Infrared and Raman spectroscopic characterization of the borate mineral hydroboracite CaMg[B3O4(OH)3]2⋅3H2O : implications for the molecular structure

We have studied the mineral hydroboracite CaMg[B3O4(OH)3]2∙3H2O using electron microscopy and vibrational spectroscopy. Both tetrahedral and trigonal boron units are observed. The nominal resolution of the Raman spectrometer is of the order of 2 cm-1 and as such is sufficient enough to identify separate bands for the stretching bands of the two boron isotopes. The Raman band at 1039 cm-1 is assigned to BO stretching vibration. Raman bands at 1144, 1157, 1229, 1318 cm-1 are attributed to the BOH in-plane bending modes. Raman bands at 825 and 925 cm-1 are attributed to the antisymmetric stretching modes of tetrahedral boron. The sharp Raman peak at 925 cm-1 is from the 11-B component such a mode, then it should have a smaller 10-B satellite near (1.03)x(925) = 952 cm-1, and indeed a small peak at 955 is observed. Four sharp Raman bands observed at 3371, 3507, 3563 and 3632 cm-1 are attributed to the stretching vibrations of hydroxyl units. The broad Raman bands at 3076, 3138, 3255, 3384 and 3551 cm-1 are assigned to water stretching vibrations. Infrared bands at 3367, 3505, 3559 and 3631 cm-1are assigned to the stretching vibration of the hydroxyl units. Broad infrared bands at 3072 and 3254 cm-1 are assigned to water stretching vibrations. Infrared bands at 1318, 1349, 1371, 1383 cm-1 are assigned to the antisymmetric stretching vibrations of trigonal boron

Molecular biomarkers in non-small-cell lung cancer : a retrospective analysis of data from the phase 3 FLEX study

Background: Findings from the phase 3 FLEX study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival, compared with cisplatin and vinorelbine alone, in the first-line treatment of EGFR-expressing, advanced non-small-cell lung cancer (NSCLC). We investigated whether candidate biomarkers were predictive for the efficacy of chemotherapy plus cetuximab in this setting. Methods: Genomic DNA extracted from formalin-fixed paraffin-embedded (FFPE) tumour tissue of patients enrolled in the FLEX study was screened for KRAS codon 12 and 13 and EGFR kinase domain mutations with PCR-based assays. In FFPE tissue sections, EGFR copy number was assessed by dual-colour fluorescence in-situ hybridisation and PTEN expression by immunohistochemistry. Treatment outcome was investigated according to biomarker status in all available samples from patients in the intention-to-treat population. The primary endpoint in the FLEX study was overall survival. The FLEX study, which is ongoing but not recruiting participants, is registered with ClinicalTrials.gov, number NCT00148798. Findings: KRAS mutations were detected in 75 of 395 (19%) tumours and activating EGFR mutations in 64 of 436 (15%). EGFR copy number was scored as increased in 102 of 279 (37%) tumours and PTEN expression as negative in 107 of 303 (35%). Comparisons of treatment outcome between the two groups (chemotherapy plus cetuximab vs chemotherapy alone) according to biomarker status provided no indication that these biomarkers were of predictive value. Activating EGFR mutations were identified as indicators of good prognosis, with patients in both treatment groups whose tumours carried such mutations having improved survival compared with those whose tumours did not (chemotherapy plus cetuximab: median 17·5 months [95% CI 11·7-23·4] vs 8·5 months [7·1-10·8], hazard ratio [HR] 0·52 [0·32-0·84], p=0·0063; chemotherapy alone: 23·8 months [15·2-not reached] vs 10·0 months [8·7-11·0], HR 0·35 [0·21-0·59], p<0·0001). Expression of PTEN seemed to be a potential indicator of good prognosis, with patients whose tumours expressed PTEN having improved survival compared with those whose tumours did not, although this finding was not significant (chemotherapy plus cetuximab: median 11·4 months [8·6-13·6] vs 6·8 months [5·9-12·7], HR 0·80 [0·55-1·16], p=0·24; chemotherapy alone: 11·0 months [9·2-12·6] vs 9·3 months [7·6-11·9], HR 0·77 [0·54-1·10], p=0·16). Interpretation: The efficacy of chemotherapy plus cetuximab in the first-line treatment of advanced NSCLC seems to be independent of each of the biomarkers assessed. Funding: Merck KGaA. © 2011 Elsevier Ltd.

EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer : analysis of data from the phase 3 FLEX study

Background: Findings from the phase 3 First-Line ErbituX in lung cancer (FLEX) study showed that the addition of cetuximab to first-line chemotherapy significantly improved overall survival compared with chemotherapy alone (hazard ratio [HR] 0·871, 95% CI 0·762-0·996; p=0·044) in patients with advanced non-small-cell lung cancer (NSCLC). To define patients benefiting most from cetuximab, we studied the association of tumour EGFR expression level with clinical outcome in FLEX study patients. Methods: We used prospectively collected tumour EGFR expression data to generate an immunohistochemistry score for FLEX study patients on a continuous scale of 0-300. We used response data to select an outcome-based discriminatory threshold immunohistochemistry score for EGFR expression of 200. Treatment outcome was analysed in patients with low (immunohistochemistry score <200) and high (≥200) tumour EGFR expression. The primary endpoint in the FLEX study was overall survival. We analysed patients from the FLEX intention-to-treat (ITT) population. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798. Findings: Tumour EGFR immunohistochemistry data were available for 1121 of 1125 (99·6%) patients from the FLEX study ITT population. High EGFR expression was scored for 345 (31%) evaluable patients and low for 776 (69%) patients. For patients in the high EGFR expression group, overall survival was longer in the chemotherapy plus cetuximab group than in the chemotherapy alone group (median 12·0 months [95% CI 10·2-15·2] vs 9·6 months [7·6-10·6]; HR 0·73, 0·58-0·93; p=0·011), with no meaningful increase in side-effects. We recorded no corresponding survival benefit for patients in the low EGFR expression group (median 9·8 months [8·9-12·2] vs 10·3 months [9·2-11·5]; HR 0·99, 0·84-1·16; p=0·88). A treatment interaction test assessing the difference in the HRs for overall survival between the EGFR expression groups suggested a predictive value for EGFR expression (p=0·044). Interpretation: High EGFR expression is a tumour biomarker that can predict survival benefit from the addition of cetuximab to first-line chemotherapy in patients with advanced NSCLC. Assessment of EGFR expression could offer a personalised treatment approach in this setting. Funding: Merck KGaA. © 2012 Elsevier Ltd.

Emergency Health Services (EHS) : demand and service delivery models. monograph 3 : patients’ reasons and perceptions

