Critical dependence of blood-borne biomarker concentrations on the half-lives of their carrier proteins

Until recently, the low-abundance (LA) range of the serum proteome was an unexplored reservoir of diagnostic information. Today it is increasingly appreciated that a diagnostic goldmine of LA biomarkers resides in the blood stream in complexed association with more abundant higher molecular weight carrier proteins such as albumin and immunoglobulins. As we now look to the possibility of harvesting these LA biomarkers more efficiently through engineered nano-scale particles, mathematical approaches are needed in order to reveal the mechanisms by which blood carrier proteins act as molecular 'mops' for LA diagnostic cargo, and the functional relationships between bound LA biomarker concentrations and other variables of interest such as biomarker intravasation and clearance rates and protein half-lives in the bloodstream. Here we show, by simple mathematical modeling, how the relative abundance of large carrier proteins and their longer half-lives in the bloodstream work together to amplify the total blood concentration of these tiny biomarkers. The analysis further suggests that alterations in the production of biomarkers lead to gradual rather than immediate changes in biomarker levels in the blood circulation. The model analysis also points to the characteristics of artificial nano-particles that would render them more efficient harvesters of tumor biomarkers in the circulation, opening up possibilities for the early detection of curable disease, rather than simply better detection of advanced disease.

Intervertebral staple grading system with micro-CT

Introduction Intervertebral stapling is a leading method of fusionless scoliosis treatment which attempts to control growth by applying pressure to the convex side of a scoliotic curve in accordance with the Hueter-Volkmann principle. In addition to that, staples have the potential to damage surrounding bone during insertion and subsequent loading. The aim of this study was to assess the extent of bony structural damage including epiphyseal injury as a result of intervertebral stapling using an in vitro bovine model. Materials and Methods Thoracic spines from 6-8 week old calves were dissected and divided into motion segments including levels T4-T11 (n=14). Each segment was potted in polymethylemethacrylate. An Instron Biaxial materials testing machine with a custom made jig was used for testing. The segments were tested in flexion/extension, lateral bending and axial rotation at 37⁰C and 100% humidity, using moment control to a maximum 1.75 Nm with a loading rate of 0.3 Nm per second for 10 cycles. The segments were initially tested uninstrumented with data collected from the tenth load cycle. Next an anterolateral 4-prong Shape Memory Alloy (SMA) staple (Medtronic Sofamor Danek, USA) was inserted into each segment. Biomechanical testing was repeated as before. The staples were cut in half with a diamond saw and carefully removed. Micro-CT scans were performed and sagittal, transverse and coronal reformatted images were produced using ImageJ (NIH, USA).The specimens were divided into 3 grades (0, 1 and 2) according to the number of epiphyses damaged by the staple prongs. Results: There were 9 (65%) segments with grade 1 staple insertions and 5 (35%) segments with grade 2 insertions. There were no grade 0 staples. Grade 2 spines had a higher stiffness level than grade 1 spines, in all axes of movement, by 28% (p=0.004). This was most noted in flexion/extension with an increase of 49% (p=0.042), followed by non-significant change in lateral bending 19% (p=0.129) and axial rotation 8% (p=0.456) stiffness. The cross sectional area of bone destruction from the prongs was only 0.4% larger in the grade 2 group compared to the grade 1 group (p=0.961). Conclusion Intervertebral staples cause epiphyseal damage. There is a difference in stiffness between grade 1 and grade 2 staple insertion segments in flexion/extension only. There is no difference in the cross section of bone destruction as a result of prong insertion and segment motion.

CRM packaged software : a study of organisational experiences

Customer Relationship Management (CRM) packaged software has become a key contributor to attempts at aligning business and IT strategies in recent years. Throughout the 1990s there was, in many organisations strategies, a shift from the need to manage transactions and toward relationship management. Where Enterprise Resource Planning packages dominated the management of transactions era, CRM packages lead in regard to relationships. At present, balanced views of CRM packages are scantly presented instead relying on vendor rhetoric. This paper uses case study research to analyse some of the issues associated with CRM packages. These issues include the limitations of CRM packages, the need for a relationship orientation and the problems of a dominant management perspective of CRM. It is suggested that these issues could be more readily accommodated by organisational detachment from beliefs in IT as utopia, consideration of prior IS theory and practice and a more informed approach to CRM package selection.

