Burden of non-communicable diseases (NCDs) in Nepal and the availability and affordability of NCD medicines

Background: Traditionally communicable diseases were the main causes of burden in developing countries like Nepal. In recent years non-communicable diseases (NCDs), mainly cardiovascular diseases (CVDs), cancer, chronic respiratory diseases and diabetes mellitus, impose a larger disease burden compared to communicable diseases. Most elements of health and medicine policies in Nepal are still focused on communicable diseases. There is limited evidence about NCDs and NCD medicines in Nepal. Aim: To explore the gap between the burden of NCDs and the availability and affordability of NCD medicines in Nepal. Methods: Biomedical databases like Medline, Scopus, Web of Science and other online sources (including Global Burden of Diseases data) were searched for data on the burden of NCDs in term of Disability Adjusted Life Years (DALYs). The Essential Medicines List (EML) of Nepal was compared with World Health Organisation (EML) for inclusion of NCD medicines. Results: In Nepal, NCDs caused nearly 45% of the total 10.5 million DALYs in 2010. CVDs (15.2%), were the leading cause of NCDs burden followed by chronic respiratory diseases (14.7%), cancer (7.3%) and diabetes mellitus (3.2%). One hospital based national survey found that 37% of hospitalised patients had NCDs. Among them, 38% had heart disease followed by COPD (33%) , and diabetes (10%). Most (23 out of 28) non-cancer NCD medicines recommended in WHO-EML were present in Nepal's EML, theoretically indicating good availability. However, it is difficult to say whether they are accessible and affordable due to the lack of adequate data on access and pricing. Conclusion: This study gives some insight into the burden of NCDs. Although NCD medicines are available in Nepal, further research is required to determine whether they are accessible and affordable to the general population.

Volatile properties of CNG and Diesel bus emissions produced during steady state and transient driving modes

An analysis of the emissions from 14 CNG and 5 Diesel buses was conducted during April & May, 2006. Studies were conducted at both steady state and transient driving modes on a vehicle dynamometer utilising a CVS dilution system. This article will focus on the volatile properties of particles from 4 CNG and 4 Diesel vehicles from within this group with a priority given to the previously un-investigated CNG emissions produced at transient loads. Particle number concentration data was collected by three CPC’s (TSI 3022, 3010 & 3782WCPC) having D50 cut-offs set to 5nm, 10nm & 20nm respectively. Size distribution data was collected using a TSI 3080 SMPS with a 3025 CPC during the steady state driving modes. During transient cycles mono-disperse “slices” of between 5nm & 25nm were measured. The volatility of these particles was determined by placing a thermodenuder before the 3022 and the SMPS and measuring the reduction in particle number concentration as the temperature in the thermodenuder was increased. This was then normalised against the total particle count given by the 3010 CPC to provide high resolution information on the reduction in particle concentration with respect to temperature.

