Australian data do not support current pharmaceutical benefits scheme criteria for use of tumour necrosis factor-α inhibitors in ankylosing spondylitis

On the basis of local data, we write in support of the conclusions of Smith and Ahern that current Pharmaceu- tical Benefits Scheme (PBS) criteria for tumour necrosis factor (TNF)-a inhibitors in ankylosing spondylitis (AS) are not evidence-based. 1 As a prerequisite to the appropriate use of biological therapy in AS, three aspects of the disease need to be defined: (i) diagnosis, (ii) activity and (iii) therapeutic failure (Table 1)....

Intra-cluster correlation structure in longitudinal data analysis: Selection criteria and misspecification tests

Selection criteria and misspecification tests for the intra-cluster correlation structure (ICS) in longitudinal data analysis are considered. In particular, the asymptotical distribution of the correlation information criterion (CIC) is derived and a new method for selecting a working ICS is proposed by standardizing the selection criterion as the p-value. The CIC test is found to be powerful in detecting misspecification of the working ICS structures, while with respect to the working ICS selection, the standardized CIC test is also shown to have satisfactory performance. Some simulation studies and applications to two real longitudinal datasets are made to illustrate how these criteria and tests might be useful.

Criteria for working-correlation-structure selection in GEE: Assessment via simulation

Efficiency of analysis using generalized estimation equations is enhanced when intracluster correlation structure is accurately modeled. We compare two existing criteria (a quasi-likelihood information criterion, and the Rotnitzky-Jewell criterion) to identify the true correlation structure via simulations with Gaussian or binomial response, covariates varying at cluster or observation level, and exchangeable or AR(l) intracluster correlation structure. Rotnitzky and Jewell's approach performs better when the true intracluster correlation structure is exchangeable, while the quasi-likelihood criteria performs better for an AR(l) structure.

Bi-criteria single machine scheduling problem with a learning effect: Aneja-Nair method to obtain the set of optimal sequences

In this paper, we consider the bi-criteria single machine scheduling problem of n jobs with a learning effect. The two objectives considered are the total completion time (TC) and total absolute differences in completion times (TADC). The objective is to find a sequence that performs well with respect to both the objectives: the total completion time and the total absolute differences in completion times. In an earlier study, a method of solving bi-criteria transportation problem is presented. In this paper, we use the methodology of solvin bi-criteria transportation problem, to our bi-criteria single machine scheduling problem with a learning effect, and obtain the set of optimal sequences,. Numerical examples are presented for illustrating the applicability and ease of understanding.

Variation in exotic and native seed arrival and recruitment of bird dispersed species in subtropical forest restoration and regrowth

Invasive bird-dispersed plants often share the same suite of dispersers as co-occurring native species, resulting in a complex management issue. Integrated management strategies could incorporate manipulation of dispersal or establishment processes. To improve our understanding of these processes, we quantified seed rain, recruit and seed bank density, and species richness for bird-dispersed invasive and native species in three early successional subtropical habitats in eastern Australia: tree regrowth, shrub regrowth and native restoration plantings. We investigated the effects of environmental factors (leaf area index (LAI), distance to edge, herbaceous ground cover and distance to nearest neighbour) on seed rain, seed bank and recruit abundance. Propagule availability was not always a good predictor of recruitment. For instance, although native tree seed rain density was similar, and species richness was higher, in native plantings, compared with tree regrowth, recruit density and species richness were lower. Native plantings also received lower densities of invasive tree seed rain than did tree regrowth habitats, but supported a similar density of invasive tree recruits. Invasive shrub seed rain was recorded in highest densities in shrub regrowth sites, but recruit density was similar between habitats. We discuss the role of microsite characteristics in influencing post-dispersal processes and recruit composition, and suggest ways of manipulating these processes as part of an integrated management strategy for bird-dispersed weeds in natural areas.

Exact solutions of linear reaction-diffusion on a uniformly growing domain: criteria for successful colonization

Many processes during embryonic development involve transport and reaction of molecules, or transport and proliferation of cells, within growing tissues. Mathematical models of such processes usually take the form of a reaction-diffusion partial differential equation (PDE) on a growing domain. Previous analyses of such models have mainly involved solving the PDEs numerically. Here, we present a framework for calculating the exact solution of a linear reaction-diffusion PDE on a growing domain. We derive an exact solution for a general class of one-dimensional linear reaction—diffusion process on 0

To reactivate or not to reactivate : Control of KSHV lytic replication is essential for apoptosis in response to p53 restoration

