bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling Reactions Catalysed by Carbohydrate-Active Enzymes
Authors: Kartal Önder , Ebenhöh Oliver
Published: September 2014

Carbohydrate polymers are ubiquitous in biological systems and their roles are highly diverse, ranging from energy storage over mechanical stabilisation to mediating cell-cell or cell-protein interactions. The functional diversity is mirrored by a chemical diversity that results from the high flexibility of how different sugar monomers can be arranged into linear, branched or cyclic polymeric structures. Mathematical models describing biochemical processes on polymers are faced with various difficulties. First, polymer-active enzymes are often specific to some local configuration within the polymer but are indifferent to other features. That is they are potentially active on a large variety of different chemical compounds, meaning that polymers of different size and structure simultaneously compete for enzymes. Second, especially large polymers interact with each other and form water-insoluble phases that restrict or exclude the formation of enzyme-substrate complexes. This heterogeneity of the reaction system has to be taken into account by explicitly considering processes at the, often complex, surface of the polymer matrix. We review recent approaches to theoretically describe polymer biochemical systems. All attempts address a particular challenge, which we discuss in more detail. We emphasise a recent attempt which draws novel analogies between polymer biochemistry and statistical thermodynamics and illustrate how this parallel leads to novel insights about non-uniform polymer reactant mixtures. Finally, we discuss the future challenges of the young and growing field of theoretical polymer biochemistry.
The cell of origin and subtype of K-Ras-induced lung tumors are modified by Notch and Sox2
Authors: Xu Xia , Huang Lingling , Futtner Christopher , Schwab Brian , Rampersad Rishi R. , Lu Yun , Sporn Thomas A. , Hogan Brigid L.M. , Onaitis Mark W.
Published: September 2014

Cell type-specific conditional activation of oncogenic K-Ras is a powerful tool for investigating the cell of origin of adenocarcinomas in the mouse lung. Our previous studies showed that K-Ras activation with a CC10(Scgb1a1)-CreER driver leads to adenocarcinoma in a subset of alveolar type II cells and hyperplasia in the bronchioalveolar duct region. However, no tumors develop in the bronchioles, although recombination occurs throughout this region. To explore underlying mechanisms, we simultaneously modulated either Notch signaling or Sox2 levels in the CC10+ cells along with activation of K-Ras. Inhibition of Notch strongly inhibits adenocarcinoma formation but promotes squamous hyperplasia in the alveoli. In contrast, activation of Notch leads to widespread Sox2+, Sox9+, and CC10+ papillary adenocarcinomas throughout the bronchioles. Chromatin immunoprecipitation demonstrates Sox2 binding to NOTCH1 and NOTCH2 regulatory regions. In transgenic mouse models, overexpression of Sox2 leads to a significant reduction of Notch1 and Notch2 transcripts, while a 50% reduction in Sox2 leads to widespread papillary adenocarcinoma in the bronchioles. Taken together, our data demonstrate that the cell of origin of K-Ras-induced tumors in the lung depends on levels of Sox2 expression affecting Notch signaling. In addition, the subtype of tumors arising from type II cells is determined in part by Notch activation or suppression.
Systemic psychotherapy for ‘harder to reach’ families; mentalization‐based therapeutic interventions for families and the politics of empiricism
Authors: Donovan Mary
Published: September 2014

In this article I explore the relationship between systemic psychotherapy and the model of mentalization‐based therapeutic interventions for families (MBT‐F) presented by Eia Asen and Peter Fonagy. I consider two important contextual elements in MBT‐F; firstly, the influence of the empiricist tradition in which it is anchored and secondly, the political context of this work. Both elements need disentangling from theoretical and clinical concerns to facilitate greater clarity in debates about mentalization and in wider therapeutic discourse. In essence, I conclude that dialogue between systemic and mentalization perspectives can extend well beyond the empiricist framing of MBT‐F in directions that are more broadly consistent with systemic concerns and interests, not least of which is the ongoing challenge to engage ‘harder to reach’ families in innovative systemic psychotherapy.

Practitioner points

A focus on mentalization draws us towards the common ground between the different therapies and their shared challenges.

Thinking about mentalization has the potential to enhance the systemic practitioner's engagement with ‘harder to reach families’.

Thinking systemically has much to offer the mentalization debate.

Creative dialogue between systemic and mentalization perspectives can take many pathways beyond the empiricist framing of the MBT‐F model.
Do the Intellectual Property Rights of Importers Matter for Promoting Australian Exports?
Authors: Salim Ruhul , Al Mawali Nasser , Islam Amirul
Published: September 2014

This article provides the first empirical evidence on the effects of intellectual property rights (IPRs) and threat of imitation on Australia's export flows. Using data from all of Australia's trading partners over the period 1995–2010, an augmented gravity model is estimated in the context of an unbalanced panel. The empirical findings show that level of IPRs of importing countries and threat of imitation posed by the importing countries is both sensitive to Australian bilateral trade flows. These results therefore support the widely accepted positive nexus between the importance of IPRs and bilateral trade flows.
Are Queensland Residents Willing and Able to Respond to Time‐Varying Electricity Prices?
Authors:   Energex Limited and Ergon Energy Corporation Limited
Published: September 2014

