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Proteolytic enzymes play a complex role in tumour growth and invasion. To explore the impact of tumour stroma on invasiveness and expression of proteolytic enzymes, we used a xenograft mouse model where tumours in tongue and skin were established from various human cancer cell lines. Gelatinolytic activity in the tumours was investigated by a novel in situ zymography technique which enables high image resolution. In vivo and in vitro expression of various proteolytic enzymes were analysed at transcriptional and protein level using RT-qPCR, immunohistochemistry and SDS–PAGE substrate zymography. At the mRNA level all cell lines were found to express MMP-2, -7, -14, uPA and uPAR. In addition, two out of three cell lines expressed MMP-9. Histological analyses revealed that tongue tumours had an invasive growth pattern, associated with reduced E-cadherin expression. In contrast, the skin tumours established from the same cell lines were non-invasive. Tongue tumours of all cell lines showed strong gelatinolytic activity especially at the invasive front, which was not seen in the non-invasive skin tumours. Our results show a close relationship between tumour invasiveness and gelatinolytic activity at the tumour front. Furthermore, in our model, both invasiveness and activity of tumour-associated proteolytic enzymes were more dependent on the tumour microenvironment than on inherent properties of the cancer cells. [Copyright &y& Elsevier]

Background: Although many studies have shown an inverse relationship between diabetes and prostate cancer, it still remains unclear why diabetes may reduce the risk of prostate cancer. An inverse association between haemoglobin A1C (HbA1C) and prostate-specific antigen (PSA) also has been reported in previous studies that assessed the association cross-sectionally. To fully understand the relationship between diabetes and prostate cancer, it is essential to examine the association in a longitudinal design. The effect of plasma volume should also be considered in examining the PSA level. The aim of this study was to determine whether changes in HbA1C were associated with PSA levels, independent of plasma volume changes, as indicated by haematocrit and weight. Methods: We investigated 5917 Japanese men aged 50 and over who visited St. Luke’s International Hospital, Tokyo for routine health check-ups in 2006 and 2007. We performed a multiple linear regression analysis to examine any association between changes in HbA1C and PSA over 1year. Results: Adjusting for age, body mass index at baseline and changes in weight and haematocrit, the increases in HbA1C and PSA were concordant (5.7% increase per 1-unit HbA1C change; 95% confidence interval, 2.8–8.5%; p <0.001). Conclusions: In contrast to previous cross-sectional observations showing an inverse association between HbA1C and PSA, longitudinal observations suggest a positive association between the two. Further studies are needed to investigate the association between diabetes and prostate cancer. [Copyright &y& Elsevier]

Aim of the study: To evaluate the prognostic significance of the initial cerebro-spinal fluid (CSF) involvement of children with ALL enrolled from 1989 to 1996 in the EORTC 58881 trial. Patients and methods: Patients (2025) were categorised according to initial central nervous system (CNS) status: CNS-1 (CNS negative, n =1866), CNS-2 (<5 leucocytes/mm3, CSF with blasts, n =50), CNS-3 (CNS positive, n =49), TLP+ (TLP with blasts, n =60). CNS-directed therapy consisted in intravenous (i.v.) methotrexate (5g/sqm) in 4–10 courses, and intrathecal methotrexate injections (10–20), according to CNS status. Cranial irradiation was omitted in all patients. Results: In the CNS1, TLP+, CNS2 and CNS3 group the 8-year EFS rate (SE%) was 69.7% (1.1%), 68.8% (6.2%), 71.3% (6.5%) and 68.3% (6.2%), respectively. The 8-year incidence of isolated CNS relapse (SE%) was 3.4% (0.4%), 1.7% (1.7%), 6.1% (3.5%) and 9.4% (4.5%), respectively, whereas the 8-year isolated or combined CNS relapse incidence was 7.6% (0.6%), 3.5% (2.4%), 10.2% (4.4%) and 11.7% (5.0%), respectively. Patients with CSF blasts had a higher rate of initial bad risk features. Multivariate analysis indicated that presence of blasts in the CSF had no prognostic value: (i) for EFS and OS; (ii) for isolated and isolated or combined CNS relapse; WBC count<25×109/L and Medac E-coli asparaginase treatment were each related to a lower CNS relapse risk. Conclusions: The presence of initial CNS involvement has no prognostic significance in EORTC 58881. Intensification of CNS-directed chemotherapy, without CNS radiation, is an effective treatment of initial meningeal leukaemic involvement. [Copyright &y& Elsevier]

Ethnopharmacological relevance: Curcuma zedoaria (Berg.) Rosc., a traditional Chinese herb, was used widely but absolutely prohibited for the pregnant in clinic. Based on that there is abundant angiogenesis in endometrium and placenta during gestation period, we hypothesized that some components from it could inhibit angiogenesis and then damaged the supply of oxygen and nutrition to the embryo, which finally led to gestation failure. Aim of the study: This study was set to demonstrate whether essential oil, major components of Curcuma zedoaria had anti-angiogenic effect. Materials and methods: Essential oil of Curcuma zedoaria (EO-CZ) was abstracted by steam distillation extraction. Cell proliferation assay and two angiogenic models, rat aortic ring assay and chick embryo chorioallantoic membrane assay were presented. Furthermore, melanoma growth and experimental lung metastasis assay in mice were performed to evaluate its anti-angiogenesis effect in vivo. Immunohistochemical analysis and enzyme-linked immunosorbent assay (ELISA) were used to respectively detect the expression of CD34 and matrix metalloproteinases (MMPs). Results: EO-CZ exhibited anti-proliferative effect on B16BL6 and SMMC-7721 cells, the IC50, respectively was 41.8μg/ml and 30.7μg/ml, and on HUVEC (Human Umbilical Vein Endothelial Cells) cells with IC50 of far more than 120μg/ml. Both 20μg/ml and 40μg/ml EO-CZ indicated significant suppression on sprouting vessels of aortic ring and formation of microvessels in chick embryo chorioallantoic membrane in vitro. Moreover, solid melanoma grown in left oxter of mice was obviously inhibited after oral intake of 100 and 200mg/kg of EO-CZ a day for 28 days, and CD34 expression indicating angiogenesis in melanoma reduced significantly compared with control; melanoma metastatic nodules in lung were detected to be inhibited, as well as MMP-2 and MMP-9 expression in serum. Conclusions: Essential oil, a fat-soluble fraction of Curcuma zedoaria, presented anti-angiogenic activity in vitro and in vivo, resulting in suppressing melanoma growth and lung metastasis. And this was associated with down-regulating MMPs. [Copyright &y& Elsevier]