Kaposi's sarcoma herpesvirus (KSHV) is an oncogenic human virus and the causative agent of three human malignancies: Kaposi's sarcoma (KS), Multicentric Castleman's Disease (MCD), and primary effusion lymphoma (PEL). In tumors, KSHV establishes latent infection during which it produces no infectious particles. Latently infected cells can enter the lytic replication cycle, and upon provision of appropriate cellular signals, produce progeny virus. PEL, commonly described in patients with AIDS, represents a diffuse large-cell non-Hodgkin's lymphoma, with median survival time less than six months after diagnosis. As tumor suppressor gene TP53 mutations occur rarely in PEL, the aim of this thesis was to investigate whether non-genotoxic activation of the p53 pathway can eradicate malignant PEL cells. This thesis demonstrates that Nutlin-3, a small-molecule inhibitor of the p53-MDM2 interaction, efficiently restored p53 function in PEL cells, leading to cell cycle arrest and massive apoptosis. Furthermore, we found that KSHV infection activated DNA damage signaling, rendering the cells more sensitive to p53-dependent cell death. We also showed in vivo the therapeutic potential of p53 restoration that led to regression of subcutaneous and intraperitoneal PEL tumor xenografts without adversely affecting normal cells. Importantly, we demonstrated that in a small subset of intraperitoneal PEL tumors, spontaneous induction of viral reactivation dramatically impaired Nutlin-3-induced p53-mediated apoptosis. Accordingly, we found that elevated KSHV lytic transcripts correlated with PEL tumor burden in animals and that inhibition of viral reactivation in vitro restored cytotoxic activity of a small-molecule inhibitor of the p53-MDM2 interaction. Latency provides a unique opportunity for KSHV to escape host immune surveillance and to establish persistent infections. However, to maintain viral reservoirs and spread to other hosts, KSHV must be reactivated from latency and enter into the lytic growth phase. We showed that phosphorylation of nucleolar phosphoprotein nucleophosmin (NPM) by viral cyclin-CDK6 is critical for establishment and maintenance of the KSHV latency. In short, this study provides evidence that the switch between latent phase and lytic replication is a critical step that determines the outcome of viral infection and the pathogenesis of KSHV-induced malignancies. Our data may thus contribute to development of novel targeted therapies for intervention and treatment of KSHV-associated cancers.

Oscillation criteria for differential equations of second order

In this article, we give sufficient condition in the form of integral inequalities to establish the oscillatory nature of non linear homogeneous differential equations of the form where r, q, p, f and g are given data. We do this by separating the two cases f is monotonous and non monotonous.

Stability criteria for single pulse solutions of cw passive mode-locked lasers

The stability of the steady-state solutions of mode-locking of cw lasers by a fast saturable absorber is imvestigated. It is shown that the solutions are stable if the condition (Ps/Pa) = (2/3) (P0Pa) is satisfied, where (Ps/Pa) is the steady-state la ser power, (P0/Pa) is the power at mode-locking threshold, and Pa is the saturated power of the absorber.

Landscape-scale soil erosion modelling and ecological restoration for a mountainous watershed in Sichuan, China

