Studies on Waterborne Cadmium Exposure to Lymnaea stagnalis in Varying Water Qualities and the Development of a Novel Tissue Residue Approach

Recent studies have shown that the use of bioaccumulation (tissue residues) as a predictor for toxic effects for metals is a flawed concept.Adams et al. (2010) suggested a novel tissue residue approach (TRA) in which bioaccumulation in resistant organismsis related to toxic effects in sensitive organisms. The goal of this thesis was to test these assumptions in relation to Cd exposure using the great pond snail, Lymnaea stagnalis by developing and improving the understanding of Cd accumulationin aquatic invertebrates. The relationship between Cd bioaccumulation and its toxicity was studied in L. stagnalisusing acute (96h) and chronic (one month) toxicity tests in moderately hard water (140 mg/L as CaCO3). Two sizes of snails (18 or 25 mm) were tested for acute toxicity and the 96 h LC50 for both sizes of snails were 350 µg Cd/L. Soft tissue accumulation reached 750 µg Cd/g dry wt.in these exposures while the shell accumulation was only 16 µg Cd/g at the highest non-lethal exposures. Three sizes of snails were tested for chronic toxicity. The 31 d LC50s for the small (5 mm), medium (10 mm) and large (15 mm) snails were 13, 50 and 46 µg Cd/L, respectively. In the smaller snails, growth was inhibited at exposure concentrations below 10 µg Cd/L. In soft water (20 mg/L CaCO3), two chronic (28 d) tests were conducted using juvenile snails (5 mm), the first with exposures from 2.3 – 8.3 µg Cd/L and the endpoints measured were survival, bioaccumulation and growth. The 28 d LC50for the first test was 7.3 µg Cd/L. Cd accumulation within the soft tissue ranged between 7 - 300 µg Cd/g dry wt. Exposure concentrations in the second test ranged from 0.3 – 2.3 µg Cd/L and the endpoints measured were whole and sub-cellular fractionation of Cd. Cd accumulation within the soft tissue reached levels as high as 117 µg Cd/g dry wt. Cd accumulation was dose dependent and reached steady state tissue burden within 14 d. Sub-cellular fractionation was measured after 28d of exposure and increasing amounts of Cd were found in the heat stable proteins and organelle fractions as Cd exposure concentration increased. Finally, to test the novel TRA approach, a side-by-side exposure using a Cd sensitive organism (Hyalella azteca; based on studies by T. Straus) and a resistant organism (L.stagnalis) was done over 28 d using a toxicologically relevant exposure range (0.4 to 2.6 µg Cd/L). Endpoints were survival, growth (dry wt.) and Cd accumulation. A relationship between mortality in Hyalella (sensitive organism) and accumulation in Lymnaea (resistant organism) was determined for d 28 of exposure. The 28 d LD20 and LD50 in Hyalella were 0.42 and 0.70 µg Cd/L, respectively. The LD20 and LD50 values in Hyalella was associated to 36 and 69 µg Cd/g dry wt. body burden in the soft tissue of Lymnaea. Therefore, this novel TRA shows potential but requires more validation for it to be used in the field

Predictive characteristics of lactation models for pasture-based Holstein-Friesian dairy cows

Mathematical functions to describe a series of milk test day records have the advantage of minimizing random variation, while simultaneously summarizing the lactation profile. Five empirical functions and two mechanistic models were used to model herd and individual milk yield profiles of multiparous Holstein-Friesian cows on 113, 290 milk yield records (8438 lactations) collected from 1994-2005. The models tested were the incomplete gamma (IG), a modified gamma (MG), an exponential (EXP), a polynomial regression (PR), a mixed log (ML), the bi-compartmental (BC), and Dijkstra (DJ) functions, the latter two being mechanistic models. Each model was fitted using the non-linear (NLIN) function of SAS. Model accuracy was evaluated based on residual mean square (RMS), the magnitude and distribution of residuals, and the correlation between the observed and predicted values. All the models, except MG, did equally well in portraying the lactation profile. Parameter estimates were significant (P<0.05), with large serial correlations indicating biased predictions, especially during mid-lactation. Correlations of residuals and observed herd average lactations ranged between -0.13 (MG) to 0.19 (IG), while that between observed and predicted was between 0.76 and 0.99 for the same models. Lactation curves of individual cow milk yields were more varied, exhibited the tendency for a second peak which were not accurately modeled. Mechanistic models performed best with herd data, the PR model fitted overall best, while the MG model fitted the profile least accurately in this study