Are Queensland residents willing and able to respond to varying electricity prices to reduce demand in peak times? To answer this, Energex and Ergon Energy conducted one of the largest tariff trials in Australia. The trial investigated time of use, dynamic peak pricing and load capacity tariffs across three climatic regions. This article presents empirical and participant survey results from the 27‐month trial. Results show participants across all regions achieved approximately a 19 per cent reduction in consumption during peak times on event days. Trial findings shed light on and challenge some long‐held views regarding pricing structures.
Should We Be Sceptical about Prospects for an ‘Asian Century’?
Authors: Walter Andrew
Published: September 2014

Many official and private commentators, particularly in Australia and in the Asian region, argue that the world is heading inexorably towards an ‘Asian Century’. They foresee a fundamental shift of economic and political power away from the West that will transform the world economy and global politics. I argue that, notwithstanding emerging Asia's undoubted economic achievements, this claim is premature and potentially misleading for three main reasons: implicit in many of these claims are implausible historical analogies with earlier eras of European and American dominance; linear projections of continued Asian growth outperformance may not be realised in practice; and even if rapid growth were to be sustained, the domestic and external obstacles to the collective global influence of Asia will probably remain profound. The implication is that businesses, citizens and policy‐makers, especially those operating in the Asian region, will face a much more uncertain and challenging environment than is sometimes acknowledged.
Another Look at the Economics of Minimum Wage Legislation
Authors: Burkhauser Richard V.
Published: September 2014

Economists have long been involved in public policy‐making, both as policy advisors and policy advocates. This article revisits the two questions that future Nobel Prize winner, George Stigler, posed to the economics profession in his seminal 1946 American Economic Review article urging us to speak out in the debate over the efficacy of increases in the minimum wage: (i) ‘Does such legislation diminish poverty?’; and (ii) ‘Are there efficient alternatives?’. I review this literature in the United States in the context of the Congressional Budget Office's answers in 2014 to these questions and what Australian policy‐makers can learn from them.
Science, Technology and Innovation Policy and Collaboration in the Asian Century
Authors: Palmer Lauren A.
Published: September 2014

Science, technology and innovation drive economies around the globe. Worldwide, governments are recognising the importance of international science collaboration and research and are investing heavily, developing programs that facilitate international collaboration. The United States and countries within Europe have long held an advantage in scientific collaboration; however, new superpowers are emerging in Asia. This provides new opportunities for Australia to strategically engage internationally, although Australia will need to act quickly to ensure it is not left behind in global science and innovation in the Asian Century.
Removable uterine compression sutures for postpartum haemorrhage
Authors: Zhang ZW , Liu CY , Yu N , Guo W
Published: September 2014

In 1997, B‐Lynch and colleagues introduced the B‐Lynch uterine compression suture for postpartum haemorrhage. Since then, various uterine compression sutures have been used and postpartum hysterectomy has been avoided in many women. However, some complications have emerged in years. In this article we discuss two types of uterine compression sutures in which stitches can be removed. The procedures have been successfully applied with no problems and no observed complications to date. This is a novel concept, with the potential to reduce morbidity related to compression sutures, but needs further evaluation.
Integrating flood depth and plant resistance with chlorantraniliprole seed treatments for management of rice water weevil, Lissorhoptrus oryzophilus (Coleoptera: Curculionidae)
Authors: Lanka Srinivas K. , Blouin David C. , Stout Michael J.
Published: September 2014

Chlorantraniliprole seed treatments in rice provide effective suppression of rice water weevil populations in the United States; however, heavy reliance on prophylactic insecticide treatments as a sole strategy could destabilize management programs for this insect. The present research evaluated the compatibility of seed treatments with two other potential management tactics—plant resistance and shallow flooding–by conducting two split‐plot experiments in 2009 and 2011. In both experiments, no substantial antagonism was found among the 3 different tactics. Statistical interactions in these experiments arose from the strong and persistent effects of chlorantraniliprole on larval densities rather than incompatibility of tactics. In 2009, weevil densities differed among varieties and were significantly lower on the cultivar “Jefferson.” In 2011, weevil densities were reduced significantly in shallow‐flooded plots compared to deep‐flooded plots. Significant reductions in weevil numbers by chlorantraniliprole seed treatments, even at application rates 5 fold lower than commercially recommended rates, demonstrated the potential to reduce application rates of this highly potent larvicide. These latter results suggest that future studies on the relationship between chlorantraniliprole seed treatment rate and weevil fitness are warranted.
Density and assemblage influence the nature of the species richness–productivity relationship in Australian dry sclerophyll forest species
Authors: Mallett Ruth K. , Hovenden Mark J.
Published: September 2014