Executive Summary Emergency health is a critical component of Australia’s health system and emergency departments (EDs) are increasingly congested from growing demand and blocked access to inpatient beds. The Emergency Health Services Queensland (EHSQ) study aims to identify the factors driving increased demand for emergency health and to evaluate strategies which may safely reduce the future demand growth. This monograph addresses the perspectives of users of both ambulance services and EDs. The research reported here aimed to identify the perspectives of users of emergency health services, both ambulance services and public hospital Emergency Departments and to identify the factors that they took into consideration when exercising their choice of location for acute health care. A cross-sectional survey design was used involving a survey of patients or their carers presenting to the EDs of a stratified sample of eight hospitals. A specific purpose questionnaire was developed based on a novel theoretical model which had been derived from analysis of the literature (Monograph 1). Two survey versions were developed: one for adult patients (self-complete); and one for children (to be completed by parents/guardians). The questionnaires measured perceptions of social support, health status, illness severity, self-efficacy; beliefs and attitudes towards ED and ambulance services; reasons for using these services, and actions taken prior to the service request. The survey was conducted at a stratified sample of eight hospitals representing major cities (four), inner regional (two) and outer regional and remote (two). Due to practical limitations, data were collected for ambulance and ED users within hospital EDs, while patients were waiting for or under treatment. A sample size quota was determined for each ED based on their 2009/10 presentation volumes. The data collection was conducted by four members of the research team and a group of eight interviewers between March and May 2011 (corresponding to autumn season). Of the total of 1608 patients in all eight emergency departments the interviewers were able to approach 1361 (85%) patients and seek their consent to participate in the study. In total, 911 valid surveys were available for analysis (response rate= 67%). These studies demonstrate that patients elected to attend hospital EDs in a considered fashion after weighing up alternatives and there is no evidence of deliberate or ill-informed misuse. • Patients attending ED have high levels of social support and self-efficacy that speak to the considered and purposeful nature of the exercise of choice. • About one third of patients have new conditions while two thirds have chronic illnesses • More than half the attendees (53.1%) had consulted a healthcare professional prior to making the decision. • The decision to seek urgent care at an ED was mostly constructed around the patient’s perception of the urgency and severity of their illness, reinforced by a strong perception that the hospital ED was the correct location for them (better specialised staff, better care for my condition, other options not as suitable). • 33% of the respondent held private hospital insurance but nevertheless attended a public hospital ED. Similarly patients exercised considered and rational judgements in their choice to seek help from the ambulance service. • The decision to call for ambulance assistance was based on a strong perception about the severity of the illness (too severe to use other means of transport) and that other options were not considered appropriate. • The decision also appeared influenced by a perception that the ambulance provided appropriate access to the ED which was considered most appropriate for their particular condition (too severe to go elsewhere, all facilities in one spot, better specialised and better care). • In 43.8% of cases a health care professional advised use of the ambulance. • Only a small number of people perceived that ambulance should be freely available regardless of severity or appropriateness. These findings confirm a growing understanding that the choice of professional emergency health care services is not made lightly but rather made by reasonable people exercising a judgement which is influenced by public awareness of the risks of acute health and which is most often informed by health professionals. It is also made on the basis of a rational weighing up of alternatives and a deliberate and considered choice to seek assistance from a service which the patient perceived was most appropriate to their needs at that time. These findings add weight to dispensing with public perceptions that ED and ambulance congestion is a result of inappropriate choice by patients. The challenge for health services is to better understand the patient’s needs and to design and validate services that meet those needs. The failure of our health system to do so should not be grounds for blaming the patient, claiming inappropriate patient choices.

A study of the phosphate mineral kapundaite NaCa(Fe3+)4(PO4)4(OH)3⋅5(H2O) using SEM/EDX and vibrational spectroscopic methods

Vibrational spectroscopy enables subtle details of the molecular structure of kapundaite to be determined. Single crystals of a pure phase from a Brazilian pegmatite were used. Kapundaite is the Fe3+ member of the wardite group. The infrared and Raman spectroscopy were applied to compare the structure of kapundaite with wardite. The Raman spectrum of kapundaite in the 800–1400 cm−1 spectral range shows two intense bands at 1089 and 1114 cm−1 assigned to the ν1PO43- symmetric stretching vibrations. The observation of two bands provides evidence for the non-equivalence of the phosphate units in the kapundaite structure. The infrared spectrum of kapundaite in the 500–1300 cm−1 shows much greater complexity than the Raman spectrum. Strong infrared bands are found at 966, 1003 and 1036 cm−1 and are attributed to the ν1PO43- symmetric stretching mode and ν3PO43- antisymmetric stretching mode. Raman bands in the ν4 out of plane bending modes of the PO43- unit support the concept of non-equivalent phosphate units in the kapundaite structure. In the 2600–3800 cm−1 spectral range, Raman bands for kapundaite are found at 2905, 3151, 3311, 3449 and 3530 cm−1. These bands are broad and are assigned to OH stretching vibrations. Broad infrared bands are also found at 2904, 3105, 3307, 3453 and 3523 cm−1 and are attributed to water. Raman spectroscopy complimented with infrared spectroscopy has enabled aspects of the structure of kapundaite to be ascertained and compared with that of other phosphate minerals.

