAU (p=0.018). No significant group by time effects were seen for any brain metabolites as measured with 1H-MRS, although myo-inositol, creatine, choline-containing compounds and NAA increased in the group receiving low-dose lithium and decreased or remained unchanged in subjects receiving TAU. Conclusions: This pilot study suggests that low-dose lithium may protect the microstructure of the hippocampus in UHR states as reflected by significantly decreasing HT2RT. Larger scale replication studies in UHR states using T2 relaxation time as a proxy for emerging brain pathology seem a feasible mean to test neuroprotective strategies such as low-dose lithium as potential treatments to delay or even prevent the progression to full-blown disorder.

Risk and school science education

In this paper I consider a role for risk understanding in school science education. Grounds for this are described in terms of current sociological analyses of the contemporary world as a ‘risk society’ and recent public understanding of science studies where science and risk are concerns commonly linked within the wider community. These concerns connect with support amongst many science educators for the goal of science education for citizenship. From this perspective scientific literacy for decision making on contemporary socioscientific issues is central. I argue that in such decision making risk understanding has an important role to play. I examine some of the challenges its inclusion in school science presents to science teachers, review previous writing about risk in the science education literature and consider how knowledge about risk might be addressed in school science. I also outline the varying conceptions of risk and suggest some future research directions which would support the inclusion of risk in classroom discussions of socioscientific issues.

A longitudinal assessment of chronic wound fluid to detect biochemical indicators of healing

Chronic venous leg ulcers are a detrimental health issue plaguing our society, resulting in long term pain, immobility and decreased quality of life for a large proportion of sufferers. The frequency of these chronic wounds has led current research to focus on the wound environment to provide important information regarding the prolonged, fluctuated or static healing patterns of these wounds. Disruption to the normal wound healing process results in release of multiple factors in the wound environment that could correlate to wound chronicity. These biochemical factors can often be detected through non-invasively sampling chronic wound fluid (CWF) from the site of injury. Of note, whilst there are numerous studies comparing acute and chronic wound fluids, there have not been any reports in the literature employing a longitudinal study in order to track biochemical changes in wound fluid as patients transition from a non-healing to healed state. Initially the objective of this study was to identify biochemical changes in CWF associated with wound healing using a proteomic approach. The proteomic approach incorporated a multi-dimensional liquid chromatography fractionation technique coupled with mass spectrometry (MS) to enable identification of proteins present in lower concentrations in CWF. Not surprisingly, many of the proteins identified in wound fluid were acute phase proteins normally expressed during the inflammatory phase of healing. However, the number of proteins positively identified by MS was quite low. This was attributed to the diverse range in concentration of protein species in CWF making it challenging to detect the diagnostically relevant low molecular weight proteins. In view of this, SELDI-TOF MS was also explored as a means to target low molecular weight proteins in sequential patient CWF samples during the course of healing. Unfortunately, the results generated did not yield any peaks of interest that were altered as wounds transitioned to a healed state. During the course of proteomic assessment of CWF, it became evident that a fraction of non-proteinaceous compounds strongly absorbed at 280 nm. Subsequent analyses confirmed that most of these compounds were in fact part of the purine catabolic pathway, possessing distinctive aromatic rings and which results in high absorbance at 254 nm. The accumulation of these purinogenic compounds in CWF suggests that the wound bed is poorly oxygenated resulting in a switch to anaerobic metabolism and consequently ATP breakdown. In addition, the presence of the terminal purine catabolite, uric acid (UA), indicates that the enzyme xanthine oxidoreductase (XOR) catalyses the reaction of hypoxanthine to xanthine and finally to UA. More importantly, the studies provide evidence for the first time of the exogenous presence of XOR in CWF. XOR is the only enzyme in humans capable of catalysing the production of UA in conjunction with a burst of the highly reactive superoxide radical and other oxidants like H2O2. Excessive release of these free radicals in the wound environment can cause cellular damage disrupting the normal wound healing process. In view of this, a sensitive and specific assay was established for monitoring low concentrations of these catabolites in CWF. This procedure involved combining high performance liquid chromatography (HPLC) with tandem mass spectrometry and multiple reaction monitoring (MRM). This application was selective, using specific MRM transitions and HPLC separations for each analyte, making it ideal for the detection and quantitation of purine catabolites in CWF. The results demonstrated that elevated levels of UA were detected in wound fluid obtained from patients with clinically worse ulcers. This suggests that XOR is active in the wound site generating significant amounts of reactive oxygen species (ROS). In addition, analysis of the amount of purine precursors in wound fluid revealed elevated levels of purine precursors in wound fluid from patients with less severe ulcers. Taken together, the results generated in this thesis suggest that monitoring changes of purine catabolites in CWF is likely to provide valuable information regarding the healing patterns of chronic venous leg ulcers. XOR catalysis of purine precursors not only provides a method for monitoring the onset, prognosis and progress of chronic venous leg ulcers, but also provides a potential therapeutic target by inhibiting XOR, thus blocking UA and ROS production. Targeting a combination of these purinogenic compounds and XOR could lead to the development of novel point of care diagnostic tests. Therefore, further investigation of these processes during wound healing will be worthwhile and may assist in elucidating the pathogenesis of this disease state, which in turn may lead to the development of new diagnostics and therapies that target these processes.