Although gender differences have been demonstrated in cardiac and stroke rehabilitation, it remains unclear whether there are gender differences in geriatric rehabilitation. The purpose of this study is to investigate the relationship between gender and rehabilitation outcomes. We studied 1795 patients in two convalescence hospitals in Hong Kong. We defined absolute functional and motor gains as Barthel Index (BI) efficacy and Elderly Mobility Scale (EMS) efficacy while BI and EMS efficiency were efficacy divided by the length of stay. Satisfactory motor and functional outcomes were defined as discharge EMS≥15 and BI≥75. Compared with men, women had higher BI but lower EMS on admission and discharge. EMS and BI efficacy and efficiency were similar in both sexes. Female gender was a significant negative predictor for satisfactory motor outcome (p =0.0002) but a positive predictor for functional outcome (p =0.0007). Other predictors for satisfactory motor outcome were: age (p <0.001); urinary incontinence (p =0.0049); living at home (p =0.0056); admission EMS (p <0.001); admission BI (p =0.044). Other predictors for satisfactory functional outcome were: age (p =0.009); infection other than chest (p =0.047); urinary incontinence (p <0.001); Mini Mental State Examination (MMSE) (p =0.0004); admission EMS (p =0.005); BI (p <0.001). Women achieved a better functional outcome but a poorer motor outcome on discharge. Female gender was a positive predictor for functional outcome but a negative factor for motor outcome. [Copyright &y& Elsevier]

The purpose of this study was to investigate transitions over time in the functional status of disabled community-living elderly. The study explored clinical and socio-demographic predictors of functional status decline. Data from the SIPA 3-year longitudinal study were analyzed (n =1164). Three categories of functional status were defined: no important disability, significant IADL disability and significant ADL disability. At baseline, results show that the prevalence rates were 26.9%, 58.6% and 14.5% for the three categories of functional status. After 12 months, about 50–60% of participants had remained in the same status, while some 10–15% of those with baseline significant disability had improved. The patterns of transitions between 12 and 36 months of follow-up were slightly different. The results indicated more deterioration (13–38%) and less improvement (6–9%). After controlling for baseline functional status, the best predictors for functional decline at 36 months were prior disability, functional limitations, cognitive impairment and comorbidity burden. We found that older adults’ functional status may decline or improve even if the participants are disabled. Disabled conditions play a crucial role in the development of future disability and preventive actions need to be implemented. [Copyright &y& Elsevier]

Objectives: To test different adherent strategies aimed at improving hip protector use among nursing care facility residents. Design, Setting and Participants: A cluster randomized controlled trial with 234 residents older than 75 years from 9 units of 7 nursing care facilities in the Northern Sydney region, Australia. Intervention: Residents were cluster randomized in 3 groups. The first group received hard shell hip protectors without cost (no cost group). The second group received an educational session, a demonstration of the use of hip protectors, and free choice of type of hip protectors without cost (combined group). The third group was the control group who received a brochure about hip protectors. Measurements: Primary outcome was adherence with the use of hip protectors at 3 and 6 months after recruitment. Secondary outcomes were falls, injuries, and fractures. Results: No participants in the control group purchased hip protectors at any stage. At 3 months, 33% of participants in the no cost group and 27% in the combined group wore a hip protector at the time of visit. This declined to 25% and 24% respectively at 6 months. No significant difference was seen in any of the 3 adherence outcomes between the 2 intervention groups. The number of falls or hospitalizations did not differ between groups, with 5 hip fractures reported during the intervention period. Residents were more likely to be adherent if they were female and had greater restriction in daily activities. Conclusion: Providing free hip protectors to older people living in nursing care facilities was necessary to increase initial acceptance and adherence. Nevertheless, after 6 months the achieved level of adherence was not high enough to be associated with a reduction of hip fractures. The provision of educational sessions and demonstrations to nursing staff and participants had no added value in this trial. [Copyright &y& Elsevier]

Background: In recent years several unstable shoe designs that cause increased instability at the ankle joint have been developed with the aims of training static and dynamic posture and postural control. However, earlier research found significant gender differences in the generation of ankle torque and in the reaction times after a perturbation. Therefore it is possible that men and women are affected differently by the instability that unstable shoes create. The purpose of this study was to investigate if gender differences exist a) during bilateral quiet stance or b) in lower extremity gait kinematics and kinetics when using unstable shoes. Methods: Seventeen females and seventeen males were included in this study. Masai Barefoot Technology® shoes were used as test shoes. Center of pressure excursion was recorded during 30s bilateral quiet stance trials using a force plate. Joint angles, resultant joint moments and joint moment impulses during walking were determined using standard gait analysis methods. Findings: In bipedal stance, female subjects had significantly greater anterior–posterior center of pressure excursion than male subjects. In the stance phase of the gait cycle gender differences were found in the ankle joint moments which had not been reported in earlier studies using barefoot or normal shoe conditions. Interpretation: The results suggest that women and men use different strategies to control the ankle joint when standing or walking in unstable shoes. Gender effects should therefore be taken into consideration if functional or therapeutic effects of unstable shoes are assessed. [Copyright &y& Elsevier]

