Sulfate anion templation of macrocycles, capsules, interpenetrated and interlocked structures

This review examines the potential of anions, in particular sulfate, to template the formation of complex molecular architectures. Until recently, sulfate has been largely overlooked in this area and the examples described herein demonstrate this anion’s versatility in templating the formation of a diverse range of molecular systems including macrocycles, helixes, molecular capsules, interpenetrated and interlocked assemblies such as catenanes. In addition sulfate has been shown to template the formation of interpenetrated structures on a range of solid surfaces including gold, polystyrene beads and silicate nanoparticles, highlighting the potential of this anion in the fabrication of functional sensory devices exhibiting highly selective binding behaviour.

CDKN2A is not the principal target of deletions on the short arm of chromosome 9 in neuroendocrine (Merkel cell) carcinoma of the skin

The majority of small-cell lung cancers (SCLCs) express p16 but not pRb. Given our previous study showing loss of pRb in Merkel cell carcinoma (MCC)/neuroendocrine carcinoma of the skin and the clinicopathological similarities between SCLC and MCC, we wished to determine if this was also the case in MCC. Twenty-nine MCC specimens from 23 patients were examined for deletions at 10 loci on 9p and 1 on 9q. No loss of heterozygosity (LOH) was seen in 9 patients including 2 for which tumour and cell line DNAs were examined. Four patients had LOH for all informative loci on 9p. Ten tumours showed more limited regions of loss on 9p, and from these 2 common regions of deletion were determined. Half of all informative cases had LOH at D9S168, the most telomeric marker examined, and 3 specimens showed loss of only D9S168. A second region (IFNA-D9S126) showed LOH in 10 (44%) cases, and case MCC26 showed LOH for only D9S126, implicating genes centromeric of the CDKN2A locus. No mutations in the coding regions of p16 were seen in 7 cell lines tested, and reactivity to anti-p16 antibody was seen in all 11 tumour specimens examined and in 6 of 7 cell lines from 6 patients. Furthermore, all cell lines examined reacted with anti-p14(ARF) antibody. These results suggest that neither transcript of the CDKN2A locus is the target of deletions on 9p in MCC and imply the existence of tumour-suppressor genes mapping both centromeric and telomeric of this locus.

Expert science teacher's notion of scientific literacy

This paper will report on the way expert science teachers’ conceive of scientific literacy in their classrooms, the values related to scientific literacy they hold and how this conception and the underpinning values affect their teaching practice. Three perceived expert science teachers who teach both at senior and middle school levels and across the range of sub-disciplines (one senior biology, one senior chemistry and one senior physics) were interviewed about their understanding of scientific literacy and how this influenced their teaching practice. The three teachers were video recorded teaching a junior science class and a senior science class. The data were analysed to identify values that underpin their conceptions of science and science education. The analysis focussed on the matching of the verbalised conceptions and values with their practice of teaching science. This paper will report on these data.

Understanding the legal implications of data sharing, access and reuse in the Australian research landscape

Researchers are increasingly involved in data-intensive research projects that cut across geographic and disciplinary borders. Quality research now often involves virtual communities of researchers participating in large-scale web-based collaborations, opening their earlystage research to the research community in order to encourage broader participation and accelerate discoveries. The result of such large-scale collaborations has been the production of ever-increasing amounts of data. In short, we are in the midst of a data deluge. Accompanying these developments has been a growing recognition that if the benefits of enhanced access to research are to be realised, it will be necessary to develop the systems and services that enable data to be managed and secured. It has also become apparent that to achieve seamless access to data it is necessary not only to adopt appropriate technical standards, practices and architecture, but also to develop legal frameworks that facilitate access to and use of research data. This chapter provides an overview of the current research landscape in Australia as it relates to the collection, management and sharing of research data. The chapter then explains the Australian legal regimes relevant to data, including copyright, patent, privacy, confidentiality and contract law. Finally, this chapter proposes the infrastructure elements that are required for the proper management of legal interests, ownership rights and rights to access and use data collected or generated by research projects.