Project-based organization as adaptation to risk and opportunity in small firms

Recent years have seen a rapid increase in SMEs working collaboratively in inter-organizational projects. But what drives the emergence of such projects, and what types of industries breed them the most? To address these questions, this paper extends the long running literature on the firm and industry antecedents of new venturing and alliance formation to the domain of project-based organization by SMEs. Based on survey data collected among 1,725 small and medium sized organizations and longitudinal industry data, we find an overall pattern that indicates that IOPV participation is primarily determined by a focal SME’s scope of innovative activities, and the munificence, dynamism and complexity of its environment. Unexpectedly, these variables have different effects on whether SMEs are likely to engage in IOPVs, compared to with how many there are in their portfolio at a time. Implications for theory development are discussed.

The power of historical causal components involved in engaging at risk youth at three alternative schools

This article addresses the causal powers associated with the social phenomena of alternative schooling for youth at risk. It stems from a doctoral thesis, Alternative Schooling Programs for At Risk Youth – Three Case Studies which addresses wider issues integral to alternative schooling: youth at risk, alternative schooling models, and literacy. This article explores one aspect of alternative schooling: the historical causal factors involved in the establishment and continuance of three alternative case study models in Queensland, Australia. By adhering to Bhaskar’s transformational model of social activity (TMSA) , social structures and individuals will be analytically distinguished to uncover their separate causal powers and how these have effected the establishment and continuance of three alternative schools.

When non-significance maybe significant: lessons learned from a study into the development, implementation and evaluation of a risk assessment tool for fleet settings

Introduction This study reports on the development of a self report assessment tool to increase the efficacy of crash prediction within Australian Fleet settings Over last 20 years an array of measures have been produced (Driver anger scale, Driving Skill Inventory, Manchester Driver Behaviour Questionnaire, Driver Attitude Questionnaire, Driver Stress Inventory, Safety Climate Questionnaire) While these tools are useful, research has demonstrated limited ability to accurately identify individuals most likely to be involved in a crash. Reasons cited include; - Crashes are relatively rare - Other competing factors may influence crash event - Ongoing questions regarding the validity of self report measures (common method variance etc) - Lack of contemporary issues relating to fleet driving performance

A focus on risk compensation and its role in motor vehicle crashes

• What is risk compensation, and why is relevant to motor vehicle crashes? • Recent simulator work that revealed risk compensation • Current and future work on risk compensation

Workforce indicators of health literacy

The concept of health literacy has evolved over the last forty years from an individual, literacy driven focus in clinical settings to one associated with a contemporary approach to health promotion. The World Health Organization has defined health literacy as ‘the cognitive and social skills which determine the motivation and ability of individuals to gain access to, understand and use information in ways which promote and maintain good health’ (World Health Organization, 1998, p. 10). The conceptual evolution of health literacy has seen a shift beyond a functional orientation to also recognise cognitive, behavioural and environmental influences. This more comprehensive view of health literacy acknowledges factors like efficacy, motivation, self-efficacy, autonomy, social support and empowerment. A health literate workforce could present benefits for the employee and employer...