Aim: To elucidate cellular features accountable for colorectal cancers’ (CRC) capability to invade normal tissue and to metastasize, we investigated the level of the collagenase matrix metalloproteinase 9 (MMP-9) and its physiological inhibitor tissue inhibitor of metalloproteinases 1 (TIMP-1) in cancer cells and supporting stroma cells of CRC. Methods: Immunoreactivity of MMP-9 and TIMP-1 by carcinoma cells, lymphocytes and fibroblasts in archival specimens of paraffin-embedded primary tumours were retrospectively associated with outcome in 340 consecutive patients completely resected for CRC stages II–IV and subsequently treated with adjuvant 5-fluorouracil. Results: Expression of MMP-9 by carcinoma cells was demonstrated in 9% of specimens without association to recurrence free survival (RFS) (HR=1.0; 95% CI: 0.6–1.8; P =0.9) or overall survival (OS) (HR=0.9; 95% CI: 0.5–1.6; P =0.6). TIMP-1 expression by carcinoma cells, which appeared in 64% of the specimens, was inversely related with RFS (HR=1.3; 95% CI: 0.9–1.8; P =0.08) and OS (HR=1.5; 95% CI: 1.1–2.1; P =0.02). Expression of TIMP-1 by fibroblasts at the invasive border was directly related to RFS (HR=0.7; 95% CI: 0.6–0.9; P =0.02) and OS (HR=0.7; 95% CI: 0.6–1.0; P =0.05). Expression of MMP-9 by lymphocytes correlated significantly with the degree of peritumoural inflammation (P =0.02) but not with RFS (HR=0.9; 95% CI: 0.7–1.1; P =0.2) or OS (HR=0.8; 95% CI: 0.7–1.0; P =0.07). Conclusion: TIMP-1 in cancer cells is associated with poor prognosis independent of its function as inhibitor of MMP-9. MMP-9 and TIMP-1 are important mediators of the host–cancer cell interaction in the tumour microenvironment with significant influence on the histopathology and on prognosis of CRC. [Copyright &y& Elsevier]

Background: To assess the agreement between the causes of death assigned by a blinded and uniform review panel of the Rotterdam section of the European Randomised Study of Screening for Prostate Cancer and the official vital statistics and to explore the possible effect of the use of either of these two sources on the outcome of the screening trial. Methods: A total of 670 deaths amongst men with prostate cancer, reviewed by the causes of death committee (CODC) up to 31st December 2006 were included in this study. The kappa statistics with confidence intervals (CI), sensitivity and specificity of the official statistics were determined, with the CODC considered the gold standard. The rate ratio (RR) and 95% confidence intervals (95% CI) for prostate cancer mortality, official statistics relative to CODC, were calculated following the Mantel–Haenszel procedure. Results: The overall concordance and the kappa between official statistics and the CODC were 90.6% and 0.76 (0.71–0.82), remaining comparable when only the CODC category definitely prostate cancer was applied, with the sensitivity of official statistics increasing from 88.3% to 91.3% and specificity hardly changing (91.3% and 90.5%). High specificity and lower sensitivity is observed in the screening arm, whilst the opposite was seen in the control arm in men aged 55–69 and 70–74years at entry. Considerable lower false positive rate was seen for both age groups in the screening arm (3.9% and 4.7%) compared to the control arm (8.4% and 14.3%). A statistically significant excess of prostate cancer death was observed for the official statistics in the age group 70–74years, 1.53 (1.07–2.19), whilst it was not significant for men aged 55–69 at entry, 1.06 (0.83–1.36). Conclusion: In the Rotterdam ERSPC section, official statistics tended to overreport prostate cancer as an underlying cause of death, particularly in the age group 70-plus in the control arm, which would overestimate the true effect in favour of screening. [Copyright &y& Elsevier]

Ethnopharmacological relevance: The stem bark powder of Hesperethusa crenulata or Thanaka has been used on the face by Myanmar women for more than a thousand years as a skin care regiment. Aim of the study: The aim of the current study was to both verify the safety and evaluate some biological activities of the Thanaka bark. Materials and methods: Maceration of the Thanaka bark powder resulted in hexane, dichloromethane, ethyl acetate, methanol, 85% ethanol and water extracts. For the safety evaluation, cytotoxicity and genotoxicity of each extract were tested. Antibacterial, tyrosinase inhibition, antioxidant and anti-inflammatory activities were evaluated for each extract. Results and conclusions: Extracts from Thanaka bark showed strong anti-inflammatory, significant antioxidation, mild tyrosinase inhibition and slight antibacterial activities. All extracts and the original bark powder showed no detectable genotoxicity while very low cytotoxicity with IC50 value of more than 12mg/ml was detected in the water extract. Thus, the use of the Thanaka bark in the form of a watery paste as a skin care regiment is not only safe but also beneficial to skin. [Copyright &y& Elsevier]

