Motorcycle protective clothing : protection from injury or just the weather?

Background Apart from helmets, little is known about the effectiveness of motorcycle protective clothing in reducing injuries in crashes. The study aimed to quantify the association between usage of motorcycle clothing and injury in crashes. Methods and findings Cross-sectional analytic study. Crashed motorcyclists (n = 212, 71% of identified eligible cases) were recruited through hospitals and motorcycle repair services. Data was obtained through structured face-to-face interviews. The main outcome was hospitalization and motorcycle crash-related injury. Poisson regression was used to estimate relative risk (RR) and 95% confidence intervals for injury adjusting for potential confounders. Results Motorcyclists were significantly less likely to be admitted to hospital if they crashed wearing motorcycle jackets (RR = 0.79, 95% CI: 0.69–0.91), pants (RR = 0.49, 95% CI: 0.25–0.94), or gloves (RR = 0.41, 95% CI: 0.26–0.66). When garments included fitted body armour there was a significantly reduced risk of injury to the upper body (RR = 0.77, 95% CI: 0.66–0.89), hands and wrists (RR = 0.55, 95% CI: 0.38–0.81), legs (RR = 0.60, 95% CI: 0.40–0.90), feet and ankles (RR = 0.54, 95% CI: 0.35–0.83). Non-motorcycle boots were also associated with a reduced risk of injury compared to shoes or joggers (RR = 0.46, 95% CI: 0.28–0.75). No association between use of body armour and risk of fracture injuries was detected. A substantial proportion of motorcycle designed gloves (25.7%), jackets (29.7%) and pants (28.1%) were assessed to have failed due to material damage in the crash. Conclusions Motorcycle protective clothing is associated with reduced risk and severity of crash related injury and hospitalization, particularly when fitted with body armour. The proportion of clothing items that failed under crash conditions indicates a need for improved quality control. While mandating usage of protective clothing is not recommended, consideration could be given to providing incentives for usage of protective clothing, such as tax exemptions for safety gear, health insurance premium reductions and rebates.

Haplotype analysis of two recurrent CDKN2A mutations in 10 melanoma families : evidence for common founders and independent mutations

Germ-line mutations in CDKN2A have been shown to predispose to cutaneous malignant melanoma. We have identified 2 new melanoma kindreds which carry a duplication of a 24bp repeat present in the 5' region of CDKN2A previously identified in melanoma families from Australia and the United States. This mutation has now been reported in 5 melanoma families from 3 continents: Europe, North America, and Australasia. The M53I mutation in exon 2 of CDKN2A has also been documented in 5 melanoma families from Australia and North America. The aim of this study was to determine whether the occurrence of the mutations in these families from geographically diverse populations represented mutation hotspots within CDKN2A or were due to common ancestors. Haplotypes of 11 microsatellite markers flanking CDKN2A were constructed in 5 families carrying the M53I mutation and 5 families carrying the 24bp duplication. There were some differences in the segregating haplotypes due primarily to recombinations and mutations within the short tandem-repeat markers; however, the data provide evidence to indicate that there were at least 3 independent 24bp duplication events and possibly only 1 original M53I mutation. This is the first study to date which indicates common founders in melanoma families from different continents.

Molecular classification of cutaneous malignant melanoma by gene expression profiling

The most common human cancers are malignant neoplasms of the skin. Incidence of cutaneous melanoma is rising especially steeply, with minimal progress in non-surgical treatment of advanced disease. Despite significant effort to identify independent predictors of melanoma outcome, no accepted histopathological, molecular or immunohistochemical marker defines subsets of this neoplasm. Accordingly, though melanoma is thought to present with different 'taxonomic' forms, these are considered part of a continuous spectrum rather than discrete entities. Here we report the discovery of a subset of melanomas identified by mathematical analysis of gene expression in a series of samples. Remarkably, many genes underlying the classification of this subset are differentially regulated in invasive melanomas that form primitive tubular networks in vitro, a feature of some highly aggressive metastatic melanomas. Global transcript analysis can identify unrecognized subtypes of cutaneous melanoma and predict experimentally verifiable phenotypic characteristics that may be of importance to disease progression.

The genetics of cutaneous melanoma

Although germline mutations in CDKN2A are present in approximately 25% of large multicase melanoma families, germline mutations are much rarer in the smaller melanoma families that make up most individuals reporting a family history of this disease. In addition, only three families worldwide have been reported with germline mutations in a gene other than CDKN2A (i.e., CDK4). Accordingly, current genomewide scans underway at the National Human Genome Research Institute hope to reveal linkage to one or more chromosomal regions, and ultimately lead to the identification of novel genes involved in melanoma predisposition. Both CDKN2A and PTEN have been identified as genes involved in sporadic melanoma development; however, mutations are more common in cell lines than uncultured tumors. A combination of cytogenetic, molecular, and functional studies suggests that additional genes involved in melanoma development are located to chromosomal regions 1p, 6q, 7p, 11q, and possibly also 9p and 10q. With the near completion of the human genome sequencing effort, combined with the advent of high throughput mutation analyses and new techniques including cDNA and tissue microarrays, the identification and characterization of additional genes involved in melanoma pathogenesis seem likely in the near future.

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.

Evidence for three tumor suppressor loci on chromosome 9p involved in melanoma development

Cytogenetic and loss of heterozygosity (LOH) studies have long indicated the presence of a tumor suppressor gene (TSG) on 9p involved in the development of melanoma. Although LOH at 9p has been reported in approximately 60% of melanoma tumors, only 5-10% of these tumors have been shown to carry CDKN2A mutations, raising the possibility that another TSG involved in melanoma maps to chromosome 9p. To investigate this possibility, a panel of 37 melanomas derived from 35 individuals was analyzed for CDKN2A mutations by single-strand conformation polymorphism analysis and sequencing. The melanoma samples were then typed for 15 markers that map to 9p13-24 to investigate LOH trends in this region. In those tumors demonstrating retention of heterozygosity at markers flanking CDKN2A and LOH on one or both sides of the gene, multiplex microsatellite PCR was performed to rule out homozygous deletion of the region encompassing CDKN2A. CDKN2A mutations were found in tumors from 5 patients [5 (14%) of 35], 4 of which demonstrated LOH across the entire region examined. The remaining tumor with no observed LOH carried two point mutations, one on each allele. Although LOH was identified at one or more markers in 22 (59%) of 37 melanoma tumors corresponding to 20 (57%) of 35 individuals, only 11 tumors from 9 individuals [9 (26%) of 35] demonstrated LOH at D9S942 and D9S1748 the markers closest to CDKN2A. Of the remaining 11 tumors with LOH 9 demonstrated LOH at two or more contiguous markers either centromeric and/or telomeric to CDKN2A while retaining heterozygosity at several markers adjacent to CDKN2A. Multiplex PCR revealed one tumor carried a homozygous deletion extending from D9S1748 to the IFN-alpha locus. In the remaining eight tumors, multiplex PCR demonstrated that the observed heterozygosity was not attributable to homozygous deletion and stromal contamination at D9S1748, D9S942, or D9S974, as measured by comparative amplification strengths, which indicates that retention of heterozygosity with flanking LOH does not always indicate a homozygous deletion. This report supports the conclusions of previous studies that a least two TSGs involved in melanoma development in addition to CDKN2A may reside on chromosome 9p.

Mutations in exon 3 of the beta-catenin gene are rare in melanoma cell lines

Mutations in exon 3 of the CTNNB1 gene encoding beta-catenin have been reported in colorectal cancer cell lines and tumours. Although one study reported mutations or deletions affecting beta-catenin in 20% of melanoma cell lines, subsequent reports detected a much lower frequency of aberrations in uncultured melanomas. To determine whether this difference in mutation frequency reflected an in vitro culturing artefact, exon 3 of CTNNB1 was screened in a panel of 62 melanoma cell lines. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect intragenic deletions affecting exon 3. One out of 62 (1.6%) cell lines was found to carry a mutation, indicating that aberration of the Wnt-1/wingless pathway through activation of beta-catenin is a rare event, even in melanoma cell lines.

PTEN inactivation is rare in melanoma tumours but occurs frequently in melanoma cell lines