Improving voltage profile of residential distribution systems using rooftop PVs and Battery Energy Storage systems

Large number of rooftop Photovoltaics (PVs) have turned traditional passive networks into active networks with intermittent and bidirectional power flow. A community based distribution network grid reinforcement process is proposed to address technical challenges associated with large integration of rooftop PVs. Probabilistic estimation of intermittent PV generation is considered. Depending on the network parameters such as the R/X ratio of distribution feeder, either reactive control from PVs or coordinated control of PVs and Battery Energy Storage (BES) has been proposed. Determination of BES capacity is one of the significant outcomes from the proposed method and several factors such as variation in PV installed capacity as well as participation from community members are analyzed. The proposed approach is convenient for the community members providing them flexibility of managing their integrated PV and BES systems

Host-pathogen checkpoints and population bottlenecks in persistent and intracellular uropathogenic Escherichia coli bladder infection

Bladder infections affect millions of people yearly, and recurrent symptomatic infections (cystitis) are very common. The rapid increase in infections caused by multidrug-resistant uropathogens threatens to make recurrent cystitis an increasingly troubling public health concern. Uropathogenic Escherichia coli (UPEC) cause the vast majority of bladder infections. Upon entry into the lower urinary tract, UPEC face obstacles to colonization that constitute population bottlenecks, reducing diversity, and selecting for fit clones. A critical mucosal barrier to bladder infection is the epithelium (urothelium). UPEC bypass this barrier when they invade urothelial cells and form intracellular bacterial communities (IBCs), a process which requires type 1 pili. IBCs are transient in nature, occurring primarily during acute infection. Chronic bladder infection is common and can be either latent, in the form of the quiescent intracellular reservoir (QIR), or active, in the form of asymptomatic bacteriuria (ASB/ABU) or chronic cystitis. In mice, the fate of bladder infection, QIR, ASB, or chronic cystitis, is determined within the first 24 h of infection and constitutes a putative host–pathogen mucosal checkpoint that contributes to susceptibility to recurrent cystitis. Knowledge of these checkpoints and bottlenecks is critical for our understanding of bladder infection and efforts to devise novel therapeutic strategies.

An economic case for providing free access to antiretroviral therapy for HIV-positive people in South Australia

Background As financial constraints can be a barrier to accessing HIV antiretroviral therapy (ART), we argue for the removal of copayment requirements from HIV medications in South Australia. Methods Using a simple mathematical model informed by available behavioural and biological data and reflecting the HIV epidemiology in South Australia, we calculated the expected number of new HIV transmissions caused by persons who are not currently on ART compared with transmissions for people on ART. The extra financial investment required to cover the copayments to prevent an HIV infection was compared with the treatment costs saved due to averting HIV infections. Results It was estimated that one HIV infection is prevented per year for every 31.4 persons (median, 24.0–42.7 interquartile range (IQR)) who receive treatment. By considering the incremental change in costs and outcomes of a change in program from the current status quo, it would cost the health sector $17 860 per infection averted (median, $13 651–24 287 IQR) if ART is provided as a three-dose, three-drug combination without requirements for user-pay copayments. Conclusions The costs of removing copayment fees for ART are less than the costs of treating extra HIV infections that would result under current conditions. Removing the copayment requirement for HIV medication would be cost-effective from a governmental perspective.

A review of preschool children's physical activity and sedentary time using objective measures

CONTEXT: Identifying current physical activity levels and sedentary time of preschool children is important for informing government policy and community initiatives. This paper reviewed studies reporting on physical activity and time spent sedentary among preschool-aged children (2-5 years) using objective measures. EVIDENCE ACQUISITION: Databases were searched for studies published up to and including April 2013 that reported on, or enabled the calculation of, the proportion of time preschool children spent sedentary and in light- and moderate to vigorous-intensity physical activity. A total of 40 publications met the inclusion criteria for physical activity and 31 met the inclusion criteria for sedentary time. Objective measures included ActiGraph, Actiwatch, Actical, Actiheart, and RT3 accelerometers, direct observation, and Quantum XL telemetry heart rate monitoring. Data were analyzed in May 2013. EVIDENCE SYNTHESIS: Considerable variation in prevalence estimates existed. The proportion of time children spent sedentary ranged from 34% to 94%. The time spent in light-intensity physical activity and moderate to vigorous-intensity physical activity ranged from 4% to 33% and 2% to 41%, respectively. CONCLUSIONS: The considerable variation of prevalence estimates makes it difficult to determine the "true" prevalence of physical activity and sedentary time in preschool children. Future research should aim to reduce inconsistencies in the employed methodologies to better understand preschoolers' physical activity levels and sedentary behavior.

