Transcription and expression of Plasmodium falciparum histidine-rich proteins in different stages and strains : implications for rapid diagnostic tests

Background: Although rapid diagnostic tests (RDTs) for Plasmodium falciparum infection that target histidine rich protein 2 (PfHRP2) are generally sensitive, their performance has been reported to be variable. One possible explanation for variable test performance is differences in expression level of PfHRP in different parasite isolates. Methods: Total RNA and protein were extracted from synchronised cultures of 7 P. falciparum lines over 5 time points of the life cycle, and from synchronised ring stages of 10 falciparum lines. Using quantitative real-time polymerase chain reaction, Western blot analysis and ELISA we investigated variations in the transcription and protein levels of pfhrp2, pfhrp3 and PfHRP respectively in the different parasite lines, over the parasite intraerythrocytic life cycle. Results: Transcription of pfhrp2 and pfhrp3 in different parasite lines over the parasite life cycle was observed to vary relative to the control parasite K1. In some parasite lines very low transcription of these genes was observed. The peak transcription was observed in ring-stage parasites. Pfhrp2 transcription was observed to be consistently higher than pfhrp3 transcription within parasite lines. The intraerythrocytic lifecycle stage at which the peak level of protein was present varied across strains. Total protein levels were more constant relative to total mRNA transcription, however a maximum 24 fold difference in expression at ring-stage parasites relative to the K1 strain was observed. Conclusions: The levels of transcription of pfhrp2 and pfhrp3, and protein expression of PfHRP varied between different P. falciparum strains. This variation may impact on the detection sensitivity of PfHRP2-detecting RDTs.

Genetic variation in cytokine-related genes and migraine susceptibility

Migraine is classified by the World Health Organization (WHO) as being one of the top 20 most debilitating diseases. According to the neurovascular hypothesis, neuroinflammation may promote the activation and sensitisation of meningeal nociceptors, inducing the persistent throbbing headache characterized in migraine. The tumor necrosis factor (TNF) gene cluster, made up of TNFα, lymphotoxin α (LTA), and lymphotoxin β (LTB), has been implicated to influence the intensity and duration of local inflammation. It is thought that sterile inflammation mediated by LTA, LTB, and TNFα contributes to threshold brain excitability, propagation of neuronal hyperexcitability and thus initiation and maintenance of a migraine attack. Previous studies have investigated variants within the TNF gene cluster region in relation to migraine susceptibility, with largely conflicting results. The aim of this study was to expand on previous research and utilize a large case-control cohort and range of variants within the TNF gene cluster to investigate the role of the TNF gene cluster in migraine. Nine single nucleotide polymorphisms (SNPs) were selected for investigation as follows: rs1800683, rs2229094, rs2009658, rs2071590, rs2239704, rs909253, rs1800630, rs1800629, and rs3093664. No significant association with migraine susceptibility was found for any of the SNPs tested, with further testing according to migraine subtype and gender also showing no association for disease risk. Haplotype analysis showed that none of the tested haplotypes were significantly associated with migraine.

Allelic variation at a single gene increases food value in a drought-tolerant staple cereal

The production of adequate agricultural outputs to support the growing human population places great demands on agriculture, especially in light of ever-greater restrictions on input resources. Sorghum is a drought-adapted cereal capable of reliable production where other cereals fail, and thus represents a good candidate to address food security as agricultural inputs of water and arable land grow scarce. A long-standing issue with sorghum grain is that it has an inherently lower digestibility. Here we show that a low-frequency allele type in the starch metabolic gene, pullulanase, is associated with increased digestibility, regardless of genotypic background. We also provide evidence that the beneficial allele type is not associated with deleterious pleiotropic effects in the modern field environment. We argue that increasing the digestibility of an adapted crop is a viable way forward towards addressing food security while maximizing water and land-use efficiency.

Variation in leaf morphology of the invasive cat's claw creeper Dolichandra unguis-cati (Bignoniaceae)

The invasive liana cat’s claw creeper Dolichandra unguis-cati (L.) L.G. Lohmann (syn. Macfadyena unguis-cati (L.) A.H. Gentry) exhibits intraspecific variation in leaf morphology, but this is rarely noted in the published literature. The present study documents variation in leaf morphology in two forms of the species that occur in Australia (long pod and short pod). Leaf morphology is compared between the two forms and the position of the shoots (trunk and ground) at the only two sites in which they co-occur. Leaves were categorised on the basis of leaflet number and the presence or absence of tendrils. Simple leaves were produced mainly on shoots growing along the ground and were more abundant in the short-pod form. Long-pod plants were dominated by bifoliate leaves with tendrils. Cat’s claw creeper exhibits considerably wider variation in leaf morphology than recorded previously. Variations in leaf morphology may be linked to differences in the genotype, developmental stage and plastic responses of the plants. Understanding these variations may have implications for taxonomic delimitation and improved management, particularly biological control involving leaf-feeding insects.