Deletions detected in cytogenetic and loss of heterozygosity (LOH) studies indicate that at least one tumour suppressor gene maps to the long arm of chromosome 10. Previous deletion mapping studies have observed LOH on 10q in about 30% of melanomas analysed. The PTEN gene, mapping to chromosome band 10q23.3, encodes a protein with both lipid and protein phosphatase activity. Somatic mutations and deletions in have been detected in a variety of cell lines and tumours, including melanoma samples. We performed mutation analyses and extensive allelic loss studies to investigate the role this gene plays in melanoma pathogenesis. We found that a total of 34 out of 57 (60%) melanoma cell lines carried hemizygous deletions of chromosome 10q encompassing the PTEN locus. A further three cell lines carried smaller deletions excluding PTEN. Inactivation of both PTEN alleles by exon-specific homozygous deletion or mutation was observed in 13 out of 57 (23%) melanoma cell lines. The mutation spectrum observed does not indicate an important role for ultraviolet radiation in the genesis of these mutations, and evidence from three cell lines supports the acquisition of PTEN aberrations in culture. Ten out of 49 (20%) matched melanoma tumour/normal samples harboured hemizygous deletions of either the whole chromosome or most of the long arm. Mutations within were detected in only one of the 10 tumours demonstrating LOH at 10q23 that were analysed. These results suggest that PTEN inactivation may be important for the propagation of melanoma cells in culture, and that another chromosome 10 tumour suppressor gene may be important for melanoma pathogenesis.

Notch and NOXA-related pathways in melanoma cells

Notch receptor-mediated intracellular events represent an ancient cell signaling system, and alterations in Notch expression are associated with various malignancies in which Notch may function as an oncogene or less commonly as a tumor suppressor. Notch signaling regulates cell fate decisions in the epidermis, including influencing stem cell dynamics and growth/differentiation control of cells in skin. Because of increasing evidence that the Notch signaling network is deregulated in human malignancies, Notch receptors have become attractive targets for selective killing of malignant cells. Compared with proliferating normal human melanocytes, melanoma cell lines are characterized by markedly enhanced levels of activated Notch-1 receptor. By using a small molecule gamma-secretase inhibitor (GSI) consisting of a tripeptide aldehyde, N-benzyloxycarbonyl-Leu-Leu-Nle-CHO, which can block processing and activation of all four different Notch receptors, we identified a specific apoptotic vulnerability in melanoma cells. GSI triggers apoptosis in melanoma cells, but only G2/M growth arrest in melanocytes without subsequent cell death. Moreover, GSI treatment induced a pro-apoptotic BH3-only protein, NOXA, in melanoma cells but not in normal melanocytes. The use of GSI to induce NOXA induction overcomes the apoptotic resistance of melanoma cells, which commonly express numerous cell survival proteins such as Mcl-1, Bcl-2, and survivin. Taken together, these results highlight the concept of synthetic lethality in which exposure to GSI, in combination with melanoma cells overexpressing activated Notch receptors, has lethal consequences, producing selective killing of melanoma cells, while sparing normal melanocytes. By identifying signaling pathways that contribute to the transformation of melanoma cells (e.g. Notch signaling), and anti-cancer agents that achieve tumor selectivity (e.g., GSI-induced NOXA), this experimental approach provides a useful framework for future therapeutic strategies in cutaneous oncology.

Scientia temporum & rerum : History or Antiquarianism? The collection of examples in Georg Calixtus' De studio historiarum oratio (1629)

This paper explores an early modern application of the Stoic principle of similitudo temporum to the study of history. In so doing, it highlights the tension between historiography and antiquarianism, suggesting that the collection of remains – whether material or immaterial – was understood in at least some early modern circles as an integral part of the historiographic process. It also emphasises the evolving meaning of “history” during this time, drawing attention to the perceived novelty of such antiquarian approaches to the study of the past, and briefly exploring subtle differences between the example at hand and the work and activities of better-known figures such as Nicolas-Claude Fabri de Peiresc and Justus Lipsius. As such, this paper makes a contribution to our evolving understanding of early modern scholarship, and draws attention to the variegated approaches of its practitioners to contemporary issues.

Political information choices in a media saturated environment : credibility or convenience?