The relationship between species richness and productivity is important from both a basic, theoretical perspective and also because it has important ramifications for applied ecology including ecosystem restoration and the design of carbon offset plantings. While a more species‐rich community is often believed to be more productive than a species‐poor community, findings from observational and experimental studies differ and our understanding of the relationship comes largely from grasslands. Consequently, we aimed to determine for the first time the nature of the species richness–productivity relationship in a southern‐hemisphere dry sclerophyll ecosystem. We investigated the impact of species richness on productivity, plant density and mean plant biomass at three sowing densities in three species assemblages. Eucalyptus globulus, Acacia mearnsii and Allocasuarina verticillata were each grown as monocultures and included in every subsequent level of species richness, forming three distinct species assemblages. Communities were grown in a glasshouse pot experiment for four months, then harvested and above‐ground biomass measured. We found no general species richness–productivity relationship in the communities studied. There were no overall increases in productivity as species richness increased and in fact in most cases the productivity of communities with 4 and 8 species was lower than monocultures of the dominants. Importantly, density influenced the way richness affected productivity and this effect was dependent upon assemblage, indicating that species identity is a key determinant of productivity. These results demonstrate important ecological principles in a previously untested system. A key outcome of this experiment is that density alters the relationship between species richness and initial productivity in assemblages of Australian dry sclerophyll species.
Whole range and regional‐based ecological niche models predict differing exposure to 21st century climate change in the key cool temperate rainforest tree southern beech (Nothofagus cunninghamii)
Authors: Worth James R. P. , Harrison Peter A. , Williamson Grant J. , Jordan Gregory J.
Published: September 2014

The warmer and drier climates projected for the mid‐ to late‐21st century may have particularly adverse impacts on the cool temperate rainforests of southeasternAustralia. Southern beech (Nothofagus cunninghamii;Nothofagaceae), a dominant tree species in these forests, may be vulnerable to minor changes in its climate envelope, especially at the edge of the species range, withHolocene fossil evidence showing local extinction of populations in response to small climate changes. We modelled the stability of this species climate envelope using the maximum entropy algorithm implemented inMaxent and two thresholds of presence/absence by projecting the modern climate envelope onto fourGlobalCirculationModels forecasted for two time periods (2050s and 2070s). The climate envelope, as estimated from the species present climatic range, is predicted to shrink by up to 49% by the 2050s and up to 64% by the 2070s. The greatest predicted reduction is inVictoria with 91–100% of its current range being climatically unsuitable by the 2070s. Climatically similar areas to the species present range are predicted to remain in mountainous areas of westernTasmania, theNortheastHighlands ofTasmania, and theBawBawPlateau in theCentralHighlands ofVictoria. However, region‐specific modelling approaches made very different predictions from the whole‐range based models, especially in the severity of the predicted decline forVictorian populations ofN. cunninghamiiwhich occur in much warmer climates than the rest of the species geographical range. This shows that, for widespread species that span a range of climate zones, the exposure of current populations to climate change may be better modelled using a regional based approach. How the species responds to climate change will depend on the species ability to respond to drier and warmer climates and the concomitant increase in fire intensity.
Preliminary data on dermis and subcutis thickness in adults with type 1 and 2 diabetes mellitus
Authors: Derraik José GB , Gusso Silmara , Peart Jane M , Rademaker Marius , Cutfield Wayne S , Hofman Paul L
Published: September 2014

We compared the thickness of both dermis and subcutis (measured using ultrasound) in overweight and obese adults with type 1 (n = 10) or type 2 (n = 8) diabetes mellitus. When adjusted for confounding factors, patients with type 1 diabetes had thicker subcutis than those with type 2 diabetes, with this difference being particularly marked in the abdomen. There were no observed differences in dermal thickness between the groups.
A retrospective review of cutaneous metastases at the National Skin Centre Singapore
Authors: Gan Emily Yiping , Chio Martin Tze‐Wei , Tan Wee Ping
Published: September 2014

Background/Objectives

Cutaneous metastases occur in up to 10% of all visceral malignancies. This study aims to determine the clinico‐epidemiological characteristics of patients diagnosed with cutaneous metastases at a leading Asian tertiary dermatological centre.

Methods

A retrospective chart review was carried out on all patients diagnosed with cutaneous metastases from 2001 to 2010, identified through the National Skin Centre's clinical and histological databases.

Results

In all, 35 patients were diagnosed with cutaneous metastases at a mean age of 65 years, with a female: male ratio of 3:2 and with most (97%) being Chinese. Cutaneous metastases were the first presentation of cancer in 34% of patients (n = 12). The two commonest primaries were breast (49%, n = 17) and lung (9%, n = 3). Most had cutaneous metastases on the chest (37%, n = 13) followed by the pelvis (17%, n = 6) and 20% (n = 7) had skin lesions on multiple sites. Clinically, 46% of patients (n = 16) presented with nodule(s), 26% (n = 9) with plaque(s) and 20% (n = 7) with heterogeneous morphologies. Cutaneous metastases were suspected in 72% of patients (n = 25), attributed to clinical features (46%, n = 16) or the presence of active metastatic disease elsewhere (26%, n = 9). All lesions appeared dermal in origin.

