Targeting aurora kinases : a novel approach to curb the growth and chemoresistance of androgen refractory prostate cancer

Aurora Kinase (AK) based therapy targeting AK-A & B is effective against some cancers. We have explored its potential against previously unreported incurable, metastatic androgen depletion independent Prostate Cancer (ADIPC). We used androgen sensitive (AS) and ADI lines derived from Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice. The relevance of this model was unequivocally established through focussed array, quantitative PCR and western blotting studies; significantly greater alteration of genes (fold change and number) representing major cancer pathways was shown in ADI cells compared to AS lines. A marked enhancement of in vivo growth of the ADI subline showing the greatest degree of gene modulations [TRAMP C1 (TC1)-T5: TC1-T5] reflected this. In contrast to the parental AS TC1 line, TC1-T5 cells grew with 100% incidence in the prostate, as lung pseudometastases and migrated to the bone and other soft tissues. The potential involvement of AKs in this transition was indicated by the significant upregulation of AK-A/B and their downstream regulators, survivin and phosphorylated-histone H3 in TC1-T5 cells compared to TC1 cells. This led to enhanced sensitivity of TC1-T5 cells to the pan-AK inhibitor, VX680 and to significant reduction in in vivo tumour growth rates when AK-A and/or B were downregulated in TC1-T5 cells. This cell growth inhibition was markedly enhanced when both AKs were downregulated and also led to substantially greater sensitivity of these cells to docetaxel, the only chemotherapeutic with activity against ADI PC. Finally, use of VX680 with docetaxel led to impressive synergies suggesting promise for treating clinical ADI metastatic PC.

The 'variety effect' is anticipated in meal planning

The 'variety effect' describes the greater consumption that is observed when multiple foods with different sensory characteristics are presented either simultaneously or sequentially. Variety increases the amount of food consumed in test of ad libitum intake. However, outside the laboratory, meals are often planned in advance and then consumed in their entirety. We sought to explore the extent to which the variety effect is anticipated in this pre-meal planning. Participants were shown two food images, each representing a first or a second course of a hypothetical meal. The two courses were either, i) exactly the same food, ii) different foods from the same sensory category (sweet or savoury) or, iii) different foods from a different sensory category. In Study 1 (N = 30) these courses comprised typical ‘main meal’ foods and in Study 2 (N = 30) they comprised snack foods. For each pair of images, participants rated their expected liking of the second course and selected ideal portion sizes, both for the second course and the first and second course, combined. In both studies, as the difference between the courses (from (i) same to (ii) similar to (iii) different) increased, the second course was selected in a larger portion and it was rated as more pleasant. To our knowledge, these are the first studies to show that the variety effect is evident in the energy content of self-selected meals. This work shows that effects of variety are learned and anticipated. This extends our characterisation beyond a passive process that develops towards the end of a meal.

Markers of cutaneous human papillomavirus infection in individuals with tumor-free skin, actinic keratoses, and squamous cell carcinoma

Separately, actinic keratosis (AK) and cutaneous squamous cell carcinoma (SCC) have been associated with cutaneous human papillomavirus (HPV) infections. To further explore the association between HPV infection and SCC development, we determined markers of cutaneous HPV infection within a single population in persons with precursor lesions (AK), cancerous lesions (SCC), and without. Serum and plucked eyebrow hairs were collected from 57 tumor-free controls, 126 AK, and 64 SCC cases. Presence of HPV L1 and E6 seroreactivity and viral DNA were determined for HPV types 5, 8, 15, 16, 20, 24, and 38. Significant positive associations with increasing severity of the lesions (controls, AK, and SCC, respectively) were observed for overall HPV L1 seropositivity (13%, 26%, and 37%) and for HPV8 (4%, 17%, and 30%). In parallel, the proportion of L1 seropositive individuals against multiple HPV types increased from 14% to 39% and 45%. The overall E6 seroreactivity, however, tended to decline with AK and SCC, especially for HPV8 (21%, 11%, and 2%). HPV DNA positivity was most prevalent in the AK cases (54%) compared with the SCC cases (44%) and the tumor-free controls (40%). Among all participants, there was a positive trend between overall HPV DNA positivity and L1 seropositivity, but not E6 seropositivity. Taken together, our data suggest that cutaneous HPV infections accompanied by detectable HPV DNA in eyebrow hairs and HPV L1 seropositivity, but not E6 seropositivity, are associated with an increased risk of AK and SCC.

Simulation architecture for the design of cooperative collision warning systems

Simulation has been widely used to estimate the benefits of Cooperative Systems (CS) based on Inter-Vehicular Communications (IVC). This paper presents a new architecture built with the SiVIC simulator and the RTMaps™ multisensors prototyping platform. We introduce several improvements from a previous similar architecture, regarding IVC modelisation and vehicles’ control. It has been tuned with on-road measurements to improve fidelity. We discuss the results of a freeway emergency braking scenario (EEBL) implemented to validate our architecture’s capabilities.

