Venous leg ulcer recurrence : deciphering long term patient adherence to preventive treatments and activities

To better understand long term adherence to self-care activities to prevent the recurrence of venous leg ulcers, participants (n=80) were recruited to a prospective longitudinal study after experiencing healing of a venous leg ulcer. Data on demographics, health, psychosocial measures and adherence to prevention strategies (compression therapy, leg elevation and lower leg exercise) were collected every three months for one year after healing. Multivariable regression modelling was used to identify the factors that were independently associated with adherence. Over the year, a significant decline in adherence to all three strategies was observed, predominantly between 6–12 months after healing (p<0.01). Several factors were associated with adherence to more than one preventive activity. Regular follow-up care and a history of multiple previous ulcers were related to improved adherence (p<0.05), while scoring at higher risk for depression and restricted mobility were related to decreasing adherence over time (p<0.05). Patients with osteoarthritis had significantly reduced adherence to compression hosiery (p=0.026). These results provide information to assist care providers plan strategies for prevention of recurrent venous leg ulcers; and suggest a need for regular follow-up care which addresses both the physical and mental health of this population.

Enzyme activities and biotechnological applications of cold-active microfungi

Fungi are eukaryotic organisms and considered to be less adaptable to extreme environments when compared to bacteria. While there are no thermophilic microfungi in a strict sense, some fungi have adapted to life in the cold. Cold-active microfungi have been isolated from the Antarctic and their enzyme activities explored with a view to finding new candidates for industrial use. On another front, environmental pollution by petroleum products in the Antarctic has led to a search for, and the subsequent discovery of, fungal isolates capable of degrading hydrocarbons. The work has paved the way to developing a bioremedial approach to containing this type of contamination in cold climates. Here we discuss our efforts to map the capability of Antarctic microfungi to degrade oil and also introduce a novel cold-active fungal lipase enzyme.

Evaluation of a community-based intervention to promote physical activity in youth : lessons from active winners

Purpose To test the effects of a community-based physical activity intervention designed to increase physical activity and to conduct an extensive process evaluation of the intervention. Design Quasi-experimental. Setting Two rural communities in South Carolina. One community received the intervention, and the other served as the comparison. Subjects Public school students who were in fifth grade at the start of the study (558 at baseline) were eligible to participate. A total of 436 students participated over the course of the study. Intervention The intervention included after-school and summer physical activity programs and home, school, and community components designed to increase physical activity in youth. The intervention took place over an 18-month period. Measures. Students reported after-school physical activity at three data collection points (prior to, during, and following the intervention) using the Previous Day Physical Activity Recall (PDPAR). They also completed a questionnaire designed to measure hypothesized psychosocial and environmental determinants of physical activity behavior The process evaluation used meeting records, documentation of program activities, interviews, focus groups, and heart rate monitoring to evaluate the planning and implementation of the intervention. Results There were no significant differences in the physical activity variables and few significant differences in the psychosocial variables between the intervention and comparison groups. The process evaluation indicated that the after-school and summer physical activity component of the intervention was implemented as planned, but because of resource and time limitations, the home, school, and community components were not implemented as planned. Conclusions The intervention did not have a significant effect on physical activity in the target population of children in the intervention community. This outcome is similar to that reported in other studies of community-based physical activity intervention.

Physical activities and sedentary pursuits in African American and Caucasian girls

The purposes of this study were to describe and compare the specific physical activity choices and sedentary pursuits of African American and Caucasian American girls. Participants were 1,124 African American and 1,068 Caucasian American eighth grade students from 31 middle schools. The 3-Day Physical Activity Recall (3DPAR) was used to measure participation in physical activities and sedentary pursuits. The most frequently reported physical activities were walking, basketball, jogging or running, bicycling, and social dancing. Differences between groups were found in 11 physical activities and 3 sedentary pursuits. Participation rates were higher in African American girls (p<.001)for social dancing, basketball, watching television, and church attendance but lower in calisthenics, ballet and other dance, jogging or running, rollerblading, soccer, softball or baseball, using an exercise machine, swimming, and homework. Cultural differences of groups should be considered when planning interventions to promote physical activity.