Objective: Explore student-involvement goals in local weliness policies (LWPs) of local education agencies (LEAs) in Pennsylvania (PA) and investigate associations with LEA characteristics. Design: An observational study that helped examine student-involvement goals. Setting: Public PA LEAs. Participants: LWPs submitted by 539 PA public LEAs. Main Outcome Measures: Six student-involvement goals analyzed as dependent variables. Correlations between demographic and policy characteristics of LEAs and student-involvement goals were measured. Analysis: Policies developed by LEAs were abstracted and analyzed. Logistic regression models were developed to analyze relationships between student-involvement goals and the demographic and policy characteristics of LEAs. Results: Majority ofLEAs included policy goals that address student involvement in an array of activities related to weilness policy, food service, and role modeling. Regression models showed that LEAs with comprehensive and strong policies were most likely to include student-involvement goals regardless of LEA location, enrollment, or socioeconomic status of students. Conclusions and Implications: Student engagement in school nutrition policies has been shown to increase student acceptance in an array of health-related areas and is therefore promising in the area of obesity prevention. Comprehensiveness and rigor of LWPs were strongly correlated with the inclusion of student-involvement goals on LWPs. The upcoming reauthorization of the Child Nutrition programs in 2010 creates a good opportunity to address student involvement in LWPs. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that in general patients are positive about cardiovascular prevention delivered by general practitioners. Further, it has been found that care by nurses for the chronically ill leads to even greater patient satisfaction. Objective: The aim of this survey was to answer the following questions: How do patients perceive cardiovascular prevention delivered by the practice nurse? Are patient characteristics and personal health status associated with experiences of received nurse-led care? Design: A cross-sectional survey after completion of a randomised trial. Setting: Six primary health care centres in the Netherlands (25 general practitioners, 6 practice nurses, 30,000 patients). Participants: Included in the randomised trial were 701 patients with at least a 10% risk of fatal cardiovascular disease within 10 years. Patients who visited a cardiovascular specialist more often than once a year and patients with diabetes were excluded from the study. In 90% of the patients it concerned secondary prevention. Half of the patients received nurse-delivered care and half received care by the general practitioner. Method: A questionnaire was sent by post to all patients after having received one year of cardiovascular prevention. A dual moderator focus group study was held for the development of the questionnaire. Findings: The response rate was 69%. Patients were more satisfied with nurse-delivered cardiovascular prevention compared to standard care by general practitioners. The majority of patients agreed with positive statements regarding received nurse-led care. Patient characteristics such as age, educational level and gender were significantly associated with patients experiences. Furthermore, a significant association between experiences and personal health status was found. In comparison with patients who did not smoke, smokers would recommend the practice nurse less to others (X 2 =4.0, p =0.047), felt more ‘rapped on their knuckles’ (X 2 =11.5, p =0.003), found the consultation more ‘awkward’ (X 2 =8.3, p =0.016) and thought the nurse less understanding of their personal situation (X 2 =6.4, p =0.041) and less able to explain clearly (X 2 =6.5, p =0.039). Conclusions: The majority of patients responded positively to nurse-delivered cardiovascular prevention. Further improvement could be gained by paying more attention to motivational interviewing. Nurses should approach high risk patients more specifically according to the type of risk factor to be treated. [Copyright &y& Elsevier]

To investigate the effect of Acorus gramineus (AG), a supposed ‘delivering servant’ according to traditional Chinese medicine principles governing multi-herb formula preparation and formulation, on facilitating the uptake of ginsenosides Rg1, Re and Rb1 to the brain after oral administration of Kai-Xin-San (KXS) preparations. Materials and methods: Ginseng extracts or KXS with or without AG were administered to rats for pharmacokinetic study and mice for behaviour tests at a dose of 3g ginseng per kg. The concentrations of ginsenosides in plasma and brain were determined by an LC–MS/MS method, whilst the effects of preparations on spatial learning were evaluated using the Morris water maze test. Results: KXS in the presence of AG tended to significantly reverse the learning impairment induced by scopolamine. The presence of AG in the KXS formula led to increases in the initial absorption rate and extent of Rg1 and Re in terms of Cmax1 and AUC0–3h compared to KXS without AG. Although KXS were found to increase the bioavailabilities and brain concentrations of ginsenosides relative to ginseng extract, the brain-to-plasma AUC0–12h ratios appeared not to be affected. Conclusions: The results suggested that the presence of AG in the KXS formula promoted the initial absorption of ginsenosides Rg1 and Re in the gastrointestinal tract, but unlikely affected the brain-to-plasma AUC ratios. [Copyright &y& Elsevier]

Abstract: Many cultures have reported end-of-life experiences (ELEs) as part of the dying process. However, few studies have examined the mental states of the dying in the weeks and days before death. Following an ELE pilot study with a palliative care team, 38 nurses, doctors and end-of-life carers from two hospices and a nursing home took part in a 5-year retrospective followed by a 1-year prospective ELE study. Interviewees’ reports (first-hand and second-hand accounts from relatives, patients and residents) suggested that ELEs are not uncommon. ELEs included deathbed phenomena (DBP) such as visions, coincidences and the desire to reconcile with estranged family members. These experiences seemed to comfort both the dying and the bereaved. Interviewees described other phenomena such as clocks stopping synchronistically at the time of death, shapes leaving the body, light surrounding the body and strange animal behavior. Interviewees confirmed that ELEs differed from drug-induced hallucinations and occurred in clear consciousness. Most expressed concern about a lack of specialist ELE training and education and recommended that ELE modules be included in their training courses. ELEs provided comfort and hope for the dying and consolation for the bereaved. Further research is required to find the true prevalence and range of ELE phenomena. [ABSTRACT FROM AUTHOR]

