Artemisinin induced dormancy in Plasmodium falciparum : duration, recovery rates and implications in treatment failure

Background Despite the remarkable activity of artemisinin and its derivatives, monotherapy with these agents has been associated with high rates of recrudescence. The temporary arrest of the growth of ring-stage parasites (dormancy) after exposure to artemisinin drugs provides a plausible explanation for this phenomenon. Methods Ring-stage parasites of several Plasmodium falciparum lines were exposed to different doses of dihydroartemisinin (DHA) alone or in combination with mefloquine. For each regime, the proportion of recovering parasites was determined daily for 20 days. Results Parasite development was abruptly arrested after a single exposure to DHA, with some parasites being dormant for up to 20 days. Approximately 50% of dormant parasites recovered to resume growth within the first 9 days. The overall proportion of parasites recovering was dose dependent, with recovery rates ranging from 0.044% to 1.313%. Repeated treatment with DHA or with DHA in combination with mefloquine led to a delay in recovery and an ∼10-fold reduction in total recovery. Strains with different genetic backgrounds appeared to vary in their capacity to recover. Conclusions These results imply that artemisinin-induced arrest of growth occurs readily in laboratory-treated parasites and may be a key factor in P. falciparum malaria treatment failure.

Solution processable low bandgap diketopyrrolopyrrole (DPP) based derivatives : novel acceptors for organic solar cells

Novel low bandgap solution processable diketopyrrolopyrrole (DPP) based derivatives functionalized with electron withdrawing end capping groups (trifluoromethylphenyl and trifluorophenyl) were synthesized, and their photophysical, electrochemical and photovoltaic properties were investigated. These compounds showed optical bandgaps ranging from 1.81 to 1.94 eV and intense absorption bands that cover a wide range from 300 to 700 nm, attributed to charge transfer transition between electron rich phenylene-thienylene moieties and the electron withdrawing diketopyrrolopyrrole core. All of the compounds were found to be fluorescent in solution with an emission wavelength ranging from 600 to 800 nm. Cyclic voltammetry indicated reversible oxidation and reduction processes with tuning of HOMO-LUMO energy levels. Bulk heterojunction (BHJ) solar cells using poly(3-hexylthiophene) (P3HT) as the electron donor with these new acceptors were used for fabrication. The best power conversion efficiencies (PCE) using 1:2 donor-acceptor by weight mixture were 1% under simulated AM 1.5 solar irradiation of 100 mW cm-2. These findings suggested that a DPP core functionalized with electron accepting end-capping groups were a promising new class of solution processable low bandgap n-type organic semiconductors for organic solar cell applications.

Synthesis and study of conductivity behaviour of blended conducting polymer films irradiated with swift heavy ions of silicon

In recent times, blended polymers have shown a lot of promise in terms of easy processability in different shapes and forms. In the present work, polyaniline emeraldine base (PANi-EB) was doped with camphor sulfonic acid (CSA) and combined with the conducting polymer polyfluorene (PF) as well as the insulating polymer polyvinyl chloride (PVC) to synthesize CSA doped PANi-PF and PANi-PVC blended polymers. It is well known that PANi when doped with CSA becomes highly conducting. However, its poor mechanical properties, such as low tensile, compressive, and flexural strength render PANi a non-ideal material to be processed for its various practical applications, such as electromagnetic shielding, anti-corrosion shielding, photolithography and microelectronic devices etc. Thus the search for polymers which are easily processable and are capable of showing high conductivity still continues. PANi-PVC blend was prepared, which showed low conductivity which is limiting factor for certain applications. Therefore, another processable polymer PF was chosen as conducting matrix. Conducting PF can be easily processed into various shapes and forms. Therefore, a blend mixture was prepared by using PANi and PF through the use of CSA as a counter ion which forms a "bridge" between the two polymeric components of the inter-polymer complex. Two blended polymers have been synthesized and investigated for their conductivity behaviour. It was observed that the blended film of CSA doped PANi-PVC showed a room temperature electrical conductivity of 2.8 × 10-7 S/cm where as the blended film made by CSA doped PANi with conducting polymer PF showed a room temperature conductivity of 1.3 × 10-5 S/cm. Blended films were irradiated with 100 MeV silicon ions with a view to increase their conductivity with a fluence ranging from 1011 ions to 1013 per cm2 from 15 UD Pelletron accelerator at NSC, New Delhi.