An exploratory study to evaluate whether medical nutrition therapy can improve dietary intake in hospital patients who eat poorly

Background and aims The Australasian Nutrition Care Day Survey (ANCDS) reported two-in-five patients consume ≤50% of the offered food in Australian and New Zealand hospitals. After controlling for confounders (nutritional status, age, disease type and severity), the ANCDS also established an independent association between poor food intake and increased in-hospital mortality. This study aimed to evaluate if medical nutrition therapy (MNT) could improve dietary intake in hospital patients eating poorly. Methods An exploratory pilot study was conducted in the respiratory, neurology and orthopaedic wards of an Australian hospital. At baseline, percentage food intake (0%, 25%, 50%, 75%, and 100%) was evaluated for each main meal and snack for a 24-hour period in patients hospitalised for ≥2 days and not under dietetic review. Patients consuming ≤50% of offered meals due to nutrition-impact symptoms were referred to ward dietitians for MNT. Food intake was re-evaluated on the seventh day following recruitment (post-MNT). Results 184 patients were observed over four weeks; 32 patients were referred for MNT. Although baseline and post-MNT data for 20 participants (68±17years, 65% females) indicated a significant increase in median energy and protein intake post-MNT (3600kJ/day, 40g/day) versus baseline (2250kJ/day, 25g/day) (p<0.05), the increased intake met only 50% of dietary requirements. Persistent nutrition impact symptoms affected intake. Conclusion In this pilot study whilst dietary intake improved, it remained inadequate to meet participants’ estimated requirements due to ongoing nutrition-impact symptoms. Appropriate medical management and early enteral feeding could be a possible solution for such patients.

Implementation of a better choice healthy food and drink supply strategy for staff and visitors in government owned health facilities in Queensland, Australia

Objective The present paper reports on a quality improvement activity examining implementation of A Better Choice Healthy Food and Drink Supply Strategy for Queensland Health Facilities (A Better Choice). A Better Choice is a policy to increase supply and promotion of healthy foods and drinks and decrease supply and promotion of energy-dense, nutrient-poor choices in all food supply areas including food outlets, staff dining rooms, vending machines, tea trolleys, coffee carts, leased premises, catering, fundraising, promotion and advertising. Design An online survey targeted 278 facility managers to collect self-reported quantitative and qualitative data. Telephone interviews were sought concurrently with the twenty-five A Better Choice district contact officers to gather qualitative information. Setting Public sector-owned and -operated health facilities in Queensland, Australia. Subjects One hundred and thirty-four facility managers and twenty-four district contact officers participated with response rates of 48·2 % and 96·0 %, respectively. Results Of facility managers, 78·4 % reported implementation of more than half of the A Better Choice requirements including 24·6 % who reported full strategy implementation. Reported implementation was highest in food outlets, staff dining rooms, tea trolleys, coffee carts, internal catering and drink vending machines. Reported implementation was more problematic in snack vending machines, external catering, leased premises and fundraising. Conclusions Despite methodological challenges, the study suggests that policy approaches to improve the food and drink supply can be implemented successfully in public-sector health facilities, although results can be limited in some areas. A Better Choice may provide a model for improving food supply in other health and workplace settings.

Wetlands : a perspective for mapping, monitoring, and modeling

Experience gained from numerous projects conducted by the U.S. Environmental Protection Agency's (EPA) Environmental Monitoring Systems Laboratory in Las Vegas, Nevada has provided insight to functional issues of mapping, monitoring, and modeling of wetland habitats. Three case studies in poster form describe these issues pertinent to managing wetland resources as mandated under Federal laws. A multiphase project was initiated by the EPA Alaska operations office to provide detailed wetland mapping of arctic plant communities in an area under petroleum development pressure. Existing classification systems did not meet EPA needs. Therefore a Habitat Classification System (HCS) derived from aerial photography was compiled. In conjunction with this photointerpretive keys were developed. These products enable EPA personnel to map large inaccessible areas of the arctic coastal plain and evaluate the sensitivity of various wetland habitats relative to petroleum development needs.

Trait and behavioural motor control is associated with resistance to overconsumption

While overall obesity rates are rising, a minority of individuals appear to resist overconsumption and remain lean in spite of an ‘obesogenic’ environment. Studying the factors hypothesised to underpin behaviours associated with resistance to overconsumption may inform weight management strategies in an adverse environment. Trait (BIS-11) and behavioural (response inhibition, GoStop) self control were assessed in the laboratory. Snack food consumption was measured covertly via a sham taste test. Lack of motor control was positively correlated (r = .32, p <. 05) and successful response inhibition was negatively correlated (r = −.35, p <. 05) with snack food intake. Low motor control was also associated with further food intake when satiated (r = .39, p < .01). These relationships were independent of self-reported palatability and perceived reward value of the food. Motor control may be an important factor implicated in ‘mindless’ eating in an environment abundant in palatable, energy-dense snack foods.