Abstract: Hypothyroidism is a common disorder in older people, and may be asymptomatic and hard to be diagnosed. The main purpose of this study was to evaluate the distribution of serum thyrotropin (thyroxin-stimulating hormone, TSH) among asymptomatic older people in Taiwan, and to evaluate the relationship between age and serum TSH. In 2007, all subjects participating in the annual elderly health examinations at Taipei Veterans General Hospital were invited for study and were enrolled when they were fully consented. In total, 1716 asymptomatic elderly people (mean age: 73.2±4.4 years, 56.3% males) participated in this study after careful exclusion of 38 subjects with past history of thyroid disorders. All participants were divided into two groups: (1) younger old (age 65–79) and (2) older old (age over 80) for further analysis. The mean serum levels of TSH were similar between younger old and older old groups (2.43±5.36μIU/ml for younger old and 2.36±3.51μIU/ml for older old, p =0.444). The overall prevalence of suspected hypothyroidism was 9.2% among asymptomatic older people in Taiwan, which was significantly lower than in Caucasians. The prevalence of suspected hypothyroidism may reach 25.9% if the TSH cutoff was lowered to 2.5μIU/ml. Further study is needed to determine the normal reference range of serum TSH in older people. [ABSTRACT FROM AUTHOR]

Objectives: To report the prevalence of Do-Not-Resuscitate (DNR) directives and to explore the factors associated with the presence of DNR directives among nursing home residents in Taiwan. Design: A cross-sectional, correlation study. Setting: Seven nursing homes in southern Taiwan. Participants: Nursing home residents and their family surrogates. Measurements: Data were collected using chart abstraction and a questionnaire survey. We used multivariate logistic regression to analyze the associations between resident, family surrogate, and facility characteristics and the presence of DNR directives. Results: Among the 201 nursing home residents, 33 (16.4%) had DNR directives and 91% of the directives had been put in place by family surrogates. Our data revealed that resident''s age (OR = 1.06, 95% CI = 1.01–1.12), cognitive function score (OR = 0.91, 95% CI = 0.85–0.97), prior DNR discussion between physician and family surrogate (OR = 4.09, 95% CI = 1.53–10.96), and nursing home with DNR policy (OR = 17.71, 95% CI = 5.87–53.46) were independently and associated with the presence of a DNR directive. Conclusions: The prevalence of DNR directives among Taiwanese nursing home residents was lower than that in other countries. Our results point out the lack of DNR policy in most Taiwanese nursing homes and highlight the need for policy makers to implement further regulations. Meanwhile, education about advance directives is warranted to increase public and professional awareness and to facilitate empowerment of the increasing number of frail elderly nursing home residents in Taiwan. [Copyright &y& Elsevier]

Background: Although the percentage of obese nursing home residents is increasing, few longitudinal studies have reported on functionality and mortality in this subpopulation. The aim of the present study was to explore functionality and mortality in obese nursing home residents during a 1-year follow-up and to compare these results with those of residents within the normal and low BMI range. Methods: Two hundred residents (147 female, 53 male, mean age 85.6 ± 7.8 years) from 2 Nuremberg nursing homes were included. Body weight and height were measured in all participants. BMI was calculated and categorized as low (<20 kg/m2), normal (20–30 kg/m2), and high (>30 kg/m2). Handgrip strength, timed “up and go” test, and Barthel''s Activities of Daily Living were applied as functional parameters. All measurements were done at baseline and after a 1-year follow-up. Results: At baseline, the prevalence of obesity was 23.5%, whereas low BMI values were present in 8.5% of the residents. After 1 year, there was no significant decline of functionality in the obese group, whereas functional parameters deteriorated significantly in study participants with normal BMI. One-year mortality was lowest in the obese (12.8%), with no deaths in residents with BMI of 35 kg/m2 or higher. Mortality was highest in residents with low BMI (58.8%). Conclusion: In nursing home residents, obesity is associated with increased survival and stable functionality. These observations may therefore be regarded as an expression of “risk factor paradox” in this specific population of older individuals. [Copyright &y& Elsevier]

Abstract: Magnetic confinement fusion devices are very integrated systems, difficult to access for measurement, and therefore they pose particular challenges to identification and to the prediction of undesired events. With regard to system identification, Bayesian statistics is a very promising methodology, which provides for the first time a sound way to include physical information about the diagnostics in the evaluation of the error bars. In a prototypical application, a Bayesian statistical approach determines the magnetic topology without any assumption on the equilibrium and provides clear confidence intervals on all the derived quantities. This technique, which complements another more traditional approach based on the Grad–Shafranov equation, can be implemented to provide results about every few milliseconds and therefore it can be envisaged to exploit for feedback purposes. Some phenomena in the evolution of Tokamak plasmas, like disruptions, are too dangerous and prohibitively difficult to control. For these cases avoidance is the best alternative and therefore specific classifiers have been trained and optimized to predict the occurrence of disruptions. The success rates of these predictors, mainly based on Support Vector Machines, are very often of the order or higher than 90%. The generalisation capability of the method has been confirmed by applying the same predictor to new campaigns without retraining. The success rate remains very high (above 80%) even 12 campaigns after the last one used for training. [ABSTRACT FROM AUTHOR]

Abstract: In the past, most comparison to control problems have dealt with comparing k test treatments to either positive or negative controls. Dasgupta et al. [2006. Using numerical methods to find the least favorable configuration when comparing k test treatments to both positive and negative controls. Journal of Statistical Computation and Simulation 76, 251–265] enumerate situations where it is imperative to compare several test treatments to both a negative as well as a positive control simultaneously. Specifically, the aim is to see if the test treatments are worse than the negative control, or if they are better than the positive control when the two controls are sufficiently apart. To find critical regions for this problem, one needs to find the least favorable configuration (LFC) under the composite null. In their paper, Dasgupta et al. [2006. Using numerical methods to find the least favorable configuration when comparing k test treatments to both positive and negative controls. Journal of Statistical Computation and Simulation 76, 251–265] came up with a numerical technique to find the LFC. In this paper we verify their result analytically. Via Monte Carlo simulation we compare the proposed method to the logical single step alternatives: Dunnett''s [1955. A multiple comparison procedure for comparing several treatments with a control. Journal of the American Statistical Association 50, 1096–1121] or the Bonferroni correction. The proposed method is superior in terms of both the Type I error and the marginal power. [Copyright &y& Elsevier]