Conclusions

Cutaneous metastases are highly variable in presentation and a high index of suspicion is required for prompt diagnosis, especially in patients with a history of cancer, regardless of stage of treatment of the primary tumour.
Leadership of herd progressions in theThornicroft's giraffe ofZambia
Authors: Berry Philip S. M. , Bercovitch Fred B.
Published: September 2014

In cohesive social groups, travel progressions are often led by dominant or older individuals, but the leadership traits of individuals residing in flexible social systems are poorly known. Giraffe reside in herds characterized by fission–fusion dynamics frequently mediated by kinship. We analyzed 41 years (1971–2012) of longitudinal data collected from a community ofThornicroft's giraffe (Giraffa camelopardalis thornicrofti) living aroundSouthLuangwaNationalPark,Zambia, to assess the characteristics of herd leaders. Movement of giraffe in a single file progression was not associated with either season or time of day, but progressions were significantly more likely to occur when giraffe traveled in open areas. The oldest female in a herd was significantly more likely to be at the front position than expected, occupying the leadership niche on 79% of observations. We reason that matriarchal leadership in giraffe, as inAfrican elephants,Loxodonta africana, is associated with resource learning. Giraffe societies are constructed on a heretofore unrecognized foundation that integrates relatedness and familiarity with matriarchal leadership in herd movement.
Variability in the Emergence Point of Transpersonal Experience in the Life Cycle
Authors: Dale Edward James
Published: September 2014

It is shown in this article that many positions that are usually considered incompatible or antagonistic can be synthesized into a unified framework, creating a model of transpersonal development based around plurality and complexity. The model focuses on evolutionary developmental biology (particularly the process of heterochrony) as well as around psychological theories. A large degree of variability in the nature of transpersonal experience in the life cycle is to be expected, due to differences in both the “timing of onset” of transpersonal characteristics and the “length of developmental period.” Numerous developmental patterns are identified, using the work of some prominent transpersonal theorists
Smooth Semi‐nonparametric Analysis for Mixture Cure Models and Its Application to Breast Cancer
Authors: Li Haifen , Zhang Jiajia , Tang Yincai
Published: September 2014

Mixture cure models are widely used when a proportion of patients are cured. The proportional hazards mixture cure model and the accelerated failure time mixture cure model are the most popular models in practice. Usually the expectation–maximisation (EM) algorithm is applied to both models for parameter estimation. Bootstrap methods are used for variance estimation. In this paper we propose a smooth semi‐nonparametric (SNP) approach in which maximum likelihood is applied directly to mixture cure models for parameter estimation. The variance can be estimated by the inverse of the second derivative of the SNP likelihood. A comprehensive simulation study indicates good performance of the proposed method. We investigate stage effects in breast cancer by applying the proposed method to breast cancer data from the South Carolina Cancer Registry.
Genetic, nongenetic and epigenetic risk determinants in developmental programming of type 2 diabetes
Authors: Vaag Allan , Brøns Charlotte , Gillberg Linn , Hansen Ninna S. , Hjort Line , Arora Geeti P. , Thomas Nihal , Broholm Christa , Ribel‐Madsen Rasmus , Grunnet Louise G.
Published: September 2014

Low birthweight (LBW) individuals and offspring of women with gestational diabetes mellitus (GDM) exhibit increased risk of developing type 2 diabetes (T2D) and associated cardiometabolic traits in adulthood, which for both groups may be mediated by adverse events and developmental changes in fetal life. T2D is a multifactorial disease occurring as a result of complicated interplay between genetic and both prenatal and postnatal nongenetic factors, and it remains unknown to what extent the increased risk of T2D associated with LBW or GDM in the mother may be due to, or confounded by, genetic factors. Indeed, it has been shown that genetic changes influencing risk of diabetes may also be associated with reduced fetal growth as a result of reduced insulin secretion and/or action. Similarly, increased risk of T2D among offspring could be explained by T2D susceptibility genes shared between the mother and her offspring. Epigenetic mechanisms may explain the link between factors operating in fetal life and later risk of developing T2D, but so far convincing evidence is lacking for epigenetic changes as a prime and direct cause of T2D. This review addresses recent literature on the early origins of adult disease hypothesis, with a special emphasis on the role of genetic compared with nongenetic and epigenetic risk determinants and disease mechanisms.
Rethinking the Corporate Financial–Social Performance Relationship: Examining the Complex, Multistakeholder Notion of Corporate Social Performance
Authors: Weber James , Gladstone Jeffrey
Published: September 2014

The corporate financial performance (CFP)–corporate social performance (CSP) relationship has been investigated many times over the past few decades, yet the notion of CSP has generally been understood to be a single, monolithic aspect of corporate strategy. This article examines the common CFP–CSP understanding in three distinct ways: (1) by extending the evaluation of CSP as a complex, multistakeholder notion; (2) by analyzing CSP's relationship with the firm's financial performance at a given point in time as a lead (independent) variable in the relationship and as a lag (dependent) variable in the relationship; and (3) for both positive and negative stakeholder relationships. The results indicate that the employee emerges as the stakeholder group most strongly linked to CFP, followed by the consumer stakeholder. The natural environment and the community stakeholder group are minimally associated with CFP. General support is found for a CFP–CSP relationship at a given point in time, with some support found for CSP as a lead (independent) variable. When used as a measure of financial performance, return on assets is more often correlated with CSP than is return on equity. These results and their implications are discussed.
A comprehensive diagnostic approach using galactomannan, targeted β‐d‐glucan, baseline computerized tomography and biopsy yields a significant burden of invasive fungal disease in at risk haematology patients
Authors: Ceesay M. Mansour , Desai Sujal R. , Berry Lisa , Cleverley Joanne , Kibbler Christopher C. , Pomplun Sabine , Nicholson Andrew G. , Douiri Abdel , Wade Jim , Smith Melvyn , Mufti Ghulam J. , Pagliuca Antonio
Published: September 2014

