Organotypic culture of normal, dysplastic and squamous cell carcinoma-derived oral cell lines reveals loss of spatial regulation of CD44 and p75(NTR) in malignancy

Oral squamous cell carcinomas (OSCC) often arise from dysplastic lesions. The role of cancer stem cells in tumour initiation is widely accepted, yet the potential existence of pre-cancerous stem cells in dysplastic tissue has received little attention. Cell lines from oral diseases ranging in severity from dysplasia to malignancy provide opportunity to investigate the involvement of stem cells in malignant progression from dysplasia. Stem cells are functionally defined by their ability to generate hierarchical tissue structures in consortium with spatial regulation. Organotypic cultures readily display tissue hierarchy in vitro; hence, in this study, we compared hierarchical expression of stem cell-associated markers in dermis-based organotypic cultures of oral epithelial cells from normal tissue (OKF6-TERT2), mild dysplasia (DOK), severe dysplasia (POE-9n) and OSCC (PE/CA P J15). Expression of CD44, p75NTR, CD24 and ALDH was studied in monolayers by flow cytometry and in organotypic cultures by immunohistochemistry. Spatial regulation of CD44 and p75NTR was evident for organotypic cultures of normal (OKF6-TERT2) and dysplasia (DOK and POE-9n) but was lacking for OSCC (PE/CA PJ15)-derived cells. Spatial regulation of CD24 was not evident. All monolayer cultures exhibited CD44, p75NTR, CD24 antigens and ALDH activity (ALDEFLUOR® assay), with a trend towards loss of population heterogeneity that mirrored disease severity. In monolayer, increased FOXA1 and decreased FOXA2 expression correlated with disease severity, but OCT3/4, Sox2 and NANOG did not. We conclude that dermis-based organotypic cultures give opportunity to investigate the mechanisms that underlie loss of spatial regulation of stem cell markers seen with OSCC-derived cells.

Optimal distribution network reinforcement considering load growth, line loss, and reliability

In this paper, a new comprehensive planning methodology is proposed for implementing distribution network reinforcement. The load growth, voltage profile, distribution line loss, and reliability are considered in this procedure. A time-segmentation technique is employed to reduce the computational load. Options considered range from supporting the load growth using the traditional approach of upgrading the conventional equipment in the distribution network, through to the use of dispatchable distributed generators (DDG). The objective function is composed of the construction cost, loss cost and reliability cost. As constraints, the bus voltages and the feeder currents should be maintained within the standard level. The DDG output power should not be less than a ratio of its rated power because of efficiency. A hybrid optimization method, called modified discrete particle swarm optimization, is employed to solve this nonlinear and discrete optimization problem. A comparison is performed between the optimized solution based on planning of capacitors along with tap-changing transformer and line upgrading and when DDGs are included in the optimization.

Thin-film analyses of silicate standards at 200 kv : the effect of temperature on element loss

Preliminary data is presented on a detailed statistical analysis of k-factor determination for a single class of minerals (amphiboles) which contain a wide range of element concentrations. These amphiboles are homogeneous, contain few (if any) subsolidus microstructures and can be readily prepared for thin film analysis. In previous studies, element loss during the period of irradiation has been assumed negligible for the determination of k-factors. Since this phenomena may be significant for certain mineral systems, we also report on the effect of temperature on k-factor determination for various elements using small probe sizes (approx.20 nm).

Pregnancy loss and psychiatric disorders in young women : an Australian birth cohort study

Background Recent evidence has linked induced abortion with later adverse psychiatric outcomes in young women. Aims To examine whether abortion or miscarriage are associated with subsequent psychiatric and substance use disorders. Method A sample (n=1223) of women from a cohort born between 1981 and 1984 in Australia were assessed at 21 years for psychiatric and substance use disorders and lifetime pregnancy histories. Results Young women reporting a pregnancy loss had nearly three times the odds of experiencing a lifetime illicit drug disorder (excluding cannabis): abortion odds ratio (OR)=3.6 (95% CI 2.0–6.7) and miscarriage OR=2.6 (95% CI 1.2–5.4). Abortion was associated with alcohol use disorder (OR=2.1, 95% CI 1.3–3.5) and 12-month depression (OR=1.9, 95% CI 1.1–3.1). Conclusions These findings add to the growing body of evidence suggesting that pregnancy loss per se, whether abortion or miscarriage, increases the risk of a range of substance use disorders and affective disorders in young women.

