Patterns of care and survival for adolescents and young adults with acute leukaemia – a population-based study

We report a population-based study of patterns of care and survival for people with acute leukaemia diagnosed at age 15–29 years during 1984–94 in regions of England and Wales covered by specialist leukaemia registries. There were 879 patients: 417 with acute lymphoblastic leukaemia (ALL) and 462 with acute myeloid leukaemia (AML). For ALL, actuarial survival rates were 43% at 5 years after diagnosis and 37% at 10 years. Survival improved significantly between 1984–88 and 1989–94 for those aged 15–19 at diagnosis. Patients entered in national clinical trials and those not entered had similar survival rates. Survival rates were similar at teaching and non-teaching hospitals and at hospitals treating different numbers of study patients per year. For AML, survival rates were 42% at 5 years after diagnosis and 39% at 10 years. Survival improved significantly between 1984–88 and 1989–94. Patients entered in the Medical Research Council AML10 trial had a higher survival rate than those who were in the earlier AML9 trial. Survival did not vary with category of hospital. We conclude that survival has improved for adolescents and young adults with acute leukaemia but that there is at present no evidence that centralized treatment results in a survival benefit for patients in this age group. © 1999 Cancer Research Campaig

Modelling the Role of the Hsp70/Hsp90 System in the Maintenance of Protein Homeostasis

Neurodegeneration is an age-related disorder which is characterised by the accumulation of aggregated protein and neuronal cell death. There are many different neurodegenerative diseases which are classified according to the specific proteins involved and the regions of the brain which are affected. Despite individual differences, there are common mechanisms at the sub-cellular level leading to loss of protein homeostasis. The two central systems in protein homeostasis are the chaperone system, which promotes correct protein folding, and the cellular proteolytic system, which degrades misfolded or damaged proteins. Since these systems and their interactions are very complex, we use mathematical modelling to aid understanding of the processes involved. The model developed in this study focuses on the role of Hsp70 (IPR00103) and Hsp90 (IPR001404) chaperones in preventing both protein aggregation and cell death. Simulations were performed under three different conditions: no stress; transient stress due to an increase in reactive oxygen species; and high stress due to sustained increases in reactive oxygen species. The model predicts that protein homeostasis can be maintained during short periods of stress. However, under long periods of stress, the chaperone system becomes overwhelmed and the probability of cell death pathways being activated increases. Simulations were also run in which cell death mediated by the JNK (P45983) and p38 (Q16539) pathways was inhibited. The model predicts that inhibiting either or both of these pathways may delay cell death but does not stop the aggregation process and that eventually cells die due to aggregated protein inhibiting proteasomal function. This problem can be overcome if the sequestration of aggregated protein into inclusion bodies is enhanced. This model predicts responses to reactive oxygen species-mediated stress that are consistent with currently available experimental data. The model can be used to assess specific interventions to reduce cell death due to impaired protein homeostasis

A novel evolutionary strategy revealed in the Phaeoviruses

Phaeoviruses infect the brown algae, which are major contributors to primary production of coastal waters and estuaries. They exploit a Persistent evolutionary strategy akin to a K- selected life strategy via genome integration and are the only known representatives to do so within the giant algal viruses that are typified by r- selected Acute lytic viruses. In screening the genomes of five species within the filamentous brown algal lineage, here we show an unprecedented diversity of viral gene sequence variants especially amongst the smaller phaeoviral genomes. Moreover, one variant shares features from both the two major sub-groups within the phaeoviruses. These phaeoviruses have exploited the reduction of their giant dsDNA genomes and accompanying loss of DNA proofreading capability, typical of an Acute life strategist, but uniquely retain a Persistent life strategy