Abstract: In the context of fast and low cost speaker recognition, this article investigates several techniques based on decision trees. A new approach is introduced where the trees are used to estimate a score function rather than returning a decision among classes. This technique is developed to approximate the GMM log-likelihood ratio (LLR) score function. On top of this approach, different solutions are derived to improve the accuracy of the proposed trees. The first one studies the quantization of the LLR function to create classification trees on the LLR values. The second one makes use of knowledge on the GMM distribution of the acoustic features in order to build oblique trees. A third extension consists in using a low-complexity score function in each of the tree leaves. Series of comparative experiments are performed on the NIST 2005 speaker recognition evaluation data in order to evaluate the impact of the proposed improvements in terms of efficiency, execution time and algorithmic complexity. Considering a baseline system with an Equal Error Rate (EER) of 9.6% on the NIST 2005 evaluation, the best tree-based configuration achieves an EER of 12.9%, with a computational cost adapted to embedded devices and an execution time suitable for real-time speaker identification. [Copyright &y& Elsevier]

Abstract: The paper considers a general interface delamination and crack kinking from an inclined core junction in a sandwich beam. This particular problem is relevant for a newly developed peel-stopper component for sandwich structures. A finite element model (FEM) was developed and calibrated against a known model by He and Hutchinson. The numerically and analytically determined solution coefficients were in a perfect agreement with each other, so the necessary generalisation of results can be obtained through the application of FEM-analyses. The FE-model was used to determine solution coefficients for a number of interface compositions of practical interest. As expected some of the coefficients were quite sensitive to the specific material combination, which confirms that accurate solution strategies are important. The solution coefficients obtained were further applied to the analysis of the crack propagation and kinking process in three different sandwich beam configurations, each of which contained an inclined junction of 20°, 30°, or 40°. The objective was to examine how the core junction angle and the fracture mechanical properties of the sandwich components influenced the crack kinking tendency. The latter is vital for the design and functionality of a newly developed peel-stopper. It was shown that smaller core junction angles will lead to longer crack propagation (delamination) along the core–core interface prior to a possible kinking. The physical insight obtained is essential for optimal design of peel-stoppers. [Copyright &y& Elsevier]

Abstract: Two different distributions may have equal Rényi entropy; thus a distribution cannot be identified by its Rényi entropy. In this paper, we explore properties of the Rényi entropy of order statistics. Several characterizations are established based on the Rényi entropy of order statistics and record values. These include characterizations of a distribution on the basis of the differences between Rényi entropies of sequences of order statistics and the parent distribution. [Copyright &y& Elsevier]

Abstract: In the present paper we find finite dimensional spaces W of alternatives with high power for a given class of tests and non-parametric alternatives. On the orthogonal complement of W the power function is flat. These methods can be used to reduce the dimension of interesting alternatives. We sketch a device how to calculate (approximately) an alternative with maximum power of a fixed test on a given ball of certain non-parametric alternatives. The calculations are done within different asymptotic models specified by signal detection tests. Specific tests are Kolmogorov–Smirnov type tests, integral tests (like the Anderson and Darling test) and Rényi tests for hazard based models. The statistical meaning and interpretation of the spaces of alternatives with high power is discussed. These alternatives belong to least favorable directions of a class of statistical functionals which are linear combinations of quantile functions. For various cases their meaning is explained for parametric submodels, in particular for location alternatives. [Copyright &y& Elsevier]

Abstract: In this paper, we consider testing the location parameter with multilevel (or hierarchical) data. A general family of weighted test statistics is introduced. This family includes extensions to the case of multilevel data of familiar procedures like the t, the sign and the Wilcoxon signed-rank tests. Under mild assumptions, the test statistics have a null limiting normal distribution which facilitates their use. An investigation of the relative merits of selected members of the family of tests is achieved theoretically by deriving their asymptotic relative efficiency (ARE) and empirically via a simulation study. It is shown that the performance of a test depends on the clusters configurations and on the intracluster correlations. Explicit formulas for optimal weights and a discussion of the impact of omitting a level are provided for 2 and 3-level data. It is shown that using appropriate weights can greatly improve the performance of the tests. Finally, the use of the new tests is illustrated with a real data example. [Copyright &y& Elsevier]

Abstract: For the model of independence in a two way contingency table, shrinkage estimators based on minimum -divergence estimators and -divergence statistics are considered. These estimators are based on the James–Stein-type rule and incorporate the idea of preliminary test estimator. The asymptotic bias and risk are obtained under contiguous alternative hypotheses, and on the basis of them a comparison study is carried out. [Copyright &y& Elsevier]

Abstract: This paper considers p-value based step-wise rejection procedures for testing multiple hypotheses. The existing procedures have used constants as critical values at all steps. With the intention of incorporating the exact magnitude of the p-values at the earlier steps into the decisions at the later steps, this paper applies a different strategy that the critical values at the later steps are determined as functions of the p-values from the earlier steps. As a result, we have derived a new equality and developed a two-step rejection procedure following that. The new procedure is a short-cut of a step-up procedure, and it possesses great simplicity. In terms of power, the proposed procedure is generally comparable to the existing ones and exceptionally superior when the largest p-value is anticipated to be less than 0.5. [Copyright &y& Elsevier]