Women and ADR

Alternative dispute resolution, or ‘ADR’, is defined by the National Alternative Dispute Resolution Advisory Council as: … an umbrella term for processes, other than judicial determination, in which an impartial person assists those in a dispute to resolve the issues between them. ADR is commonly used as an abbreviation for alternative dispute resolution, but can also be used to mean assisted or appropriate dispute resolution. Some also use the term ADR to include approaches that enable parties to prevent or manage their own disputes without outside assistance. A broad range of ADR processes are used in legal practice contexts, including, for example, arbitration, conciliation, mediation, negotiation, conferencing, case appraisal and neutral evaluation. Hybrid processes are also used, such as med-arb in which the practitioner starts by using mediation, and then shifts to using arbitration. ADR processes generally fall into one of three general categories: facilitative, advisory or determinative. In a facilitative process, the ADR practitioner has the role of assisting the parties to reach a mutually agreeable outcome to the dispute by helping them to identify the issues in dispute, and to develop a range of options for resolving the dispute. Mediation and facilitated negotiation are examples of facilitative processes. ADR processes that are advisory involve the practitioner appraising the dispute, providing advice as to the facts of the dispute, the law and then, in some cases, articulating possible or appropriate outcomes and how they might be achieved. Case appraisal and neutral evaluation are examples of advisory processes. In a determinative ADR process, the practitioner evaluates the dispute (which may include the hearing of formal evidence from the parties) and makes a determination. Arbitration is an example of a determinative ADR process. The use of ADR processes has increased significantly in recent years. Indeed, in a range of contemporary legal contexts the use of an ADR process is now required before a party is able to file a matter in court. For example, Juliet Behrens discusses in Chapter 11 of this book how the Family Law Act 1975 (Cth) now effectively mandates attendance at pre-filing family dispute resolution in parenting disputes. At the state level, in Queensland, for example, attendance at a conciliation conference can be required in anti-discrimination matters, and is encouraged in residential tenancy matters, and in personal injuries matters the parties must attend a preliminary compulsory conference. Certain ADR processes are used more commonly in the resolution of particular disputes. For example, in family law contexts, mediation and conciliation are generally used because they provide the parties with flexibility in terms of process and outcome while still ensuring that the negotiations occur in a positive, structured and facilitated framework. In commercial contexts, arbitration and neutral evaluation are often used because they can provide the parties with a determination of the dispute that is factually and legally principled, but which is also private and more timely than if the parties went to court. Women, as legal personalities and citizens of society, can find themselves involved in any sort of legal dispute, and therefore all forms of ADR are relevant to women. Perhaps most commonly, however, women come into contact with facilitative ADR processes. For example, through involvement in family law disputes women will encounter family dispute resolution processes, such as mediation. In this chapter, therefore, the focus is on facilitative ADR processes and, particularly, issues for women in terms of their participation in such processes. The aim of this chapter is to provide legal practitioners with an understanding of issues for women in ADR to inform your approach to representing women clients in such processes, and to guide you in preparing women clients for their participation in ADR. The chapter begins with a consideration of the ways in which facilitative ADR processes are positive for women participants. Next, some of the disadvantages for women in ADR are explored. Finally, the chapter offers ways in which legal practitioners can effectively prepare women clients for participation in ADR. Before embarking on a discussion of issues for women in ADR, it is important to acknowledge that women’s experiences in these dispute resolution environments, whilst often sharing commonalities, are diverse and informed by a range of factors specific to each individual woman; for example, her race or socio-economic background. This discussion, therefore, addresses some common issues for women in ADR that are fundamentally gender based. It must be noted, however, that providing advice to women clients about participating in ADR processes requires legal practitioners to have a very good understanding of the client as an individual, and her particular needs and interests. Some sources of diversity are discussed in Chapters 13, 14 and 15.

Elevated YKL40 is associated with advanced prostate cancer (PCa) and positively regulates invasion and migration of PCa cells

Chitinase 3-like 1 (CHI3L1 or YKL40) is a secreted glycoprotein highly expressed in tumours from patients with advanced stage cancers, including prostate cancer (PCa). The exact function of YKL40 is poorly understood, but it has been shown to play an important role in promoting tumour angiogenesis and metastasis. The therapeutic value and biological function of YKL40 are unknown in PCa. The objective of this study was to examine the expression and function of YKL40 in PCa. Gene expression analysis demonstrated that YKL40 was highly expressed in metastatic PCa cells when compared with less invasive and normal prostate epithelial cell lines. In addition, the expression was primarily limited to androgen receptor-positive cell lines. Evaluation of YKL40 tissue expression in PCa patients showed a progressive increase in patients with aggressive disease when compared with those with less aggressive cancers and normal controls. Treatment of LNCaP and C4-2B cells with androgens increased YKL40 expression, whereas treatment with an anti-androgen agent decreased the gene expression of YKL40 in androgen-sensitive LNCaP cells. Furthermore, knockdown of YKL40 significantly decreased invasion and migration of PCa cells, whereas overexpression rendered them more invasive and migratory, which was commensurate with an enhancement in the anchorage-independent growth of cells. To our knowledge, this study characterises the role of YKL40 for the first time in PCa. Together, these results suggest that YKL40 plays an important role in PCa progression and thus inhibition of YKL40 may be a potential therapeutic strategy for the treatment of PCa.

Coping strategies used by ballet dancers : effects of individual differences in competitive trait anxiety

The world of classical ballet exerts considerable physical and psychological stress upon those who participate, and yet the process of coping with such stressors is not well understood. The purpose of the present investigation was to examine relationships between coping strategies and competitive trait anxiety among ballet dancers. Participants were 104 classical dancers (81 females and 23 males) ranging in age from 15 to 35 years (M = 19.4 yr., SD = 3.8 yr.) from three professional ballet companies, two private dance schools, and two full-time, university dance courses in Australia. Participants had a mean of 11.5 years of classical dance training (SD = 5.2 yr.), having started dance training at 6.6 years of age (SD = 3.4 yr.). Coping strategies were assessed using the Modified COPE scale (MCOPE: Crocker & Graham, 1995), a 48-item measure comprising 12 coping subscales (Seeking Social Support for Instrumental Reasons, Seeking Social Support for Emotional Reasons, Behavioral Disengagement, Planning, Suppression of Competing Activities, Venting of Emotions, Humor, Active Coping, Denial, Self-Blame, Effort, and Wishful Thinking). Competitive trait anxiety was assessed using the Sport Anxiety Scale (SAS: Smith, Smoll, & Schutz, 1990), a 21-item measure comprising three anxiety subscales (Somatic Anxiety, Worry, Concentration Disruption). Standard multiple regression analyses showed that trait anxiety scores, in particular for Somatic Anxiety and Worry, were significant predictors of seven of the 12 coping strategies (Suppression of Competing Activities: R2 = 27.1%; Venting of Emotions: R2 = 23.2%; Active Coping: R2 = 14.3%; Denial: R2 = 17.7%; Self-Blame: R2 = 35.7%; Effort: R2 = 16.6%; Wishful Thinking: R2 = 42.3%). High trait anxious dancers reported more frequent use of all categories of coping strategies. A separate two-way MANOVA showed no significant main effect for gender nor status (professional versus students) and no significant interaction effect. The present findings are generally consistent with previous research in the sport psychology domain (Crocker & Graham, 1995; Giacobbi & Weinberg, 2000) which has shown that high trait anxious athletes tend, in particular, to use more maladaptive, emotion-focused coping strategies when compared to low trait anxious athletes; a tendency which has been proposed to lead to negative performance effects. The present results emphasize the need for the effectiveness of specific coping strategies to be considered during the process of preparing young classical dancers for a career in professional ballet. In particular, the results suggest that dancers who are, by nature, anxious about performance may need special attention to help them to learn to cope with performance-related stress. Given the absence of differences in coping strategies between student and professional dancers and between males and females, it appears that such educational efforts should begin at an early career stage for all dancers.

Fine-mapping the HOXB region detects common variants tagging a rare coding allele : evidence for synthetic association in prostate cancer

The HOXB13 gene has been implicated in prostate cancer (PrCa) susceptibility. We performed a high resolution fine-mapping analysis to comprehensively evaluate the association between common genetic variation across the HOXB genetic locus at 17q21 and PrCa risk. This involved genotyping 700 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of 3195 SNPs in 20,440 PrCa cases and 21,469 controls in The PRACTICAL consortium. We identified a cluster of highly correlated common variants situated within or closely upstream of HOXB13 that were significantly associated with PrCa risk, described by rs117576373 (OR 1.30, P = 2.62×10(-14)). Additional genotyping, conditional regression and haplotype analyses indicated that the newly identified common variants tag a rare, partially correlated coding variant in the HOXB13 gene (G84E, rs138213197), which has been identified recently as a moderate penetrance PrCa susceptibility allele. The potential for GWAS associations detected through common SNPs to be driven by rare causal variants with higher relative risks has long been proposed; however, to our knowledge this is the first experimental evidence for this phenomenon of synthetic association contributing to cancer susceptibility.

Prevalence and visual risk factors for falls in bilateral cataract patients in Ho Chi Minh City, Vietnam

Purpose To determine the prevalence of falls in the 12 months prior to cataract surgery and examine the associations between visual and other risk factors and falls among older bilateral cataract patients in Vietnam. Methods Data collected from 413 patients in the week before scheduled cataract surgery included a questionnaire and three objective visual tests. Results The outcome of interest was self-reported falls in the previous 12 months. A total of 13% (n = 53) of bilateral cataract patients reported 60 falls within the previous 12 months. After adjusting for age, sex, race, employment status, comorbidities, medication usage, refractive management, living status and the three objective visual tests in the worse eye, women (odds ratio, OR, 4.64, 95% confidence interval, CI, 1.85–11.66), and those who lived alone (OR 4.51, 95% CI 1.44–14.14) were at increased risk of a fall. Those who reported a comorbidity were at decreased risk of a fall (OR 0.43, 95% CI 0.19–0.95). Contrast sensitivity (OR 0.31, 95% CI 0.10–0.95) was the only significant visual test associated with a fall. These results were similar for the better eye, except the presence of a comorbidity was not significant (OR 0.45, 95% CI 0.20–1.02). Again, contrast sensitivity was the only significant visual factor associated with a fall (OR 0.15, 95% CI 0.04–0.53). Conclusion Bilateral cataract patients in Vietnam are potentially at high risk of falls and in need of falls prevention interventions. It may also be important for ophthalmologists and health professionals to consider contrast sensitivity measures when prioritizing cataract patients for surgery and assessing their risk of falls.

Serosorting may increase the risk of HIV acquisition among men who have sex with men

Background: Serosorting, the practice of seeking to engage in unprotected anal intercourse with partners of the same HIV status as oneself, has been increasing among men who have sex with men. However, the effectiveness of serosorting as a strategy to reduce HIV risk is unclear, especially since it depends on the frequency of HIV testing. Methods: We estimated the relative risk of HIV acquisition associated with serosorting compared with not serosorting by using a mathematical model, informed by detailed behavioral data from a highly studied cohort of gay men. Results: We demonstrate that serosorting is unlikely to be highly beneficial in many populations of men who have sex with men, especially where the prevalence of undiagnosed HIV infections is relatively high. We find that serosorting is only beneficial in reducing the relative risk of HIV transmission if the prevalence of undiagnosed HIV infections is less than ∼20% and ∼40%, in populations of high (70%) and low (20%) treatment rates, respectively, even though treatment reduces the absolute risk of HIV transmission. Serosorting can be expected to lead to increased risk of HIV acquisition in many settings. In settings with low HIV testing rates serosorting can more than double the risk of HIV acquisition. Conclusions: Therefore caution should be taken before endorsing the practice of serosorting. It is very important to continue promotion of frequent HIV testing and condom use, particularly among people at high risk.

Relationship between EGFR expression, EGFR mutation status, and the efficacy of chemotherapy plus cetuximab in FLEX study patients with advanced non-small-cell lung cancer

INTRODUCTION: The phase III FLEX study (NCT00148798) in advanced non-small-cell lung cancer indicated that the survival benefit associated with the addition of cetuximab to cisplatin and vinorelbine was limited to patients whose tumors expressed high levels of epidermal growth factor receptor (EGFR) (immunohistochemistry score of >/=200; scale 0-300). We assessed whether the treatment effect was also modulated in FLEX study patients by tumor EGFR mutation status. METHODS: A tumor mutation screen of EGFR exons 18 to 21 included 971 of 1125 (86%) FLEX study patients. Treatment outcome in low and high EGFR expression groups was analyzed across efficacy endpoints according to tumor EGFR mutation status. RESULTS: Mutations in EGFR exons 18 to 21 were detected in 133 of 971 tumors (14%), 970 of which were also evaluable for EGFR expression level. The most common mutations were exon 19 deletions and L858R (124 of 133 patients; 93%). In the high EGFR expression group (immunohistochemistry score of >/=200), a survival benefit for the addition of cetuximab to chemotherapy was demonstrated in patients with EGFR wild-type (including T790M mutant) tumors. Although patient numbers were small, those in the high EGFR expression group whose tumors carried EGFR mutations may also have derived a survival benefit from the addition of cetuximab to chemotherapy. Response data suggested a cetuximab benefit in the high EGFR expression group regardless of EGFR mutation status. CONCLUSIONS: The survival benefit associated with the addition of cetuximab to first-line chemotherapy for advanced non-small-cell lung cancer expressing high levels of EGFR is not limited by EGFR mutation status.

Improving treatment for obese women with early stage cancer of the uterus : rationale and design of the levonorgestrel intrauterine device ±Metformin ±weight loss in endometrial cancer (feMME) trial

Purpose Endometrial adenocarcinoma (EC) is the most common gynaecologic cancer. Up to 90% of EC patients are obese which poses a health threat to patients post-treatment. Standard treatment for EC includes hysterectomy, although this has significant side effects for obese women at high risk of surgical complications and for women of childbearing age. This trial investigates the effectiveness of non-surgical or conservative treatment options for obese women with early stage EC. The primary aim is to determine the efficacy of: levonorgestrel intrauterine device (LNG-IUD); with or without metformin (an antidiabetic drug); and with or without a weight loss intervention to achieve a pathological complete response (pCR) in EC at six months from study treatment initiation. The secondary aim is to enhance understanding of the molecular processes and to predict a treatment response by investigating EC biomarkers. Methods An open label, three-armed, randomised, phase-II, multi-centre trial of LNG-IUD ± metformin ± weight loss intervention. 165 participants from 28 centres are randomly assigned in a 3:3:5 ratio to the treatment arms. Clinical, quality of life and health behavioural data will be collected at baseline, six weeks, three and six months. EC biomarkers will be assessed at baseline, three and six months. Conclusions There is limited prospective evidence for conservative treatment for EC. Trial results could benefit patients and reduce health system costs through a reduction in hospitalisations and through lower incidence of adverse events currently observed with standard treatment.

Seed germination may explain differences in invasiveness and prevalence : a case study using cat's claw creeper (Dolichandra unguis-cati)

High germination rates and rapid germination behavior in response to different environmental cues are traits that may be associated with invasiveness. Cat’s claw creeper (Dolichandra unguis-cati (L.) Lohmann (syn. Macfadyena unguis-cati (L.) Gentry), a Weed of National Significance has two forms, a long-pod (LP) form and a short-pod (SP) from. The LP form occurs in only a few localities in southeast Queensland while the SP form is widely distributed in Queensland and New South Wales. The aims of this investigation were: to evaluate whether there are significant differences in germination traits between the two forms of cat’s claw creeper; and if there are any significant differences, to find out whether the differences in germination can be related to prevalence and invasiveness levels for the two forms. Long pod and short pod seeds collected in 2009, 2010, 2011, 2012 and 2013 from various localities in Qld were germinated in growth chambers in early 2013. The growth chambers were set to 10/20 ºC, 15/25 ºC and 20/30 ºC temperature cycles. Seeds from 2009-2012 of either form did not germinate, while for the fresh seeds (2013), SP exhibited significantly higher total germination percentage and rates than LP. Assuming that the two forms were introduced in Australia at around the same period, these results could explain why SP is widely distributed (and therefore more invasive) in Qld and NSW while LP is only confined to a few localities in southeast Qld.