Physical activity, walking and quality of life in women with depressive symptoms

Background Physical activity (PA) has a positive association with health-related quality of life (HRQL) in the general population. The association between PA and HRQL in those with poor mental health is less clear. Purpose To examine the concurrent and prospective dose-response relationships between total physical activity (TPA) and walking only with HRQL in women aged 50-55 with depressive symptoms in 2001. Methods Participants were 1904 women born in 1946-1951 who completed mailed surveys for the Australian Longitudinal Study on Women's Health in 2001, 2004, 2007 and 2010 and who, in 2001, reported depressive symptoms. At each time point, they reported their weekly minutes of walking, moderate PA, and vigorous PA. A summary TPA score was created that accounted for differences in energy expenditure among the three PA types. Mixed models were used to examine associations between TPA and HRQL (SF-36 component and subscale scores) and between walking and HRQL, for women who reported walking as their only PA. Analyses were conducted in 2013-2014. Results Concurrently, higher levels of TPA and walking were associated with better HRQL (p<0.05). The strongest associations were found for physical functioning, vitality, and social functioning subscales. In prospective models, associations were attenuated, yet compared with women doing no TPA or walking, women doing “sufficient” TPA or walking had significantly better HRQL over time for most SF-36 scales. Conclusions This study extends previous work by demonstrating trends between both TPA and walking and HRQL in women reporting depressive symptoms.

Role of capsule and O antigen in the virulence of uropathogenic Escherichia coli

Urinary tract infection (UTI) is one of the most common bacterial infections in humans, with uropathogenic Escherichia coli (UPEC) the leading causative organism. UPEC has a number of virulence factors that enable it to overcome host defenses within the urinary tract and establish infection. The O antigen and the capsular polysaccharide are two such factors that provide a survival advantage to UPEC. Here we describe the application of the rpsL counter selection system to construct capsule (kpsD) and O antigen (waaL) mutants and complemented derivatives of three reference UPEC strains: CFT073 (O6:K2:H1), RS218 (O18:K1:H7) and 1177 (O1:K1:H7). We observed that while the O1, O6 and O18 antigens were required for survival in human serum, the role of the capsule was less clear and linked to O antigen type. In contrast, both the K1 and K2 capsular antigens provided a survival advantage to UPEC in whole blood. In the mouse urinary tract, mutation of the O6 antigen significantly attenuated CFT073 bladder colonization. Overall, this study contrasts the role of capsule and O antigen in three common UPEC serotypes using defined mutant and complemented strains. The combined mutagenesis-complementation strategy can be applied to study other virulence factors with complex functions both in vitro and in vivo.

Representation of facial expression categories in continuous arousal-valence space: Feature and correlation

Representation of facial expressions using continuous dimensions has shown to be inherently more expressive and psychologically meaningful than using categorized emotions, and thus has gained increasing attention over recent years. Many sub-problems have arisen in this new field that remain only partially understood. A comparison of the regression performance of different texture and geometric features and investigation of the correlations between continuous dimensional axes and basic categorized emotions are two of these. This paper presents empirical studies addressing these problems, and it reports results from an evaluation of different methods for detecting spontaneous facial expressions within the arousal-valence dimensional space (AV). The evaluation compares the performance of texture features (SIFT, Gabor, LBP) against geometric features (FAP-based distances), and the fusion of the two. It also compares the prediction of arousal and valence, obtained using the best fusion method, to the corresponding ground truths. Spatial distribution, shift, similarity, and correlation are considered for the six basic categorized emotions (i.e. anger, disgust, fear, happiness, sadness, surprise). Using the NVIE database, results show that the fusion of LBP and FAP features performs the best. The results from the NVIE and FEEDTUM databases reveal novel findings about the correlations of arousal and valence dimensions to each of six basic emotion categories.

Primary and substance-induced psychotic disorders in methamphetamine users

This study investigates the rates of primary psychotic disorders (PPD) and substance induced psychotic disorders (SIPDs) in methamphetamine (MA) users accessing needle and syringe programs (NSPs). The aim was to determine if there are systematic differences in the characteristics of MA users with PPDs and SIPDs compared to those with no psychotic disorder. Participants were 198 MA users reporting use in the previous month. Diagnosis was determined using the Psychiatric Research Interview for DSM-IV Substance and Mental Disorders (PRISM-IV). Current psychiatric symptoms and substance use were also measured. Just over half (N=101) of participants met DSM-IV criteria for a lifetime psychotic disorder, including 81 (80%) with a SIPD and 20 (20%) with a PPD. Those with a younger age of onset of weekly MA use were at increased risk of a lifetime SIPD. A current psychotic disorder was found in 62 (39%), comprising 49 SIPDs (79%) and 13 PPDs (21%). MA users with a current PPD were more likely to have received psychiatric treatment in the past month than those with a current SIPD, despite a similar level of psychotic symptom severity. A high proportion of MA users accessing NSPs have psychotic disorders, the majority of which are substance-induced.