Postprandial total and HMW adiponectin following a high-fat meal in lean, obese and diabetic men

BACKGROUND/OBJECTIVES: Recent work suggests that macronutrients are pro-inflammatory and promote oxidative stress. Reports of postprandial regulation of total adiponectin have been mixed, and there is limited information regarding postprandial changes in high molecular weight (HMW) adiponectin. The aim of this study was to assess the effect of a standardised high-fat meal on metabolic variables, adiponectin (total and HMW), and markers of inflammation and oxidative stress in: (i) lean, (ii) obese non-diabetic and (iii) men with type 2 diabetes mellitus (T2DM). SUBJECTS/METHODS: Male subjects: lean (n=10), obese (n=10) and T2DM (n=10) were studied for 6 h following both a high-fat meal and water control. Metabolic variables (glucose, insulin, triglycerides), inflammatory markers (interleukin-6 (IL6), tumour necrosis factor (TNF)α, high-sensitivity C-reactive protein (hsCRP), nuclear factor (NF)κB expression in peripheral blood mononuclear cells (p65)), indicators of oxidative stress (oxidised low density lipoprotein (oxLDL), protein carbonyl) and adiponectin (total and HMW) were measured. RESULTS: No significant changes in TNFα, p65, oxLDL or protein carbonyl concentrations were observed. Overall, postprandial IL6 decreased in subjects with T2DM but increased in lean subjects, whereas hsCRP decreased in the lean cohort and increased in obese subjects. There was no overall postprandial change in total or HMW adiponectin in any group. Total adiponectin concentrations changed over time following the water control, and the response was significantly different in lean subjects compared with subjects with T2DM (P=0.04). CONCLUSIONS: No consistent significant postprandial inflammation, oxidative stress or regulation of adiponectin was observed in this study. Findings from the water control suggest differential basal regulation of total adiponectin in T2DM compared with lean controls.

Quantification of ebullitive and diffusive methane release to atmosphere from a water storage

Accurately quantifying total freshwater storage methane release to atmosphere requires the spatial–temporal measurement of both diffusive and ebullitive emissions. Existing floating chamber techniques provide localised assessment of methane flux, however, significant errors can arise when weighting and extrapolation to the entire storage, particularly when ebullition is significant. An improved technique has been developed that compliments traditional chamber based experiments to quantify the storage-scale release of methane gas to atmosphere through ebullition using the measurements from an Optical Methane Detector (OMD) and a robotic boat. This provides a conservative estimate of the methane emission rate from ebullition along with the bubble volume distribution. It also georeferences the area of ebullition activity across entire storages at short temporal scales. An assessment on Little Nerang Dam in Queensland, Australia, demonstrated whole storage methane release significantly differed spatially and throughout the day. Total methane emission estimates showed a potential 32-fold variation in whole-of-dam rates depending on the measurement and extrapolation method and time of day used. The combined chamber and OMD technique showed that 1.8–7.0% of the surface area of Little Nerang Dam is accounting for up to 97% of total methane release to atmosphere throughout the day. Additionally, over 95% of detectable ebullition occurred in depths less than 12 m during the day and 6 m at night. This difference in spatial and temporal methane release rate distribution highlights the need to monitor significant regions of, if not the entire, water storage in order to provide an accurate estimate of ebullition rates and their contribution to annual methane emissions.

