Immobilisation in Australian paediatric medical imaging: A pilot study.

AIMS: The primary aim of this study is to document the use of paediatric immobilisation techniques in medical imaging. Secondary aims are to investigate differences between current practice of paediatric and non-paediatric facilities and radiographer gender and to investigate immobilisation protocols. METHODS: A SurveyMonkey link was distributed through the Australian Society of Medical Imaging and Radiation Therapy (ASMIRT) newsletter. Radiographer members of ASMIRT were invited to participate. Frequency percentage analysis was undertaken; as the 'frequency of immobilisation' response was on a Likert scale and the ages categorical, a Fisher's exact test could determine dependency. RESULTS: The use of paediatric immobilisation techniques was determined to be related to age. The most commonly used technique in general X-ray was "other people"; in computed tomography, Velcro, verbal reminders and distraction techniques; and in magnetic resonance imaging, sedation and Velcro. A comparison of immobilisation techniques demonstrated that Velcro use in X-ray was dependent on facility (p = 0.017) with paediatric facilities using it up to 17 years. Immobilisation frequency was dependent in 13-17 years (p = 0.035) with paediatric facilities rarely immobilising and non-paediatric facilities never. No dependencies resulted upon comparing genders. Immobilisation frequency was not dependent between protocols or current practice. CONCLUSION: The use of paediatric immobilisation technique is related to age with "other people", sedation, Velcro, verbal reminders and distraction techniques being regularly used. The dependency of Velcro use and immobilisation frequency in 13-17 years is for unknown reasons and further investigation is required. A larger study should be carried out to validate these findings.

Host-associated coral reef microbes respond to the cumulative pressures of ocean warming and ocean acidification.

Key calcifying reef taxa are currently threatened by thermal stress associated with elevated sea surface temperatures (SST) and reduced calcification linked to ocean acidification (OA). Here we undertook an 8 week experimental exposure to near-future climate change conditions and explored the microbiome response of the corals Acropora millepora and Seriatopora hystrix, the crustose coralline algae Hydrolithon onkodes, the foraminifera Marginopora vertebralis and Heterostegina depressa and the sea urchin Echinometra sp. Microbial communities of all taxa were tolerant of elevated pCO2/reduced pH, exhibiting stable microbial communities between pH 8.1 (pCO2 479-499 µatm) and pH 7.9 (pCO2 738-835 µatm). In contrast, microbial communities of the CCA and foraminifera were sensitive to elevated seawater temperature, with a significant microbial shift involving loss of specific taxa and appearance of novel microbial groups occurring between 28 and 31 °C. An interactive effect between stressors was also identified, with distinct communities developing under different pCO2 conditions only evident at 31 °C. Microbiome analysis of key calcifying coral reef species under near-future climate conditions highlights the importance of assessing impacts from both increased SST and OA, as combinations of these global stressors can amplify microbial shifts which may have concomitant impacts for coral reef structure and function.

Nintedanib, a novel triple angiokinase inhibitor for the treatment of non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide. Recent advances involving targeted therapies are promising, but most patients do not have an "oncogene addicted" disease. A platinum doublet chemotherapy regimen has been the mainstay of therapy since 1997. The addition of antiangiogenic agents to traditional chemotherapy has improved survival in patients with non-small cell lung cancer. However, these agents are limited by serious adverse events such as thromboembolism, bowel perforation and hemorrhage and by the development of resistance. Nintedanib is a novel, orally available triple angiokinase inhibitor that targets three important pathways involved in the initiation and propagation of angiogenesis in tumors, the VEGF, FGF and PDGFR pathways. Phase I and II trials have identified the maximum tolerated dose in monotherapy and in combination with traditional chemotherapy. The toxicity profile is tolerable and reversible, dominated by transaminitis and gastrointestinal side effects. The phase III LUME-lung 1 study (NCT00805194) compared docetaxel, a standard treatment in the second line, with docetaxel in combination with nintedanib. Progression-free survival was 3.4 months in the combination group compared to 2.7 months in the docetaxel group, (HR 0.79, 95% CI 0.68-0.92, P = 0.0019). There was a significant improvement in overall survival in adenocarcinoma patients, 12.6 vs. 10.3 months (HR 0.83, 95% CI 0.7-0.99, P = 0.036). Based on the results of this study, nintedanib has been approved by the EMA in Europe, as a second-line treatment in patients with adenocarcinoma. It is a promising, well-tolerated therapy that is currently being investigated in multiple different tumor types.

In situ changes of tropical crustose coralline algae along carbon dioxide gradients.

