Expression of thrombospondin-1 in resected colorectal liver metastases predicts poor prognosis

Purpose The aim of this study was to examine the expression and prognostic relevance of thrombospondin-1 (TSP-1) in tumor biopsies taken from a consecutive series of liver resections done at the University Hospitals of Leicester and the Royal Liverpool Hospital. Experimental Design Patients having undergone a liver resection for colorectal liver metastases at our institutions between 1993 and 1999 inclusive were eligible. Inclusion criteria were curative intent, sufficient tumor biopsy, and patient follow-up data. One hundred eighty-two patients were considered in this study. Standard immunohistochemical techniques were used to study the expression of TSP-1 in 5-μm tumor sections from paraffin-embedded tissue blocks. TSP-1 was correlated with survival using the Kaplan-Meier method and log-rank test for univariate analysis and the Cox proportional hazard model for multivariate analysis. Results One hundred eighty-two patients (male, n = 122 and female, n = 60) ages between 25 and 81 years (mean, 61 years) were included. TSP-1 was expressed around blood vessels (n = 45, 25%) or in the stroma (n = 59, 33%). No expression was detected in the remaining tumors. TSP-1 significantly correlated with poor survival on univariate (P = 0.01 for perivascular expression and P = 0.03 for stromal expression) and multivariate analysis (P = 0.01 for perivascular expression). Conclusion TSP-1 is a negatively prognostic factor for survival in resected colorectal liver metastases. © 2005 American Association for Cancer Research.

Prognostic value of hTERT mRNA expression in surgical samples of lung cancer patients : the European Early Lung Cancer Project

Lung cancer is the most important cause of cancer-related mortality. Resectability and eligibility for treatment with adjuvant chemotherapy is determined by staging according to the TNM classification. Other determinants of tumour behaviour that predict disease outcome, such as molecular markers, may improve decision-making. Activation of the gene encoding human telomerase reverse transcriptase (hTERT) is implicated in the pathogenesis of lung cancer, and consequently detection of hTERT mRNA might have prognostic value for patients with early stage lung cancer. A cohort of patients who underwent a complete resection for early stage lung cancer was recruited as part of the European Early Lung Cancer (EUELC) project. In 166 patients expression of hTERT mRNA was determined in tumour tissue by quantitative real-time RT-PCR and related to that of a house-keeping gene (PBGD). Of a subgroup of 130 patients tumour-distant normal tissue was additionally available for hTERT mRNA analysis. The correlation between hTERT levels of surgical samples and disease-free survival was determined using a Fine and Gray hazard model. Although hTERT mRNA positivity in tumour tissue was significantly associated with clinical stage (Fisher's exact test p=0.016), neither hTERT mRNA detectability nor hTERT mRNA levels in tumour tissue were associated with clinical outcome. Conversely, hTERT positivity in adjacent normal samples was associated with progressive disease, 28% of patients with progressive disease versus 7.5% of disease-free patients had detectable hTERT mRNA in normal tissue [adjusted HR: 3.60 (1.64-7.94), p=0.0015]. hTERT mRNA level in tumour tissue has no prognostic value for patients with early stage lung cancer. However, detection of hTERT mRNA expression in tumour-distant normal lung tissue may indicate an increased risk of progressive disease.

Impacts of vessel capacity reduction programmes on efficiency in fisheries : the case of Australia’s multispecies northern prawn fishery

Capacity reduction programmes, in the form of buybacks or decommissioning, have had relatively widespread application in fisheries in the US, Europe and Australia. A common criticism of such programmes is that they remove the least efficient vessels first, resulting in an increase in average efficiency of the remaining fleet, which tends to increase the effective fishing power of the remaining fleet. In this paper, the effects of a buyback programme on average technical efficiency in Australia’s Northern Prawn Fishery are examined using a multi-output production function approach with an explicit inefficiency model. As expected, the results indicate that average efficiency of the remaining vessels was generally greater than that of the removed vessels. Further, there was some evidence of an increase in average scale efficiency in the fleet as the remaining vessels were closer, on average, to the optimal scale. Key factors affecting technical efficiency included company structure and the number of vessels fishing. In regard to fleet size, our model suggests positive externalities associated with more boats fishing at any point in time (due to information sharing and reduced search costs), but also negative externalities due to crowding, with the latter effect dominating the former. Hence, the buyback resulted in a net increase in the individual efficiency of the remaining vessels due to reduced crowding, as well as raising average efficiency through removal of less efficient vessels.

