Analysis of human immunodeficiency virus type 1 drug resistance in children receiving nucleoside analogue reverse-transcriptase inhibitors plus nevirapine, nelfinavir, or ritonavir (Pediatric AIDS Clinical Trials Group 377)

In Pediatric AIDS Clinical Trials Group 377, antiretroviral therapy-experienced children were randomized to 4 treatment arms that included different combinations of stavudine, lamivudine (3TC), nevirapine (Nvp), nelfinavir (Nfv), and ritonavir (Rtv). Previous treatment with zidovudine (Zdv), didanosine (ddI), or zalcitabine (ddC) was acceptable. Drug resistance ((R)) mutations were assessed before study treatment (baseline) and at virologic failure. Zdv(R), ddI(R), and ddC(R) mutations were detected frequently at baseline but were not associated with virologic failure. Children with drug resistance mutations at baseline had greater reductions in virus load over time than did children who did not. Nvp(R) and 3TC(R) mutations were detected frequently at virologic failure, and Nvp(R) mutations were more common among children receiving 3-drug versus 4-drug Nvp-containing regimens. Children who were maintained on their study regimen after virologic failure accumulated additional Nvp(R) and 3TC(R) mutations plus Rtv(R) and Nfv(R) mutations. However, Rtv(R) and Nfv(R) mutations were detected at unexpectedly low rates.

Serum immunoreactive cationic trypsinogen: A useful indicator of severe exocrine dysfunction in the paediatric patient without cystic fibrosis

We evaluated serum cationic trypsinogen as a marker of exocrine pancreatic function in children without cystic fibrosis. The ability of this test to determine steatorrhoea of pancreatic origin, and its relationship to a wide range of exocrine pancreatic function were assessed. Serum trypsinogen was measured in 32 children with steatorrhoea, 10 with pancreatic and 22 with non-pancreatic causes. In patients with pancreatic steatorrhoea, serum cationic trypsinogen was 4·9±4·9 μg/l (mean ±SD), significantly below values in patients with non-pancreatic steatorrhoea (47·0±22·1 μg/l, p<0·001) and 50 control subjects (31·4±7·4 μg/l, p<0·001). Serum cationic trypsinogen values in patients with pancreatic steatorrhoea all fell below the lower limit of our control range and below all values for patients with non-pancreatic steatorrhoea. Serum cationic trypsinogen was also evaluated against pancreatic trypsin output in 47 patients (range 0·2-17·0 yr) who underwent a hormonal pancreatic stimulation test. In 17 patients, serum cationic trypsinogen was low (<-2SD or 16·6 μg/l), and associated with greatly impaired pancreatic trypsin output, ranging from 0-8% of mean normal trypsin output. Five of these 17 patients did not have steatorrhoea. In 30 patients with normal or raised serum cationic trypsinogen (≥16·6 μg/l), pancreatic trypsin output ranged from 15-183% of mean normal values. In conclusion, low serum cationic trypsinogen suggests severely impaired exocrine pancreatic function, with sensitivity extending above the steatorrhoeic threshold. In the presence of steatorrhoea, low serum cationic trypsinogen indicates a pancreatic aetiology. Normal serum cationic trypsinogen, however, does not exclude impaired pancreatic function, above the steatorrhoeic threshold.

A dosimetric retrospective planning study comparing volumetric arc therapy (VMAT) and stereotactic body radiotherapy (SBRT) treatment plans for non-small cell lung cancer (NSCLC)

Purpose A retrospective planning study comparing volumetric arc therapy (VMAT) and stereotactic body radiotherapy (SBRT) treatment plans for non-small cell lung cancer (NSCLC). Methods and materials Five randomly selected early stage lung cancer patients were included in the study. For each patient, four plans were created: the SBRT plan and three VMAT plans using different optimisation methodologies. A total of 20 different plans were evaluated. The dose parameters of dose conformity results and the target dose constraints results were compared for these plans. Results The mean planning target volume (PTV) for all the plans (SBRT and VMAT) was 18·3 cm3, with a range from 15·6 to 20·1 cm3. The maximum dose tolerance to 1 cc of all the plans was within 140% (84 Gy) of the prescribed dose, and 95% of the PTV of all the plans received 100% of the prescribed dose (60 Gy). In all the plans, 99% of the PTV received a dose >90% of the prescribed dose, and the mean dose in all the plans ranged from 67 to 72 Gy. The planning target dose conformity for the SBRT and the VMAT (0°, 15° collimator single arc plans and dual arc) plans showed the tightness of the prescription isodose conformity to the target. Conclusions SBRT and VMAT are radiotherapy approaches that increase doses to small tumour targets without increasing doses to the organs at risk. Although VMAT offers an alternative to SBRT for NSCLC and the potential advantage of VMAT is the reduced treatment times over SBRT, the statistical results show that there was no significant difference between the SBRT and VMAT optimised plans in terms of dose conformity and organ-at-risk sparing.

Transdisciplinary collaboration in wound care research

The highly complex disorder of chronic wounds is a significant problem. Information is often lacking, dynamically changing, or contradictory and thus acts to impede the progression of research and its translation into clinical care. Transdisciplinary collaboration may play an important role in chronic wound research, permitting key stakeholders with a single, central goal to take a unified approach towards addressing the problem. While transdisciplinary collaboration is not a new concept, its implementation within chronic wound research is relatively new. This is because the research area is still largely dominated by single-discipline researchers or by multiple disciplines working in isolation. Transdisciplinary research is a transcending approach, requiring a greater level of understanding between disciplines and may represent the next leap forward in wound care research. This approach necessitates a deeper understanding by all team members of the co-disciplines involved; where key stakeholders are better equipped to respond to dynamic changes and problems that arise in chronic wound research. In this paper, we illustrate what a transdisciplinary approach in wound care research may entail, with the ultimate goal of such an undertaking to improve understanding of the complexities of wound care, which could lead to potential benefits in wound management.