Blackleg of rapeseed

Unless blackleg can be controlled there is little future for rapeseed as a major commercial crop in W.A. Until 1972, oilseed rape showed great promise as an alternative cash crop for Western Australian farmers, especially in the Great Southern and south coastal areas. However, like most other cruciferous crops, rape is prone to attack from diseases and insect pests. Most of these can be controlled, but the fungus disease blackleg (Leptosphaeria maculans) emerged as a major threat to the industry. Clearly, unless the disease can be controlled, there is little future for rapeseed as a major commercial crop in Western Australia

Associations Between Left Ventricular Dysfunction and Brain Structure and Function: Findings From the SABRE (Southall and Brent Revisited) Study

Background Subclinical left ventricular (LV) dysfunction has been inconsistently associated with early cognitive impairment, and mechanistic pathways have been poorly considered. We investigated the cross‐sectional relationship between LV dysfunction and structural/functional measures of the brain and explored the role of potential mechanisms. Method and Results A total of 1338 individuals (69±6 years) from the Southall and Brent Revisited study underwent echocardiography for systolic (tissue Doppler imaging peak systolic wave) and diastolic (left atrial diameter) assessment. Cognitive function was assessed and total and hippocampal brain volumes were measured by magnetic resonance imaging. Global LV function was assessed by circulating N‐terminal pro–brain natriuretic peptide. The role of potential mechanistic pathways of arterial stiffness, atherosclerosis, microvascular disease, and inflammation were explored. After adjusting for age, sex, and ethnicity, lower systolic function was associated with lower total brain (beta±standard error, 14.9±3.2 cm3; P<0.0001) and hippocampal volumes (0.05±0.02 cm3, P=0.01). Reduced diastolic function was associated with poorer working memory (−0.21±0.07, P=0.004) and fluency scores (−0.18±0.08, P=0.02). Reduced global LV function was associated with smaller hippocampal volume (−0.10±0.03 cm3, P=0.004) and adverse visual memory (−0.076±0.03, P=0.02) and processing speed (0.063±0.02, P=0.006) scores. Separate adjustment for concomitant cardiovascular risk factors attenuated associations with hippocampal volume and fluency only. Further adjustment for the alternative pathways of microvascular disease or arterial stiffness attenuated the relationship between global LV function and visual memory. Conclusions In a community‐based sample of older people, measures of LV function were associated with structural/functional measures of the brain. These associations were not wholly explained by concomitant risk factors or potential mechanistic pathways

Common infections and neuroimaging markers of dementia in three UK cohort studies

INTRODUCTION: We aimed to investigate associations between common infections and neuroimaging markers of dementia risk (brain volume, hippocampal volume, white matter lesions) across three population-based studies. METHODS: We tested associations between serology measures (pathogen serostatus, cumulative burden, continuous antibody responses) and outcomes using linear regression, including adjustments for total intracranial volume and scanner/clinic information (basic model), age, sex, ethnicity, education, socioeconomic position, alcohol, body mass index, and smoking (fully adjusted model). Interactions between serology measures and apolipoprotein E (APOE) genotype were tested. Findings were meta-analyzed across cohorts (Nmain  = 2632; NAPOE-interaction  = 1810). RESULTS: Seropositivity to John Cunningham virus associated with smaller brain volumes in basic models (β = -3.89 mL [-5.81, -1.97], Padjusted  < 0.05); these were largely attenuated in fully adjusted models (β = -1.59 mL [-3.55, 0.36], P = 0.11). No other relationships were robust to multiple testing corrections and sensitivity analyses, but several suggestive associations were observed. DISCUSSION: We did not find clear evidence for relationships between common infections and markers of dementia risk. Some suggestive findings warrant testing for replication