Sichuanissa Tiibetin ylängön metsäkato on pysähtynyt mutta eroosio-ongelmat jatkuvat Viikin tropiikki-instituutin tutkija Ping ZHOU kartoitti trooppisen metsänhoidon alaan kuuluvassa väitöskirjatyössään maaperän eroosioalttiutta ja sen riippuvuutta metsäkasvillisuudesta Jangtsen tärkeää sivuhaaraa Min-jokea ympäröivällä n. 7400 neliökilometrin suuruisella valuma-alueella Sichuanin Aba-piirikunnassa. Aineistonaan hän käytti muun muassa satelliittikartoitustietoja ja mittaustuloksia yli 600 maastokoealalta. Tutkimuksen nimi suomeksi on "Maaperän eroosion mallinnus ja vuoristoisen valuma-alueen ekologinen ennallistaminen Sichuanissa Kiinassa". Aikaisempien tutkimusten perusteella oli tiedossa että metsien häviäminen tällä alueella pysähtyi jo 1980-luvun alussa. Sen jälkeen on metsien pinta-ala hitaasti kasvanut etupäässä sen vuoksi, että teollinen puunhakkuu luonnonmetsissä kiellettiin kokonaan v. 1998 ja 25 astetta jyrkemmillä rinteillä myös maatalouden harjoittaminen on saatu lopetetuksi viljelijöille tarjottujen taloudellisten houkuttimien avulla. Täten myös pelto- ja laidunmaata on voitu ennallistaa metsäksi. Ping Zhou pystyi jakamaan 5700 metrin korkeuteen saakka kohoavan vuoristoalueen eroosioalttiudeltaan erilaisiin vyöhykkeisiin rinteen kaltevuuden, sademäärän, kasvipeitteen ja maalajin perusteella. Noin 15 prosentilla tutkitun valuma-alueen pinta-alasta, lähinnä Min-joen pääuomaa ympäröivillä jyrkillä rinteillä, eroosioriski oli suuri tai erittäin suuri. Eri tyyppisellä kasvillisuudella oli hyvin erilainen vaikutus eroosioalttiuteen, ja myös alueen sijainti vuoriston eri korkeuksilla vaikutti eroosioon. Säästyneet lähes luonnontilaiset havumetsät, joita on etupäässä vuoriston ylimmissä osissa 2600-4000 metrin korkeudella, edistävät tehokkaasti metsän luontaista uudistumista ja levittäytymistä vaurioituneille alueille. Säilyneiden metsien puulajikoostumus antoi tutkimuksessa mahdollisuuden ennustaa metsien tulevaa kehitystä koko tutkitulla valuma-alueella sen eri korkeusvyöhykkeissä ja eri maaperätyypeillä. Ennallistamisen kannalta ongelmallisimpia olivat alueet joilta metsäpeite oli lähinnä puiden teollisen hakkuun vuoksi kokonaan hävinnyt ja joilla maaperä yleisesti oli eroosion pahoin kuluttama. Näillä alueilla ei ole tehty juuri mitään uudistamis- tai ennallistamistoimenpiteitä. Niillä metsien ennallistaminen vaatii myös puiden tai pensaiden istuttamista. Tähän sopivia ovat erityisesti ilmakehän typpeä sitovat lajit, joista alueella kasvaa luontaisena mm. sama tyrnilaji joka esiintyy myös Suomessa. Työssä tutkittiin yli kahdeksankymmenen paikallisen luontaisen puulajin (joista peräti noin kolmannes on havupuulajeja) ekologisia ominaisuuksia ja soveltuvuutta metsien ennallistamiseen. Avainasemassa työn onnistumisen kannalta ovat nyt paikalliset asukkaat, joiden maankäytön muutokset ovat jo selvästi edistänet luonnonmetsän ennalleen palautumista. Suomen Akatemia rahoitti vuosina 2004-2006 VITRI:n tutkimushanketta, josta Ping Zhou'n väitöskirjatyö muodosti keskeisen osan. Kenttätyö Sichuanissa avasi mahdollisuuden hedelmälliseen monitieteiseen yhteistyöhön ja tutkijavaihtoon Kiinan tiedeakatemian alaisen Chengdun biologiainstituutin (CIB) kanssa; tämä tieteellinen kanssakäyminen jatkuu edelleen.

Ecological restoration of forests in Fennoscandia : Defining reference stand structures and immediate effects of restoration.

The first aim of this thesis was to explore the structural characteristics of near-natural forests and to quantify how human utilization has changed them. For this, we examined the stand characteristics in Norway spruce Picea abies (L.) Karst-dominated old-growth stands in northwestern Russia and in old Scots pine Pinus sylvestris L.-dominated stands in three regions from southern Finland to northwestern Russia. In the second study, we also compared stands with different degrees of human impact, from near-natural stands and stands selectively cut in the past to managed stands. Secondly, we used an experimental approach to study the short-term effects of different restorative treatments on forest structure and regeneration in managed Picea abies stands in southern Finland. Restorative treatments consisted of a partial cut combined with three levels of coarse woody debris retention, and a fire/no-fire treatment. In addition, we examined burned and unburned reference stands without cutting treatments. Results from near-natural Picea abies forests emphasize the dynamic character of old-growth forests, the variety of late-successional forest structures, and the fact that extended time periods are needed to attain certain late-successional stages with specific structural and habitat attributes, such as large-diameter deciduous trees and a variety of deadwood. The results from old Pinus sylvestris-dominated forests showed that human impact in the form of forest utilization and fire exclusion has strongly modified and reduced the structural complexity of stands. Consequently, small protected forest fragments in Finland may not serve as valid natural reference areas for forest restoration. However, results from the restoration experiment showed that early-successional natural stand characteristics can be restored to structurally impoverished managed Picea abies stands, despite a significant portion of wood volume being harvested. A variety of restoration methods is needed, due to differences in the condition of the forest when restoration is initiated and the variety of successional stages of forest structures after anthropogenic and natural disturbances. Keywords: dead wood, disturbance dynamic, fire, near-natural stand, rehabilitation, succession

Soil nitrogen—crop response calibration relationships and criteria for winter cereal crops grown in Australia