First flush behaviour in urban residential catchments

The current state of knowledge in relation to first flush does not provide a clear understanding of the role of rainfall and catchment characteristics in influencing this phenomenon. This is attributed to the inconsistent findings from research studies due to the unsatisfactory selection of first flush indicators and how first flush is defined. The research study discussed in this thesis provides the outcomes of a comprehensive analysis on the influence of rainfall and catchment characteristics on first flush behaviour in residential catchments. Two sets of first flush indicators are introduced in this study. These indicators were selected such that they are representative in explaining in a systematic manner the characteristics associated with first flush. Stormwater samples and rainfall-runoff data were collected and recorded from stormwater monitoring stations established at three urban catchments at Coomera Waters, Gold Coast, Australia. In addition, historical data were also used to support the data analysis. Three water quality parameters were analysed, namely, total suspended solids (TSS), total phosphorus (TP) and total nitrogen (TN). The data analyses were primarily undertaken using multi criteria decision making methods, PROMETHEE and GAIA. Based on the data obtained, the pollutant load distribution curve (LV) was determined for the individual rainfall events and pollutant types. Accordingly, two sets of first flush indicators were derived from the curve, namely, cumulative load wash-off for every 10% of runoff volume interval (interval first flush indicators or LV) from the beginning of the event and the actual pollutant load wash-off during a 10% increment in runoff volume (section first flush indicators or P). First flush behaviour showed significant variation with pollutant types. TSS and TP showed consistent first flush behaviour. However, the dissolved fraction of TN showed significant differences to TSS and TP first flush while particulate TN showed similarities. Wash-off of TSS, TP and particulate TN during the first 10% of the runoff volume showed no influence from corresponding rainfall intensity. This was attributed to the wash-off of weakly adhered solids on the catchment surface referred to as "short term pollutants" or "weakly adhered solids" load. However, wash-off after 10% of the runoff volume showed dependency on the rainfall intensity. This is attributed to the wash-off of strongly adhered solids being exposed when the weakly adhered solids diminish. The wash-off process was also found to depend on rainfall depth at the end part of the event as the strongly adhered solids are loosened due to impact of rainfall in the earlier part of the event. Events with high intensity rainfall bursts after 70% of the runoff volume did not demonstrate first flush behaviour. This suggests that rainfall pattern plays a critical role in the occurrence of first flush. Rainfall intensity (with respect to the rest of the event) that produces 10% to 20% runoff volume play an important role in defining the magnitude of the first flush. Events can demonstrate high magnitude first flush when the rainfall intensity occurring between 10% and 20% of the runoff volume is comparatively high while low rainfall intensities during this period produces low magnitude first flush. For events with first flush, the phenomenon is clearly visible up to 40% of the runoff volume. This contradicts the common definition that first flush only exists, if for example, 80% of the pollutant mass is transported in the first 30% of runoff volume. First flush behaviour for TN is different compared to TSS and TP. Apart from rainfall characteristics, the composition and the availability of TN on the catchment also play an important role in first flush. The analysis confirmed that events with low rainfall intensity can produce high magnitude first flush for the dissolved fraction of TN, while high rainfall intensity produce low dissolved TN first flush. This is attributed to the source limiting behaviour of dissolved TN wash-off where there is high wash-off during the initial part of a rainfall event irrespective of the intensity. However, for particulate TN, the influence of rainfall intensity on first flush characteristics is similar to TSS and TP. The data analysis also confirmed that first flush can occur as high magnitude first flush, low magnitude first flush or non existence of first flush. Investigation of the influence of catchment characteristics on first flush found that the key factors that influence the phenomenon are the location of the pollutant source, spatial distribution of the pervious and impervious surfaces in the catchment, drainage network layout and slope of the catchment. This confirms that first flush phenomenon cannot be evaluated based on a single or a limited set of parameters as a number of catchment characteristics should be taken into account. Catchments where the pollutant source is located close to the outlet, a high fraction of road surfaces, short travel time to the outlet, with steep slopes can produce high wash-off load during the first 50% of the runoff volume. Rainfall characteristics have a comparatively dominant impact on the wash-off process compared to the catchment characteristics. In addition, the pollutant characteristics also should be taken into account in designing stormwater treatment systems due to different wash-off behaviour. Analysis outcomes confirmed that there is a high TSS load during the first 20% of the runoff volume followed by TN which can extend up to 30% of the runoff volume. In contrast, high TP load can exist during the initial and at the end part of a rainfall event. This is related to the composition of TP available for the wash-off.

Complications of perioperative warfarin therapy in total knee arthroplasty

Patients presenting for knee replacement on warfarin for medical reasons often require higher levels of anticoagulation peri-operatively than primary thromboprophylaxis and may require bridging therapy with heparin. We performed a retrospective case control study on 149 consecutive primary knee arthroplasty patients to investigate whether anti-coagulation affected short-term outcomes. Specific outcome measures indicated significant increases in prolonged wound drainage (26.8% of cases vs 7.3% of controls, p<0.001); superficial infection (16.8% vs 3.3%, p<0.001); deep infection (6.0% vs 0%, p<0.001); return-to-theatre for washout (4.7% vs 0.7%, p=0.004); and revision (4.7% vs 0.3%, p=0.001). Management of patients on long-term warfarin therapy following TKR is particularly challenging, as the surgeon must balance risk of thromboembolism against post-operative complications on an individual patient basis in order to optimise outcomes.