Invasive fungal disease (IFD) is difficult to diagnose. We investigated the incidence of IFD and risk factors using the revised European Organization for Research and Treatment of Cancer (EORTC) and the Mycoses Study Group (MSG) definitions. Patients (N = 203) undergoing intensive therapy with expected neutropenia ≥10 d were recruited prospectively and followed for a median (range) of 556 (12–730) d. Baseline chest computerized tomography (CT) was performed pre‐therapy. Twice‐weekly surveillance with galactomannan (GM) was combined with targeted β‐d‐glucan (BDG) testing on patients with possible IFD or who were GM‐positive. Tissue diagnosis was obtained whenever possible. The cumulative incidence of proven/probable IFD among the 202 evaluable cases after 2 years follow‐up was 21%, including 14 proven and 30 probable IFDs. Using either GM or BDG as the sole biomarker (plus host and clinical evidence) the apparent overall incidence of proven/probable IFD was 11% and 16%, respectively. Combined GM/BDG detected all biopsy‐proven mould IFD. Baseline CT abnormalities were found in 76/202 (38%) patients. Baseline CT abnormalities and Karnofsky score <90, monocytopenia >10 d and bacteraemia were independent risk factors associated with greater than twofold increased IFD risk. This combined diagnostic approach identified a high incidence of IFD and important risk factors in this cohort.
Side effect profile of 5‐HT treatments for Parkinson's disease and L‐DOPA‐induced dyskinesia in rats
Authors: Lindenbach D , Palumbo N , Ostock C Y , Vilceus N , Conti M M , Bishop C
Published: September 2014

Background and Purpose

Treatment of Parkinson's disease (PD) with L‐DOPA eventually causes abnormal involuntary movements known as dyskinesias in most patients. Dyskinesia can be reduced using compounds that act as direct or indirect agonists of the 5‐HT1A receptor, but these drugs have been reported to worsen PD features and are known to produce ‘5‐HT syndrome’, symptoms of which include tremor, myoclonus, rigidity and hyper‐reflexia.

Experimental Approach

Sprague‐Dawley rats were given unilateral nigrostriatal dopamine lesions with 6‐hydroxydopamine. Each of the following three purportedly anti‐dyskinetic 5‐HT compounds were administered 15 min before L‐DOPA: the full 5‐HT1A agonist ±‐8‐hydroxy‐2‐dipropylaminotetralin (±8‐OH‐DPAT), the partial 5‐HT1A agonist buspirone or the 5‐HT transporter inhibitor citalopram. After these injections, animals were monitored for dyskinesia, 5‐HT syndrome, motor activity and PD akinesia.

Key Results

Each 5‐HT drug dose‐dependently reduced dyskinesia by relatively equal amounts (±8‐OH‐DPAT ≥ citalopram ≥ buspirone), but 5‐HT syndrome was higher with ±8‐OH‐DPAT, lower with buspirone and not present with citalopram. Importantly, with or without L‐DOPA, all three compounds provided an additional improvement of PD akinesia. All drugs tempered the locomotor response to L‐DOPA suggesting dyskinesia reduction, but vertical rearing was reduced with 5‐HT drugs, potentially reflecting features of 5‐HT syndrome.

Conclusions and Implications

The results suggest that compounds that indirectly facilitate 5‐HT1A receptor activation, such as citalopram, may be more effective therapeutics than direct 5‐HT1A receptor agonists because they exhibit similar anti‐dyskinesia efficacy, while possessing a reduced side effect profile.
A Public‐Health Approach to Improving Parenting and Promoting Children's Well‐Being
Authors: Sanders Matthew R. , Kirby James N.
Published: September 2014

Randomized controlled trials and meta‐analyses have demonstrated the efficacy of evidence‐based parenting programs (EBPPs) to improve social, emotional, and behavioral outcomes for children. Although EBPPs are effective, their reach is limited, and many families that could benefit do not have an opportunity to participate. In this article, we argue for a paradigm shift—from traditional, highly targeted approaches of program delivery to a more inclusive public‐health framework that blends universal and targeted elements. The Triple P—Positive Parenting Program is an EBPP that has applied a public‐health framework to increase parenting support in communities. The approach seeks to improve the reach of the program while increasing capacity to reduce the prevalence of children's social, emotional, and behavioral problems, as well as of child maltreatment.
Periodontal treatment needs and workforce requirements: comparisons between the normative and sociodental approaches using different skill mix models
Authors: Ab‐Murat Norintan , Sheiham Aubrey , Tsakos Georgios , Watt Richard
Published: September 2014

Objectives

Assessment of dental treatment needs has predominantly been based on the normative approach, despite its numerous limitations. The sociodental approach is a more rational method of needs assessment as it incorporates broader concepts of health and needs and behavioural propensity. This study compares estimates of periodontal dental treatment needs and workforce requirements for different skill mixes using normative and sociodental approaches among a sample of adults in Malaysia.