More than 1200 wheat and 120 barley experiments conducted in Australia to examine yield responses to applied nitrogen (N) fertiliser are contained in a national database of field crops nutrient research (BFDC National Database). The yield responses are accompanied by various pre-plant soil test data to quantify plant-available N and other indicators of soil fertility status or mineralisable N. A web application (BFDC Interrogator), developed to access the database, enables construction of calibrations between relative crop yield ((Y0/Ymax) × 100) and N soil test value. In this paper we report the critical soil test values for 90% RY (CV90) and the associated critical ranges (CR90, defined as the 70% confidence interval around that CV90) derived from analysis of various subsets of these winter cereal experiments. Experimental programs were conducted throughout Australia’s main grain-production regions in different eras, starting from the 1960s in Queensland through to Victoria during 2000s. Improved management practices adopted during the period were reflected in increasing potential yields with research era, increasing from an average Ymax of 2.2 t/ha in Queensland in the 1960s and 1970s, to 3.4 t/ha in South Australia (SA) in the 1980s, to 4.3 t/ha in New South Wales (NSW) in the 1990s, and 4.2 t/ha in Victoria in the 2000s. Various sampling depths (0.1–1.2 m) and methods of quantifying available N (nitrate-N or mineral-N) from pre-planting soil samples were used and provided useful guides to the need for supplementary N. The most regionally consistent relationships were established using nitrate-N (kg/ha) in the top 0.6 m of the soil profile, with regional and seasonal variation in CV90 largely accounted for through impacts on experimental Ymax. The CV90 for nitrate-N within the top 0.6 m of the soil profile for wheat crops increased from 36 to 110 kg nitrate-N/ha as Ymax increased over the range 1 to >5 t/ha. Apparent variation in CV90 with seasonal moisture availability was entirely consistent with impacts on experimental Ymax. Further analyses of wheat trials with available grain protein (~45% of all experiments) established that grain yield and not grain N content was the major driver of crop N demand and CV90. Subsets of data explored the impact of crop management practices such as crop rotation or fallow length on both pre-planting profile mineral-N and CV90. Analyses showed that while management practices influenced profile mineral-N at planting and the likelihood and size of yield response to applied N fertiliser, they had no significant impact on CV90. A level of risk is involved with the use of pre-plant testing to determine the need for supplementary N application in all Australian dryland systems. In southern and western regions, where crop performance is based almost entirely on in-crop rainfall, this risk is offset by the management opportunity to split N applications during crop growth in response to changing crop yield potential. In northern cropping systems, where stored soil moisture at sowing is indicative of minimum yield potential, erratic winter rainfall increases uncertainty about actual yield potential as well as reducing the opportunity for effective in-season applications.

Soil phosphorus–crop response calibration relationships and criteria for winter cereal crops grown in Australia

Soil testing is the most widely used tool to predict the need for fertiliser phosphorus (P) application to crops. This study examined factors affecting critical soil P concentrations and confidence intervals for wheat and barley grown in Australian soils by interrogating validated data from 1777 wheat and 150 barley field treatment series now held in the BFDC National Database. To narrow confidence intervals associated with estimated critical P concentrations, filters for yield, crop stress, or low pH were applied. Once treatment series with low yield (<1 t/ha), severe crop stress, or pHCaCl2 <4.3 were screened out, critical concentrations were relatively insensitive to wheat yield (>1 t/ha). There was a clear increase in critical P concentration from early trials when full tillage was common compared with those conducted in 1995–2011, which corresponds to a period of rapid shift towards adoption of minimum tillage. For wheat, critical Colwell-P concentrations associated with 90 or 95% of maximum yield varied among Australian Soil Classification (ASC) Orders and Sub-orders: Calcarosol, Chromosol, Kandosol, Sodosol, Tenosol and Vertosol. Soil type, based on ASC Orders and Sub-orders, produced critical Colwell-P concentrations at 90% of maximum relative yield from 15 mg/kg (Grey Vertosol) to 47 mg/kg (Supracalcic Calcarosols), with other soils having values in the range 19–27 mg/kg. Distinctive differences in critical P concentrations were evident among Sub-orders of Calcarosols, Chromosols, Sodosols, Tenosols, and Vertosols, possibly due to differences in soil properties related to P sorption. However, insufficient data were available to develop a relationship between P buffering index (PBI) and critical P concentration. In general, there was no evidence that critical concentrations for barley would be different from those for wheat on the same soils. Significant knowledge gaps to fill to improve the relevance and reliability of soil P testing for winter cereals were: lack of data for oats; the paucity of treatment series reflecting current cropping practices, especially minimum tillage; and inadequate metadata on soil texture, pH, growing season rainfall, gravel content, and PBI. The critical concentrations determined illustrate the importance of recent experimental data and of soil type, but also provide examples of interrogation pathways into the BFDC National Database to extract locally relevant critical P concentrations for guiding P fertiliser decision-making in wheat and barley.