Anatomic fitting of total artificial hearts for in vivo evaluation

Successful anatomic fitting of a total artificial heart (TAH) is vital to achieve optimal pump hemodynamics after device implantation. Although many anatomic fitting studies have been completed in humans prior to clinical trials, few reports exist that detail the experience in animals for in vivo device evaluation. Optimal hemodynamics are crucial throughout the in vivo phase to direct design iterations and ultimately validate device performance prior to pivotal human trials. In vivo evaluation in a sheep model allows a realistically sized representation of a smaller patient, for which smaller third-generation TAHs have the potential to treat. Our study aimed to assess the anatomic fit of a single device rotary TAH in sheep prior to animal trials and to use the data to develop a threedimensional, computer-aided design (CAD)-operated anatomic fitting tool for future TAH development. Following excision of the native ventricles above the atrio-ventricular groove, a prototype TAH was inserted within the chest cavity of six sheep (28–40 kg).Adjustable rods representing inlet and outlet conduits were oriented toward the center of each atrial chamber and the great vessels, with conduit lengths and angles recorded for future analysis. A threedimensional, CAD-operated anatomic fitting tool was then developed, based on the results of this study, and used to determine the inflow and outflow conduit orientation of the TAH. The mean diameters of the sheep left atrium, right atrium, aorta, and pulmonary artery were 39, 33, 12, and 11 mm, respectively. The center-to-center distance and outer-edge-to-outer-edge distance between the atria, found to be 39 ± 9 mm and 72 ± 17 mm in this study, were identified as the most critical geometries for successful TAH connection. This geometric constraint restricts the maximum separation allowable between left and right inlet ports of a TAH to ensure successful alignment within the available atrial circumference.

A nanometre-scale non-periodic structural variation in high temperature superconducting ceramics and the implications for properties

Non-periodic structural variation has been found in the high Tc cuprates, YBa2Cu3O7-x and Hg0.67Pb0.33Ba2Ca2Cu 3O8+δ, by image analysis of high resolution transmission electron microscope (HRTEM) images. We use two methods for analysis of the HRTEM images. The first method is a means for measuring the bending of lattice fringes at twin planes. The second method is a low-pass filter technique which enhances information contained by diffuse-scattered electrons and reveals what appears to be an interference effect between domains of differing lattice parameter in the top and bottom of the thin foil. We believe that these methods of image analysis could be usefully applied to the many thousands of HRTEM images that have been collected by other workers in the high temperature superconductor field. This work provides direct structural evidence for phase separation in high Tc cuprates, and gives support to recent stripes models that have been proposed to explain various angle resolved photoelectron spectroscopy and nuclear magnetic resonance data. We believe that the structural variation is a response to an opening of an electronic solubility gap where holes are not uniformly distributed in the material but are confined to metallic stripes. Optimum doping may occur as a consequence of the diffuse boundaries between stripes which arise from spinodal decomposition. Theoretical ideas about the high Tc cuprates which treat the cuprates as homogeneous may need to be modified in order to take account of this type of structural variation.

Using technology to change adult sedentary behaviour, physical activity levels and total wellness

This thesis studied technology’s role in promoting and supporting active lifestyles through behavioural strategies to reduce sedentary time and increase physical activity. The five studies included (1) development of a self-report instrument quantifying daily sedentary behaviour and light-intensity physical activity; (2) establishment of instrument validity and reliability; (3) use of an online personal activity monitor to successfully reduce sedentary time and increase physical activity; (4) identification of positive differences in total wellness as related to high/low levels of sitting time combined with insufficient/sufficient physical activity; and (5) improvement of total wellness through positive changes in sedentary behaviour and physical activity.

Physical activity, sedentary behavior and total wellness changes among sedentary adults : a 4-week randomized controlled trial

Background The construct of total wellness includes a holistic approach to the body, mind and spirit components of life. While the health benefits of reducing sedentary behavior and increasing physical activity are well documented, little is known about the influence on total wellness of an internet-based physical activity monitor designed to help people to achieve higher physical activity levels. Purpose The purpose of this four-week, personal activity monitor-based intervention program was to reduce sedentary behavior and increase physical activity levels in daily living for sedentary adults and to determine if these changes would also be associated with improvement in total wellness. Methods Twenty-two men and 11 women (27 years ± 4.0) were randomly assigned to either an intervention (n = 18) or control group (n = 15). The intervention group interacted with an online personal activity monitor (Gruve Solution™) designed to reduce sedentary time and increase physical activity during activities of daily living. The control group did not interact with the monitor, as they were asked to follow their normal daily physical activities and sedentary behavior routines. The Wellness Evaluation of Lifestyle (WEL) inventory was used to assess total wellness. Sedentary time, light, walking, moderate and vigorous intensity physical activities were assessed for both intervention and control groups at baseline and at week-4 by the 7-day Sedentary and Light Intensity Physical Activity Log (7-day SLIPA Log) and the International Physical Activity Questionnaire (IPAQ). Results Significant increases in pre-post total wellness scores (from 64% ± 5.7 to 75% ± 8.5) (t (17) = -6.5, p < 0.001) were observed in the intervention group by the end of week four. Intervention participants decreased their sedentary time (21%, 2.3 hours/day) and increased their light (36.7%, 2.5 hours/day), walking (65%, 1057 MET-min/week), moderate (67%, 455 MET-min/week) and vigorous intensity (60%, 442 MET-min/week) physical activity (all p < 0.001). No significant differences for total wellness were observed between the groups at baseline and no pre-post significant differences were observed for any outcome variable in the control group. Conclusion Total wellness is improved when sedentary, but sufficiently physically active adults, reduce sedentary time and increase physical activity levels (i.e. light, walking, moderate and vigorous).