Methods

A cross‐sectional study was carried out on 732 Malaysian adults aged 30–54 years. Subjects' normative and sociodental needs for periodontal treatment were assessed using WHO criteria, an oral health‐related quality of life measure (the Oral Impacts on Daily Performances index), and behavioural propensity measures for toothbrushing and smoking behaviour. The proportion of subjects requiring periodontal treatment and the numbers of dentists and dental therapists required to treat them using the normative and sociodental approach were compared using different skill mix models.

Results

The estimates of need for periodontal treatment using the sociodental approach were 90% lower than the respective estimates using the normative need method. Overall, 14.43 dentists would be required per 100 000 people using the normative approach compared to 2.32 for the sociodental approach. When skill mix models were used, the number of dentists required decreased by almost 70% when more periodontal procedures were delegated to dental therapists.

Conclusions

Using the sociodental approach resulted in much lower estimates of dental need and workforce requirements for periodontal treatment than using the normative method. Using dental therapists markedly reduced the numbers of dentists needed for periodontal treatment.
Distribution of interleukin-10 family cytokines in serum and synovial fluid of patients with inflammatory arthritis reveals different contribution to systemic and joint inflammation
Authors: Scrivo R , Conigliaro P , Riccieri V , Di Franco M , Alessandri C , Spadaro A , Perricone R , Valesini G
Published: September 2014

Evidence exists that interleukin (IL)-10 family cytokines may be involved in the pathogenesis of rheumatoid arthritis (RA). We sought to determine whether or not these cytokines are involved in psoriatic arthritis (PsA). We conducted a prospective study on patients with PsA, RA and osteoarthritis (OA); healthy controls (HC) were also included. We analysed IL-20, IL-24 and IL-19 serum and synovial fluid (SF) levels and change of serum levels following treatment with biological agents. IL-20 serum levels were increased in PsA and RA compared with OA patients and HC and with matched SF levels. IL-24 serum levels in PsA, RA and OA patients were higher than those in HC and also with respect to matched SF in PsA. IL-19 serum levels were higher in HC and OA compared with PsA and RA patients; IL-19 SF levels were higher in PsA and RA compared with OA patients, and in PsA compared with RA patients. PsA and RA patients showed a reduction of IL-19 serum levels after biological treatment. Therefore, IL-19 seems to be involved mainly in the joint inflammation, whereas IL-20 and IL-24 appear to participate mainly in the systemic responses. These findings may further the comprehension of the contribution of these cytokines to the inflammatory response involved in chronic arthritis, as well as to the development of novel therapeutic strategies.
Prospective, Multicenter Evaluation of Trabecular Metal‐Enhanced Titanium Dental Implants Placed in Routine Dental Practices: 1‐Year Interim Report From the Development Period (2010 to 2011)
Authors: Schlee Markus , Pradies Guillermo , Mehmke Wolf‐Ullrich , Beneytout Arnaud , Stamm Matthais , Meda Ramón Gómez , Kamm Torsten , Poiroux Francois , Weinlich Franz , del Canto Pingarron Mariano , Crichton Eric , Poulet Jean‐Baptiste , Bousquet Philippe
Published: September 2014

Background

A prospective, multicenter study is currently evaluating a novel titanium implant with a highly porous tantalum midsection (tantalum material [TM]) placed in an uncontrolled patient population.

Purpose

Interim 1‐year results from the development period (2010–2011) are reported.

Materials and Methods

Investigators in 22 clinical sites located in five European countries randomly selected and treated partially edentulous patients in accordance with the implant's instructions for use and the investigators' professional judgments. Oversight was provided by the local institutional review boards. Subjects were treated with 1 to 2 TM dental implants in maxillary or mandibular location(s).

Results

To date, 105 patients with 57 maxillary and 88 mandibular implants have completed 1 year of clinical monitoring. Within this interim group, 28 patients had concomitant health conditions that may elevate risks for long‐term crestal bone loss and/or implant survival. Three implants failed due to local or systemic infection, and four implants failed to integrate. Cumulative implant survival was 95.2% (n = 138/145) with 0.43 ± 0.57 mm of mean marginal bone loss in this interim group.

Conclusion

TM dental implants were clinically effective under various clinical conditions in an uncontrolled patient population with and without concomitant health conditions.
Digital vs. conventional implant prosthetic workflows: a cost/time analysis
Authors: Joda Tim , Brägger Urs
Published: September 2014

Objectives

The aim of this prospective cohort trial was to perform a cost/time analysis for implant‐supported single‐unit reconstructions in the digital workflow compared to the conventional pathway.

Materials and Methods

A total of 20 patients were included for rehabilitation with 2 × 20 implant crowns in a crossover study design and treated consecutively each with customized titanium abutments plus CAD/CAM‐zirconia‐suprastructures (test: digital) and with standardized titanium abutments plus PFM‐crowns (control conventional). Starting with prosthetic treatment, analysis was estimated for clinical and laboratory work steps including measure of costs in Swiss Francs (CHF), productivity rates and cost minimization for first‐line therapy. Statistical calculations were performed with Wilcoxon signed‐rank test.