Evaluation of brief dietary questions to estimate vegetable and fruit consumption – using serum carotenoids and red-cell folate

Objective: To evaluate responses to self-administered brief questions regarding consumption of vegetables and fruit by comparison with blood levels of serum carotenoids and red-cell folate. Design: A cross-sectional study in which participants reported their usual intake of fruit and vegetables in servings per day, and serum levels of five carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin and lycopene) and red-cell folate were measured. Serum carotenoid levels were determined by high-performance liquid chromatography, and red-cell folate by an automated immunoassay system. Settings and subjects: Between October and December 2000, a sample of 1598 adults aged 25 years and over, from six randomly selected urban centres in Queensland, Australia, were examined as part of a national study conducted to determine the prevalence of diabetes and associated cardiovascular risk factors. Results: Statistically significant (P<0.01) associations with vegetable and fruit intake (categorised into groups: ≤1 serving, 2–3 servings and ≥4 servings per day) were observed for α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin and red-cell folate. The mean level of these carotenoids and of red-cell folate increased with increasing frequency of reported servings of vegetables and fruit, both before and after adjusting for potential confounding factors. A significant association with lycopene was observed only for vegetable intake before adjusting for confounders. Conclusions: These data indicate that brief questions may be a simple and valuable tool for monitoring vegetable and fruit intake in this population.

Timing and source constraints on the relationship between mafic and felsic intrusions in the Emeiashan large igneous province

Several I- and A-type granite, syenite plutons and spatially associated, giant Fe–Ti–V deposit-bearing mafic ultramafic layered intrusions occur in the Pan–Xi(Panzhihua–Xichang) area within the inner zone of the Emeishan large igneous province (ELIP). These complexes are interpreted to be related to the Emeishan mantle plume. We present LA-ICP-MS and SIMS zircon U–Pb ages and Hf–Nd isotopic compositions for the gabbros, syenites and granites from these complexes. The dating shows that the age of the felsic intrusive magmatism (256.2 ± 3.0–259.8 ± 1.6 Ma) is indistinguishable from that of the mafic intrusive magmatism (255.4 ± 3.1–259.5 ± 2.7 Ma) and represents the final phase of a continuous magmatic episode that lasted no more than 10 Myr. The upper gabbros in the mafic–ultramafic intrusions are generally more isotopically enriched (lower eNd and eHf) than the middle and lower gabbros, suggesting that the upper gabbros have experienced a higher level of crustal contamination than the lower gabbros. The significantly positive eHf(t) values of the A-type granites and syenites (+4.9 to +10.8) are higher than those of the upper gabbros of the associated mafic intrusion, which shows that they cannot be derived by fractional crystallization of these bodies. They are however identical to those of the mafic enclaves (+7.0 to +11.4) and middle and lower gabbros, implying that they are cogenetic. We suggest that they were generated by fractionation of large-volume, plume-related basaltic magmas that ponded deep in the crust. The deep-seated magma chamber erupted in two stages: the first near a density minimum in the basaltic fractionation trend and the second during the final stage of fractionation when the magma was a low density Fe-poor, Si-rich felsic magma. The basaltic magmas emplaced in the shallowlevel magma chambers differentiated to form mafic–ultramafic layered intrusions accompanied by a small amount of crustal assimilation through roof melting. Evolved A-type granites (synenites and syenodiorites) were produced dominantly by crystallization in the deep crustal magma chamber. In contrast, the I-type granites have negative eNd(t) [-6.3 to -7.5] and eHf(t) [-1.3 to -6.7] values, with the Nd model ages (T Nd DM2) of 1.63-1.67 Ga and Hf model ages (T Hf DM2) of 1.56-1.58 Ga, suggesting that they were mainly derived from partial melting of Mesoproterozoic crust. In combination with previous studies, this study also shows that plume activity not only gave rise to reworking of ancient crust, but also significant growth of juvenile crust in the center of the ELIP.