Physical activity patterns among South-Asian adults : a systematic review

Physical activity (PA) has many beneficial physical and mental health effects. Physical inactivity is considered the fourth leading risk factor for global mortality. At present there are no systematic reviews on PA patterns among South Asian adults residing in the region. The present study aims to systematically evaluate studies on PA patterns in South Asian countries. A five-staged comprehensive search of the literature was conducted in Medline, Web of Science and SciVerse Scopus using keywords ‘Exercise’, ‘Walking’, ‘Physical activity’, ‘Inactivity’, ‘Physical Activity Questionnaire’, ‘International Physical Activity Questionnaire’, ‘IPAQ’, ‘Global Physical Activity Questionnaire’ and ‘GPAQ’, combined with individual country names. The search was restricted to English language articles conducted in humans and published before 31st December 2012. To obtain additional data a manual search of the reference lists of articles was performed. Data were also retrieved from the search of relevant web sites and online resources. The total number of hits obtained from the initial search was 1,771. The total number of research articles included in the present review is eleven (India-8, Sri Lanka-2, Pakistan-1). In addition, eleven country reports (Nepal-3, Bangladesh-2, India-2, Sri Lanka-2, Bhutan-1, Maldives-1) of World Health Organization STEPS survey from the South-Asian countries were retrieved online. In the research articles the overall prevalence of inactivity was as follows; India (18.5%-88.4%), Pakistan (60.1%) and Sri Lanka (11.0%-31.8%). STEPS survey reports were available from all countries except Pakistan. Overall in majority of STEPS surveys females were more inactive compared to males. Furthermore, leisure related inactivity was >75% in studies reporting inactivity in this domain and people were more active in transport domain when compared with the other domains. In conclusion, our results show that there is a wide variation in the prevalence of physical inactivity among South-Asian adults within and between countries. Furthermore, physical inactivity in South Asian adults was associated with several socio-demographic characteristics. Majority of South Asian adults were inactive during their leisure time. These Factors need to be considered when planning future interventions and research aimed at improving PA in the region.

Quality demand in vaccination and how to improve service quality under Total Quality Control [论全面质量管理模式下预防接种工作的质量要求与改进对策]

Under the concept of Total Quality Control, based on their experience, the authors discussed potential demand for quality of immunization services and possible solutions to these demands. Abstract in Chinese 全面质量管理(total quality control,TQC)是在20世纪60年代由美国人V,Feigonbaum和J.unan先后提出的新的质量管理观念,众所周知的ISO9000族标准即建立在TQC理念下的质量管理标准,该标准已成为当今世界全球一致、最具权威的质量管理和质量保证的国际规则[1-2].21世纪是质量世纪,推行TQC,不断改进产品和服务质量,目前已成为我国各行各业在不断激烈的市场竞争下完善自我、保证生存和发展的重要手段.实施预防接种是预防和控制传染病,保护人群健康的重要措施,预防接种工作中,产品即预防接种服务,需方(顾客)为接受预防接种服务的广大人群,是产品的消费者.随社会的迅速发展,人们对健康需求的不断提高,对预防接种工作也提出了更高的质量要求.本文对TQC模式下顾客对预防接种服务的质量要求进行了综合分析,并对如何改进服务质量进行了初步探讨.

Beginning inference in fourth grade : exploring variation in measurement

This paper addresses one of the foundational components of beginning infernce, namely variation, with 5 classes of Year 4 students undertaking a measurement activity using scaled instruments in two contexts: all students measuring one person's arm span and recording the values obtained, and each student having his/her own arm span measured and recorded. The results included documentation of students' explicit appreciation of the variety of ways in which varitation can occur, including outliers, and their ability to create and describe valid representations of their data.