Prevalence of malnutrition risk and its relationship with risk factors of hospital re-admission in older adults

Background: Risk of malnutrition in older people continues to be a global problem. Malnutrition is often unrecognized and under-treated across health care settings and may result in undesirable health consequences, impaired recovery from illness and a poorer quality of life. Aim: This study aimed to determine the prevalence of malnutrition risk in a sample of older people at high risk of hospital re-admission. The association between risk factors of hospital re-admission and risk of malnutrition were also explored. Methods: One hundred and twenty five hospitalised patients aged 65 years and older at risk of hospital readmission (24% male, 76% female, mean age 77 ± 6 years) were recruited from a tertiary metropolitan hospital in Australia. The valid and reliable Malnutrition Screen Tool (MST) was employed to screen for malnutrition risk. It consists of two questions related to recent weight loss and appetite. Results: Prevalence of older adults at risk of malnutrition was 27.4%. Risk of malnutrition was not associated with age, gender and living arrangement. However, among risk factors of hospital readmission, lack of social support (χ2 = 4.18, N = 125, p = 0.028), and fair –poor self-rating of health (χ2 = 4.13, N = 125, p = 0.042) were statistically significant associated with risk of malnutrition. Conclusion: Risk of malnutrition in older people continues to be a concern in health care, and increasing psycho social support may help shed light on reducing risk of malnutrition.

Validity of the malnutrition screening tool for older adults at high risk of hospital readmission

Malnutrition is a serious problem in older adults, particularly for those at risk of hospital readmission. The essential step in managing malnutrition is early identification using a valid nutrition screening tool. The purpose of this study was to validate the Malnutrition Screening Tool (MST) in older adults at high risk of hospital readmission. Two registered nurses administered the MST to identify malnutrition risk, and compared it to the comprehensive Subjective Global Assessment (SGA) to assess nutritional status for patients aged 65 years who had at least one risk factor for hospital readmission. The MST demonstrates substantial sensitivity, specificity and agreement with the SGA. These findings indicate that nursing staff can use the MST as a valid tool for routine screening and rescreening to identify patients at risk of malnutrition. Use of the MST may prevent hospital-acquired malnutrition for acute hospitalized older adults at high risk of readmission.

A software framework for risk-aware business process management

With the large diffusion of Business Process Managemen (BPM) automation suites, the possibility of managing process-related risks arises. This paper introduces an innovative framework for process-related risk management and describes a working implementation realized by extending the YAWL system. The framework covers three aspects of risk management: risk monitoring, risk prevention, and risk mitigation. Risk monitoring functionality is provided using a sensor-based architecture, where sensors are defined at design time and used at run-time for monitoring purposes. Risk prevention functionality is provided in the form of suggestions about what should be executed, by who, and how, through the use of decision trees. Finally, risk mitigation functionality is provided as a sequence of remedial actions (e.g. reallocating, skipping, rolling back of a work item) that should be executed to restore the process to a normal situation.

Risk, uncertainty and complexity in science education

Increasingly societies and their governments are facing important social issues that have science and technology as key features. A number of these socio-scientific issues have two features that distinguish them from the restricted contexts in which school science has traditionally been presented. Some of their science is uncertain and scientific knowledge is not the only knowledge involved. As a result, the concepts of uncertainty, risk and complexity become essential aspects of the science underlying these issues. In this chapter we discuss the nature and role of these concepts in the public understanding of science and consider their links with school science. We argue that these same concepts and their role in contemporary scientific knowledge need to be addressed in school science curricula. The new features for content, pedagogy and assessment of this urgent challenge for science educators are outlined. These will be essential if the goal of science education for citizenship is to be achieved with our students, who will increasingly be required to make personal and collective decisions on issues involving science and technology.

Risk factors for Mycobacterium tuberculosis infection among children in Greenland

Objective To examine the risk factors for Mycobacterium tuberculosis infection (MTI) among Greenlandic children for the purpose of identifying those at highest risk of infection. Methods Between 2005 and 2007, 1797 Greenlandic schoolchildren in five different areas were tested for MTI with an interferon gamma release assay (IGRA) and a tuberculin skin test (TST). Parents or guardians were surveyed using a standardized self-administered questionnaire to obtain data on crowding in the household, parents’ educational level and the child’s health status. Demographic data for each child – i.e. parents’ place of birth, number of siblings, distance between siblings (next younger and next older), birth order and mother’s age when the child was born – were also extracted from a public registry. Logistic regression was used to check for associations between these variables and MTI, and all results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). Children were considered to have MTI if they tested positive on both the IGRA assay and the TST. Findings The overall prevalence of MTI was 8.5% (152/1797). MTI was diagnosed in 26.7% of the children with a known TB contact, as opposed to 6.4% of the children without such contact. Overall, the MTI rate was higher among Inuit children (OR: 4.22; 95% CI: 1.55–11.5) and among children born less than one year after the birth of the next older sibling (OR: 2.48; 95% CI: 1.33–4.63). Self-reported TB contact modified the profile to include household crowding and low mother’s education. Children who had an older MTI-positive sibling were much more likely to test positive for MTI themselves (OR: 14.2; 95% CI: 5.75–35.0) than children without an infected older sibling. Conclusion Ethnicity, sibling relations, number of household residents and maternal level of education are factors associated with the risk of TB infection among children in Greenland. The strong household clustering of MTI suggests that family sources of exposure are important.

