Gene expression analysis of diagnostic biopsies predicts pathological response to neoadjuvant chemoradiotherapy of esophageal cancer

OBJECTIVE: This study explored gene expression differences in predicting response to chemoradiotherapy in esophageal cancer. PURPOSE:: A major pathological response to neoadjuvant chemoradiation is observed in about 40% of esophageal cancer patients and is associated with favorable outcomes. However, patients with tumors of similar histology, differentiation, and stage can have vastly different responses to the same neoadjuvant therapy. This dichotomy may be due to differences in the molecular genetic environment of the tumor cells. BACKGROUND DATA: Diagnostic biopsies were obtained from a training cohort of esophageal cancer patients (13), and extracted RNA was hybridized to genome expression microarrays. The resulting gene expression data was verified by qRT-PCR. In a larger, independent validation cohort (27), we examined differential gene expression by qRT-PCR. The ability of differentially-regulated genes to predict response to therapy was assessed in a multivariate leave-one-out cross-validation model. RESULTS: Although 411 genes were differentially expressed between normal and tumor tissue, only 103 genes were altered between responder and non-responder tumor; and 67 genes differentially expressed >2-fold. These included genes previously reported in esophageal cancer and a number of novel genes. In the validation cohort, 8 of 12 selected genes were significantly different between the response groups. In the predictive model, 5 of 8 genes could predict response to therapy with 95% accuracy in a subset (74%) of patients. CONCLUSIONS: This study has identified a gene microarray pattern and a set of genes associated with response to neoadjuvant chemoradiation in esophageal cancer. The potential of these genes as biomarkers of response to treatment warrants further investigation. Copyright © 2009 by Lippincott Williams & Wilkins.

Follicular variant of papillary thyroid carcinoma : a diagnostic challenge for clinicians and pathologists

The follicular variant of papillary thyroid carcinoma (FVPTC) presents a type of papillary thyroid cancer that has created continuous diagnosis and treatment controversies among clinicians and pathologists. In this review, we describe the nomenclature, the clinical features, diagnostic problems and the molecular biology of FVPTC. It is important for clinicians to understand this entity as the diagnosis and management of this group of patient may be different from other patients with conventional PTC. The literature suggests that FVPTC behaves in a way similar, clinically, to conventional papillary thyroid carcinoma. However, there are some genotypic differences which may characterise this neoplasm. These parameters may account for the phenotypic variation described by some scientists in this type of cancer. Further understanding can only be achieved by defining strict pathological criteria, in-depth study of the molecular biology and long term follow-up of the optional patients with FVPTC.

Behçet's syndrome involving the gastrointestinal tract: a diagnostic dilemma in childhood

Behçet's syndrome is very rare in children, especially those under 10 years of age. Clinical and radiological features are described in 4 children, including 2 under the age of 5 years, with the syndrome. As in other pediatric cases reported, the incomplete form of Behçet's syndrome was present in each case. All 4 patients had oral and genital mucosal effects, arthritis and gastrointestinal and dermatological manifestations. Ophthalmological symptoms occurred in only 1 patient. Radiologically, the 4 cases demonstrated the spectrum of gastrointestinal involvement, from minimal irregularity and thickening of the terminal ileum to gross irregularity and deformity of the terminal ileum and cecum. Because of the difficulty in differentiating Behçet's syndrome from other forms of inflammatory bowel disease it is suggested that in children with gastrointestinal involvement, 3 major criteria be present before the diagnosis of Behçet's syndrome is made.

A three species model to simulate application of hyperbaric oxygen therapy to chronic wounds

Chronic wounds are a significant socioeconomic problem for governments worldwide. Approximately 15% of people who suffer from diabetes will experience a lower-limb ulcer at some stage of their lives, and 24% of these wounds will ultimately result in amputation of the lower limb. Hyperbaric Oxygen Therapy (HBOT) has been shown to aid the healing of chronic wounds; however, the causal reasons for the improved healing remain unclear and hence current HBOT protocols remain empirical. Here we develop a three-species mathematical model of wound healing that is used to simulate the application of hyperbaric oxygen therapy in the treatment of wounds. Based on our modelling, we predict that intermittent HBOT will assist chronic wound healing while normobaric oxygen is ineffective in treating such wounds. Furthermore, treatment should continue until healing is complete, and HBOT will not stimulate healing under all circumstances, leading us to conclude that finding the right protocol for an individual patient is crucial if HBOT is to be effective. We provide constraints that depend on the model parameters for the range of HBOT protocols that will stimulate healing. More specifically, we predict that patients with a poor arterial supply of oxygen, high consumption of oxygen by the wound tissue, chronically hypoxic wounds, and/or a dysfunctional endothelial cell response to oxygen are at risk of nonresponsiveness to HBOT. The work of this paper can, in some way, highlight which patients are most likely to respond well to HBOT (for example, those with a good arterial supply), and thus has the potential to assist in improving both the success rate and hence the costeffectiveness of this therapy.

Development of diagnostic and prognostic algorithms for SF6 puffer circuit breakers from transient waveforms : a validation proposal

- This paper presents a validation proposal for development of diagnostic and prognostic algorithms for SF6 puffer circuit-breakers reproduced from actual site waveforms. The re-ignition/restriking rates are duplicated in given circuits and the cumulative energy dissipated in interrupters by the restriking currents. The targeted objective is to provide a simulated database for diagnosis of re-ignition/restrikes relating to the phase to earth voltage and the number of re-ignition/restrikes as well as estimating the remaining life of SF6 circuit-breakers. The model-based diagnosis of a tool will be useful in monitoring re-ignition/restrikes as well as predicting a nozzle’s lifetime. This will help ATP users with practical study cases and component data compilation for shunt reactor switching and capacitor switching. This method can be easily applied with different data for the different dielectric curves of circuit breakers and networks. This paper presents modelling details and some of the available cases, required project support, the validation proposal, the specific plan for implementation and the propsed main contributions.