Abstract: We consider estimation and test problems for some semiparametric two-sample density ratio models. The profile empirical likelihood (EL) poses an irregularity problem under the null hypothesis that the laws of the two samples are equal. We show that a dual form of the profile EL is well defined even under the null hypothesis. A statistical test, based on the dual form of the EL ratio statistic (ELRS), is then proposed. We give an interpretation for the dual form of the ELRS through -divergences and duality techniques. The asymptotic properties of the test statistic are presented both under the null and the alternative hypotheses, and approximation of the power function of the test is deduced. [Copyright &y& Elsevier]

Abstract: This paper introduces the confidence interval estimate for measuring the bullwhip effect, which has been observed across most industries. Calculating a confidence interval usually needs the assumption about the underlying distribution. Bootstrapping is a non-parametric, but computer intensive, estimation method. In this paper, a simulation study on the behavior of the 95% bootstrap confidence interval for estimating bullwhip effect is made. Effects of sample size, autocorrelation coefficient of customer demand, lead time, and bootstrap methods on the 95% bootstrap confidence interval of bullwhip effect are presented and discussed. [Copyright &y& Elsevier]

Abstract: Consider the partially balanced one-way layout for comparing k treatments with a control . We propose a new test which is similar to the test statistics of Marcus [1976. The powers of some tests of the equality of normal means against an ordered alternative. Biometrika 63, 177–183]. By simulation we find that the proposed test has a good power performance when compared with other tests. Moreover, it can produce confidence intervals for [Copyright &y& Elsevier]

Abstract: Exact confidence intervals for a proportion of total variance, based on pivotal quantities, only exist for mixed linear models having two variance components. Generalized confidence intervals (GCIs) introduced by Weerahandi [1993. Generalized confidence intervals (Corr: 94V89 p726). J. Am. Statist. Assoc. 88, 899–905] are based on generalized pivotal quantities (GPQs) and can be constructed for a much wider range of models. In this paper, the author investigates the coverage probabilities, as well as the utility of GCIs, for a proportion of total variance in mixed linear models having more than two variance components. Particular attention is given to the formation of GPQs and GCIs in mixed linear models having three variance components in situations where the data exhibit complete balance, partial balance, and partial imbalance. The GCI procedure is quite general and provides a useful method to construct confidence intervals in a variety of applications. [Copyright &y& Elsevier]

Abstract: Rechtschaffner designs are saturated designs of resolution V in which main effects and two-factor interactions are estimable if three-factor and higher order interactions are negligible. Statistical properties of Rechtschaffner designs are studied in this paper. Best linear unbiased estimators of main effects and two-factor interactions are given explicitly and asymptotic properties of correlations between these estimators are studied as well. It is shown that designs recommended by Rechtschaffner [1967. Saturated fractions of and factorial designs, Technometrics 9, 569–576] are not only A-optimal but also D-optimal. Comparisons of Rechtschaffner designs with other A- and D-optimal designs of resolution V are also discussed. [Copyright &y& Elsevier]

For exponentially distributed failure times under general progressive censoring schemes, testing procedures for ordered failure rates are proposed using the likelihood ratio principle. Constrained maximum likelihood estimators of the failure rates are found. The asymptotic distributions of the test statistics are shown to be mixtures of chi-square distributions. When testing the equality of the failure rates, a simulation study shows that the proposed test with restricted alternative has improved power over the usual chi-square statistic with an unrestricted alternative. The proposed methods are illustrated using data of survival times of patients with squamous carcinoma of the oropharynx. [Copyright &y& Elsevier]

Abstract: It is suggested that power analysis should be formally incorporated into quantification experiment reports in order to substantiate the conclusions derived from experimental data more effectively. The article addressed the issues of power analysis calculation, sample size estimation and appropriate data reporting in quantitative analytical comparisons. Illustrative examples from the literature are used to show how the described power analysis theory could be applied in practice. [Copyright &y& Elsevier]

Abstract: In many statistical problems, the variances of the populations cannot be assumed to be equal. These inhomogeneity problems are often more difficult to handle than the corresponding homogeneity problems. In sequential estimation, this often means that only first order sequential procedures are available in the statistics literature for inhomogeneity problems. The purpose of this paper is to illustrate by using the classical Behrens–Fisher problem how to construct a second order sequential procedure using the batch sampling idea of Hall [Ann. Statist. 9 (1981) 1229–1238]; the cost of assuming variance inhomogeneity even when the two variances are equal turns out to be very limited. The approach of this paper can readily be applied to many other inhomogeneous problems. [Copyright &y& Elsevier]

Abstract: Location-scale invariant Bickel–Rosenblatt goodness-of-fit tests (IBR tests) are considered in this paper to test the hypothesis that f, the common density function of the observed independent d-dimensional random vectors, belongs to a null location-scale family of density functions. The asymptotic behaviour of the test procedures for fixed and non-fixed bandwidths is studied by using an unifying approach. We establish the limiting null distribution of the test statistics, the consistency of the associated tests and we derive its asymptotic power against sequences of local alternatives. These results show the asymptotic superiority, for fixed and local alternatives, of IBR tests with fixed bandwidth over IBR tests with non-fixed bandwidth. [Copyright &y& Elsevier]

Abstract: This editorial discusses some statistical principles that may be useful in guiding authors of manuscripts submitted to Animal Feed Science and Technology (AFST) for consideration for publication. The editorial also discusses some common experimental designs and statistical models used by AFST authors, including some of the most frequent problems that cause misunderstandings and disputes among authors, reviewers and editors. The editorial is not meant as an exhaustive treatise on all possible experimental design and statistical issues that could arise, but as a general guide to correctly interpret results that are not meant to limit anyone''s imagination, as there are many ways to evaluate and examine biological responses. [Copyright &y& Elsevier]