The prolongation of length of stay because of Clostridium difficile infection

Background Clostridium difficile infection (CDI) possibly extends hospital length of stay (LOS); however, the current evidence does not account for the time-dependent bias, ie, when infection is incorrectly analyzed as a baseline covariate. The aim of this study was to determine whether CDI increases LOS after managing this bias. Methods We examined the estimated extra LOS because of CDI using a multistate model. Data from all persons hospitalized >48 hours over 4 years in a tertiary hospital in Australia were analyzed. Persons with health care-associated CDIs were identified. Cox proportional hazards models were applied together with multistate modeling. Results One hundred fifty-eight of 58,942 admissions examined had CDI. The mean extra LOS because of infection was 0.9 days (95% confidence interval: −1.8 to 3.6 days, P = .51) when a multistate model was applied. The hazard of discharge was lower in persons who had CDI (adjusted hazard ratio, 0.42; P < .001) when a Cox proportional hazard model was applied. Conclusion This study is the first to use multistate models to determine the extra LOS because of CDI. Results suggest CDI does not significantly contribute to hospital LOS, contradicting findings published elsewhere. Conversely, when methods prone to result in time-dependent bias were applied to the data, the hazard of discharge significantly increased. These findings contribute to discussion on methods used to evaluate LOS and health care-associated infections.

Surveillance protocols for management of invasive plants: modelling Chilean needle grass (Nassella neesiana) in Australia

Aim: To develop a surveillance support model that enables prediction of areas susceptible to invasion, comparative analysis of surveillance methods and intensity and assessment of eradication feasibility. To apply the model to identify surveillance protocols for generalized invasion scenarios and for evaluating surveillance and control for a context-specific plant invasion. Location: Australia. Methods: We integrate a spatially explicit simulation model, including plant demography and dispersal vectors, within a Geographical Information System. We use the model to identify effective surveillance protocols using simulations of generalized plant life-forms spreading via different dispersal mechanisms in real landscapes. We then parameterize the surveillance support model for Chilean needle grass [CNG; Nassella neesiana (Trin. & Rupr.) Barkworth], a highly invasive tussock grass, which is an eradication target in south-eastern Queensland, Australia. Results: General surveillance protocols that can guide rapid response surveillance were identified; suitable habitat that is susceptible to invasion through particular dispersal syndromes should be targeted for surveillance using an adaptive seek-and-destroy method. The search radius of the adaptive method should be based on maximum expected dispersal distances. Protocols were used to define a surveillance strategy for CNG, but simulations indicated that despite effective and targeted surveillance, eradication is implausible at current intensities. Main conclusions: Several important surveillance protocols emerged and simulations indicated that effectiveness can be increased if they are followed in rapid response surveillance. If sufficient data are available, the surveillance support model should be parameterized to target areas susceptible to invasion and determine whether surveillance is effective and eradication is feasible. We discovered that for CNG, regardless of a carefully designed surveillance strategy, eradication is implausible at current intensities of surveillance and control and these efforts should be doubled if they are to be successful. This is crucial information in the face of environmentally and economically damaging invasive species and large, expensive and potentially ineffective control programmes.