Corneal markers of diabetic neuropathy

Diabetic neuropathy is a significant clinical problem that currently has no effective therapy, and in advanced cases, leads to foot ulceration and lower limb amputation. The accurate detection, characterization and quantification of this condition are important in order to define at-risk patients, anticipate deterioration, monitor progression, and assess new therapies This review evaluates novel corneal methods of assessing diabetic neuropathy. Two new non-invasive corneal markers have emerged, and in cross-sectional studies have demonstrated their ability to stratify the severity of this disease. Corneal confocal microscopy allows quantification of corneal nerve parameters and non-contact corneal esthesiometry, the functional correlate of corneal structure, assesses the sensitivity of the cornea. Both these techniques are quick to perform, produce little or no discomfort for the patient, and are suitable for clinical settings. Each has advantages and disadvantages over traditional techniques for assessing diabetic neuropathy. Application of these new corneal markers for longitudinal evaluation of diabetic neuropathy has the potential to reduce dependence on more invasive, costly, and time-consuming assessments, such as skin biopsy.

An exploration of young students' ability to generalise function tasks

The Early Years Generalising Project involves Australian students, Years 1-4 (age 5-9), and explores how the students grasp and express generalisations. This paper focuses on the data collected from clinical interviews with Year 3 and 4 cohorts in an investigative study focusing on the identifications, prediction and justification of function rules. It reports on students' attempts to generalise from function machine contexts, describing the various ways students express generalisation and highlighting the different levels of justification given by students. Finally, we conjecture that there are a set of stages in the expression and justification of generalisations that assist students to reach generality within tasks.

Comparing the cost-effectiveness of MRSA control strategies between ICU and non-ICU settings

Introduction / objectives Many strategies are used to control MRSA in hospitals. Only a few have been assessed in clinical trials and it is not obvious how findings should be generalised between settings. Uncertainty remains about which strategies represent the most appropriate use of scarce resources. We assess the cost-effectiveness of alternative MRSA screening and infection control strategies in England and Wales and discuss international relevance. Methods Models of MRSA transmission in ICUs and general medical (GM) wards were developed and used to evaluate different screening methods combined with decolonisation or isolation. Strategies were compared in terms of costs and health benefits (quality adjusted life years, QALYs). Different prevalences, proportions of high risk patients and ward sizes were investigated, and probabilistic sensitivity analyses (PSA) conducted. Results Decolonisation strategies were cost-saving in ICUs at a 5% admission prevalence, with admission and weekly PCR screening the most cost-effective (£3,929/QALY). In ICUs, screening and isolation reduced infection rates by ~10%. With admission prevalence ≤5%, targeting screening and isolation to high risk patients was optimal. In GM wards decolonisation and isolation strategies, though able to reduce MRSA infection rates up to ~50%, were not cost-effective. Conclusion The largest reductions in MRSA infection were achieved by screening and decolonisation strategies, and were cost-effective in ICU settings. In comparison, there is limited potential for screening and control strategies to be cost-effective in GM wards due to lower infection and mortality rates.

Reliability of ultrasonographic measurement of the architecture of the vastus lateralis and gastrocnemius medialis muscles in older adults

Objective To determine the test-retest reliability of measurements of thickness, fascicle length (Lf) and pennation angle (θ) of the vastus lateralis (VL) and gastrocnemius medialis (GM) muscles in older adults. Participants Twenty-one healthy older adults (11 men and ten women; average age 68·1 ± 5·2 years) participated in this study. Methods Ultrasound images (probe frequency 10 MHz) of the VL at two sites (VL site 1 and 2) were obtained with participants seated with knee at 90º flexion. For GM measures, participants lay prone with ankle fixed at 15º dorsiflexion. Measures were taken on two separate occasions, 7 days apart (T1 and T2). Results The ICCs (95% CI) were: VL site 1 thickness = 0·96(0·90–0·98); VL site 2 thickness = 0·96(0·90–0·98), VL θ = 0·87(0·68–0·95), VL Lf = 0·80(0·50–0·92), GM thickness = 0·97(0·92–0·99), GM θ = 0·85(0·62–0·94) and GM Lf =0·90(0·75–0·96). The 95% ratio limits of agreement (LOAs) for all measures, calculated by multiplying the standard deviation of the ratio of the results between T1 and T2 by 1·96, ranged from 10·59 to 38·01%. Conclusion The ability of these tests to determine a real change in VL and GM muscle architecture is good on a group level but problematic on an individual level as the relatively large 95% ratio LOAs in the current study may encompass the changes in architecture observed in other training studies. Therefore, the current findings suggest that B-mode ultrasonography can be used with confidence by researchers when investigating changes in muscle architecture in groups of older adults, but its use is limited in showing changes in individuals over time.