Abstract: We extend a basic result of Huber''s on least favorable distributions to the setting of conditional inference, using an approach based on the notion of log-Gâteaux differentiation and perturbed models. Whereas Huber considered intervals of fixed width for location parameters and their average coverage rates, we study error models having longest confidence intervals, conditional on the location configuration of the sample. Our version of the problem does not have a global solution, but one that changes from configuration to configuration. Asymptotically, the conditionally least-informative shape minimizes the conditional Fisher information. We characterize the asymptotic solution within Huber''s contamination model. [Copyright &y& Elsevier]

Abstract: A number of authors have proposed clinical trial designs involving the comparison of several experimental treatments with a control treatment in two or more stages. At the end of the first stage, the most promising experimental treatment is selected, and all other experimental treatments are dropped from the trial. Provided it is good enough, the selected experimental treatment is then compared with the control treatment in one or more subsequent stages. The analysis of data from such a trial is problematic because of the treatment selection and the possibility of stopping at interim analyses. These aspects lead to bias in the maximum-likelihood estimate of the advantage of the selected experimental treatment over the control and to inaccurate coverage for the associated confidence interval. In this paper, we evaluate the bias of the maximum-likelihood estimate and propose a bias-adjusted estimate. We also propose an approach to the construction of a confidence region for the vector of advantages of the experimental treatments over the control based on an ordering of the sample space. These regions are shown to have accurate coverage, although they are also shown to be necessarily unbounded. Confidence intervals for the advantage of the selected treatment are obtained from the confidence regions and are shown to have more accurate coverage than the standard confidence interval based upon the maximum-likelihood estimate and its asymptotic standard error. [Copyright &y& Elsevier]

Abstract: Copulas are often used in finance to characterize the dependence between assets. However, a choice of the functional form for the copula is an open question in the literature. This paper develops a goodness-of-fit test for copulas based on positive definite bilinear forms. The suggested test avoids the use of plug-in estimators that is the common practice in the literature. The test statistics can be consistently computed on the basis of V-estimators even in the case of large dimensions. The test is applied to a dataset of US large cap stocks to assess the performance of the Gaussian copula for the portfolios of assets of various dimension. The Gaussian copula appears to be inadequate to characterize the dependence between assets. [Copyright &y& Elsevier]

Abstract: It has been argued that the frequency domain accuracy of high model-order estimates obtained on the basis of closed-loop data is largely invariant to whether direct or indirect approaches are used. The analysis underlying this conclusion has employed variance expressions that are asymptotic both in the data length and the model order, and hence are approximations when either of these are finite. However, recent work has provided variance expressions that are exact for finite (possibly low) model order, and hence can potentially deliver more accurate quantification of estimation accuracy. This paper, and a companion one, revisits the study of identification from closed-loop data in light of these new quantifications and establishes that, under certain assumptions, there can be significant differences in the accuracy of frequency response estimates. These discrepencies are established here and in the companion paper to be dependent on what type of direct, indirect or joint input–output identification strategy is pursued. [Copyright &y& Elsevier]

This paper proposes a methodology based on Bayesian statistics to assess the validity of reliability computational models when full-scale testing is not possible. Sub-module validation results are used to derive a validation measure for the overall reliability estimate. Bayes networks are used for the propagation and updating of validation information from the sub-modules to the overall model prediction. The methodology includes uncertainty in the experimental measurement, and the posterior and prior distributions of the model output are used to compute a validation metric based on Bayesian hypothesis testing. Validation of a reliability prediction model for an engine blade under high-cycle fatigue is illustrated using the proposed methodology. [Copyright &y& Elsevier]

Introduction: Our institution previously described a surgical technique for preservation of accessory pudendal arteries at radical retropubic prostatectomy. Since then, we have expanded our experience. We now report our refinements in the surgical technique, illustrated with video, and the influence of accessory artery preservation on the recovery of sexual function after radical retropubic prostatectomy (RRP).Technical Considerations: Between 1987 and 2003, 2399 potent men underwent RRP. Of the 2399 men, 84 (4%) were identified with accessory pudendal arteries. Of the 84 men, 52, who underwent bilateral nerve-sparing surgery, were available for evaluation. We identified a control population, without accessory pudendal arteries, who were matched for age, stage, and neurovascular bundle status. Potency was defined as the ability to achieve unassisted intercourse with or without the use of sildenafil. In a Cox proportional hazards model, the effect of artery preservation increased the likelihood of potency more than twofold (relative risk 2.65; 95% confidence interval 1.11 to 6.32; P = 0.028). Kaplan-Meier analysis showed a significantly shorter median time to regain potency among those with artery preservation, 6 versus 12 months (P = 0.020).Conclusions: Preservation of accessory pudendal arteries may favorably influence the recovery of sexual function and interval to recovery after RRP. [ABSTRACT FROM AUTHOR]

The US National Toxicology Program (NTP) is assessed by a statistician. In the NTP-program groups of rodents are fed for a certain period of time with different doses of the substance that is being investigated. Then the animals are sacrificed and all organs are examined pathologically. Such an investigation facilitates many statistical tests. Technical Report TR 578 on Ginkgo biloba is used as an example. More than 4800 statistical tests are possible with the investigations performed. Due to a thought experiment we expect >240 false significant tests. In actuality, 209 significant pathological findings were reported. The readers of Toxicology Letters should carefully distinguish between confirmative and explorative statistics. A confirmative interpretation of a significant test rejects the null-hypothesis and delivers "statistical proof". It is only allowed if (i) a precise hypothesis was established independently from the data used for the test and (ii) the computed p-values are adjusted for multiple testing if more than one test was performed. Otherwise an explorative interpretation generates a hypothesis. We conclude that NTP-reports -- including TR 578 on Ginkgo biloba -- deliver explorative statistics, i.e. they generate hypotheses, but do not prove them. [ABSTRACT FROM AUTHOR]