Results

Both protocols worked successfully for all test and control reconstructions. Direct treatment costs were significantly lower for the digital workflow 1815.35 CHF compared to the conventional pathway 2119.65 CHF [P = 0.0004]. For subprocess evaluation, total laboratory costs were calculated as 941.95 CHF for the test group and 1245.65 CHF for the control group, respectively [P = 0.003]. The clinical dental productivity rate amounted to 29.64 CHF / min (digital) and 24.37 CHF / min (conventional) [P = 0.002]. Overall, cost minimization analysis exhibited an 18% cost reduction within the digital process.

Conclusion

The digital workflow was more efficient than the established conventional pathway for implant‐supported crowns in this investigation.
Overexpression of metadherin mediates metastasis of osteosarcoma by regulating epithelial–mesenchymal transition
Authors: Tang J. , Shen L. , Yang Q. , Zhang C.
Published: September 2014

Objectives

Osteosarcoma (OS) is one of the most common primary malignant bone tumours of childhood and adolescence, and is characterized by high propensity for metastasis (specially to the lung), which is the main cause of death. However, molecular mechanisms underlying metastasis of OS are still poorly understood.

Materials and methods

Metadherin (MTDH) was identified to be significantly upregulated in OS tissues that had metastasized compared to OS without metastasis, using a two‐dimensional approach of electrophoresis, coupled with mass spectrometry. To understand the function of MTDH in OS, OS cell lines U2OS and SOSP‐M were transfected with retroviral shRNA vector against MTDH.

Results

It was found that metastatic propensity as well as cell proliferation were significantly reduced in both U2OS and SOSP‐M. Migration and invasion of U2OS and SOSP‐M cells were significantly lower after knock‐down of MTDH. In addition, epithelial–mesenchymal transition (EMT) was reduced after knock‐down of MTDH. Clinicopathologically, overexpression of MTDH was significantly associated with metastasis and poor survival of patients with OS.

Conclusion

Taken together, our results demonstrate that MTDH mediated metastasis of OS through regulating EMT. This could be an ideal therapeutic target against metastasis of OS.
Canagliflozin in Asian patients with type 2 diabetes on metformin alone or metformin in combination with sulphonylurea
Authors: Ji L. , Han P. , Liu Y. , Yang G. , Dieu Van N. K. , Vijapurkar U. , Qiu R. , Meininger G.
Published: September 2014

Aims

To evaluate the efficacy and safety of canagliflozin, a sodium glucose co‐transporter 2 inhibitor, in Asian patients with type 2 diabetes mellitus (T2DM) inadequately controlled by metformin or metformin in combination with sulphonylurea.

Methods

In this 18‐week, randomized, double‐blind, placebo‐controlled phase III study, patients (N = 676) received canagliflozin 100 or 300 mg or placebo once daily. The primary efficacy endpoint was change in glycated haemoglobin (HbA1c) level from baseline at week 18. Additional endpoints included change in fasting plasma glucose (FPG) and percent change in body weight. Adverse events (AEs) were recorded throughout the study. Efficacy and safety were assessed in the overall population and in two strata based on background therapy.

Results

At week 18, canagliflozin 100 and 300 mg provided significant reductions from baseline in HbA1c compared with placebo (−0.97, −1.06 and −0.47%, respectively; p < 0.001). Relative to placebo, canagliflozin 100 and 300 mg also significantly reduced FPG (−1.0 and −1.4 mmol/l) and body weight [−2.2% (−1.5 kg) and −2.3% (−1.6 kg)]. Both canagliflozin doses lowered systolic blood pressure (BP) compared with placebo. The overall incidence of AEs was 38.6, 43.2 and 42.0% with canagliflozin 100 and 300 mg and placebo, respectively. The incidence of genital mycotic infections and urinary tract infections was low and similar across groups. Efficacy and safety findings in the two strata were generally consistent with the overall population.

Conclusions

Canagliflozin provided glycaemic improvements and reductions in body weight and systolic BP, and was generally well tolerated in Asian patients with T2DM on metformin or metformin in combination with sulphonylurea.
Clinical spectrum and outcomes of patients with encephalitis requiring intensive care
Authors: Sonneville R. , Gault N. , de Montmollin E. , Klein I. F. , Mariotte E. , Chemam S. , Tubach F. , Mourvillier B. , Timsit J. F. , Wolff M. , Bouadma L.
Published: September 2014

Background and purpose

Our aim was to characterize the clinical profile, temporal changes and outcomes of patients with severe encephalitis.

Methods

A retrospective cohort study was conducted on adult patients with encephalitis admitted to the medical intensive care unit (ICU) of a university hospital over a 20‐year period. Patients' characteristics and outcomes were compared between two 10‐year periods: (i) 1991–2001 and (ii) 2002–2012. Multivariate logistic regression was used to analyze factors associated with a poor outcome, as defined by a modified Rankin scale (mRS) score of 4–6 (severe disability or death) 90 days after admission.