Bird pollination of Canary Island endemic plants

The Canary Islands are home to a guild of endemic, threatened bird pollinated plants. Previous work has suggested that these plants evolved floral traits as adaptations to pollination by flower specialist sunbirds, but subsequently they appear to be have co-opted passerine birds as sub-optimal pollinators. To test this idea we carried out a quantitative study of the pollination biology of three of the bird pollinated plants, Canarina canariensis (Campanulaceae), Isoplexis canariensis (Veronicaceae) and Lotus berthelotii (Fabaceae), on the island of Tenerife. Using colour vision models, we predicted the detectability of flowers to bird and bee pollinators. We measured pollinator visitation rates, nectar standing crops, as well as seed set and pollen removal and deposition. These data showed that the plants are effectively pollinated by non-flower specialist passerine birds that only occasionally visit flowers. The large nectar standing crops and extended flower longevities (>10days) of Canarina and Isoplexis suggests that they have evolved bird pollination system that effectively exploits these low frequency non-specialist pollen vectors and is in no way suboptimal. Seed set in two of the three species was high, and was significantly reduced or zero in flowers where pollinator access was restricted. In L. berthelotii, however, no fruit set was observed, probably because the plants were self incompatible horticultural clones of a single genet. We also show that, while all three species are easily detectable for birds, the orange Canarina and the red Lotus (but less so the yellow-orange Isoplexis) should be difficult to detect for insect pollinators without specialised red receptors, such as bumblebees. Contrary to expectations if we accept that the flowers are primarily adapted to sunbird pollination, the chiffchaff (Phylloscopus canariensis) was an effective pollinator of these species

Outcome of a risk-related therapeutic strategy used prospectively in a population-based study of Hodgkin's lymphoma in adolescents

The aim was to assess outcome in a population-based cohort of adolescents with Hodgkin's lymphoma (HL) diagnosed in the UK's northern region over a 10-year period. Among a population of 3.09 million, 55 of 676 patients (8%) diagnosed with HL were aged 13–19. Seven had nodular lymphocyte-predominant HL, 48 classical HL (cHL). Of the latter, 36 were ⩾16 years. Application of the Scottish and Newcastle Lymphoma Group (SNLG) prognostic index meant 21 patients were considered high risk (index ⩾0.5). They received PVACEBOP multi-agent chemotherapy as primary therapy. Standard risk patients (SNLG index <0.5) were treated with standard ChlVPP or ABVD chemotherapy±radiotherapy. Scottish and Newcastle Lymphoma Group indexing is not valid for patients under 16. Twelve patients therefore received UKCCSG protocols (n=8), ABVD plus radiotherapy (n=2), or PVACEBOP (n=2). Forty-six patients with cHL (96%) achieved complete remission. Seven patients relapsed but all entered complete remission after salvage therapy. Five patients died: three of HL, one in an accident and one of disseminated varicella complicating cystic fibrosis. Five- and 10-year overall survival was 93 and 86%, respectively; disease-specific survival was 95 and 92%. The data suggest that older adolescents with high-risk HL require intensive protocols as primary therapy to secure optimal outcome

What is ‘anti’ about anti-reaches? Reference frames selectively affect reaction times and endpoint variability

Reach movement planning involves the representation of spatial target information in different reference frames. Neurons at parietal and premotor stages of the cortical sensorimotor system represent target information in eye- or hand-centered reference frames, respectively. How the different neuronal representations affect behavioral parameters of motor planning and control, i.e. which stage of neural representation is relevant for which aspect of behavior, is not obvious from the physiology. Here, we test with a behavioral experiment if different kinematic movement parameters are affected to a different degree by either an eye- or hand-reference frame. We used a generalized anti-reach task to test the influence of stimulus-response compatibility (SRC) in eye- and hand-reference frames on reach reaction times, movement times, and endpoint variability. While in a standard anti-reach task, the SRC is identical in the eye- and hand-reference frames, we could separate SRC for the two reference frames. We found that reaction times were influenced by the SRC in eye- and hand-reference frame. In contrast, movement times were only influenced by the SRC in hand-reference frame, and endpoint variability was only influenced by the SRC in eye-reference frame. Since movement time and endpoint variability are the result of planning and control processes, while reaction times are consequences of only the planning process, we suggest that SRC effects on reaction times are highly suited to investigate reference frames of movement planning, and that eye- and hand-reference frames have distinct effects on different phases of motor action and different kinematic movement parameters