Self-rated health in Pakistan: results of a national health survey

BACKGROUND: Self-rated health (SRH) is a robust predictor of mortality. In UK, migrants of South Asian descent, compared to native Caucasian populations, have substantially poorer SRH. Despite its validation among migrant South Asian populations and its popularity in developed countries as a useful public health tool, the SRH scale has not been used at a population level in countries in South Asia. We determined the prevalence of and risk factors for poor/fair SRH among individuals aged ≥15 years in Pakistan (n = 9442). METHODS: The National Health Survey of Pakistan was a cross-sectional population-based survey, conducted between 1990 and 1994, of 18 135 individuals aged 6 months and above; 9442 of them were aged ≥15 years. Our main outcome was SRH which was assessed using the question: "Would you say your health in general is excellent, very good, good, fair, or poor?" SRH was dichotomized into poor/fair, and good (excellent, very good, or good). RESULTS: Overall 65.1% respondents – 51.3 % men vs. 77.2 % women – rated their health as poor/fair. We found a significant interaction between sex and age (p < 0.0001). The interaction was due to the gender differences only in the ages 15–19 years, whereas poor/fair SRH at all older ages was more prevalent among women and increased at the same rate as it did among men. We also found province of dwelling, low or middle SES, literacy, rural dwelling and current tobacco use to be independently associated with poor/fair SRH. CONCLUSION: This is the first study reporting on poor/fair SRH at a population-level in a South Asian country. The prevalence of poor/fair health in Pakistan, especially amongst women, is one of the worst ever reported, warranting immediate attention. Further research is needed to explain why women in Pakistan have, at all ages, poorer SRH than men

Cerebral Blood Flow and Cognitive Functioning in a Community-Based, Multi-Ethnic Cohort: The SABRE Study

Introduction: Lower cerebral blood flow (CBF) is associated with cardiovascular disease and vascular risk factors, and is increasingly acknowledged as an important contributor to cognitive decline and dementia. In this cross-sectional study, we examined the association between CBF and cognitive functioning in a community-based, multi-ethnic cohort.Methods: From the SABRE (Southall and Brent Revisited) study, we included 214 European, 151 South Asian and 87 African Caribbean participants (71 ± 5 years; 39%F). We used 3T pseudo-continuous arterial spin labeling to estimate whole-brain, hematocrit corrected CBF. We measured global cognition and three cognitive domains (memory, executive functioning/attention and language) with a neuropsychological test battery. Associations were investigated using linear regression analyses, adjusted for demographic variables, vascular risk factors and MRI measures.Results: Across groups, we found an association between higher CBF and better performance on executive functioning/attention (standardized ß [stß] = 0.11, p &lt; 0.05). Stratification for ethnicity showed associations between higher CBF and better performance on memory and executive functioning/attention in the white European group (stß = 0.14; p &lt; 0.05 and stß = 0.18; p &lt; 0.01 respectively), associations were weaker in the South Asian and African Caribbean groups.Conclusions: In a multi-ethnic community-based cohort we showed modest associations between CBF and cognitive functioning. In particular, we found an association between higher CBF and better performance on executive functioning/attention and memory in the white European group. The observations are consistent with the proposed role of cerebral hemodynamics in cognitive decline

Tracing Personalized Health Curves during Infections

By concentrating on the relationship between health and microbe number over the course of infections, most pathogenic and mutualistic infections can be summarized by a small alphabet of curves, which has implications not only for basic research but for how we might treat patients

The influence of HLA genotype on the development of metal hypersensitivity following joint replacement

We thank Innovate UK Edge for providing funding to allow this research to be carried out.Background  Over five million joint replacements are performed across the world each year. Cobalt chrome (CoCr) components are used in most of these procedures. Some patients develop delayed type hypersensitivity (DTH) responses to CoCr implants, resulting in tissue damage and revision surgery. DTH is unpredictable and genetic links have yet to be definitively established. Methods At a single site, we carried out an initial investigation to identify HLA alleles associated with development of DTH following metal-on-metal hip arthroplasty. We then recruited patients from other centres to train and validate an algorithm incorporating patient age, gender, HLA genotype44 and blood metal concentrations to predict the development of DTH. Accuracy of the modelling was assessed using performance metrics including time dependent receiver operator curves. Results Using next generation sequencing, here we determine the HLA genotypes of 606 patients. 176 of these patients had experienced failure of their prostheses; the remaining 430 remain asymptomatic at a mean follow up of twelve years. We demonstrate that the development of DTH is associated with patient age, gender, the magnitude of metal exposure and the presence of certain HLA class II alleles. We show that the predictive algorithm developed from this investigation performs to an accuracy suitable for clinical use, with weighted mean survival probability errors of 1.8% and 3.1%53 for pre-operative and post-operative models respectively. Conclusions The development of DTH following joint replacement appears to be determined by the interaction between implant wear and a patient’s genotype. The algorithm described in this paper may improve implant selection and help direct patient surveillance following surgery. Further consideration should be given towards understanding patient specific responses to different biomaterials.Publisher PDFPeer reviewe