Final report : a software diagnostic tool for evaluating distress mechanisms in bridges exposed to aggressive environments

Durability issues of reinforced concrete construction cost millions of dollars in repair or demolition. Identification of the causes of degradation and a prediction of service life based on experience, judgement and local knowledge has limitations in addressing all the associated issues. The objective of this CRC CI research project is to develop a tool that will assist in the interpretation of the symptoms of degradation of concrete structures, estimate residual capacity and recommend cost effective solutions. This report is a documentation of the research undertaken in connection with this project. The primary focus of this research is centred on the case studies provided by Queensland Department of Main Roads (QDMR) and Brisbane City Council (BCC). These organisations are endowed with the responsibility of managing a huge volume of bridge infrastructure in the state of Queensland, Australia. The main issue to be addressed in managing these structures is the deterioration of bridge stock leading to a reduction in service life. Other issues such as political backlash, public inconvenience, approach land acquisitions are crucial but are not within the scope of this project. It is to be noted that deterioration is accentuated by aggressive environments such as salt water, acidic or sodic soils. Carse, 2005, has noted that the road authorities need to invest their first dollars in understanding their local concretes and optimising the durability performance of structures and then look at potential remedial strategies.

A review of non-traditional occupational therapy practice placement education : a focus on role-emerging and project placements

Practice placement education has been recognised as an integral and critical component of the training of occupational therapy students. Although there is an extensive body of literature on clinical education and traditional practice placement education models, there has been limited research on alternative placements.-------- This paper reviews the literature on various practice placement education models and presents a contemporary view on how it is currently delivered. The literature is examined with a particular focus on the increasing range of practice placement education opportunities, such as project and role-emerging placements. The drivers for non-traditional practice placement education include shortages of traditional placement options, health reform and changing work practices, potential for role development and influence on practice choice. The benefits and challenges of non-traditional practice placement education are discussed, including supervision issues, student evaluation, professional and personal development and the opportunity to practise clinical skills.--------- Further research is recommended to investigate occupational therapy graduates' perceptions of role-emerging and project placements in order to identify the benefits or otherwise of these placements and to contribute to the limited body of knowledge of emerging education opportunities.

Prevalence and correlates of low back pain among occupational therapy students in Northern Queensland

Background: Although low back pain (LBP) is an important issue for the health profession, few studies have examined LBP among occupational therapy students. Purpose. To investigate the prevalence and distribution of LBP, its adverse sequelae; and to identify potential risk factors.----------- Methods: In 2005, a self-reported questionnaire was administered to occupational therapy students in Northern Queensland.----------- Findings: The 12-month period-prevalence of LBP was 64.6%. Nearly half (46.9%) had experienced pain for over 2 days, 38.8% suffered LBP that affected their daily lives, and 24.5% had sought medical treatment. The prevalence of LBP ranged from 45.5 to 77.1% (p=0.004), while the prevalence of LBP symptoms persisting longer than two days was 34.1 to 62.5% (p=0.020). Logistic regression analysis indicated that year of study and weekly computer usage were statistically-significant LBP risk factors.----------- Implications: The occupational therapy profession will need to further investigate the high prevalence of student LBP identified in this study.

Upper body musculoskeletal disorders among Australian occupational therapy students

Although upper body musculoskeletal disorders (MSDs) represent an increasingly important issue for university students, few if any studies have targeted the occupational therapy faculty. Given this dearth of information, it was considered necessary to investigate a cross-section of Australian occupational therapy students by means of an established questionnaire survey. Completed replies were obtained from 95.7%, 100% and 97.7% (n = 44, 55 and 48) of students in the first, second and fourth years of a large occupational therapy school in northern Queensland, Australia.---------- The 12-month period prevalence of MSDs was as follows: neck (67.4%), shoulder (46.3%) and upper back (39.5%). Three-quarters of all students (75.5%) reported an MSD occurring in at least one of these body regions. Over half (56.5%) reported an MSD over 2 days' duration in the past year. Almost 40% (39.5%) reported an MSD that had affected their daily life, while one-quarter (25.2%) needed some type of treatment.---------- Logistic regression indicated that students aged over 21 years were almost four times more likely to report shoulder-related MSD (OR 3.7, 95%CI: 1.4-10.2). Year of study in the occupational therapy course was another important MSD correlate, with adjusted odds ratios ranging from 3.3 at the upper back (OR 3.3, 95%CI: 1.2-9.6) to 10.9 at the neck (OR 10.9, 95%CI: 3.2-43.8). Computer usage also incurred a certain degree of risk, with students who spent over 5 hours per week on the computer having an increased risk of MSD at the neck (OR 5.0, 95%CI: 1.3-21.5) and shoulder (OR 4.7, 95%CI: 1.4-18.3).---------- Overall, this study suggests that Australian occupational therapy students have a large burden from MSDs in the upper body region, even more so than other student groups and some working populations. Since the distribution of MSD risk is not uniform among them, interventions to help reduce these conditions need to be carefully targeted. Further longitudinal investigations would also be useful in determining the mechanisms and contributory factors for MSDs among this unique student population.