A relocatable ocean model in support of environmental emergencies

During the Costa Concordia emergency case, regional, subregional, and relocatable ocean models have been used together with the oil spill model, MEDSLIK-II, to provide ocean currents forecasts, possible oil spill scenarios, and drifters trajectories simulations. The models results together with the evaluation of their performances are presented in this paper. In particular, we focused this work on the implementation of the Interactive Relocatable Nested Ocean Model (IRENOM), based on the Harvard Ocean Prediction System (HOPS), for the Costa Concordia emergency and on its validation using drifters released in the area of the accident. It is shown that thanks to the capability of improving easily and quickly its configuration, the IRENOM results are of greater accuracy than the results achieved using regional or subregional model products. The model topography, and to the initialization procedures, and the horizontal resolution are the key model settings to be configured. Furthermore, the IRENOM currents and the MEDSLIK-II simulated trajectories showed to be sensitive to the spatial resolution of the meteorological fields used, providing higher prediction skills with higher resolution wind forcing.MEDESS4MS Project; TESSA Project; MyOcean2 Projectinfo:eu-repo/semantics/publishedVersio

Acute health effects after accidental exposure to styrene from drinking water in Spain

OBJECTIVES: We studied subjective health symptoms in a population accidentally exposed to high styrene concentrations in drinking tap water. The contamination occurred during the reparation of a water tank. METHODS: Residents of 27 apartments in two buildings using the contaminated water were contacted. A questionnaire on subjective symptoms was administered to 84 out of 93 persons living in the apartments at the time of the accident. Styrene concentration was measured in samples of water collected two days after the accident. The means of exposure associated with appearance of symptoms were examined through case-control analyses. RESULTS: Styrene in water reached concentrations up to 900 μg/L. Symptoms were reported by 46 persons (attack rate 55 %). The most frequent symptoms were irritation of the throat (26%), nose (19%), eyes (18%) and the skin (14%). General gastrointestinal symptoms were observed with 11% reporting abdominal pain and 7% diarrhea. The factors most strongly associated with symptoms were drinking tap water (OR = 7.8, 95% CI 1.3–48), exposure to vapors from the basement (OR = 10.4, 2.3–47) and eating foods prepared with tap water (OR = 8.6, 1.9–40). All residents in the ground floor reported symptoms. CONCLUSIONS: This accidental contamination led to very high styrene concentrations in water and was related to a high prevalence of subjective symptoms of the eyes, respiratory tract and skin. Similar exposures have been described in workers but not in subjects exposed at their residence. Various gastrointestinal symptoms were also observed in this population probably due to a local irritative effect

A conceptual framework for invasion in microbial communities

There is a growing interest in controlling-promoting or avoiding-the invasion of microbial communities by new community members. Resource availability and community structure have been reported as determinants of invasion success. However, most invasion studies do not adhere to a coherent and consistent terminology nor always include rigorous interpretations of the processes behind invasion. Therefore, we suggest that a consistent set of definitions and a rigorous conceptual framework are needed. We define invasion in a microbial community as the establishment of an alien microbial type in a resident community and argue how simple criteria to define aliens, residents, and alien establishment can be applied for a wide variety of communities. In addition, we suggest an adoption of the community ecology framework advanced by Vellend (2010) to clarify potential determinants of invasion. This framework identifies four fundamental processes that control community dynamics: dispersal, selection, drift and diversification. While selection has received ample attention in microbial community invasion research, the three other processes are often overlooked. Here, we elaborate on the relevance of all four processes and conclude that invasion experiments should be designed to elucidate the role of dispersal, drift and diversification, in order to obtain a complete picture of invasion as a community process