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Employees’ eldercare demands, strain, and perceived support

Purpose In many countries, both the number of older people in need of care and the number of employed caregivers of elderly relatives will increase over the next decades. The purpose of this paper is to examine the extent to which perceived organizational, supervisor, and coworker support for eldercare reduce employed caregivers’ strain and weaken the relationship between eldercare demands and strain. Design/methodology/approach Survey data were collected from 100 employed caregivers from one organization. Findings Results showed that eldercare demands were positively related to strain, and perceived organizational eldercare support (POES) was negatively related to strain. In addition, high POES weakened the relationship between eldercare demands and strain. Research limitations/implications The cross-sectional design and use of self-report scales constitute limitations of the study. Practical implications POES is a resource for employed caregivers, especially when their eldercare demands are high. Originality/value This research highlights the relative importance of different forms of perceived support for reducing employed caregivers’ strain and weakening the relationship between eldercare demands and strain.

Environmental applications of inorganic-organic clays for recalcitrant organic pollutants removal: Bisphenol A

Bisphenol-A (BPA) adsorption onto inorganic-organic clays (IOCs) was investigated. For this purpose, IOCs synthesised using octadecyltrimethylammonium bromide (ODTMA, organic modifier) and hydroxy aluminium (Al13, inorganic modifier) were used. Three intercalation methods were employed with varying ODTMA concentration in the synthesis of IOCs. Molecular interactions of clay surfaces with ODTMA and Al13 and their arrangements within the interlayers were determined using Fourier transform infrared spectroscopy (FTIR). Surface area and porous structure of IOCs were determined by applying Brunauer, Emmett, and Teller (BET) method to N2 adsorption-desorption isotherms. Surface area decreased upon ODTMA intercalation while it increased with Al13 pillaring. As a result, BET specific surface area of IOCs was considerably higher than those of organoclays. Initial concentration of BPA, contact time and adsorbent dose significantly affected BPA adsorption into IOCs. Pseudo-second order kinetics model is the best fit for BPA adsorption into IOCs. Both Langmuir and Freundlich adsorption isotherms were applicable for BPA adsorption (R2 > 0.91) for IOCs. Langmuir maximum adsorption capacity for IOCs was as high as 109.89 mg g‒1 and it was closely related to the loaded ODTMA amount into the clay. Hydrophobic interactions between long alkyl chains of ODTMA and BPA are responsible for BPA adsorption into IOCs.

Natural recovery from cannabis use in people with psychosis: A qualitative study

- Objective There is rapidly growing evidence of natural recovery from cannabis use in people with psychosis, but little is known about how it occurs. This qualitative study explores what factors influence the decision to cease cannabis use, maintain cessation, and prevent relapse. - Methods Ten people with early psychosis and lifetime cannabis misuse, who had been abstinent for at least a month, were recruited from public adult mental health services. These six men and four women participated in a semi-structured qualitative interview assessing reasons for addressing cannabis use, effective change strategies, lapse contexts, and methods used to regain control. Interpretative phenomenological analysis was used to identify themes in their responses. - Results Participants had a mean age of 23 years (SD = 3.7), started using cannabis at age 13.7 (SD = 1.6), began daily use at 17 (SD = 3.1), and had abstained from cannabis for 7.9 months (SD = 5.4). Awareness of the negative impact of substance use across multiple domains and the presence of social support for cannabis cessation were seen as vital to sustained success, as was utilization of a combination of coping strategies. The ability to address pressure from substance-using peers was commonly mentioned. - Conclusions Maximally effective treatment may need to focus on eliciting a range of benefits of cessation and control strategies and on maximizing both support for change and resistance to peer pressure. Further research might focus on comparing perceived effective strategies between individuals who obtain sustained cessation versus those who relapse.

Corporate accountability in relation to human rights: Have RIOs done enough?

This chapter focuses on the development of corporate human rights standards since the United Nations Conference on Environment and Development, better known as the Earth Summit was held in Rio de Janeiro in 1992. One of the important agendas for this Summit was human rights (apart from the climate change issue). This chapter provides a critical evaluation of institutional change in human rights guidelines and associated corporate (non) accountability in relation to human rights in line with the RIO summit. Based on a review of the media reports, archival documents and a case study, we argue that while there are a number of international organisations working towards the creation of corporate accountability in relation to human rights, there is limited real change in corporate action when faced with no government regulation. A radical (reform-based) approach, such as mandatory monitoring (compliance audit) and disclosure requirements is necessary to ensure corporate accountability in relation to human rights.

Spotless decided per incuriam? - A contrary view

The article considers the implications of the decision of the High Court in Spotless Services Pty Ltd (1996) 141 ALR 92; 34 ATR 183. It argues in particular that the decision was made per incuriam.

Evidence-based practice

This chapter traces the history of evidence-based practice (EBP) from its roots in evidence-based medicine to contemporary thinking about its usefulness to public health practice. It defines EBP and differentiates it from ‘evidence-based medicine’, ‘evidence-based policy’ and ‘evidence-based healthcare’. As it is important to understand the subjective nature of knowledge and the research process, this chapter describes the nature and production of knowledge. This chapter considers the necessary skills for EBP, and the processes of attaining the necessary evidence. We examine the barriers and facilitators to identifying and implementing ‘best practice’, and when EBP is appropriate to use. There is a discussion about the limitations of EBP and the use of other information sources to guide practice, and concluding information about the application of evidence to guide policy and practice.