Crustose coralline algae (CCA) fulfill important ecosystem functions in coral reefs, including reef framework stabilization and induction of larval settlement. To investigate in situ the effects of high carbon dioxide on CCA communities, we deployed settlement tiles at three tropical volcanic CO2 seeps in Papua New Guinea along gradients spanning from 8.1 to 7.4 pH. After 5 and 13 months deployment, there was a steep transition from CCA presence to absence around pH 7.8 (660 µatm pCO2): 98% of tiles had CCA at pH > 7.8, whereas only 20% of tiles had CCA at pH ≤ 7.8. As pH declined from 8.0 to 7.8, the least and most sensitive CCA species lost 43% and 85% of cover, respectively. Communities on upward facing surfaces exposed to high light and high grazing pressure showed less steep losses than those on shaded surfaces with low grazing. Direct CO2 effects on early life stages were the main mechanisms determining CCA cover, rather than competitive interactions with other benthic groups. Importantly, declines were steepest at near-ambient pH, suggesting that CCA may have already declined in abundance due to the recent seawater pH decline of 0.1 units, and that future severe losses are likely with increasing ocean acidification.

Alectinib for the treatment of ALK-positive stage IV non-small cell lung cancer.

Our increased understanding of the molecular subsets of non-small cell lung cancer (NSCLC) has led to the development of highly effective targeted therapies. In particular, the outcomes of patients with advanced NSCLC driven by the EML4-ALK fusion protein, which comprise 3-5% of cases, have remarkably improved with the use of crizotinib, an oral multi-tyrosine kinase inhibitor that targets ALK. However, patients inevitably develop progression while on crizotinib due to various mechanisms of resistance. Alectinib is a novel oral small molecule that inhibits ALK with high potency and selectivity, and demonstrates promising antitumor effects in NSCLC. Preclinical studies have shown that it is also active against several mutant forms of ALK that confer resistance to crizotinib, including the gatekeeper mutation L1196M. Moreover, an objective response rate of over 90% was observed in a phase I trial. Due to the impressive results of early phase studies, alectinib was approved for the treatment of advanced ALK-positive NSCLC in Japan, while it has been granted a breakthrough therapy designation by the FDA. A phase III trial is currently ongoing. This review will describe the biology and significance of ALK rearrangements in NSCLC, ALK inhibition by crizotinib and mechanisms of resistance, as well as the preclinical and clinical evidence for the novel ALK inhibitor alectinib.

Physiological and ecological performance differs in four coral taxa at a volcanic carbon dioxide seep.

Around volcanic carbon dioxide (CO2) seeps in Papua New Guinea, partial pressures of CO2 (pCO2) approximate those as predicted for the end of this century, and coral communities have low diversity and low structural complexity. To assess the mechanisms for such community shifts in response to ocean acidification, we examined the physiological performance of two hard corals that occur with increased or unaltered abundance at a seep site (mean pHTotal=7.8, pCO2=862 µatm) compared to a control site (mean pHTotal=8.1, pCO2=323 µatm), namely massive Porites spp. and Pocillopora damicornis, and two species with reduced abundance, Acropora millepora and Seriatopora hystrix. Oxygen fluxes, calcification, and skeletal densities were analyzed in corals originating from the seep and control site. Net photosynthesis rates increased considerably in Porites spp. and A. millepora and slightly in P. damicornis at increased pCO2, but remained unaltered in S. hystrix. Dark respiration rates remained constant in all corals investigated from both sites. Rates of light calcification declined in S. hystrix at high pCO2, but were unaffected by pCO2 in the other three coral taxa. Dark and net calcification rates remained unchanged in massive Porites and P. damicornis, but were drastically reduced at high pCO2 in A. millepora and S. hystrix. However, skeletal densities were similar at both seep and control sites in all coral taxa investigated. Our data suggest that the pCO2-tolerant corals were characterized by an increased ability to acclimatize to ocean acidification, e.g. by maintaining net calcification. Thus, robust corals, such as Porites spp. and P. damicornis, are more likely to persist for longer in a future high pCO2 world than those unable to acclimatize.

Ecological effects of ocean acidification and habitat complexity on reef-associated macroinvertebrate communities.

The ecological effects of ocean acidification (OA) from rising atmospheric carbon dioxide (CO2) on benthic marine communities are largely unknown. We investigated in situ the consequences of long-term exposure to high CO2 on coral-reef-associated macroinvertebrate communities around three shallow volcanic CO2 seeps in Papua New Guinea. The densities of many groups and the number of taxa (classes and phyla) of macroinvertebrates were significantly reduced at elevated CO2 (425-1100 µatm) compared with control sites. However, sensitivities of some groups, including decapod crustaceans, ascidians and several echinoderms, contrasted with predictions of their physiological CO2 tolerances derived from laboratory experiments. High CO2 reduced the availability of structurally complex corals that are essential refugia for many reef-associated macroinvertebrates. This loss of habitat complexity was also associated with losses in many macroinvertebrate groups, especially predation-prone mobile taxa, including crustaceans and crinoids. The transition from living to dead coral as substratum and habitat further altered macroinvertebrate communities, with far more taxa losing than gaining in numbers. Our study shows that indirect ecological effects of OA (reduced habitat complexity) will complement its direct physiological effects and together with the loss of coral cover through climate change will severely affect macroinvertebrate communities in coral reefs.