African Burkitt Lymphoma: Age-Specific Risk and Correlations with Malaria Biomarkers

African Burkitt lymphoma is an aggressive B-cell, non-Hodgkin lymphoma linked to Plasmodium falciparum malaria. Malaria biomarkers related to onset of African Burkitt lymphoma are unknown. We correlated age-specific patterns of 2,602 cases of African Burkitt lymphoma (60% male, mean ± SD age = 7.1 ± 2.9 years) from Uganda, Ghana, and Tanzania with malaria biomarkers published from these countries. Age-specific patterns of this disease and mean multiplicity of P. falciparum malaria parasites, defined as the average number of distinct genotypes per positive blood sample based on the merozoite surface protein-2 assessed by polymerase chain reaction, were correlated and both peaked between 5 and 9 years. This pattern, which was strong and consistent across regions, contrasted parasite prevalence, which peaked at 2 years and decreased slightly, and geometric mean parasite density, which peaked between 2 and 3 years and decreased sharply. Our findings suggest that concurrent infection with multiple malaria genotypes may be related to onset of African Burkitt lymphoma.

Risk of Human Papillomavirus-Associated Cancers Among Persons With AIDS

Background Although risk of human papillomavirus (HPV)–associated cancers of the anus, cervix, oropharynx, penis, vagina, and vulva is increased among persons with AIDS, the etiologic role of immunosuppression is unclear and incidence trends for these cancers over time, particularly after the introduction of highly active antiretroviral therapy in 1996, are not well described. Methods Data on 499 230 individuals diagnosed with AIDS from January 1, 1980, through December 31, 2004, were linked with cancer registries in 15 US regions. Risk of in situ and invasive HPV-associated cancers, compared with that in the general population, was measured by use of standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). We evaluated the relationship of immunosuppression with incidence during the period of 4–60 months after AIDS onset by use of CD4 T-cell counts measured at AIDS onset. Incidence during the 4–60 months after AIDS onset was compared across three periods (1980–1989, 1990–1995, and 1996–2004). All statistical tests were two-sided. Results Among persons with AIDS, we observed statistically significantly elevated risk of all HPV-associated in situ (SIRs ranged from 8.9, 95% CI = 8.0 to 9.9, for cervical cancer to 68.6, 95% CI = 59.7 to 78.4, for anal cancer among men) and invasive (SIRs ranged from 1.6, 95% CI = 1.2 to 2.1, for oropharyngeal cancer to 34.6, 95% CI = 30.8 to 38.8, for anal cancer among men) cancers. During 1996–2004, low CD4 T-cell count was associated with statistically significantly increased risk of invasive anal cancer among men (relative risk [RR] per decline of 100 CD4 T cells per cubic millimeter = 1.34, 95% CI = 1.08 to 1.66, P = .006) and non–statistically significantly increased risk of in situ vagina or vulva cancer (RR = 1.52, 95% CI = 0.99 to 2.35, P = .055) and of invasive cervical cancer (RR = 1.32, 95% CI = 0.96 to 1.80, P = .077). Among men, incidence (per 100 000 person-years) of in situ and invasive anal cancer was statistically significantly higher during 1996–2004 than during 1990–1995 (61% increase for in situ cancers, 18.3 cases vs 29.5 cases, respectively; RR = 1.71, 95% CI = 1.24 to 2.35, P < .001; and 104% increase for invasive cancers, 20.7 cases vs 42.3 cases, respectively; RR = 2.03, 95% CI = 1.54 to 2.68, P < .001). Incidence of other cancers was stable over time. Conclusions Risk of HPV-associated cancers was elevated among persons with AIDS and increased with increasing immunosuppression. The increasing incidence for anal cancer during 1996–2004 indicates that prolonged survival may be associated with increased risk of certain HPV-associated cancers.