Pregnancy loss and mental health

Between 8 and 20 percent of depression in young men and women aged 18-23 is associated with pregnancy loss, according to a recent analysis of the 30 year Mater Hospital longitudinal study of mothers and children. Dr Kaeleen Dingle from the University of Queensland explains the study and discusses the implications for both men and women.

FP01-5 Pregnancy loss and psychiatric disorders in young men and women : results from Australian longitudinal cohort study

Recent evidence has linked induced abortion with later adverse psychiatric outcomes in young women. Little is known about later adverse psychiatric outcomes in young men whose partners have fallen pregnant and either go on to have a child, have an abortion or miscarry. 1223 women and 1159 men, from an Austrailan cohort born between 1981 and 1984, were assessed at 21 years for psychiatric and substance misuse and lifetime pregnancy histories. Young women reporting a pregnancy loss (either miscarriage or abortion) had nearly three times the odds of experiencing a illicit drug disorder (excluding cannabis), and nearly twice the odds of an alcohol misuse compared to never pregnant women. Young men whose partner had an abortion, but not a miscarriage, had nearly twice the odds of cannabis disorder, illicit drug disorder, and mood disorder compared to men that had never fathered a pregnancy. Young women who have lost a pregnancy have an increased risk of developing alcohol or substance abuse in later life. Young men whose partner aborted a pregnancy only had an increased of substance abuse and mood disorder in later life. These findings add to the growing body of evidence suggesting that pregnancy loss per se increases the risk of a range of substance use disorders in young women. The findings for young men are novel and raise the possibility that the associations measured may be due to common unmeasured factors associated with early pregnancy in young people rather than pregnancy loss.

High-resolution loss of heterozygosity screening implicates PTPRJ as a potential tumor suppressor gene that affects susceptibility to non-Hodgkin's Lymphoma

We employed a Hidden-Markov-Model (HMM) algorithm in loss of heterozygosity (LOH) analysis of high-density single nucleotide polymorphism (SNP) array data from Non-Hodgkin’s lymphoma (NHL) entities, follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). This revealed a high frequency of LOH over the chromosomal region 11p11.2, containing the gene encoding the protein tyrosine phosphatase receptor type J (PTPRJ). Although PTPRJ regulates components of key survival pathways in B-cells (i.e., BCR, MAPK, and PI3K signaling), its role in B-cell development is poorly understood. LOH of PTPRJ has been described in several types of cancer but not in any hematological malignancy. Interestingly, FL cases with LOH exhibited down-regulation of PTPRJ, in contrast no significant variation of expression was shown in DLBCLs. In addition, sequence screening in Exons 5 and 13 of PTPRJ identified the G973A (rs2270993), T1054C (rs2270992), A1182C (rs1566734), and G2971C (rs4752904) coding SNPs (cSNPs). The A1182 allele was significantly more frequent in FLs and in NHLs with LOH. Significant over-representation of the C1054 (rs2270992) and the C2971 (rs4752904) alleles were also observed in LOH cases. A haplotype analysis also revealed a significant lower frequency of haplotype GTCG in NHL cases, but it was only detected in cases with retention. Conversely, haplotype GCAC was over-representated in cases with LOH. Altogether, these results indicate that the inactivation of PTPRJ may be a common lymphomagenic mechanism in these NHL subtypes and that haplotypes in PTPRJ gene may play a role in susceptibility to NHL, by affecting activation of PTPRJ in these B-cell lymphomas.

A new method to detect loss of heterozygosity using cohort heterozygosity comparisons