Interactive processes link the multiple symptoms of fatigue in sport competition

Muscle physiologists often describe fatigue simply as a decline of muscle force and infer this causes an athlete to slow down. In contrast, exercise scientists describe fatigue during sport competition more holistically as an exercise-induced impairment of performance. The aim of this review is to reconcile the different views by evaluating the many performance symptoms/measures and mechanisms of fatigue. We describe how fatigue is assessed with muscle, exercise or competition performance measures. Muscle performance (single muscle test measures) declines due to peripheral fatigue (reduced muscle cell force) and/or central fatigue (reduced motor drive from the CNS). Peak muscle force seldom falls by >30% during sport but is often exacerbated during electrical stimulation and laboratory exercise tasks. Exercise performance (whole-body exercise test measures) reveals impaired physical/technical abilities and subjective fatigue sensations. Exercise intensity is initially sustained by recruitment of new motor units and help from synergistic muscles before it declines. Technique/motor skill execution deviates as exercise proceeds to maintain outcomes before they deteriorate, e.g. reduced accuracy or velocity. The sensation of fatigue incorporates an elevated rating of perceived exertion (RPE) during submaximal tasks, due to a combination of peripheral and higher CNS inputs. Competition performance (sport symptoms) is affected more by decision-making and psychological aspects, since there are opponents and a greater importance on the result. Laboratory based decision making is generally faster or unimpaired. Motivation, self-efficacy and anxiety can change during exercise to modify RPE and, hence, alter physical performance. Symptoms of fatigue during racing, team-game or racquet sports are largely anecdotal, but sometimes assessed with time-motion analysis. Fatigue during brief all-out racing is described biomechanically as a decline of peak velocity, along with altered kinematic components. Longer sport events involve pacing strategies, central and peripheral fatigue contributions and elevated RPE. During match play, the work rate can decline late in a match (or tournament) and/or transiently after intense exercise bursts. Repeated sprint ability, agility and leg strength become slightly impaired. Technique outcomes, such as velocity and accuracy for throwing, passing, hitting and kicking, can deteriorate. Physical and subjective changes are both less severe in real rather than simulated sport activities. Little objective evidence exists to support exercise-induced mental lapses during sport. A model depicting mind-body interactions during sport competition shows that the RPE centre-motor cortex-working muscle sequence drives overall performance levels and, hence, fatigue symptoms. The sporting outputs from this sequence can be modulated by interactions with muscle afferent and circulatory feedback, psychological and decision-making inputs. Importantly, compensatory processes exist at many levels to protect against performance decrements. Small changes of putative fatigue factors can also be protective. We show that individual fatigue factors including diminished carbohydrate availability, elevated serotonin, hypoxia, acidosis, hyperkalaemia, hyperthermia, dehydration and reactive oxygen species, each contribute to several fatigue symptoms. Thus, multiple symptoms of fatigue can occur simultaneously and the underlying mechanisms overlap and interact. Based on this understanding, we reinforce the proposal that fatigue is best described globally as an exercise-induced decline of performance as this is inclusive of all viewpoints.

Melanoma cell invasiveness is regulated by miR-211 suppression of the BRN2 transcription factor

To identify microRNAs potentially involved in melanomagenesis, we compared microRNA expression profiles between melanoma cell lines and cultured melanocytes. The most differentially expressed microRNA between the normal and tumor cell lines was miR-211. We focused on this pigment-cell-enriched miRNA as it is derived from the microphthalmia-associated transcription factor (MITF)-regulated gene, TRPM1 (melastatin). We find that miR-211 expression is greatly decreased in melanoma cells and melanoblasts compared to melanocytes. Bioinformatic analysis identified a large number of potential targets of miR-211, including POU3F2 (BRN2). Inhibition of miR-211 in normal melanocytes resulted in increased BRN2 protein, indicating that endogenous miR-211 represses BRN2 in differentiated cells. Over-expression of miR-211 in melanoma cell lines changed the invasive potential of the cells in vitro through directly targeting BRN2 translation. We propose a model for the apparent non-overlapping expression levels of BRN2 and MITF in melanoma, mediated by miR-211 expression.