Results

A total of 279 patients were studied. Causes of encephalitis were infections (n = 149, 53%), immune‐mediated causes (n = 41, 15%) and undetermined causes (n = 89, 32%). The distribution of causes differed significantly between the two periods, with an increase in the proportion of encephalitis recognized to be of immune‐mediated causes. At day 90, 208 (75%) patients had an mRS = 0–3 and 71 (25%) had an mRS = 4–6. After adjustment for functional status before admission, the following parameters were independently associated with a poor outcome: coma [odds ratio (OR) 7.09, 95% confidence interval (95% CI) 3.06–17.03], aspiration pneumonia (OR 4.02, 95% CI 1.47–11.03), a lower body temperature (per 1 degree, OR 0.72, 95% CI 0.53–0.97), elevated cerebrospinal fluid protein levels (per 1 g/l, OR 1.55, 95% CI 1.17–2.11) and delayed ICU admission (per 1 day, OR 1.04, 95% CI 1.01–1.07).

Conclusions

Indicators of outcome in adult patients with severe encephalitis reflect both the severity of illness and systemic complications. Our data suggest that patients with acute encephalitis may benefit from early ICU admission.
Biophysical and structural characterization of a folded core domain within the proregion of growth and differentiation factor‐5
Authors: Thieme Tino , Patzschke Rica , Job Florian , Liebold Jens , Seemann Petra , Lilie Hauke , Balbach Jochen , Schwarz Elisabeth
Published: September 2014

The structure and function(s) of the very large proregions of the transforming growth factor‐β structure family are known in only a few cases. The proregion of growth and differentiation factor (GDF)5 comprises 354 residues.GDF5 therefore belongs to the group of those growth factors with the largest proregions. Here, we report a biophysical analysis of the proform (proGDF5) and the separate proregion. In the absence of the mature part, the proregion folds reversibly to form a monomeric polypeptide that is stabilized by an intramolecular disulfide bond. In the context of the mature part, i.e. in proGDF5, the proregion shows increased thermodynamic stability and contains a higher proportion of secondary structural elements than in its isolated form. A subdomain within the proregion represents a well‐folded structure as monitored via biophysical analysis andNMRspectroscopy. Furthermore, two point mutations that are associated with skeletal malformations lead to reduced thermodynamic stability, which is interpreted on the basis of a homology model with the structure of the related latency‐associated peptide, representing the proregion of transforming growth factor‐β1.
Increased behavioral responses to ethanol in Lmo3 knockout mice
Authors: Savarese A. , Zou M. E. , Kharazia V. , Maiya R. , Lasek A. W.
Published: September 2014

LIM‐domain‐only 3 (LMO3) is a transcriptional regulator involved in central nervous system development and neuroblastoma. Our previous studies implicated a potential role for LMO3 in regulating ethanol sensitivity and consumption. Here, we examined behavioral responses to ethanol in a line of Lmo3 null (Lmo3Z) mice, utilizing the ethanol‐induced loss‐of‐righting‐reflex (LORR) test, two‐bottle choice ethanol consumption and the drinking in the dark (DID) test, which models binge‐like ethanol consumption. We found that Lmo3Z mice exhibited increased sedation time in response to ethanol in the LORR test and drank significantly more ethanol in the DID test compared with their wild‐type counterparts, but showed no differences in two‐bottle choice ethanol consumption. To explore where LMO3 may be acting in the brain to produce an ethanol phenotype, we also examined reporter gene (β‐galactosidase) expression in heterozygous Lmo3Z mice and found strong expression in subcortical areas, particularly in those areas implicated in drug abuse, including the nucleus accumbens (Acb), cortex, hippocampus and amygdala. We also examined Lmo3 expression in the brains of wild‐type mice who had undergone the DID test and found a negative correlation between Lmo3 expression in the Acb and the amount of ethanol consumed, consistent with the increased binge‐like drinking observed in Lmo3Z mice. These results support a role for LMO3 in regulating behavioral responses to ethanol, potentially through its actions in the Acb.
Anticipative management for coral reef ecosystem services in the 21st century
Authors: Rogers Alice , Harborne Alastair R. , Brown Christopher J. , Bozec Yves‐Marie , Castro Carolina , Chollett Iliana , Hock Karlo , Knowland Cheryl A. , Marshell Alyssa , Ortiz Juan C. , Razak Tries , Roff George , Samper‐Villarreal Jimena , Saunders Megan I. , Wolff Nicholas H. , Mumby Peter J.
Published: September 2014

Under projections of global climate change and other stressors, significant changes in the ecology, structure and function of coral reefs are predicted. Current management strategies tend to look to the past to set goals, focusing on halting declines and restoring baseline conditions. Here, we explore a complementary approach to decision making that is based on the anticipation of future changes in ecosystem state, function and services. Reviewing the existing literature and utilizing a scenario planning approach, we explore how the structure of coral reef communities might change in the future in response to global climate change and overfishing. We incorporate uncertainties in our predictions by considering heterogeneity in reef types in relation to structural complexity and primary productivity. We examine 14 ecosystem services provided by reefs, and rate their sensitivity to a range of future scenarios and management options. Our predictions suggest that the efficacy of management is highly dependent on biophysical characteristics and reef state. Reserves are currently widely used and are predicted to remain effective for reefs with high structural complexity. However, when complexity is lost, maximizing service provision requires a broader portfolio of management approaches, including the provision of artificial complexity, coral restoration, fish aggregation devices and herbivore management. Increased use of such management tools will require capacity building and technique refinement and we therefore conclude that diversification of our management toolbox should be considered urgently to prepare for the challenges of managing reefs into the 21st century.