Background Loss of heterozygosity (LOH) is an important marker for one of the 'two-hits' required for tumor suppressor gene inactivation. Traditional methods for mapping LOH regions require the comparison of both tumor and patient-matched normal DNA samples. However, for many archival samples, patient-matched normal DNA is not available leading to the under-utilization of this important resource in LOH studies. Here we describe a new method for LOH analysis that relies on the genome-wide comparison of heterozygosity of single nucleotide polymorphisms (SNPs) between cohorts of cases and un-matched healthy control samples. Regions of LOH are defined by consistent decreases in heterozygosity across a genetic region in the case cohort compared to the control cohort. Methods DNA was collected from 20 Follicular Lymphoma (FL) tumor samples, 20 Diffuse Large B-cell Lymphoma (DLBCL) tumor samples, neoplastic B-cells of 10 B-cell Chronic Lymphocytic Leukemia (B-CLL) patients and Buccal cell samples matched to 4 of these B-CLL patients. The cohort heterozygosity comparison method was developed and validated using LOH derived in a small cohort of B-CLL by traditional comparisons of tumor and normal DNA samples, and compared to the only alternative method for LOH analysis without patient matched controls. LOH candidate regions were then generated for enlarged cohorts of B-CLL, FL and DLBCL samples using our cohort heterozygosity comparison method in order to evaluate potential LOH candidate regions in these non-Hodgkin's lymphoma tumor subtypes. Results Using a small cohort of B-CLL samples with patient-matched normal DNA we have validated the utility of this method and shown that it displays more accuracy and sensitivity in detecting LOH candidate regions compared to the only alternative method, the Hidden Markov Model (HMM) method. Subsequently, using B-CLL, FL and DLBCL tumor samples we have utilised cohort heterozygosity comparisons to localise LOH candidate regions in these subtypes of non-Hodgkin's lymphoma. Detected LOH regions included both previously described regions of LOH as well as novel genomic candidate regions. Conclusions We have proven the efficacy of the use of cohort heterozygosity comparisons for genome-wide mapping of LOH and shown it to be in many ways superior to the HMM method. Additionally, the use of this method to analyse SNP microarray data from 3 common forms of non-Hodgkin's lymphoma yielded interesting tumor suppressor gene candidates, including the ETV3 gene that was highlighted in both B-CLL and FL.

A systematic review of baseline psychosocial characterisation in dietary randomised controlled trials for weight loss

BACKGROUND/OBJECTIVE: To investigate the extent of baseline psychosocial characterisation of subjects in published dietary randomised controlled trials (RCTs) for weight loss. SUBJECTS/METHODS: Systematic review of adequately sized (nX10) RCTs comprising X1 diet-alone arm for weight loss were included for this systematic review. More specifically, trials included overweight (body mass index 425 kg/m2) adults, were of duration X8 weeks and had body weight as the primary outcome. Exclusion criteria included specific psychological intervention (for example, Cognitive Behaviour Therapy (CBT)), use of web-based tools, use of supplements, liquid diets, replacement meals and very-low calorie diets. Physical activity intervention was restricted to general exercise only (not supervised or prescribed, for example, VO2 maximum level). RESULTS: Of 176 weight-loss RCTs published during 2008–2010, 15 met selection criteria and were assessed for reported psychological characterisation of subjects. All studies reported standard characterisation of clinical and biochemical characteristics of subjects. Eleven studies reported no psychological attributes of subjects (three of these did exclude those taking psychoactive medication). Three studies collected data on particular aspects of psychology related to specific research objectives (figure scale rating, satiety and quality-of-life). Only one study provided a comprehensive background on psychological attributes of subjects. CONCLUSION: Better characterisation in behaviour-change interventions will reduce potential confounding and enhance generalisability of such studies.

A method of extracting switching loss from a high efficiency MOSFET based half bridge converter

The measurement of losses in high efficiency / high power converters is difficult. Measuring the losses directly from the difference between the input and output power results in large errors. Calorimetric methods are usually used to bypass this issue but introduce different problems, such as, long measurement times, limited power loss measurement range and/or large set up cost. In this paper the total losses of a converter are measured directly and switching losses are exacted. The measurements can be taken with only three multimeters and a current probe and a standard bench power supply. After acquiring two or three power loss versus output current sweeps, a series of curve fitting processes are applied and the switching losses extracted.

Depression scores predict adherence in a dietary weight loss intervention trial

Background & aims Depression has a complex association with cardiometabolic risk, both directly as an independent factor and indirectly through mediating effects on other risk factors such as BMI, diet, physical activity, and smoking. Since changes to many cardiometabolic risk factors involve behaviour change, the rise in depression prevalence as a major global health issue may present further challenges to long-term behaviour change to reduce such risk. This study investigated associations between depression scores and participation in a community-based weight management intervention trial. Methods A group of 64 overweight (BMI > 27), otherwise healthy adults, were recruited and randomised to follow either their usual diet, or an isocaloric diet in which saturated fat was replaced with monounsaturated fat (MUFA), to a target of 50% total fat, by adding macadamia nuts to the diet. Subjects were assessed for depressive symptoms at baseline and at ten weeks using the Beck Depression Inventory (BDI-II). Both control and intervention groups received advice on National Guidelines for Physical Activity and adhered to the same protocol for food diary completion and trial consultations. Anthropometric and clinical measurements (cholesterol, inflammatory mediators) also were taken at baseline and 10 weeks. Results During the recruitment phase, pre-existing diagnosed major depression was one of a range of reasons for initial exclusion of volunteers from the trial. Amongst enrolled participants, there was a significant correlation (R = −0.38, p < 0.05) between BDI-II scores at baseline and duration of participation in the trial. Subjects with a baseline BDI ≥10 (moderate to severe depression symptoms) were more likely to dropout of the trial before week 10 (p < 0.001). BDI-II scores in the intervention (MUFA) diet group decreased, but increased in the control group over the 10-week period. Univariate analysis of variance confirmed these observations (adjusted R2 = 0.257, p = 0.01). Body weight remained static over the 10-week period in the intervention group, corresponding to a relative increase in the control group (adjusted R2 = 0.097, p = 0.064). Conclusions Depression symptoms have the potential to affect enrolment in and adherence to dietbased risk reduction interventions, and may consequently influence the generalisability of such trials. Depression scores may therefore be useful for characterising, screening and allocating subjects to appropriate treatment pathways.