Small signal stability analysis of power systems with high penetration of wind power

The integration of large amount of wind power into a power system imposes a new challenge for the secure and economic operation of the system. It is necessary to investigate the impacts of wind power generation on the dynamic behavior of the power system concerned. This paper investigates the impacts of large amount of wind power on small signal stability and the corresponding control strategies to mitigate the negative effects. The concepts of different types of wind turbine generators (WTGs) and the principles of the grid-connected structures of wind power generation systems are first briefly introduced. Then, the state-of-the-art of the studies on the impacts of WTGs on small signal stability as well as potential problems to be studied are clarified. Finally, the control strategies on WTGs to enhance power system damping characteristics are presented.

Stiffness-damping matching method of an ECAS system based on LQG control

A novel method of matching stiffness and continuous variable damping of an ECAS (electronically controlled air suspension) based on LQG (linear quadratic Gaussian) control was proposed to simultaneously improve the road-friendliness and ride comfort of a two-axle school bus. Taking account of the suspension nonlinearities and target-height-dependent variation in suspension characteristics, a stiffness model of the ECAS mounted on the drive axle of the bus was developed based on thermodynamics and the key parameters were obtained through field tests. By determining the proper range of the target height for the ECAS of the fully-loaded bus based on the design requirements of vehicle body bounce frequency, the control algorithm of the target suspension height (i.e., stiffness) was derived according to driving speed and road roughness. Taking account of the nonlinearities of a continuous variable semi-active damper, the damping force was obtained through the subtraction of the air spring force from the optimum integrated suspension force, which was calculated based on LQG control. Finally, a GA (genetic algorithm)-based matching method between stepped variable damping and stiffness was employed as a benchmark to evaluate the effectiveness of the LQG-based matching method. Simulation results indicate that compared with the GA-based matching method, both dynamic tire force and vehicle body vertical acceleration responses are markedly reduced around the vehicle body bounce frequency employing the LQG-based matching method, with peak values of the dynamic tire force PSD (power spectral density) decreased by 73.6%, 60.8% and 71.9% in the three cases, and corresponding reduction are 71.3%, 59.4% and 68.2% for the vehicle body vertical acceleration. A strong robustness to variation of driving speed and road roughness is also observed for the LQG-based matching method.

The relationship between cannabis outcome expectancies and cannabis refusal self-efficacy in a treatment population

Background and aims Self-efficacy beliefs and outcome expectancies are central to Social Cognitive Theory (SCT). Alcohol studies demonstrate the theoretical and clinical utility of applying both SCT constructs. This study examined the relationship between refusal self-efficacy and outcome expectancies in a sample of cannabis users, and tested formal mediational models. Design Patients referred for cannabis treatment completed a comprehensive clinical assessment, including recently validated cannabis expectancy and refusal self-efficacy scales. Setting A hospital alcohol and drug out-patient clinic. Participants Patients referred for a cannabis treatment [n = 1115, mean age 26.29, standard deviation (SD) 9.39]. Measurements The Cannabis Expectancy Questionnaire (CEQ) and Cannabis Refusal Self-Efficacy Questionnaire (CRSEQ) were completed, along with measures of cannabis severity [Severity of Dependence Scale (SDS)] and cannabis consumption. Findings Positive (β = −0.29, P < 0.001) and negative (β = −0.19, P < 0.001) cannabis outcome expectancies were associated significantly with refusal self-efficacy. Refusal self-efficacy, in turn, fully mediated the association between negative expectancy and weekly consumption [95% confidence interval (CI) = 0.03, 0.17] and partially mediated the effect of positive expectancy on weekly consumption (95% CI = 0.06, 0.17). Conclusions Consistent with Social Cognitive Theory, refusal self-efficacy (a person's belief that he or she can abstain from cannabis use) mediates part of the association between cannabis outcome expectancies (perceived consequences of cannabis use) and cannabis use.