Durability performance of carbon fibre-reinforced polymer strengthened circular hollow steel members under cold weather

The use of circular hollow steel members has attracted a great deal of attention during past few years because of having excellent structural properties, aesthetic appearance, corrosion and fire protection capability. However, no one can deny the structural deficiency of such structures due to reduction of strength when they are exposed to severe environmental conditions such as marine environment, cold and hot weather. Hence strengthening and retrofitting of structural steel members is now very imperative. This paper presents the findings of a research program that was conducted to study the bond durability of carbon fibre-reinforced polymer (CFRP) strengthened steel tubular members under cold weather and tested under four-point bending. Six number of CFRP-strengthened specimens and one unstrengthened specimen were considered in this program. The three specimens having sand blasted surface to be strengthened was pre-treated with MBrace primer and other three were remained untreated and then cured under ambient temperature at least four weeks and cold weather (3 C) for three and six months period of time. Quasi-static tests were then performed on beams to failure under four-point bending. The structural response of each specimen was predicted in terms of failure load, mid-span deflection, composite beam behaviour and failure mode. The research outcomes show that the cold weather immersion had an adverse effect on durability of CFRP-strengthened steel structures. Moreover, the epoxy based adhesion promoter was found to enhance the bond durability in plastic range. The analytical models presented in this study were found to be in good agreement in terms of predicting ultimate load and deflection. Finally, design factors are proposed to address the short-terms durability performance under cold weather.

“This is not a burning issue for me”: How citizens justify their use of wood heaters in a city with a severe air pollution problem

Although wood smoke pollution has been linked to health problems, wood burning remains a popular form of domestic heating in many countries across the world. In this paper, we describe the rhetoric of resistance to wood heater regulation amongst citizens in the regional Australian town of Armidale, where wood smoke levels regularly exceed national health advisory limits. We discuss how this is related to particular sources of resistance, such as affective attachment to wood heating and socio-cultural norms. The research draws on six focus groups with participants from households with and without wood heating. With reference to practice theory, we argue that citizen discourses favouring wood burning draw upon a rich suite of justifications and present this activity as a natural and traditional activity promoting comfort and cohesion. Such discourses also emphasise the identity of the town as a rural community and the supposed gemeinschaft qualities of such places. We show that, in this domain of energy policy, it is not enough to present ‘facts’ which have little emotional association or meaning for the populace. Rather, we need understand how social scripts, often localised, inform identity and practice.

Natural convection due to differential heating of inclined walls and heat source placed on bottom wall of an attic shaped space

Numerical investigation of free convection heat transfer in an attic shaped enclosure with differentially heated two inclined walls and filled with air is performed in this study. The left inclined surface is uniformly heated whereas the right inclined surface is uniformly cooled. There is a heat source placed on the right side of the bottom surface. Rest of the bottom surface is kept as adiabatic. Finite volume based commercial software ANSYS 15 (Fluent) is used to solve the governing equations. Dependency of various flow parameters of fluid flow and heat transfer is analyzed including Rayleigh number, Ra ranging from 103 to 106, heater size from 0.2 to 0.6, heater position from 0.3 to 0.7 and aspect ratio from 0.2 to 1.0 with a fixed Prandtl number of 0.72. Outcomes have been reported in terms of temperature and stream function contours and local Nusselt number for various Ra, heater size, heater position, and aspect ratio. Grid sensitivity analysis is performed and numerically obtained results have been compared with those results available in the literature and found good agreement.

Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis

Systems-level identification and analysis of cellular circuits in the brain will require the development of whole-brain imaging with single-cell resolution. To this end, we performed comprehensive chemical screening to develop a whole-brain clearing and imaging method, termed CUBIC (clear, unobstructed brain imaging cocktails and computational analysis). CUBIC is a simple and efficient method involving the immersion of brain samples in chemical mixtures containing aminoalcohols, which enables rapid whole-brain imaging with single-photon excitation microscopy. CUBIC is applicable to multicolor imaging of fluorescent proteins or immunostained samples in adult brains and is scalable from a primate brain to subcellular structures. We also developed a whole-brain cell-nuclear counterstaining protocol and a computational image analysis pipeline that, together with CUBIC reagents, enable the visualization and quantification of neural activities induced by environmental stimulation. CUBIC enables time-course expression profiling of whole adult brains with single-cell resolution.