Hyperlinking history and illegitimate imagination : the historiographic metafictional E-novel

‘Historiographic Metafiction’ (HM) is a literary term first coined by creative writing academic Linda Hutcheon in 1988, and which refers to the postmodern practice of a fiction author inserting imagined--or illegitimate--characters into narratives that are intended to be received as authentic and historically accurate, that is, ostensibly legitimate. Such adventurous and bold authorial strategies frequently result in “novels which are both intensely self-reflexive and yet paradoxically also lay claim to historical events and personages” (Hutcheon, A Poetics 5). They can be so entertaining and engaging that the overtly intertextual, explicitly inventive work of biographical HM can even change the “hegemonic discourse of history” (Nunning 353) for, as Philippa Gregory, the author of HM novel The Other Boleyn Girl (2001), has said regarding this genre of creative writing: “Fiction is about imagined feelings and thoughts. History depends on the outer life. The novel is always about the inner life. Fiction can sometimes do more than history. It can fill the gaps” (University of Sussex). In a way, this article will be filling one of the gaps regarding HM...

Nursing casualisation and communication : a critical ethnography

Aim The aim was to explore the relationship between nursing casualization and the culture of communication for nurses in a healthcare facility. Background Casualization, or non-standard work, is the use of temporary, contract, part-time and casual labour. An increase in casual labour has been part of a global shift in work organization aimed at creating a more flexible and cheaper workforce. It has been argued that flexibility of labour has enabled nurses to manage both non-work related needs and an increasingly complex work environment. Yet no research has explored casualization and how it impacts on the communication culture for nurses in a healthcare facility. Design Critical ethnography. Methods Methods included observation, field notes, formal interviews and focus groups. Data collection was undertaken over the 2 years 2008–2009. Results The concepts of knowing and belonging were perceived as important to nursing teamwork and yet the traditional time/task work model, designed for a full-time workforce, marginalized non-standard workers. The combination of medical dominance and traditional stereotyping of the nurse and work as full-time shaped the behaviours of nurses and situated casual workers on the periphery. The overall finding was that entrenched systemic structures and processes shaped the physical and cultural dimensions of a contemporary work environment and contributed to an ineffective communication culture. Conclusion Flexible work is an important feature of contemporary nursing. Traditional work models and nurse attitudes and practices have not progressed and are discordant with a contemporary approach to nursing labour management.

Does school type affect cognitive and non-cognitive development in children? Evidence from Australian primary schools

This paper investigates the effects of primary school choices on cognitive and non-cognitive development in children using data from the Longitudinal Study of Australian Children (LSAC). We militate against the measurement problems that are associated with individual unobserved heterogeneity by exploiting the richness of LSAC data and applying contemporary econometric approaches. We find that sending children to Catholic or other independent primary schools has no significant effect on their cognitive and non-cognitive outcomes. The literature now has evidence from three different continents that the returns to attending Catholic primary schools are no different than public schools.

Reconceptualizing green infrastructure for climate change adaptation: Barriers to adoption and drivers for uptake by spatial planners

Urban green infrastructure can help cities adapt to climate change. Spatial planning can play an important role in utilizing green infrastructure for adaptation. Yet climate change risks represent a different sort of challenge for planning institutions. This paper aims to address two issues arising from this challenge. First, it defines the concept of green infrastructure within the context of climate adaptation. Second, it identifies and puts into perspective institutional barriers to adopting green infrastructure for climate adaptation, including path dependence. We begin by arguing that there is growing confusion among planners and policy makers about what constitutes green infrastructure. Definitional ambiguity may contribute to inaction on climate change adaptation, because it muddies existing programs and initiatives that are to do with green-space more broadly, which in turn feeds path dependency. We then report empirical findings about how planners perceive the institutional challenge arising from climate change and the adoption of green infrastructure as an adaptive response. The paper concludes that spatial planners generally recognize multiple rationales associated with green infrastructure. However they are not particularly keen on institutional innovation and there is a tendency for path dependence. We propose a conceptual model that explicitly recognizes such institutional factors. This paper contributes to the literature by showing that agency and institutional dimensions are a limiting factor in advancing the concept of green infrastructure within the context of climate change adaptation.

Numerical analysis for the time distributed-order and Riesz space fractional diffusions on bounded domains

Subdiffusion equations with distributed-order fractional derivatives describe some important physical phenomena. In this paper, we consider the time distributed-order and Riesz space fractional diffusions on bounded domains with Dirichlet boundary conditions. Here, the time derivative is defined as the distributed-order fractional derivative in the Caputo sense, and the space derivative is defined as the Riesz fractional derivative. First, we discretize the integral term in the time distributed-order and Riesz space fractional diffusions using numerical approximation. Then the given equation can be written as a multi-term time–space fractional diffusion. Secondly, we propose an implicit difference method for the multi-term time–space fractional diffusion. Thirdly, using mathematical induction, we prove the implicit difference method is unconditionally stable and convergent. Also, the solvability for our method is discussed. Finally, two numerical examples are given to show that the numerical results are in good agreement with our theoretical analysis.