Comprehensive Addictive Behaviors and Disorders, Volume 3 : Interventions for Addiction

"Interventions for Addiction examines a wide range of responses to addictive behaviors, including psychosocial treatments, pharmacological treatments, provision of health care to addicted individuals, prevention, and public policy issues. Its focus is on the practical application of information covered in the two previous volumes of the series, Comprehensive Addictive Behaviors and Disorders. Readers will find information on treatments beyond commonly used methods, including Internet-based and faith-based therapies, and criminal justice interventions. The volume features extensive coverage of pharmacotherapies for each of the major drugs of abuse-including disulfiram, buprenorphine, naltrexone, and others-as well as for behavioral addictions. In considering public policy, the book examines legislative efforts, price controls, and limits on advertising, as well as World Health Organization (WHO) efforts. Interventions for Addiction is one of three volumes comprising the 2,500-page series, Comprehensive Addictive Behaviors and Disorders. This series provides the most complete collection of current knowledge on addictive behaviors and disorders to date. In short, it is the definitive reference work on addictions."--publisher website

Symptom control and quality of life in lux-lung 3 : a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations

Purpose Patient-reported symptoms and health-related quality of life (QoL) benefits were investigated in a randomized, phase III trial of afatinib or cisplatin/pemetrexed. Patients and Methods Three hundred forty-five patients with advanced epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma were randomly assigned 2:1 to afatinib 40 mg per day or up to six cycles of cisplatin/pemetrexed. Lung cancer symptoms and health-related QoL were assessed every 21 days until progression using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Lung Cancer-13 questionnaires. Analyses of cough, dyspnea, and pain were preplanned, including percentage of patients who improved on therapy, time to deterioration of symptoms, and change in symptoms over time. Results Questionnaire compliance was high. Compared with chemotherapy, afatinib significantly delayed the time to deterioration for cough (hazard ratio [HR], 0.60; 95% CI, 0.41 to 0.87; P = .007) and dyspnea (HR, 0.68; 95% CI, 0.50 to 0.93; P = .015), but not pain (HR, 0.83; 95% CI, 0.62 to 1.10; P = .19). More patients on afatinib (64%) versus chemotherapy (50%) experienced improvements in dyspnea scores (P lt; .010). Differences in mean scores over time significantly favored afatinib over chemotherapy for cough (P lt; .001) and dyspnea (P = .001). Afatinib showed significantly better mean scores over time in global health status/QoL (P = .015) and physical (P = .001), role (P = .004), and cognitive (P lt; .007) functioning compared with chemotherapy. Fatigue and nausea were worse with chemotherapy, whereas diarrhea, dysphagia, and sore mouth were worse with afatinib (all P = .01). Conclusion In patients with lung adenocarcinoma with EGFR mutations, first-line afatinib was associated with better control of cough and dyspnea compared with chemotherapy, although diarrhea, dysphagia, and sore mouth were worse. Global health status/QoL was also improved over time with afatinib compared with chemotherapy.

Distribution of NMDA and AMPA receptor subunits at thalamo-amygdaloid dendritic spines

Synapses onto dendritic spines in the lateral amygdala formed by afferents from the auditory thalamus represent a site of plasticity in Pavlovian fear conditioning. Previous work has demonstrated that thalamic afferents synapse onto LA spines expressing glutamate receptor (GluR) subunits, but the GluR subunit distribution at the synapse and within the cytoplasm has not been characterized. Therefore, we performed a quantitative analysis for α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor subunits GluR2 and GluR3 and N-methyl-D-aspartate (NMDA) receptor subunits NR1 and NR2B by combining anterograde labeling of thalamo-amygdaloid afferents with postembedding immunoelectron microscopy for the GluRs in adult rats. A high percentage of thalamo- amygdaloid spines was immunoreactive for GluR2 (80%), GluR3 (83%), and NR1 (83%), while a smaller proportion of spines expressed NR2B (59%). To compare across the various subunits, the cytoplasmic to synaptic ratios of GluRs were measured within thalamo-amygdaloid spines. Analyses revealed that the cytoplasmic pool of GluR2 receptors was twice as large compared to the GluR3, NR1, and NR2B subunits. Our data also show that in the adult brain, the NR2B subunit is expressed in the majority of in thalamo-amygdaloid spines and that within these spines, the various GluRs are differentially distributed between synaptic and non-synaptic sites. The prevalence of the NR2B subunit in thalamo-amygdaloid spines provides morphological evidence supporting its role in the fear conditioning circuit while the differential distribution of the GluR subtypes may reflect distinct roles for their involvement in this circuitry and synaptic plasticity.