Validation of accelerometry for physical activity measurement in ambulant adolescents with cerebral palsy

Background Promoting participation physical activity (PA) is an important means of promoting healthy growth and development in children with cerebral palsy (CP). The ActiGraph is a uniaxial accelerometer that provides a realtime measure of PA intensity, duration and frequency. Its small, light weight design makes it a promising measure of activity in children with CP. To date no study has validated the use of accelerometry as a measure of PA in ambulant adolescents with CP. Objectives To evaluate the validity of the ActiGraph accelerometer for measuring PA intensity in adolescents with CP, using oxygen consumption (VO2), measured using portable indirect calorimetry (Cosmed K4b2), as the criterion measure. Design Validation Study Participants/Setting: Ambulant adolescents with CP aged 10–16 years, GMFCS rating of I-III. The recruitment target is 30 (10 in each GMFCS level). Materials/Methods Participants wore the ActiGraph (counts/min) and a Cosmed K4b2 indirect calorimeter (mL/kg/min) during six activity trials: quiet sitting (QS), comfortable paced walking (CPW), brisk paced walking (BPW), fast paced walking (FPW), a ball-kicking protocol (KP) and a ball-throwing protocol (TP). MET levels (multiples of resting metabolism) for each activity were predicted from ActiGraph counts using the Freedson age-specific equation (Freedson et al. 2005) and compared with actual MET levels measured by the Cosmed. Predicted and measured METs for each activity trial were classified as light (> 1.5 METs and <4.6 METs) or moderate to vigorous intensity (≥ 4.6 METs). Results To date 36 bouts of activity have been completed (6 participants x 6 activities). Mean VO2 increased linearly as the intensity of the walking activity increased (CPW=9.47±2.16, BPW=14.06±4.38, FPW=19.21±5.68 ml/kg/min) and ActiGraph counts reflected this pattern (CPW=1099±574, BPW=2233±797 FPW=4707±1013 counts/min). The throwing protocol recording the lowest VO2 (TP=7.50±3.86 ml/kg/min) and lowest overall counts/min (TP=31±27 counts/min). When each of the 36 bouts were classified as either light or moderate to vigorous intensity using measured VO2 as the criterion measure, the Freedson equation correctly classified 28 from 36 bouts (78%). Conclusion/Clinical Implications These preliminary findings suggest that there is a relationship between the intensity of PA and direct measure of oxygen consumption and that therefore the ActiGraph may be a promising tool for accurately measuring free living PA in the community. Further data collection of the complete sample will enable secondary analysis of the relationship between PA and severity of CP (GMFCS level).

Wheat breeding nurseries, target environments, and indirect selection for grain yield

Use of appropriate nursery environments will maximize gain from selection for yield of wheat (Triticum aestivum L.) in the target population of environments of a breeding program. The objective of this study was to investigate how well-irrigated (low-stress) nursery environments predict yield of lines in target environments that varied in degree of water limitation. Fifteen lines were sampled from the preliminary yield evaluation stage of the Queensland wheat breeding program and tested in 26 trials under on-farm conditions (Target Environments) across nine years (1985 to 1993) and also in 27 trials conducted at three research stations (Nursery Environments) in three years (1987 to 1989). The nursery environments were structured to impose different levels of water and nitrogen (N) limitation, whereas the target environments represented a random sample of on-farm conditions from the target population of environments. Indirect selection and pattern analysis methods were used to investigate selection for yield in the nursery environments and gain from selection in the target environments. Yield under low-stress nursery conditions was an effective predictor of yield under similar low-stress target environments (r = 0.89, P < 0.01). However, the value of the low-stress nursery as a predictor of yield in the water-limited target environments decreased with increasing water stress (moderate stress r = 0.53, P < 0.05, to r = 0.38, P > 0.05; severe stress r = -0.08, P > 0.05). Yield in the stress nurseries was a poor predictor of yield in the target environments. Until there is a clear understanding of the physiological-genetic basis of variation for adaptation of wheat to the water-limited environments in Queensland, yield improvement can best be achieved by selection for a combination of yield potential in an irrigated low-stress nursery and yield in on-farm trials that sample the range of water-limited environments of the target population of environments.