An oncolytic mutant of herpes simplex virus type-1 in which replication is governed by a promoter/enhancer of human papillomavirus type-16.

Although herpes simplex virus type-1 (HSV-1) can be used as an oncolytic virus it has the undesirable side effect of neurotoxicity. To create a virus with improved specificity for oral cancer we used a fragment of human papillomavirus type-16, which is frequently found in oral and cervical cancers, but not elsewhere. The upstream regulatory region, URR16, was shown to have a high level of transcriptional activity in three of four oral cancer cell lines but low activity in three cell lines derived from brain cancers. URR16 was therefore placed in HSV-1, replacing the promoter of the essential gene ICP4, and the resulting virus was named HSPV-1. When cells were infected with HSPV-1, ICP4 was expressed at levels that were not associated with the level of activity of URR16. The virus replicated in each type of cell to a final titer that showed a correlation with the level of expression of ICP4, but with no correlation to either the tumor of origin or the presence of HPV sequences in the cells. To find if some function of HSV-1 was affecting the activity of URR16, oral cancer cells were transfected with a URR-reporter construct and were then infected with virus. This induced transcription, which was attributed to immediate-early viral genes other than ICP4. A promoter/enhancer from a papillomavirus therefore has the potential to regulate the functions of an oncolytic strain of HSV-1, and is affected by functions of both the host cell and of HSV-1 itself.

Preventing recurrent rheumatic fever: the role of register based programmes.

Despite dramatic gains of the last century, acute rheumatic fever and rheumatic heart disease remain major preventable causes of morbidity and mortality in many parts of the world.

Novel in vitro functional assays for the determination of anthrax toxin components.

The characterisation and evaluation of the UK licensed human anthrax vaccine depends on several in vivo tests that determine its safety and potency. Assays for the determination of functionally active and/or immunoreactive toxin components and S-layer proteins have been developed and applied to the characterisation of anthrax vaccine. These technologies may support production of consistent and effective vaccines, and may ultimately reduce the requirements for in vivo testing.

Racial disparities in access to renal transplantation--clinically appropriate or due to underuse or overuse?

BACKGROUND: Despite abundant evidence of racial disparities in the use of surgical procedures, it is uncertain whether these disparities reflect racial differences in clinical appropriateness or overuse or underuse of inappropriate care. METHODS: We performed a literature review and used an expert panel to develop criteria for determining the appropriateness of renal transplantation for patients with end-stage renal disease. Using data from five states and the District of Columbia on patients who had started to undergo dialysis in 1996 or 1997, we selected a random sample of 1518 patients (age range, 18 to 54 years), stratified according to race and sex. We classified the appropriateness of patients as data on candidates for transplantation and analyzed rates of referral to a transplantation center for evaluation, placement on a waiting list, and receipt of a transplant according to race. RESULTS: Black patients were less likely than white patients to be rated as appropriate candidates for transplantation according to appropriateness criteria based on expert opinion (71 blacks [9.0 percent] vs. 152 whites [20.9 percent]) and were more likely to have had incomplete evaluations (368 [46.5 percent] vs. 282 [38.8 percent], P<0.001 for the overall chi-square). Among patients considered to be appropriate candidates for transplantation, blacks were less likely than whites to be referred for evaluation, according to the chart review (90.1 percent vs. 98.0 percent, P=0.008), to be placed on a waiting list (71.0 percent vs. 86.7 percent, P=0.007), or to undergo transplantation (16.9 percent vs. 52.0 percent, P<0.001). Among patients classified as inappropriate candidates, whites were more likely than blacks to be referred for evaluation (57.8 percent vs. 38.4 percent), to be placed on a waiting list (30.9 percent vs. 17.4 percent), and to undergo transplantation (10.3 percent vs. 2.2 percent, P<0.001 for all three comparisons). CONCLUSIONS: Racial disparities in rates of renal transplantation stem from differences in clinical characteristics that affect appropriateness as well as from underuse of transplantation among blacks and overuse among whites. Reducing racial disparities will require efforts to distinguish their specific causes and the development of interventions tailored to address them.

Strength and specificity of different gene promoters in oral cancer cells.