This thesis examines the ways in which citizens find out about socio-political issues. The project set out to discover how audience characteristics such as scepticism towards the media, gratifications sought, need for cognition and political interest influence information selection. While most previous information choice studies have focused on how individuals select from a narrow range of media types, this thesis considered a much wider sweep of the information landscape. This approach was taken to obtain an understanding of information choices in a more authentic context - in everyday life, people are not simply restricted to one or two news sources. Rather, they may obtain political information from a vast range of information sources, including media sources (e.g. radio, television, newspapers) and sources from beyond the media (eg. interpersonal sources, public speaking events, social networking websites). Thus, the study included both media and non-news media information sources. Data collection for the project consisted of a written, postal survey. The survey was administered to a probability sample in the greater Brisbane region, which is the third largest city in Australia. Data was collected during March and April 2008, approximately four months after the 2007 Australian Federal Election. Hence, the study was conducted in a non-election context. 585 usable surveys were obtained. In addition to measuring the attitudinal characteristics listed above, respondents were surveyed as to which information sources (eg. television shows, radio stations, websites and festivals) they usually use to find out about socio-political issues. Multiple linear regression analysis was conducted to explore patterns of influence between the audience characteristics and information consumption patterns. The results of this analysis indicated an apparent difference between the way citizens use news media sources and the way they use information sources from beyond the news media. In essence, it appears that non-news media information sources are used very deliberately to seek socio-political information, while media sources are used in a less purposeful way. If media use in a non-election context, such as that of the present study, is not primarily concerned with deliberate information seeking, media use must instead have other primary purposes, with political information acquisition as either a secondary driver, or a by-product of that primary purpose. It appears, then, that political information consumption in a media-saturated society is more about routine ‘practices’ than it is about ‘information seeking’. The suggestion that media use is no longer primarily concerned with information seeking, but rather, is simply a behaviour which occurs within the broader set of everyday practices reflects Couldry’s (2004) media as practice paradigm. These findings highlight the need for more authentic and holistic contexts for media research. It is insufficient to consider information choices in isolation, or even from a wider range of information sources, such as that incorporated in the present study. Future media research must take greater account of the broader social contexts and practices in which media-oriented behaviours occur. The findings also call into question the previously assumed centrality of trust to information selection decisions. Citizens regularly use media they do not trust to find out about politics. If people are willing to use information sources they do not trust for democratically important topics such as politics, it is important that citizens possess the media literacy skills to effectively understand and evaluate the information they are presented with. Without the application of such media literacy skills, a steady diet of ‘fast food’ media may result in uninformed or misinformed voting decisions, which have implications for the effectiveness of democratic processes. This research has emphasized the need for further holistic and authentically contextualised media use research, to better understand how citizens use information sources to find out about important topics such as politics.

Factors associated with recall of media reports about vitamin D and sun protection

Objective: To assess the recall of media reports about vitamin D and associated factors. Methods: Analysis of cross-sectional telephone interview data (2,001 Queensland adults, 18-70 years) on vitamin D and personal sun protection, recall of media reports and participant characteristics. Results: 83.7% of participants had heard of vitamin D, 47.5% through the media. Only 513 (25.6%) participants recalled the media content within four main themes: vitamin D is beneficial/comes from the sun (47.0%); some people aren’t getting enough vitamin D, need more sun (27.9%); need to balance sun exposure and skin protection (11.5%); or other (13.6%). Only 65 of the 950 participants (6.8%) reported a change to their behaviour(s) due to the media report. Conclusion: Although the media were the main source of information about vitamin D for almost 50% of participants, recall of the content and direct effect on behaviour was low. Only a small minority recalled a balanced media report of beneficial and harmful aspects of sun exposure. Implications Health professionals often supply media with background information. To achieve best public health practice for sun protection and vitamin D, information to foster balanced media reports should be provided.

Bioimpedance in the assessment of unilateral lymphedema of a limb: the optimal frequency

Background: Bioimpedance techniques provide a reliable method of assessing unilateral lymphedema in a clinical setting. Bioimpedance devices are traditionally used to assess body composition at a current frequency of 50 kHz. However, these devices are not transferable to the assessment of lymphedema, as the sensitivity of measuring the impedance of extracellular fluid is frequency dependent. It has previously been shown that the best frequency to detect extracellular fluid is 0 kHz (or DC). However, measurement at this frequency is not possible in practice due to the high skin impedance at DC, and an estimate is usually determined from low frequency measurements. This study investigated the efficacy of various low frequency ranges for the detection of lymphedema. Methods and Results: Limb impedance was measured at 256 frequencies between 3 kHz and 1000 kHz for a sample control population, arm lymphedema population, and leg lymphedema population. Limb impedance was measured using the ImpediMed SFB7 and ImpediMed L-Dex® U400 with equipotential electrode placement on the wrists and ankles. The contralateral limb impedance ratio for arms and legs was used to calculate a lymphedema index (L-Dex) at each measurement frequency. The standard deviation of the limb impedance ratio in a healthy control population has been shown to increase with frequency for both the arm and leg. Box and whisker plots of the spread of the control and lymphedema populations show that there exists good differentiation between the arm and leg L-Dex measured for lymphedema subjects and the arm and leg L-Dex measured for control subjects up to a frequency of about 30 kHz. Conclusions: It can be concluded that impedance measurements above a frequency of 30 kHz decrease sensitivity to extracellular fluid and are not reliable for early detection of lymphedema.