Phosphoprotein pathway mapping: Akt/Mammalian target of rapamycin activation is negatively associated with childhood rhabdomyosarcoma survival

Mapping of protein signaling networks within tumors can identify new targets for therapy and provide a means to stratify patients for individualized therapy. Despite advances in combination chemotherapy, the overall survival for childhood rhabdomyosarcoma remains ∼60%. A critical goal is to identify functionally important protein signaling defects associated with treatment failure for the 40% nonresponder cohort. Here, we show, by phosphoproteomic network analysis of microdissected tumor cells, that interlinked components of the Akt/mammalian target of rapamycin (mTOR) pathway exhibited increased levels of phosphorylation for tumors of patients with short-term survival. Specimens (n = 59) were obtained from the Children's Oncology Group Intergroup Rhabdomyosarcoma Study (IRS) IV, D9502 and D9803, with 12-year follow-up. High phosphorylation levels were associated with poor overall and poor disease-free survival: Akt Ser473 (overall survival P < 0.001, recurrence-free survival P < 0.0009), 4EBP1 Thr37/46 (overall survival P < 0.0110, recurrence-free survival P < 0.0106), eIF4G Ser1108 (overall survival P < 0.0017, recurrence-free survival P < 0.0072), and p70S6 Thr389 (overall survival P < 0.0085, recurrence-free survival P < 0.0296). Moreover, the findings support an altered interrelationship between the insulin receptor substrate (IRS-1) and Akt/mTOR pathway proteins (P < 0.0027) for tumors from patients with poor survival. The functional significance of this pathway was tested using CCI-779 in a mouse xenograft model. CCI-779 suppressed phosphorylation of mTOR downstream proteins and greatly reduced the growth of two different rhabdomyosarcoma (RD embryonal P = 0.00008; Rh30 alveolar P = 0.0002) cell lines compared with controls. These results suggest that phosphoprotein mapping of the Akt/mTOR pathway should be studied further as a means to select patients to receive mTOR/IRS pathway inhibitors before administration of chemotherapy.

Clinical impacts of mammalian target of rapamycin expression in human colorectal cancers

This study investigated the clinicopathologic roles of mammalian target of rapamycin (mTOR) expression and its relationship to carcinogenesis and tumor progression in a colorectal adenoma-adenocarcinoma model. Two colon cancer cell lines with different pathologic stages (SW480 and SW48) and 1 normal colonic epithelial cell line (FHC) were used, in addition to 119 colorectal adenocarcinomas and 32 adenomas. mTOR expression profiles at messenger RNA (mRNA) and protein levels were investigated in the cells and tissues using real-time quantification polymerase chain reaction and immunohistochemistry. The findings were correlated with the clinicopathologic features of the tumors. The colon cell line from stage III cancer (SW48) showed higher expression of mTOR mRNA than that from stage II cancer (SW480). At the tissue level, mTOR showed higher mRNA and protein expression in colorectal carcinoma than in adenoma. The mRNA and protein expression was correlated with each other in approximately one-third of the carcinomas and adenomas. High levels of mTOR mRNA expression were noted more in carcinoma or adenoma arising from the distal portion of the large intestine (P = .025 and .019, respectively). Within the colorectal cancer population, a high level of expression of mTOR mRNA was related to the presence of lymph node metastases (P = .031), advanced pathologic stage (P = .05), and presence of persistent disease or tumor recurrence (P = .035). To conclude, the study has indicated that mTOR is likely to be involved in the development and progression of colorectal cancer and is linked to cancer initiation, invasiveness, and progression.

Predicting movie ratings from audience behaviors

We propose a method of representing audience behavior through facial and body motions from a single video stream, and use these features to predict the rating for feature-length movies. This is a very challenging problem as: i) the movie viewing environment is dark and contains views of people at different scales and viewpoints; ii) the duration of feature-length movies is long (80-120 mins) so tracking people uninterrupted for this length of time is still an unsolved problem, and; iii) expressions and motions of audience members are subtle, short and sparse making labeling of activities unreliable. To circumvent these issues, we use an infrared illuminated test-bed to obtain a visually uniform input. We then utilize motion-history features which capture the subtle movements of a person within a pre-defined volume, and then form a group representation of the audience by a histogram of pair-wise correlations over a small-window of time. Using this group representation, we learn our movie rating classifier from crowd-sourced ratings collected by rottentomatoes.com and show our prediction capability on audiences from 30 movies across 250 subjects (> 50 hrs).