A vibrational spectroscopic study of tengerite-(Y) Y2(CO3)3 2–3H2O

The mineral tengerite-(Y) has been studied by vibrational spectroscopy. Multiple carbonate stretching modes are observed and support the concept of non-equivalent carbonate units in the tengerite-(Y) structure. Intense sharp bands at 464, 479 and 508 cm−1 are assigned to YO stretching modes. Raman bands at 765 and 775 cm−1 are assigned to the CO32− ν4 bending modes and Raman bands at 589, 611, 674 and 689 cm−1 are assigned to the CO32− ν2 bending modes. Multiple Raman and infrared bands in the OH stretching region are observed, proving the existence of water in different molecular environments in the structure of tengerite-(Y).

Hospital infection control units: Staffing, costs, and priorities

Background: This article describes infection prevention and control professionals’ (ICPs’) staffing levels, patient outcomes, and costs associated with the provision of infection prevention and control services in Australian hospitals. A secondary objective was to determine the priorities for infection control units. Methods: A cross-sectional study design was used. Infection control units in Australian public and private hospitals completed a Web-based anonymous survey. Data collected included details about the respondent; hospital demographics; details and services of the infection control unit; and a description of infection prevention and control-related outputs, patient outcomes, and infection control priorities. Results: Forty-nine surveys were undertaken, accounting for 152 Australian hospitals. The mean number of ICPs was 0.66 per 100 overnight beds (95% confidence interval, 0.55-0.77). Privately funded hospitals have significantly fewer ICPs per 100 overnight beds compared with publicly funded hospitals (P < .01). Staffing costs for nursing staff in infection control units in this study totaled $16,364,392 (mean, $380,566). Infection control units managing smaller hospitals (<270 beds) identified the need for increased access to infectious diseases or microbiology support. Conclusion: This study provides valuable information to support future decisions by funders, hospital administrators, and ICPs on service delivery models for infection prevention and control. Further, it is the first to provide estimates of the resourcing and cost of staffing infection control in hospitals at a national level. Copyright

Design and evaluation of decision and control strategies for autonomous vision-based see and avoid systems

This paper details the design and performance assessment of a unique collision avoidance decision and control strategy for autonomous vision-based See and Avoid systems. The general approach revolves around re-positioning a collision object in the image using image-based visual servoing, without estimating range or time to collision. The decision strategy thus involves determining where to move the collision object, to induce a safe avoidance manuever, and when to cease the avoidance behaviour. These tasks are accomplished by exploiting human navigation models, spiral motion properties, expected image feature uncertainty and the rules of the air. The result is a simple threshold based system that can be tuned and statistically evaluated by extending performance assessment techniques derived for alerting systems. Our results demonstrate how autonomous vision-only See and Avoid systems may be designed under realistic problem constraints, and then evaluated in a manner consistent to aviation expectations.

The influence of family history of hypertension on disease prevalence and associated metabolic risk factors among Sri Lankan adults

Background Hypertension is a major contributor to the global non-communicable disease burden. Family history is an important non-modifiable risk factor for hypertension. The present study aims to describe the influence of family history (FH) on hypertension prevalence and associated metabolic risk factors in a large cohort of South Asian adults, from a nationally representative sample from Sri Lanka. Methods A cross-sectional survey among 5,000 Sri Lankan adults, evaluating FH at the levels of parents, grandparents, siblings and children. A binary logistic regression analysis was performed in all patients with ‘presence of hypertension’ as dichotomous dependent variable and using family history in parents, grandparents, siblings and children as binary independent variables. The adjusted odds ratio controlling for confounders (age, gender, body mass index, diabetes, hyperlipidemia and physical activity) are presented below. Results In all adults the prevalence of hypertension was significantly higher in patients with a FH (29.3 %, n = 572/1951) than those without (24.4 %, n = 616/2530) (p < 0.001). Presence of a FH significantly increased the risk of hypertension (OR:1.29; 95 % CI:1.13-1.47), obesity (OR:1.36; 95 % CI: 1.27–1.45), central obesity (OR:1.30; 95 % CI 1.22–1.40) and metabolic syndrome (OR:1.19; 95 % CI: 1.08–1.30). In all adults presence of family history in parents (OR:1.28; 95 % CI: 1.12–1.48), grandparents (OR:1.34; 95 % CI: 1.20–1.50) and siblings (OR:1.27; 95 % CI: 1.21–1.33) all were associated with significantly increased risk of developing hypertension. Conclusions Our results show that the prevalence of hypertension was significantly higher in those with a FH of hypertension. FH of hypertension was also associated with the prevalence of obesity, central obesity and metabolic syndrome. Individuals with a FH of hypertension form an easily identifiable group who may benefit from targeted interventions.