Gene therapy of oral cancer will require expression of genes by promoters that are both powerful and relatively tumor specific. We compared the level of expression of a reporter gene from promoters of human cytomegalovirus (CMV), SV40 virus, mouse mammary tumor virus (MMTV), human papillomaviruses (HPV) types 16 and 18, and the human multi-drug-resistance gene (mdr1), in several lines of oral cancer cells. In the oral cancer cell line 686LN the rank order of expression levels was: CMV > SV40 > HPV > mdr1 > MMTV. Unlike in previous reports the mdr1 promoter was no more active in two cancer cell lines with mutations in the p53 gene than in two other lines with wild-type p53, and its expression level could not be increased by either doxorubicin or taxol. On the other hand, expression from the MMTV promoter was increased over 10-fold by the presence of 1 microM dexamethasone. Thus, by an appropriate choice of promoter and inducer a wide variety of expression levels, over a 3-log range, could be attained in 686LN cells. The oral cancer-specificity of each promoter was judged by comparing expression in the neuroblastoma line IMR32. The most specific promoters were those from papillomaviruses, which were up to 45 times more active in the oral cancer cells, and the least specific was the CMV promoter. In order to find if an HPV-derived promoter was sufficient to produce expression of a suicide phenotype the 686 promoter was cloned adjacent to the thymidine kinase gene of herpes simplex and the construct was expressed from an adenovirus vector. The vector reduced the growth of 686LN cells over a 5-day period by up to 32% when optimal concentrations of virus and ganciclovir were used. These data will be valuable in the design of new constructs for gene therapy of oral cancer.

A prescription for trouble.

An elderly arthritis patient repeatedly asks her doctor to prescribe a weight-loss drug for her, and repeatedly, he refuses. But during one visit the harried doctor, intending to write a prescription for Feldene, an arthritis agent, wrote one for Fastin. The script caught the attention of the dispensing pharmacist, who called the physician to confirm the order, and with that telephone call, a medication error was caught before any damage was done.

Sickle cell patients find a brand New World.

As recently as the 1970s, sickle cell anemia patients had little hope of living past their teen years and little relief from painful crises. With the 1980s came the use of prophylactic penicillin to significantly reduce morbidity and mortality from infection in sickle cell youngsters. One of the sickle cell breakthroughs of the 1990s is the use of hydroxyurea for sickle cell treatment in adult patients. In the future, gene therapy may be the answer to the complex problems sickle cell anemia presents.

Women and headache pain. Breaking the cycle.

Hormone-related migraines correspond with a woman's reproductive life cycle. Migraines first occur as a girl enters puberty and are rare after menopause. Is there medical relief available for this pain?

Taking action on arthritis.

The statistics regarding arthritis are mind boggling: one out of every six Americans have arthritis. In New Jersey, more than one million people are affected by arthritis diseases. The condition costs the U.S. economy $65 billion annually in medical care and lost wages. The Centers for Disease Control and Prevention (CDC) projects that in the year 2020, one in five Americans will have arthritis--an estimated 59.4 million people. Increasing awareness of this disease among physicians is a necessity.

Oxalate content of foods and its effect on humans.

Oxalic acid and its salts occur as end products of metabolism in a number of plant tissues. When these plants are eaten they may have an adverse effect because oxalates bind calcium and other minerals. While oxalic acid is a normal end product of mammalian metabolism, the consumption of additional oxalic acid may cause stone formation in the urinary tract when the acid is excreted in the urine. Soaking and cooking of foodstuffs high in oxalate will reduce the oxalate content by leaching. The mean daily intake of oxalate in English diets has been calculated to be 70-150 mg, with tea appearing to contribute the greatest proportion of oxalate in these diets; rhubarb, spinach and beet are other common high oxalate-content foods. Vegetarians who consume greater amounts of vegetables will have a higher intake of oxalates, which may reduce calcium availability. This may be an increased risk factor for women, who require greater amounts of calcium in the diet. In humans, diets low in calcium and high in oxalates are not recommended but the occasional consumption of high oxalate foods as part of a nuritious diet does not pose any particular problem.

Transduction of normal and malignant oral epithelium by particle bombardment.

Although genetic approaches to the treatment and prevention of oral cancer are being developed, there are no suitable methods of transduction of the oral mucosa or early cancers. We therefore tested the technique of particle bombardment for its ability to transduce oral cancer cells in vitro and normal epithelium of the hamster cheek pouch in vivo. A gene gun was used to transfer a plasmid that encoded a marker/suicide fusion gene, beta-galactosidase-thymidine kinase (GAL-TEK), under control of a CMV promoter. For comparison we used the method of lipofection and an adenovirus vector. Particle bombardment transduced up to 13% of cells in culture, resulting in a 24.3% reduction in growth in the presence of ganciclovir. The efficiency of transduction was similar to that of lipofection but was much less than that of the adenovirus vector, which transduced 54% of cells and completely inhibited their growth in the presence of ganciclovir. Transduction of the hamster cheek pouch by particle bombardment produced expression of beta-galactosidase as judged by macroscopic staining, for up to 5 days. However, histological examination showed that the transduced cells were rare and superficial, and that administration of systemic ganciclovir did not lead to any changes in the tissue. Improvements in efficiency are necessary before the gene gun can be used in the management of oral cancer.