Identification of optimal epitopes for Plasmodium falciparum rapid diagnostic tests that target histidine-rich proteins 2 and 3

Rapid diagnostic tests (RDTs) represent important tools to diagnose malaria infection. To improve understanding of the variable performance of RDTs that detect the major target in Plasmodium falciparum, namely, histidine-rich protein 2 (HRP2), and to inform the design of better tests, we undertook detailed mapping of the epitopes recognized by eight HRP-specific monoclonal antibodies (MAbs). To investigate the geographic skewing of this polymorphic protein, we analyzed the distribution of these epitopes in parasites from geographically diverse areas. To identify an ideal amino acid motif for a MAb to target in HRP2 and in the related protein HRP3, we used a purpose-designed script to perform bioinformatic analysis of 448 distinct gene sequences from pfhrp2 and from 99 sequences from the closely related gene pfhrp3. The frequency and distribution of these motifs were also compared to the MAb epitopes. Heat stability testing of MAbs immobilized on nitrocellulose membranes was also performed. Results of these experiments enabled the identification of MAbs with the most desirable characteristics for inclusion in RDTs, including copy number and coverage of target epitopes, geographic skewing, heat stability, and match with the most abundant amino acid motifs identified. This study therefore informs the selection of MAbs to include in malaria RDTs as well as in the generation of improved MAbs that should improve the performance of HRP-detecting malaria RDTs.

Integrin-linked kinase as a target for ERG-mediated invasive properties in prostate cancer models

Approximately half of prostate cancers (PCa) carry TMPRSS2-ERG translocations; however, the clinical impact of this genomic alteration remains enigmatic. Expression of v-ets erythroblastosis virus E26 oncogene like (avian) gene (ERG) promotes prostatic epithelial dysplasia in transgenic mice and acquisition of epithelial-to-mesenchymal transition (EMT) characteristics in human prostatic epithelial cells (PrECs). To explore whether ERG-induced EMT in PrECs was associated with therapeutically targetable transformation characteristics, we established stable populations of BPH-1, PNT1B and RWPE-1 immortalized human PrEC lines that constitutively express flag-tagged ERG3 (fERG). All fERG-expressing populations exhibited characteristics of in vitro and in vivo transformation. Microarray analysis revealed >2000 commonly dysregulated genes in the fERG-PrEC lines. Functional analysis revealed evidence that fERG cells underwent EMT and acquired invasive characteristics. The fERG-induced EMT transcript signature was exemplified by suppressed expression of E-cadherin and keratins 5, 8, 14 and 18; elevated expression of N-cadherin, N-cadherin 2 and vimentin, and of the EMT transcriptional regulators Snail, Zeb1 and Zeb2, and lymphoid enhancer-binding factor-1 (LEF-1). In BPH-1 and RWPE-1-fERG cells, fERG expression is correlated with increased expression of integrin-linked kinase (ILK) and its downstream effectors Snail and LEF-1. Interfering RNA suppression of ERG decreased expression of ILK, Snail and LEF-1, whereas small interfering RNA suppression of ILK did not alter fERG expression. Interfering RNA suppression of ERG or ILK impaired fERG-PrEC Matrigel invasion. Treating fERG-BPH-1 cells with the small molecule ILK inhibitor, QLT-0267, resulted in dose-dependent suppression of Snail and LEF-1 expression, Matrigel invasion and reversion of anchorage-independent growth. These results suggest that ILK is a therapeutically targetable mediator of ERG-induced EMT and transformation in PCa.

Burglar target selection : a cross-national comparison

Objectives This study builds on research undertaken by Bernasco and Nieuwbeerta and explores the generalizability of a theoretically derived offender target selection model in three cross-national study regions. Methods Taking a discrete spatial choice approach, we estimate the impact of both environment- and offender-level factors on residential burglary placement in the Netherlands, the United Kingdom, and Australia. Combining cleared burglary data from all study regions in a single statistical model, we make statistical comparisons between environments. Results In all three study regions, the likelihood an offender selects an area for burglary is positively influenced by proximity to their home, the proportion of easily accessible targets, and the total number of targets available. Furthermore, in two of the three study regions, juvenile offenders under the legal driving age are significantly more influenced by target proximity than adult offenders. Post hoc tests indicate the magnitudes of these impacts vary significantly between study regions. Conclusions While burglary target selection strategies are consistent with opportunity-based explanations of offending, the impact of environmental context is significant. As such, the approach undertaken in combining observations from multiple study regions may aid criminology scholars in assessing the generalizability of observed findings across multiple environments.