Court finds solicitor in breach of fiduciary duty owed to client but loss not caused by the breach

A solicitor owes fiduciary obligations to his or her client including the obligations of loyalty and disclosure. The Court of Appeal in Mantonella Pty Ltd v Thompson (2009) 255 ALR 367; [2009] QCA 80; BC200902311 recently considered when the fiduciary duty owed by a solicitor to a client is breached and the consequent liability of the solicitor...

Characteristics of on-road driving performance of persons with central vision loss who use bioptic telescopes

Purpose. To compare the on-road driving performance of visually impaired drivers using bioptic telescopes with age-matched controls. Methods. Participants included 23 persons (mean age = 33 ± 12 years) with visual acuity of 20/63 to 20/200 who were legally licensed to drive through a state bioptic driving program, and 23 visually normal age-matched controls (mean age = 33 ± 12 years). On-road driving was assessed in an instrumented dual-brake vehicle along 14.6 miles of city, suburban, and controlled-access highways. Two backseat evaluators independently rated driving performance using a standardized scoring system. Vehicle control was assessed through vehicle instrumentation and video recordings used to evaluate head movements, lane-keeping, pedestrian detection, and frequency of bioptic telescope use. Results. Ninety-six percent (22/23) of bioptic drivers and 100% (23/23) of controls were rated as safe to drive by the evaluators. There were no group differences for pedestrian detection, or ratings for scanning, speed, gap judgments, braking, indicator use, or obeying signs/signals. Bioptic drivers received worse ratings than controls for lane position and steering steadiness and had lower rates of correct sign and traffic signal recognition. Bioptic drivers made significantly more right head movements, drove more often over the right-hand lane marking, and exhibited more sudden braking than controls. Conclusions. Drivers with central vision loss who are licensed to drive through a bioptic driving program can display proficient on-road driving skills. This raises questions regarding the validity of denying such drivers a license without the opportunity to train with a bioptic telescope and undergo on-road evaluation.

An instrument to measure adherence to weight loss programs : the Compliance Praxis Survey-Diet (COMPASS-Diet)

Adherence to behavioral weight loss strategies is important for weight loss success. We aimed to examine the reliability and validity of a newly developed compliance praxis-diet (COMPASS-diet) survey with participants in a 10-week dietary intervention program. During the third of five sessions, participants of the “slim-without-diet” weight loss program (n = 253) completed the COMPASS-diet survey and provided data on demographic and clinical characteristics, and general self-efficacy. Group facilitators completed the COMPASS-diet-other scale estimating participants’ likely adherence from their perspective. We calculated internal consistency, convergent validity, and predictive value for objectively measured weight loss. Mean COMPASS-diet-self score was 82.4 (SD 14.2) and COMPASS-diet-other score 80.9 (SD 13.6) (possible range 12–108), with lowest scores in the normative behavior subscale. Cronbach alpha scores of the COMPASS-diet-self and -other scale were good (0.82 and 0.78, respectively). COMPASS-diet-self scores (r = 0.31) correlated more highly with general self-efficacy compared to COMPASS-diet-other scores (r = 0.04) providing evidence for validity. In multivariable analysis adjusted for age and gender, both the COMPASS-diet-self (F = 10.8, p < 0.001, r2 = 0.23) and other (F = 5.5, p < 0.001, r2 = 0.19) scales were significantly associated with weight loss achieved at program conclusion. COMPASS-diet surveys will allow group facilitators or trainers to identify patients who need additional support for optimal weight loss.