Microeconometric Studies on Unemployment and Business Cycles

Väitöskirja koostuu neljästä esseestä, joissa tutkitaan empiirisen työntaloustieteen kysymyksiä. Ensimmäinen essee tarkastelee työttömyysturvan tason vaikutusta työllistymiseen Suomessa. Vuonna 2003 ansiosidonnaista työttömyysturvaa korotettiin työntekijöille, joilla on pitkä työhistoria. Korotus oli keskimäärin 15 % ja se koski ensimmäistä 150 työttömyyspäivää. Tutkimuksessa arvioidaan korotuksen vaikutus vertailemalla työllistymisen todennäköisyyksiä korotuksen saaneen ryhmän ja vertailuryhmän välillä ennen uudistusta ja sen jälkeen. Tuloksien perusteella työttömyysturvan korotus laski työllistymisen todennäköisyyttä merkittävästi, keskimäärin noin 16 %. Korotuksen vaikutus on suurin työttömyyden alussa ja se katoaa kun oikeus korotettuun ansiosidonnaiseen päättyy. Toinen essee tutkii työttömyyden pitkän aikavälin kustannuksia Suomessa keskittyen vuosien 1991 – 1993 syvään lamaan. Laman aikana toimipaikkojen sulkeminen lisääntyi paljon ja työttömyysaste nousi yli 13 prosenttiyksikköä. Tutkimuksessa verrataan laman aikana toimipaikan sulkemisen vuoksi työttömäksi jääneitä parhaassa työiässä olevia miehiä työllisinä pysyneisiin. Työttömyyden vaikutusta tarkastellaan kuuden vuoden seurantajaksolla. Vuonna 1999 työttömyyttä laman aikana kokeneen ryhmän vuosiansiot olivat keskimäärin 25 % alemmat kuin vertailuryhmässä. Tulojen menetys johtui sekä alhaisemmasta työllisyydestä että palkkatasosta. Kolmannessa esseessä tarkastellaan Suomen 1990-luvun alun laman aiheuttamaa työttömyysongelmaa tutkimalla työttömyyden kestoon vaikuttavia tekijöitä yksilötasolla. Kiinnostuksen kohteena on työttömyyden rakenteen ja työn kysynnän muutoksien vaikutus keskimääräiseen kestoon. Usein oletetaan, että laman seurauksena työttömäksi jää keskimääräistä huonommin työllistyviä henkilöitä, jolloin se itsessään pidentäisi keskimääräistä työttömyyden kestoa. Tuloksien perusteella makrotason kysyntävaikutus oli keskeinen työttömyyden keston kannalta ja rakenteen muutoksilla oli vain pieni kestoa lisäävä vaikutus laman aikana. Viimeisessä esseessä tutkitaan suhdannevaihtelun vaikutusta työpaikkaonnettomuuksien esiintymiseen. Tutkimuksessa käytetään ruotsalaista yksilötason sairaalahoitoaineistoa, joka on yhdistetty populaatiotietokantaan. Aineiston avulla voidaan tutkia vaihtoehtoisia selityksiä onnettomuuksien lisääntymiselle noususuhdanteessa, minkä on esitetty johtuvan esim. stressin tai kiireen vaikutuksesta. Tuloksien perusteella työpaikkaonnettomuudet ovat syklisiä, mutta vain tiettyjen ryhmien kohdalla. Työvoiman rakenteen vaihtelu saattaa selittää osan naisten onnettomuuksien syklisyydestä. Miesten kohdalla vain vähemmän vakavat onnettomuudet ovat syklisiä, mikä saattaa johtua strategisesta käyttäytymisestä.

Dynamics of Finnish starlings in 1951-2005 : from monitoring to population modelling

Farmland bird species have been declining in Europe. Many declines have coincided with general intensification of farming practices. In Finland, replacement of mixed farming, including rotational pastures, with specialized cultivation has been one of the most drastic changes from the 1960s to the 1990s. This kind of habitat deterioration limits the persistence of populations, as has been previously indicated from local populations. Integrated population monitoring, which gathers species-specific information of population size and demography, can be used to assess the response of a population to environment changes also at a large spatial scale. I targeted my analysis at the Finnish starling (Sturnus vulgaris). Starlings are common breeders in farmland habitats, but severe declines of local populations have been reported from Finland in the 1970s and 1980s and later from other parts of Europe. Habitat deterioration (replacement of pasture and grassland habitats with specialized cultivation areas) limits reproductive success of the species. I analysed regional population data in order to exemplify the importance of agricultural change to bird population dynamics. I used nestling ringing and nest-card data from 1951 to 2005 in order to quantify population trends and per capita reproductive success within several geographical regions (south/north and west/east aspects). I used matrix modelling, acknowledging age-specific survival and fecundity parameters and density-dependence, to model population dynamics. Finnish starlings declined by 80% from the end of the 1960s up to the end of the 1980s. The observed patterns and the model indicated that the population decline was due to the decline of the carrying capacity of farmland habitats. The decline was most severe in north Finland where populations largely become extinct. However, habitat deterioration was most severe in the southern breeding areas. The deteriorations in habitat quality decreased reproduction, which finally caused the decline. I suggest that poorly-productive northern populations have been partly maintained by immigration from the highly-productive southern populations. As the southern populations declined, ceasing emigration caused the population extinction in north. This phenomenon was explained with source sink population dynamics, which I structured and verified on the basis of a spatially explicit simulation model. I found that southern Finnish starling population exhibits ten-year cyclic regularity, a phenomenon that can be explained with delayed density-dependence in reproduction.