Nutrition and physical activity policies and practices in family child care homes

Background Family child care homes (FCCHs) are the second-largest provider of nonrelative care in the U.S. However, despite providing care for nearly 1.9 million children aged <5 years, little is known about the nutrition and physical activity practices of FCCHs. Purpose To address this gap, this study aims to describe policies and practices related to nutrition and physical activity in a representative sample of FCCHs. Methods A stratified random sample of registered FCCHs operating in Kansas (N=297) completed the Nutrition and Physical Activity Self Assessment for Child Care (NAPSACC) instrument. Prevalence estimates and 95% CIs for meeting or exceeding accepted child care standards were calculated using SAS PROC SURVEYFREQ. Results Most providers either met or exceeded child care standards related to serving fruit and vegetables and provision of daily physical activity. Very few providers reported serving fried meats or vegetables or unhealthy snack foods on a regular basis. Areas of concern included infrequent servings of low-fat milk, frequent use of unhealthy foods for celebrations, widespread use of TV and video games throughout the day, restricting physical activity for children who misbehave, and lack of appropriate indoor spaces for physical activity. Only a small percentage of providers reported receiving regular training in nutrition or physical activity. Relatively few providers had written guidelines on nutrition or physical activity. Conclusions Some strengths were exhibited by FCCHs, but substantial weaknesses were shown with respect to meeting established child care standards for nutrition and physical activity. Interventions to promote healthy eating and regular physical activity in FCCHs are thus warranted.

Physical activity levels among children attending after-school programs

Purpose To describe the physical activity (PA) levels of children attending after-school programs, 2) examine PA levels in specific after-school sessions and activity contexts, and 3) evaluate after-school PA differences in groups defined by sex and weight status. Methods One hundred forty-seven students in grades 3-6 (mean age: 10.1 +/- 0.7, 54.4% male, 16.5% overweight (OW), 22.8% at-risk for OW) from seven after-school programs in the midwestern United States wore Actigraph GT1M accelerometers for the duration of their attendance to the program. PA was objectively assessed on six occasions during an academic year (three fall and three spring). Stored activity counts were uploaded to a customized data-reduction program to determine minutes of sedentary (SED), light (LPA), moderate (MPA), vigorous (VPA), and moderate-to-vigorous (MVPA) physical activity. Time spent in each intensity category was calculated for the duration of program attendance, as well as specific after-school sessions (e.g., free play, snack time). Results On average, participants exhibited 42.6 min of SED, 40.8 min of LPA, 13.4 min of MPA, and 5.3 min of VPA. The average accumulation of MVPA was 20.3 min. Boys exhibited higher levels of MPA, VPA, and MVPA, and lower levels of SED and LPA, than girls. OW and at-risk-for-OW students exhibited significantly less VPA than nonoverweight students, but similar levels of LPA, MPA, and MVPA. MVPA levels were significantly higher during free-play activity sessions than during organized or structured activity sessions. Conclusion After-school programs seem to be an important contributor to the PA of attending children. Nevertheless, ample room for improvement exists by making better use of existing time devoted to physical activity.

Objectively measured physical activity behavior in children attending a half day preschool program

Obesity rates are increasing in children of all ages, and reduced physical activity (PA) is a likely contributor to this trend. Little is known about the physical activity behavior of preschool-age children, or about the influence of preschool attendance on physical activity. Purpose The purpose of this study was to quantify the physical activity levels of children attending a center-based half-day preschool program. Methods Forty-two 3-to-5-year old children (Mean age = 4.0 ± 0.7, 54.8% Male, Mean BMI = 16.5 ± 5.5, Mean BMI %tile = 52.1 ± 33.5) from four class groups (two morning and two afternoon), wore an Actigraph 7164 accelerometer for the entire halfday program (including classroom learning experiences, snack and recess time) 2 times per week, for 10 weeks (20 activity monitoring records in total). Activity counts for each 5-sec interval were uploaded to a customized data reduction program to determine total counts, minutes of moderate PA (MPA) (3–5.9 METs), and minutes of vigorous PA (VPA) (> = 6 METs) per session. Counts were categorized as either MPA or VPA using the cutpoints developed by Sirard and colleagues (2001). Results Across the four 2.5 hour programs, the average MPA, VPA and total counts (× 103) were 12.4 ± 3.1 minutes, 18.3 ± 4.6 minutes, and 171.1 ± 29.7 counts, respectively. Thus, on average, children accumulated just over 12 minutes of moderateto-vigorous PA per hour of program attendance. The PA variables did not differ significantly by gender, weight status, or time of day. There were, however, significant age differences, with 3-year-olds exhibiting significantly less PA than their 4- and 5-year-old counterparts. Conclusions These results suggest that young children are relatively lowactive while attending preschool. Accordingly, interventions to increase movement opportunities during the preschool day are warranted.