Nutritional support in chronic obstructive Pulmonary Disease (COPD) a randomised trial

Rationale Nutritional support is effective in managing malnutrition in COPD (Collins et al., 2012) leading to functional improvements (Collins et al., 2013). However, comparative trials of first line interventions are lacking. This randomised trial compared the effectiveness of individualised dietary advice by a dietitian (DA) versus oral nutritional supplements (ONS). Methods A target sample of 200 stable COPD outpatients at risk of malnutrition (‘MUST’; medium + high risk) were randomised to either a 12-week intervention of ONS (ONS: ~400 kcal/d, ~40 g/d protein) or DA with supportive written advice. The primary outcome was quality of life (QoL) measured using St George’s Respiratory Questionnaire with secondary outcomes including handgrip strength, body weight and nutritional intake. Both the change from baseline and the differences between groups was analysed using SPSS version 20. Results 84 outpatients were recruited (ONS: 41 vs. DA: 43), 72 completed the intervention (ONS: 33 vs. DA: 39). Mean BMI was 18.2 SD 1.6 kg/m2, age 72.6 SD 10 years, FEV1% predicted 36 SD 15% (severe COPD). In comparison to the DA group, the ONS group experienced significantly greater improvements in protein intakes above baseline values at both week 6 (+21.0 SEM 4.3 g/d vs. +0.52 SEM 4.3 g/d; p < 0.001) and week 12 (+19.0 SEM 5.0 g/d vs. +1.0 SEM 3.6 g/d; p = 0.033;ANOVA). QoL and secondary outcomes remained stable at 12 weeks in both groups with slight improvements in the ONS group but no differences between groups. Conclusion In outpatients at risk of malnutrition with severe COPD, nutritional support involving either ONS or DA appears to maintain in tritional status, functional capacity and QoL. However, larger trials, and earlier, multi-modal nutritional interventions for an extended duration should be explored.

Motivational interventions may have greater sustained impact if they trained imagery-based self-management

McCambridge & Rollnick [1] argue that increased benefits from brief motivational interventions (MIs) for alcohol abuse may be obtained if they addressed patients’ con- cerns more directly, especially in severe dependence and primary care. We agree, but take the idea a step further. Recent research on comorbidity has illustrated the power of simultaneously addressing multiple issues in an integrated manner, especially when these changes have synergistic effects (as typically occurs with psycho- sis and substance use [2]). Integrated MI for comorbidity can even be used productively in a single-session format [3]. This idea may have wider application. Recent work in remote Indigenous Australian communities has highlighted the benefits of a broad-ranging discussion of key relationships, activities and resources that confer strength, as well as aspects that worry them or cause dissatisfaction [4]. If excessive drinking is present, its impact on other life areas is reviewed, as in standard MI. However, it is considered alongside other highly valued goals. While the approach has demonstrated effects on both alcohol use and mental health [5], its impact is restricted only by the range of goals that are selected...

Decision support for the efficient annotation of bioacoustic events

Acoustic sensors allow scientists to scale environmental monitoring over large spatiotemporal scales. The faunal vocalisations captured by these sensors can answer ecological questions, however, identifying these vocalisations within recorded audio is difficult: automatic recognition is currently intractable and manual recognition is slow and error prone. In this paper, a semi-automated approach to call recognition is presented. An automated decision support tool is tested that assists users in the manual annotation process. The respective strengths of human and computer analysis are used to complement one another. The tool recommends the species of an unknown vocalisation and thereby minimises the need for the memorization of a large corpus of vocalisations. In the case of a folksonomic tagging system, recommending species tags also minimises the proliferation of redundant tag categories. We describe two algorithms: (1) a “naïve” decision support tool (16%–64% sensitivity) with efficiency of O(n) but which becomes unscalable as more data is added and (2) a scalable alternative with 48% sensitivity and an efficiency ofO(log n). The improved algorithm was also tested in a HTML-based annotation prototype. The result of this work is a decision support tool for annotating faunal acoustic events that may be utilised by other bioacoustics projects.