Association between molecular variation in the phosphoglucose isomerase (Pgi) locus and migration propensity in the Glanville fritillary butterfly

Habitat fragmentation produces patches of suitable habitat surrounded by unfavourable matrix habitat. A species may persist in such a fragmented landscape in an equilibrium between the extinctions and recolonizations of local populations, thus forming a metapopulation. Migration between local populations is necessary for the long-term persistence of a metapopulation. The Glanville fritillary butterfly (Melitaea cinxia) forms a metapopulation in the Åland islands in Finland. There is migration between the populations, the extent of which is affected by several environmental factors and variation in the phenotype of individual butterflies. Different allelic forms of the glycolytic enzyme phosphoglucose isomerase (Pgi) has been identified as a possible genetic factor influencing flight performance and migration rate in this species. The frequency of a certain Pgi allele, Pgi-f, follows the same pattern in relation to population age and connectivity as migration propensity. Furthermore, variation in flight metabolic performance, which is likely to affect migration propensity, has been linked to genetic variation in Pgi or a closely linked locus. The aim of this study was to investigate the association between Pgi genotype and the migration propensity in the Glanville fritillary both at the individual and population levels using a statistical modelling approach. A mark-release-recapture (MRR) study was conducted in a habitat patch network of M. cinxia in Åland to collect data on the movements of individual butterflies. Larval samples from the study area were also collected for population level examinations. Each butterfly and larva was genotyped at the Pgi locus. The MRR data was parameterised with two mathematical models of migration: the Virtual Migration Model (VM) and the spatially explicit diffusion model. VM model predicted and observed numbers of emigrants from populations with high and low frequencies of Pgi-f were compared. Posterior predictive data sets were simulated based on the parameters of the diffusion model. Lack-of-fit of observed values to the model predicted values of several descriptors of movements were detected, and the effect of Pgi genotype on the deviations was assessed by randomizations including the genotype information. This study revealed a possible difference in the effect of Pgi genotype on migration propensity between the two sexes in the Glanville fritillary. The females with and males without the Pgi-f allele moved more between habitat patches, which is probably related to differences in the function of flight in the two sexes. Females may use their high flight capacity to migrate between habitat patches to find suitable oviposition sites, whereas males may use it to acquire mates by keeping a territory and fighting off other intruding males, possibly causing them to emigrate. The results were consistent across different movement descriptors and at the individual and population levels. The effect of Pgi is likely to be dependent on the structure of the landscape and the prevailing environmental conditions.

Triplet excited electronic state switching induced by hydrogen bonding: A transient absorption spectroscopy and time-dependent DFT study

The solvent plays a decisive role in the photochemistry and photophysics of aromatic ketones. Xanthone (XT) is one such aromatic ketone and its triplet-triplet (T-T) absorption spectra show intriguing solvatochromic behavior. Also, the reactivity of XT towards H-atom abstraction shows an unprecedented decrease in protic solvents relative to aprotic solvents. Therefore, a comprehensive solvatochromic analysis of the triplet-triplet absorption spectra of XT was carried out in conjunction with time dependent density functional theory using the ad hoc explicit solvent model approach. A detailed solvatochromic analysis of the T-T absorption bands of XT suggests that the hydrogen bonding interactions are different in the corresponding triplet excited states. Furthermore, the contributions of non-specific and hydrogen bonding interactions towards differential solvation of the triplet states in protic solvents were found to be of equal magnitude. The frontier molecular orbital and electron density difference analysis of the T-1 and T-2 states of XT indicates that the charge redistribution in these states leads to intermolecular hydrogen bond strengthening and weakening, respectively, relative to the S-0 state. This is further supported by the vertical excitation energy calculations of the XT-methanol supra-molecular complex. The intermolecular hydrogen bonding potential energy curves obtained for this complex in the S-0, T-1, and T-2 states support the model. In summary, we propose that the different hydrogen bonding mechanisms exhibited by the two lowest triplet excited states of XT result in a decreasing role of the n pi* triplet state, and are thus responsible for its reduced reactivity towards H-atom abstraction in protic solvents. (C) 2016 AIP Publishing LLC.