Integrin αvβ3 upregulates integrin-linked kinase expression in human ovarian cancer cells via enhancement of ILK gene transcription

We previously showed that integrin alphavbeta3 overexpression and engagement by its ligand vitronectin increased adhesion, motility, and proliferation of human ovarian cancer cells. In search of differentially regulated genes involved in these tumor biological events, we previously identified the integrin-linked kinase (ILK) to be under control of alphavbeta3. In the present investigation we demonstrated significantly upregulated ILK protein as a function of alphavbeta3 in two ovarian cancer cell lines, OV-MZ-6 and OVCAR-3, and proved co-localization at the surface of alphavbeta3-overexpressing cells adherent to vitronectin. Increase of ILK protein was reflected by enhanced ILK promoter activity, an effect, which we further characterized with regard to transcriptional response elements involved. Abrogation of NF-kappaB/c-rel or p53 binding augmented ILK promoter activity and preserved induction by alphavbeta3. The AP1-mutant exhibited decreased promoter activity but was also still inducible by alphavbeta3. Disruption of the two DNA consensus motifs for Ets proteins led to divergent observations: mutation of the Ets motif at promoter position -462 bp did not significantly alter promoter activity but still allowed response to alphavbeta3. In contrast, disruption of the second Ets motif at position -85 bp did not only lead to slightly diminished promoter activity but also, in that case, abrogated ILK promoter induction by alphavbeta3. Subsequent co-transfection studies with ets-1 in the presence of the second Ets motif led to additional induction of ILK promoter activity. Taken together, these data suggest that ets-1 binding to the second Ets DNA motif strongly contributes to alphavbeta3-mediated ILK upregulation. By increasing ILK as an important integrin-proximal kinase, alphavbeta3 may promote its intracellular signaling and tumor biological processes arising thereof in favor of ovarian cancer metastasis.

Quality of life of women with lower limb swelling or lymphedema 3-5 years following endometrial cancer

Objective To quantitatively assess and compare the quality of life (QoL) of women with a self-reported diagnosis of lower limb lymphedema (LLL), to women with lower limb swelling (LLS), and to women without LLL or LLS following treatment for endometrial cancer. Methods 1399 participants in the Australian National Endometrial Cancer Study were sent a follow-up questionnaire 3–5 years after diagnosis. Women were asked if they had experienced swelling in the lower limbs and, if so, whether they had received a diagnosis of lymphedema by a health professional. The 639 women who responded were categorised as: Women with LLL (n = 68), women with LLS (n = 177) and women without LLL or LLS (n = 394). Multivariable-adjusted generalized linear models were used to compare women’s physical and mental QoL by LLL status. Results On average, women were 65 years of age and 4 years after diagnosis. Women with LLL had clinically lower physical QoL (M= 41.8, SE= 1.4) than women without LLL or LLS (M= 45.1, SE= 0.8, p = .07), however, their mental QoL was within the normative range (M= 49.6; SE= 1.1 p = 1.0). Women with LLS had significantly lower physical (M= 41.0, SE= 1.0, p = .003) and mental QoL (M= 46.8; SE= 0.8, p < .0001) than women without LLL or LLS (Mental QoL: M= 50.6, SE= 0.8). Conclusion Although LLL was associated with reductions in physical QoL, LLS was related to reductions in both physical and mental QoL 3-5 years after cancer treatment. Early referral to evidence-based lymphedema programs may prevent long-term impairments to women’s QoL.