Product stability and sequestration mechanisms in Solanum tuberosum engineered to biosynthesize high value ketocarotenoids

To produce commercially valuable ketocarotenoids in Solanum tuberosum, the 4, 4′ β-oxygenase (crtW) and 3, 3′ β-hydroxylase (crtZ) genes from Brevundimonas spp. have been expressed in the plant host under constitutive transcriptional control. The CRTW and CRTZ enzymes are capable of modifying endogenous plant carotenoids to form a range of hydroxylated and ketolated derivatives. The host (cv. Désirée) produced significant levels of nonendogenous carotenoid products in all tissues, but at the apparent expense of the economically critical metabolite, starch. Carotenoid levels increased in both wild-type and transgenic tubers following cold storage; however, stability during heat processing varied between compounds. Subcellular fractionation of leaf tissues revealed the presence of ketocarotenoids in thylakoid membranes, but not predominantly in the photosynthetic complexes. A dramatic increase in the carotenoid content of plastoglobuli was determined. These findings were corroborated by microscopic analysis of chloroplasts. In tuber tissues, esterified carotenoids, representing 13% of the total pigment found in wild-type extracts, were sequestered in plastoglobuli. In the transgenic tubers, this proportion increased to 45%, with esterified nonendogenous carotenoids in place of endogenous compounds. Conversely, nonesterified carotenoids in both wild-type and transgenic tuber tissues were associated with amyloplast membranes and starch granules.

Choose wisely: Network, ontology and annotation resources for the analysis of Staphylococcus aureus omics data

Staphylococcus aureus (S. aureus) is a prominent human and livestock pathogen investigated widely using omic technologies. Critically, due to availability, low visibility or scattered resources, robust network and statistical contextualisation of the resulting data is generally under-represented. Here, we present novel meta-analyses of freely-accessible molecular network and gene ontology annotation information resources for S. aureus omics data interpretation. Furthermore, through the application of the gene ontology annotation resources we demonstrate their value and ability (or lack-there-of) to summarise and statistically interpret the emergent properties of gene expression and protein abundance changes using publically available data. This analysis provides simple metrics for network selection and demonstrates the availability and impact that gene ontology annotation selection can have on the contextualisation of bacterial omics data.

The prevention, detection and management of cancer treatment-induced cardiotoxicity: a meta-review

Background The benefits associated with some cancer treatments do not come without risk. A serious side effect of some common cancer treatments is cardiotoxicity. Increased recognition of the public health implications of cancer treatment-induced cardiotoxicity has resulted in a proliferation of systematic reviews in this field to guide practice. Quality appraisal of these reviews is likely to limit the influence of biased conclusions from systematic reviews that have used poor methodology related to clinical decision-making. The aim of this meta-review is to appraise and synthesise evidence from only high quality systematic reviews focused on the prevention, detection or management of cancer treatment-induced cardiotoxicity. Methods Using Cochrane methodology, we searched databases, citations and hand-searched bibliographies. Two reviewers independently appraised reviews and extracted findings. A total of 18 high quality systematic reviews were subsequently analysed, 67 % (n = 12) of these comprised meta-analyses. Results One systematic review concluded that there is insufficient evidence regarding the utility of cardiac biomarkers for the detection of cardiotoxicity. The following strategies might reduce the risk of cardiotoxicity: 1) The concomitant administration of dexrazoxane with anthracylines; 2) The avoidance of anthracyclines where possible; 3) The continuous administration of anthracyclines (>6 h) rather than bolus dosing; and 4) The administration of anthracycline derivatives such as epirubicin or liposomal-encapsulated doxorubicin instead of doxorubicin. In terms of management, one review focused on medical interventions for treating anthracycline-induced cardiotoxicity during or after treatment of childhood cancer. Neither intervention (enalapril and phosphocreatine) was associated with statistically significant improvement in ejection fraction or mortality. Conclusion This review highlights the lack of high level evidence to guide clinical decision-making with respect to the detection and management of cancer treatment-associated cardiotoxicity. There is more evidence with respect to the prevention of this adverse effect of cancer treatment. This evidence, however, only applies to anthracycline-based chemotherapy in a predominantly adult population. There is no high-level evidence to guide clinical decision-making regarding the prevention, detection or management of radiation-induced cardiotoxicity.