Sobrevida e fatores prognósticos para o câncer de mama em Juiz de Fora, Minas Gerais, na coorte diagnosticada entre 1998 e 2000

Este estudo teve como objetivo analisar a sobrevida e fatores prognósticos para o câncer de mama feminino, com ênfase no papel de variáveis relacionadas aos serviços de saúde. Foram analisadas 782 mulheres com câncer invasivo da mama e submetidas à cirurgia curativa, que realizaram tratamento cirúrgico e/ou terapia complementar no município de Juiz de Fora, Minas Gerais, com diagnóstico da doença entre 1998 e 2000. O recrutamento dos casos foi efetuado a partir de busca ativa nos registros médicos de todos os serviços de saúde que prestam atendimento em oncologia na cidade. O seguimento foi realizado mediante retorno aos prontuários e complementado por busca no banco do Sistema de Informação sobre Mortalidade (SIM), contato telefônico e consulta de situação cadastral no Cadastro de Pessoas Físicas (CPF). As principais variáveis analisadas foram: cor da pele, idade ao diagnóstico, tamanho do tumor, comprometimento de linfonodos, estadiamento, cidade de residência e variáveis relativas aos serviços de saúde, entre outras. As funções de sobrevida foram calculadas por meio do método de Kaplan-Meier. Foi utilizado o modelo de riscos proporcionais de Cox para avaliação dos fatores prognósticos. No primeiro artigo, foi observada taxa de sobrevida específica em cinco anos de 80,9%, sendo identificados tamanho tumoral e comprometimento de linfonodos axilares como importantes fatores prognósticos associados de forma independente à sobrevida pela doença na população de estudo (HR=1,99, IC95%: 1,27-3,10 e HR=3,92, IC95%: 2,49-6,16, respectivamente). No segundo artigo, quando consideradas as variáveis relativas aos serviços de saúde, foi verificada pior sobrevida para as mulheres assistidas no serviço público, embora com significância limítrofe (p=0,05), e para aquelas que não tinham plano privado de saúde, apesar de não significativa (p=0,1). As funções de sobrevida não ajustadas e estratificadas por natureza do serviço de saúde exibiram sobrevida mais desfavorável para as mulheres não brancas e para os casos com nenhum ou menos de 10 linfonodos isolados somente no serviço público, embora com significâncias estatísticas apenas marginais (p=0,09 e p=0,07, respectivamente). Na análise multivariada, foi observado maior risco de óbito nas mulheres que não fizeram uso de hormonioterapia apenas para os casos assistidos no serviço público (HR=1,56; IC95%: 1,01-2,41), independentemente do tamanho tumoral e do status ganglionar axilar. Tais achados sugerem desigualdades sociais e disparidades na prevenção primária e secundária da doença na região estudada, com desvantagem para o serviço público de saúde, enfatizando a maior necessidade de esclarecimento sobre a doença, assim como de diagnóstico e tratamento dos casos em estádios mais precoces. Destacou-se, ainda, o valor de se trabalhar com informações produzidas pelos serviços de saúde responsáveis pela assistência oncológica no país, possibilitando a caracterização do perfil e da sobrevida das pacientes assistidas e fornecendo subsídios aos órgãos competentes do setor saúde local para nortear a adoção de estratégias de prevenção direcionadas ao controle da doença na população avaliada.

Fault-tolerant aspects of MPC

The architecture of model predictive control (MPC), with its explicit internal model and constrained optimization is presented. Since MPC relies on an explicit internal model, one can imagine dealing with failures by updating the internal model, and letting the on-line optimizer work out how to control the system in its new condition. This aspects rely on assumptions such that the nature of the fault can be located, and the model can be updated automatically. A standard form of MPC, with linear inequality constraints on inputs and outputs, linear internal model, and quadriatic cost function.

POMDP-based statistical spoken dialog systems: A review

Statistical dialog systems (SDSs) are motivated by the need for a data-driven framework that reduces the cost of laboriously handcrafting complex dialog managers and that provides robustness against the errors created by speech recognizers operating in noisy environments. By including an explicit Bayesian model of uncertainty and by optimizing the policy via a reward-driven process, partially observable Markov decision processes (POMDPs) provide such a framework. However, exact model representation and optimization is computationally intractable. Hence, the practical application of POMDP-based systems requires efficient algorithms and carefully constructed approximations. This review article provides an overview of the current state of the art in the development of POMDP-based spoken dialog systems. © 1963-2012 IEEE.

不同森林管理预案下友好林业局森林景观的动态变化

Knowledge about cumulative effects of forest management alternatives on forest landscape is required to make forest management decision. In this paper,a spatially explicit landscape model,LANDIS,was applied to simulate forest landscape changes in 200 years under four management alternatives (no cutting,clearcutting,selective cutting I and II) in Youhao Forestry Bureau located in Small Khingan Mountains. APACK was used to calculate distribution area of the representative species and species age cohort for six species. The results showed:1) timber harvest decreased area percentage of representative conifer species,Pinus koraiensis,Picea koraiensis and Picea jezoensis,Larix gmelinii to some extent compared to no cutting. The most influencing cutting mode for the area percentage of Tilia amurensis and Quercus mongolica was selective cutting II,followed by selective cutting I and clearcutting. To the contrast,the change of area percentage of Betula phatyphylla was contrary to the management alternatives; 2) As to species age cohort composition,timber harvest significantly changed age structure,that is,it decreased over-matured age cohort of representative species,and increased seedling and middle-age cohort (B. phatyphylla was not included,because its area percentage of over-mature age cohort was the highest under clearcutting than other three scenarios).

地理信息系统与基于个体的空间直观景观模型

In this paper,the development of Individual-based Spatial Explicit Landscape Model was outlined at first.Then several issues,pertaining to develop Individual-based Spatial Explicit Landscape Models,were discussed in details.And at last,the application perspectives of such models were illustrated,including animal movement,plant competition and landscape change.This study has relatively important significance guiding roles in developing Individual-based Spatial Explicit Landscape Model in our country and in landscape management.

Survival analysis of adult tuberculosis disease

Background: We conducted a survival analysis of all the confirmed cases of Adult Tuberculosis (TB) patients treated in Cork-City, Ireland. The aim of this study was to estimate Survival time (ST), including median time of survival and to assess the association and impact of covariates (TB risk factors) to event status and ST. The outcome of the survival analysis is reported in this paper. Methods: We used a retrospective cohort study research design to review data of 647 bacteriologically confirmed TB patients from the medical record of two teaching hospitals. Mean age 49 years (Range 18–112). We collected information on potential risk factors of all confirmed cases of TB treated between 2008–2012. For the survival analysis, the outcome of interest was ‘treatment failure’ or ‘death’ (whichever came first). A univariate descriptive statistics analysis was conducted using a non- parametric procedure, Kaplan -Meier (KM) method to estimate overall survival (OS), while the Cox proportional hazard model was used for the multivariate analysis to determine possible association of predictor variables and to obtain adjusted hazard ratio. P value was set at <0.05, log likelihood ratio test at >0.10. Data were analysed using SPSS version 15.0. Results: There was no significant difference in the survival curves of male and female patients. (Log rank statistic = 0.194, df = 1, p = 0.66) and among different age group (Log rank statistic = 1.337, df = 3, p = 0.72). The mean overall survival (OS) was 209 days (95%CI: 92–346) while the median was 51 days (95% CI: 35.7–66). The mean ST for women was 385 days (95%CI: 76.6–694) and for men was 69 days (95%CI: 48.8–88.5). Multivariate Cox regression showed that patient who had history of drug misuse had 2.2 times hazard than those who do not have drug misuse. Smokers and alcohol drinkers had hazard of 1.8 while patients born in country of high endemicity (BICHE) had hazard of 6.3 and HIV co-infection hazard was 1.2. Conclusion: There was no significant difference in survival curves of male and female and among age group. Women had a higher ST compared to men. But men had a higher hazard rate compared to women. Anti-TNF, immunosuppressive medication and diabetes were found to be associated with longer ST, while alcohol, smoking, RICHE, BICHE was associated with shorter ST.