Healthcare channel consumer insights : supermarkets, pharmacy & general practitioners

Why are consumers different: Heterogeneity in the way consumers categorise products and services – Snack Food Influenced by the individual needs, personal traits, values and goals – Blood Donation Consumers base their choices on information from external sources and prior experiences stored in memory. Intrinsic – prior experience Extrinsic – advertising, blogs, etc

Psychological predictors of opportunistic snacking in the absence of hunger

Increased frequency of eating in the absence of homeostatic need, notably through snacking, is an important contributor to overconsumption and may be facilitated by increased availability of palatable food in the obesogenic environment. Opportunistic initiation of snacking is likely to be subject to individual differences, although these are infrequently studied in laboratory-based research paradigms. This study examined psychological factors associated with opportunistic initiation of snacking, and predictors of intake in the absence of homeostatic need. Fifty adults (mean age 34.5 years, mean BMI 23.9 kg/m2, 56% female) participated in a snack taste test in which they ate a chocolate snack to satiation, after which they were offered an unanticipated opportunity to initiate a second eating episode. Trait and behavioural measures of self control, sensitivity to reward, dietary restraint and disinhibited eating were taken. Results showed that, contrary to expectations, those who initiated snacking were better at inhibitory control compared with those who did not initiate. However, amongst participants who initiated snacking, intake (kcal) was predicted by higher food reward sensitivity, impulsivity and BMI. These findings suggest that snacking initiation in the absence of hunger is an important contributor to overconsumption. Consideration of the individual differences promoting initiation of eating may aid in reducing elevated eating frequency in at-risk individuals.

Probabilistic multi-tensor estimation using the tensor distribution function

Diffusion weighted magnetic resonance (MR) imaging is a powerful tool that can be employed to study white matter microstructure by examining the 3D displacement profile of water molecules in brain tissue. By applying diffusion-sensitized gradients along a minimum of 6 directions, second-order tensors can be computed to model dominant diffusion processes. However, conventional DTI is not sufficient to resolve crossing fiber tracts. Recently, a number of high-angular resolution schemes with greater than 6 gradient directions have been employed to address this issue. In this paper, we introduce the Tensor Distribution Function (TDF), a probability function defined on the space of symmetric positive definite matrices. Here, fiber crossing is modeled as an ensemble of Gaussian diffusion processes with weights specified by the TDF. Once this optimal TDF is determined, the diffusion orientation distribution function (ODF) can easily be computed by analytic integration of the resulting displacement probability function.

Health-related quality of life of individuals with transfemoral amputation fitted with the Transcutaneous Bone Anchoring Prosthesis following the OGAAP

Background The benefits and safety transcutaneous bone anchored prosthesis relying on a screw fixation are well reported.[1-17] However, most of the studies on press-fit implants and joint replacement technology have focused on surgical techniques.[3, 18-23] One European centre using this technique has reported on health related quality of life (HRQOL) for a group of individuals with transfemoral amputation (TFA).[3] Data from other centres are needed to assess the effectiveness of the technique in different settings. Aim This study aimed at reporting HRQOL data at baseline and up to 2-year follow-up for a group of TFAs treated by Osseointegration Group of Australia who followed the Osseointegration Group of Australia Accelerated Protocol (OGAAP), in Sydney between 08/12/2011 and 09/04/2014. Method A total of 16 TFAs (7 females and 9 males, age 51 ± 12 y, height 1.73 ± 0.12 m, weight 83 ±18 kg) participated in this study. The cause of amputation was trauma or congenital limb deficiency for 11 (69%) and 5 (31%) participants, respectively. A total of 12 (75%) participants were prosthetic users while 4(25%) were wheelchair bound prior the surgery. The HRQOL were obtained from Questionnaire for Persons with Transfemoral Amputation (Q-TFA) using the four main scales (i.e., Prosthetic use, Mobility, Problem, Global) one year before and between 6.5 and 24 months after the Stage 1 of the surgeries for the baseline and follow-up, respectively. Results The lapse of time before and after Stage 1 was -6.19±3.54 and 10.83±3.58 months respectively. The raw score and percentage of improvement are presented in Figures 1 and 2, respectively. Discussion & Conclusion The average results demonstrated an improvement in each domain, particularly in the reduction of problems and an increase in global state. Furthermore, 56%, 75%, 94% and 69% of the participants reported an improvement in Prosthetic use, Mobility, Problem, Global scales, respectively. These results were comparable to previous studies relying of screwed fixation confirming that press-fit implantation is a viable alternative for bone-anchored prostheses.[1, 7, 8]