Biowealth: all creatures great and small

Published as part of Chapter 2: Living in a changing environmentAustralia’s financial wealth, health and wellbeing depend on its biowealth – the diversity of species that support all life.Corey Bradsha

The structure of the cysteine protease and lectin-like domains of Cwp84, a surface layer-associated protein from <em>Clostridium</em> <em>difficile</em>

Clostridium difficile is a major problem as an aetiological agent for antibiotic-associated diarrhoea. The mechanism by which the bacterium colonizes the gut during infection is poorly understood, but undoubtedly involves a myriad of components present on the bacterial surface. The mechanism of C. difficile surface-layer (S-layer) biogenesis is also largely unknown but involves the post-translational cleavage of a single polypeptide (surface-layer protein A; SlpA) into low- and high-molecular-weight subunits by Cwp84, a surface-located cysteine protease. Here, the first crystal structure of the surface protein Cwp84 is described at 1.4 Å resolution and the key structural components are identified. The truncated Cwp84 active-site mutant (amino-acid residues 33–497; C116A) exhibits three regions: a cleavable propeptide and a cysteine protease domain which exhibits a cathepsin L-like fold followed by a newly identified putative carbohydrate-binding domain with a bound calcium ion, which is referred to here as a lectin-like domain. This study thus provides the first structural insights into Cwp84 and a strong base to elucidate its role in the C. difficile S-layer maturation mechanism

International Study of the Epidemiology of Paediatric Trauma : PAPSA Research Study

Objectives: Trauma is a significant cause of morbidity and mortality worldwide. The literature on paediatric trauma epidemiology in low- and middle-income countries (LMICs) is limited. This study aims to gather epidemiological data on paediatric trauma. Methods: This is a multicentre prospective cohort study of paediatric trauma admissions, over 1&nbsp;month, from 15 paediatric surgery centres in 11 countries. Epidemiology, mechanism of injury, injuries sustained, management, morbidity and mortality data were recorded. Statistical analysis compared LMICs and high-income countries (HICs). Results: There were 1377 paediatric trauma admissions over 31&nbsp;days; 1295 admissions across ten LMIC centres and 84 admissions across five HIC centres. Median number of admissions per centre was 15 in HICs and 43 in LMICs. Mean age was 7&nbsp;years, and 62% were boys. Common mechanisms included road traffic accidents (41%), falls (41%) and interpersonal violence (11%). Frequent injuries were lacerations, fractures, head injuries and burns. Intra-abdominal and intra-thoracic injuries accounted for 3 and 2% of injuries. The mechanisms and injuries sustained differed significantly between HICs and LMICs. Median length of stay was 1&nbsp;day and 19% required an operative intervention; this did not differ significantly between HICs and LMICs. No mortality and morbidity was reported from HICs. In LMICs, in-hospital morbidity was 4.0% and mortality was 0.8%. Conclusion: The spectrum of paediatric trauma varies significantly, with different injury mechanisms and patterns in LMICs. Healthcare structure, access to paediatric surgery and trauma prevention strategies may account for these differences. Trauma registries are needed in LMICs for future research and to inform local policy

Planck early results. VI. The High Frequency Instrument data processing

We describe the processing of the 336 billion raw data samples from the High Frequency Instrument (HFI) which we performed to produce six temperature maps from the first 295 days of Planck-HFI survey data. These maps provide an accurate rendition of the sky emission at 100, 143, 217, 353, 545 and 857GHz with an angular resolution ranging from 9.9 to 4.4 . The white noise level is around 1.5 μK degree or less in the 3 main CMB channels (100–217 GHz). The photometric accuracy is better than 2% at frequencies between 100 and 353 GHz and around 7% at the two highest frequencies. The maps created by the HFI Data Processing Centre reach our goals in terms of sensitivity, resolution, and photometric accuracy. They are already sufficiently accurate and well-characterised to allow scientific analyses which are presented in an accompanying series of early papers. At this stage, HFI data appears to be of high quality and we expect that with further refinements of the data processing we should be able to achieve, or exceed, the science goals of the Planck project

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems

Planck early results. II. The thermal performance of Planck

The performance of the Planck instruments in space is enabled by their low operating temperatures, 20 K for LFI and 0.1 K for HFI, achieved through a combination of passive radiative cooling and three active mechanical coolers. The scientific requirement for very broad frequency coverage led to two detector technologies with widely different temperature and cooling needs. Active coolers could satisfy these needs; a helium cryostat, as used by previous cryogenic space missions (IRAS, COBE, ISO, Spitzer, AKARI), could not. Radiative cooling is provided by three V-groove radiators and a large telescope baffle. The active coolers are a hydrogen sorption cooler (<20 K), a 4He Joule-Thomson cooler (4.7 K), and a 3He-4He dilution cooler (1.4 K and 0.1 K). The flight system was at ambient temperature at launch and cooled in space to operating conditions. The HFI bolometer plate reached 93 mK on 3 July 2009, 50 days after launch. The solar panel always faces the Sun, shadowing the rest of Planck, and operates at a mean temperature of 384 K. At the other end of the spacecraft, the telescope baffle operates at 42.3 K and the telescope primary mirror operates at 35.9 K. The temperatures of key parts of the instruments are stabilized by both active and passive methods. Temperature fluctuations are driven by changes in the distance from the Sun, sorption cooler cycling and fluctuations in gas-liquid flow, and fluctuations in cosmic ray flux on the dilution and bolometer plates. These fluctuations do not compromise the science data

Planck early results II : The thermal performance of Planck

Peer reviewe

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR