Universal structure of dark matter haloes over a mass range of 20 orders of magnitude.

Cosmological models in which dark matter consists of cold elementary particles predict that the dark halo population should extend to masses many orders of magnitude below those at which galaxies can form1-3. Here we report a cosmological simulation of the formation of present-day haloes over the full range of observed halo masses (20 orders of magnitude) when dark matter is assumed to be in the form of weakly interacting massive particles of mass approximately 100 gigaelectronvolts. The simulation has a full dynamic range of 30 orders of magnitude in mass and resolves the internal structure of hundreds of Earth-mass haloes in as much detail as it does for hundreds of rich galaxy clusters. We find that halo density profiles are universal over the entire mass range and are well described by simple two-parameter fitting formulae4,5. Halo mass and concentration are tightly related in a way that depends on cosmology and on the nature of the dark matter. For a fixed mass, the concentration is independent of the local environment for haloes less massive than those of typical galaxies. Haloes over the mass range of 10-3 to 1011 solar masses contribute about equally (per logarithmic interval) to the luminosity produced by dark matter annihilation, which we find to be smaller than all previous estimates by factors ranging up to one thousand3.

Ice front blocking of ocean heat transport to an Antarctic ice shelf.

Mass loss from the Antarctic Ice Sheet to the ocean has increased in recent decades, largely because the thinning of its floating ice shelves has allowed the outflow of grounded ice to accelerate1,2. Enhanced basal melting of the ice shelves is thought to be the ultimate driver of change2,3, motivating a recent focus on the processes that control ocean heat transport onto and across the seabed of the Antarctic continental shelf towards the ice4-6. However, the shoreward heat flux typically far exceeds that required to match observed melt rates2,7,8, suggesting that other critical controls exist. Here we show that the depth-independent (barotropic) component of the heat flow towards an ice shelf is blocked by the marked step shape of the ice front, and that only the depth-varying (baroclinic) component, which is typically much smaller, can enter the sub-ice cavity. Our results arise from direct observations of the Getz Ice Shelf system and laboratory experiments on a rotating platform. A similar blocking of the barotropic component may occur in other areas with comparable ice-bathymetry configurations, which may explain why changes in the density structure of the water column have been found to be a better indicator of basal melt rate variability than the heat transported onto the continental shelf9. Representing the step topography of the ice front accurately in models is thus important for simulating ocean heat fluxes and induced melt rates.

Socio-economic and ethnic disparities in childhood cancer survival, Yorkshire, UK.

BACKGROUND: Establishing the existence of health inequalities remains a high research and policy agenda item in the United Kingdom. We describe ethnic and socio-economic differences in paediatric cancer survival, focusing specifically on the extent to which disparities have changed over a 20-year period. METHODS: Cancer registration data for 2674 children (0-14 years) in Yorkshire were analysed. Five-year survival estimates by ethnic group (south Asian/non-south Asian) and Townsend deprivation fifths (I-V) were compared over time (1997-2016) for leukaemia, lymphoma, central nervous system (CNS) and other solid tumours. Hazard ratios (HR: 95% CI) from adjusted Cox models quantified the joint effect of ethnicity and deprivation on mortality risk over time, framed through causal interpretation of the deprivation coefficient. RESULTS: Increasing deprivation was associated with significantly higher risk of death for children with leukaemia (1.11 (1.03-1.20)) and all cancers between 1997 and 2001. While we observed a trend towards reducing differences in survival over time in this group, a contrasting trend was observed for CNS tumours whereby sizeable variation in outcome remained for cases diagnosed until 2012. South Asian children with lymphoma had a 15% reduced chance of surviving at least 5 years compared to non-south Asian, across the study period. DISCUSSION: Even in the United Kingdom, with a universally accessible healthcare system, socio-economic and ethnic disparities in childhood cancer survival exist. Findings should inform where resources should be directed to provide all children with an equitable survival outcome following a cancer diagnosis.

Sub-ice-shelf sediments record history of twentieth-century retreat of Pine Island Glacier.

The West Antarctic Ice Sheet is one of the largest potential sources of rising sea levels. Over the past 40 years, glaciers flowing into the Amundsen Sea sector of the ice sheet have thinned at an accelerating rate, and several numerical models suggest that unstable and irreversible retreat of the grounding line-which marks the boundary between grounded ice and floating ice shelf-is underway. Understanding this recent retreat requires a detailed knowledge of grounding-line history, but the locations of the grounding line before the advent of satellite monitoring in the 1990s are poorly dated. In particular, a history of grounding-line retreat is required to understand the relative roles of contemporaneous ocean-forced change and of ongoing glacier response to an earlier perturbation in driving ice-sheet loss. Here we show that the present thinning and retreat of Pine Island Glacier in West Antarctica is part of a climatically forced trend that was triggered in the 1940s. Our conclusions arise from analysis of sediment cores recovered beneath the floating Pine Island Glacier ice shelf, and constrain the date at which the grounding line retreated from a prominent seafloor ridge. We find that incursion of marine water beyond the crest of this ridge, forming an ocean cavity beneath the ice shelf, occurred in 1945 (±12 years); final ungrounding of the ice shelf from the ridge occurred in 1970 (±4 years). The initial opening of this ocean cavity followed a period of strong warming of West Antarctica, associated with El Niño activity. Thus our results suggest that, even when climate forcing weakened, ice-sheet retreat continued.

Corrigendum: Sub-ice-shelf sediments record history of twentieth-century retreat of Pine Island Glacier.

This corrects the article DOI: 10.1038/nature20136.

Evidence of bacterial biofilms within acute wounds: a systematic review.

OBJECTIVE: The prevalence and role of biofilm formation in acute wounds has seldom been investigated. Understanding the presence of biofilm in acute wounds would allow earlier, biofilm-targeted management, thus decreasing the morbidity and mortality associated with wound infection, improving patient experience and potentially reducing healthcare costs. The purpose of this study was to summarise the evidence for biofilm formation within acute wounds. METHOD: We conducted a systematic literature review for studies which reported evidence of bacterial biofilm formation in acute wounds. An electronic search of four databases was carried out, without restrictions on date. The search terms included 'bacteria', 'biofilm', 'acute' and 'wound'. RESULTS: A total of 13 studies met the inclusion criteria. Of the studies, 69.2% showed evidence of biofilm formation within 14 days of acute wound formation, with 38.5% showing evidence of biofilm 48 hours after wound formed. CONCLUSION: The evidence from this review suggests that biofilm formation plays a greater role within acute wounds than previously considered.

Mobile genes in the human microbiome are structured from global to individual scales.

Recent work has underscored the importance of the microbiome in human health, and has largely attributed differences in phenotype to differences in the species present among individuals. However, mobile genes can confer profoundly different phenotypes on different strains of the same species. Little is known about the function and distribution of mobile genes in the human microbiome, and in particular whether the gene pool is globally homogenous or constrained by human population structure. Here, we investigate this question by comparing the mobile genes found in the microbiomes of 81 metropolitan North Americans with those of 172 agrarian Fiji islanders using a combination of single-cell genomics and metagenomics. We find large differences in mobile gene content between the Fijian and North American microbiomes, with functional variation that mirrors known dietary differences such as the excess of plant-based starch degradation genes found in Fijian individuals. Notably, we also observed differences between the mobile gene pools of neighbouring Fijian villages, even though microbiome composition across villages is similar. Finally, we observe high rates of recombination leading to individual-specific mobile elements, suggesting that the abundance of some genes may reflect environmental selection rather than dispersal limitation. Together, these data support the hypothesis that human activities and behaviours provide selective pressures that shape mobile gene pools, and that acquisition of mobile genes is important for colonizing specific human populations.

Physical effects of sound exposure from underwater explosions on Pacific mackerel (Scomber japonicus): Effects on non-auditory tissues.

Underwater explosions from activities such as construction, demolition, and military activities can damage non-auditory tissues in fishes. To better understand these effects, Pacific mackerel (Scomber japonicus) were placed in mid-depth cages with water depth of approximately 19.5 m and exposed at distances of 21 to 807 m to a single mid-depth detonation of C4 explosive (6.2 kg net explosive weight). Following exposure, potential correlations between blast acoustics and observed physical effects were examined. Primary effects were damage to the swim bladder and kidney that exceeded control levels at ≤333 m from the explosion [peak sound pressure level 226 dB re 1 µPa, sound exposure level (SEL) 196 dB re 1 µPa2 s, pressure impulse 98 Pa s]. A proportion of fish were dead upon retrieval at 26-40 min post exposure in 6 of 12 cages located ≤157 m from the explosion. All fish that died within this period suffered severe injuries, especially swim bladder and kidney rupture. Logistic regression models demonstrated that fish size or mass was not important in determining susceptibility to injury and that peak pressure and SEL were better predictors of injury than was pressure impulse.

Physical effects of sound exposure from underwater explosions on Pacific mackerel (Scomber japonicus): Effects on the inner ear.

Studies of the effects of sounds from underwater explosions on fishes have not included examination of potential effects on the ear. Caged Pacific mackerel (Scomber japonicus) located at seven distances (between approximately 35 and 800 m) from a single detonation of 4.5 kg of C4 explosives were exposed. After fish were recovered from the cages, the sensory epithelia of the saccular region of the inner ears were prepared and then examined microscopically. The number of hair cell (HC) ciliary bundles was counted at ten preselected 2500 µm2 regions. HCs were significantly reduced in fish exposed to the explosion as compared to the controls. The extent of these differences varied by saccular region, with damage greater in the rostral and caudal ends and minimal in the central region. The extent of effect also varied in animals at different distances from the explosion, with damage occurring in fish as far away as 400 m. While extrapolation to other species and other conditions (e.g., depth, explosive size, and distance) must be performed with extreme caution, the effects of explosive sounds should be considered when environmental impacts are estimated for marine projects.

Skin autofluorescence in people with type 1 diabetes and people without diabetes: An eight-decade cross-sectional study with evidence of accelerated aging and associations with complications.

AIM: To measure skin autofluorescence in youth (<18 y.o.) and adults (≥18 y.o.) and to assess its relationship with type 1 diabetes, chronic complications and smoking. METHODS: In a cross-sectional study (n = 383) skin autofluorescence was measured in 269 people with type 1 diabetes (67 with vascular complications) and 114 people without diabetes, covering eight decades of age. Associations of skin autofluorescence with demographics and traditional risk factors were assessed. RESULTS: Skin autofluorescence increased with age in people with diabetes: for those with complications it increased by a mean ± se of 0.029 ± 0.003 arbitrary units per year (r = 0.76) and, for those without complications, it increased by 0.028 ± 0.002 arbitrary units (r = 0.77). These increases were higher than for people without diabetes, whose skin autofluorescence increased by 0.022 ± 0.002 arbitrary units (r = 0.78) per year (p = 0.004). Mean ±se age-adjusted skin autofluorescence was higher in people with diabetes complications vs people without diabetes complications (1.85 ± 0.04 vs 1.66 ± 0.02 arbitrary units) and people without diabetes (1.48 ± 0.03 arbitrary units; all P < 0.0001). Age-adjusted skin autofluorescence was higher in current smokers and recent ex-smokers vs non-smokers and longer-term ex-smokers (1.86 ± 0.06 vs 1.63 ± 0.02 arbitrary units; P = 0.0005). Skin autofluorescence area under the receiver-operating characteristic curve was 0.89 (95% CI 0.85-0.94) for retinopathy and 0.56 (95% CI 0.47-0.65) for nephropathy. CONCLUSIONS: Skin autofluorescence increases with age, but faster in people with diabetes, particularly in those with complications and in smokers, consistent with accelerated aging. Skin autofluorescence may facilitate complication screening and prediction. Longitudinal studies are merited.

Assessment of mutations induced by cold atmospheric plasma jet treatment relative to known mutagens in Escherichia coli.

The main bactericidal components of cold atmospheric plasma (CAP) are thought to be reactive oxygen and nitrogen species (RONS) and UV-radiation, both of which have the capacity to cause DNA damage and mutations. Here, the mutagenic effects of CAP on Escherichia coli were assessed in comparison to X- and UV-irradiation. DNA damage and mutagenesis were screened for using a diffusion-based DNA fragmentation assay and modified Ames test, respectively. Mutant colonies obtained from the latter were quantitated and sequenced. CAP was found to elicit a similar mutation spectrum to X-irradiation, which did not resemble that for UV implying that CAP-produced RONS are more likely the mutagenic component of CAP. CAP treatment was also shown to promote resistance to the antibiotic ciprofloxacin. Our data suggest that CAP treatment has mutagenic effects that may have important phenotypic consequences.

Physical effects of sound exposure from underwater explosions on Pacific sardines (Sardinops sagax).

Explosions from activities such as construction, demolition, and military activities are increasingly encountered in the underwater soundscape. However, there are few scientifically rigorous data on the effects of underwater explosions on aquatic animals, including fishes. Thus, there is a need for data on potential effects on fishes collected simultaneously with data on the received signal characteristics that result in those effects. To better understand potential physical effects on fishes, Pacific sardines (Sardinops sagax) were placed in cages at mid-depth at distances of 18 to 246 m from a single mid-depth detonation of C4 explosive (4.66 kg net explosive weight). The experimental site was located in the coastal ocean with a consistent depth of approximately 19.5 m. Following exposure, potential correlations between blast acoustics and observed physical effects were examined. Acoustic metrics were calculated as a function of range, including peak pressure, sound exposure level, and integrated pressure over time. Primary effects related to exposure were damage to the swim bladder and kidney. Interestingly, the relative frequency of these two injuries displayed a non-monotonic dependence with range from the explosion in relatively shallow water. A plausible explanation connecting swim bladder expansion with negative pressure as influenced by bottom reflection is proposed.

Health-related behaviours in a remote Indigenous population with Type 2 diabetes: a Central Australian primary care survey in the Telehealth Eye and Associated Medical Services Network [TEAMSnet] project.

AIM: There is a wealth of data concerning the health behaviours of Indigenous Australians, but the health behaviours of Indigenous Australians with diabetes are not systematically documented. At the clinical level, understanding a person's health behaviours can help identify and address barriers to diabetes care and promote good clinical outcomes. METHODS: We used a novel survey tool to systematically collect health behaviour data on Smoking, Nutrition, Alcohol consumption, Physical activity and Emotional well-being (SNAPE) from Indigenous Australians with Type 2 diabetes in a remote primary care setting in Alice Springs. RESULTS: At least one of the five surveys in the SNAPE tool was completed by 210 participants: 30% male, mean age 52.6 years (range 22.9 - 87.4). Fifty per cent of men and 23% of women were current smokers (P < 0.001). None of the participants reported an adequate intake of vegetables. Only 9.6% reported an adequate fruit intake. Some 49% of men and 32% of women consumed alcohol in the past year (P = 0.022), and 46% of drinkers were considered high-risk or likely-dependent drinkers. On average, participants walked 10 min or more at a time 6.0 days a week and spent 4.8 h sitting on a weekday. Mean adapted Patient Health Questionnaire 9 score was 4.61, with 34% of participants having mild depressive symptoms and 11% having moderate-severe depressive symptoms. CONCLUSIONS: Our SNAPE survey tool results present a high-risk, disadvantaged Indigenous population with Type 2 diabetes. More resources will be needed to sustainably implement interventions with the goal of improving health behaviours and subsequent long-term health.

An ESIPT Probe for the Ratiometric Imaging of Peroxynitrite Facilitated by Binding to Aß-Aggregates.

A series of 3-hydroxyflavone (3-HF) ESIPT (excited-state intramolecular proton transfer) boronate-based fluorescent probes have been developed for the detection of peroxynitrite (ONOO-). The dyes are environmentally sensitive, and each probe exhibited a ratiometric response toward ONOO- in a micellar environment. The probes were used to image different aggregation states of amyloid-ß (Aß) in the presence of ONOO-. The 3-HF-OMe probe was found to produce a ratiometric response toward ONOO- when bound to Aß aggregates, resulting in a novel host-guest ensemble, which adds insight into the development of other ESIPT-based probes for the simultaneous sensing of fibrous proteins/peptides and environmental ROS/RNS.

Revitalizing the drug pipeline: AntibioticDB, an open access database to aid antibacterial research and development.

The current state of antibiotic discovery, research and development is insufficient to respond to the need for new treatments for drug-resistant bacterial infections. The process has changed over the last decade, with most new agents that are in Phases 1-3, or recently approved, having been discovered in small- and medium-sized enterprises or academia. These agents have then been licensed or sold to large companies for further development with the goal of taking them to market. However, early drug discovery and development, including the possibility of developing previously discontinued agents, would benefit from a database of antibacterial compounds for scrutiny by the developers. This article describes the first free, open-access searchable database of antibacterial compounds, including discontinued agents, drugs under pre-clinical development and those in clinical trials: AntibioticDB (AntibioticDB.com). Data were obtained from publicly available sources. This article summarizes the compounds and drugs in AntibioticDB, including their drug class, mode of action, development status and propensity to select drug-resistant bacteria. AntibioticDB includes compounds currently in pre-clinical development and 834 that have been discontinued and that reached varying stages of development. These may serve as starting points for future research and development.

Diabetic retinopathy in a remote Indigenous primary healthcare population: a Central Australian diabetic retinopathy screening study in the Telehealth Eye and Associated Medical Services Network project.

AIM: To determine diabetic retinopathy prevalence and severity among remote Indigenous Australians. METHODS: A cross-sectional diabetic retinopathy screening study of Indigenous adults with Type 2 diabetes was conducted by locally trained non-ophthalmic retinal imagers in a remote Aboriginal community-controlled primary healthcare clinic in Central Australia and certified non-ophthalmic graders in a retinal grading centre in Melbourne, Australia. The main outcome measure was prevalence of any diabetic retinopathy and sight-threatening diabetic retinopathy. RESULTS: Among 301 participants (33% male), gradable image rates were 78.7% (n = 237) for diabetic retinopathy and 83.1% (n = 250) for diabetic macular oedema, and 77.7% (n = 234) were gradable for both diabetic retinopathy and diabetic macular oedema. For the gradable subset, the median (range) age was 48 (19-86) years and known diabetes duration 9.0 (0-24) years. The prevalence of diabetic retinopathy was 47% (n = 110) and for diabetic macular oedema it was 14.4% (n = 36). In the fully gradable imaging studies, sight-threatening diabetic retinopathy prevalence was 16.2% (n = 38): 14.1% (n = 33) for clinically significant macular oedema, 1.3% (n = 3) for proliferative diabetic retinopathy and 0.9% (n = 2) for both. Sight-threatening diabetic retinopathy had been treated in 78% of detected cases. CONCLUSIONS: A novel telemedicine diabetic retinopathy screening service detected a higher prevalence of 'any' diabetic retinopathy and sight-threatening diabetic retinopathy in a remote primary care setting than reported in earlier surveys among Indigenous and non-Indigenous populations. Whether the observed high prevalence of diabetic retinopathy was attributable to greater detection, increasing diabetic retinopathy prevalence, local factors, or a combination of these requires further investigation and, potentially, specific primary care guidelines for diabetic retinopathy management in remote Australia. Clinical Trials registration number: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN 12616000370404.

Urinary B-cell-activating factor of the tumour necrosis factor family (BAFF) in systemic lupus erythematosus.

INTRODUCTION: We examined the clinical relevance of urinary concentrations of B-cell-activating factor of the tumour necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) in systemic lupus erythematosus (SLE). METHODS: We quantified urinary BAFF (uBAFF) by enzyme-linked immunosorbent assay in 85 SLE, 28 primary Sjögren syndrome (pSS), 40 immunoglobulin A nephropathy (IgAN) patients and 36 healthy controls (HCs). Urinary APRIL (uAPRIL) and monocyte chemoattractant protein 1 (uMCP-1) were also quantified. Overall and renal SLE disease activity were assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000. RESULTS: uBAFF was detected in 12% (10/85) of SLE patients, but was undetectable in HCs, IgAN and pSS patients. uBAFF was detectable in 28% (5/18) of SLE patients with active nephritis vs 5/67 (7%) of those without ( p = 0.03), and uBAFF was significantly higher in active renal patients ( p = 0.02) and more likely to be detected in patients with persistently active renal disease. In comparison, uAPRIL and uMCP-1 were detected in 32% (25/77) and 46% (22/48) of SLE patients, respectively. While no difference in proportion of samples with detectable uAPRIL was observed between SLE, HCs and IgAN patients, both uAPRIL and uMCP-1 were significantly detectable in higher proportions of patients with active renal disease. CONCLUSIONS: uBAFF was detectable in a small but a significant proportion of SLE patients but not in other groups tested, and was higher in SLE patients with active renal disease.

Higher skin autofluorescence in young people with Type 1 diabetes and microvascular complications.

AIM: To test the hypothesis that non-invasive skin autofluorescence, a measure of advanced glycation end products, would provide a surrogate measure of long-term glycaemia and be associated with early markers of microvascular complications in adolescents with Type 1 diabetes. METHODS: Forearm skin autofluorescence (arbitrary units) was measured in a cross-sectional study of 135 adolescents with Type 1 diabetes [mean ± sd age 15.6 ± 2.1 years, diabetes duration 8.7 ± 3.5 years, HbA1c 72 ± 16 mmol/mol (8.7 ± 1.5%)]. Retinopathy, assessed using seven-field stereoscopic fundal photography, was defined as ≥1 microaneurysm or haemorrhage. Cardiac autonomic function was measured by standard deviation of consecutive RR intervals on a 10-min continuous electrocardiogram recording, as a measure of heart rate variability. RESULTS: Skin autofluorescence was significantly associated with age (R2 = 0.15; P < 0.001). Age- and gender-adjusted skin autofluorescence was associated with concurrent HbA1c (R2 = 0.32; P < 0.001) and HbA1c over the previous 2.5-10 years (R2 = 0.34-0.43; P < 0.002). Age- and gender-adjusted mean skin autofluorescence was higher in adolescents with retinopathy vs those without retinopathy [mean 1.38 (95% CI 1.29, 1.48) vs 1.22 (95% CI 1.17, 1.26) arbitrary units; P = 0.002]. In multivariable analysis, retinopathy was significantly associated with skin autofluorescence, adjusted for duration (R2 = 0.19; P = 0.03). Cardiac autonomic dysfunction was also independently associated with skin autofluorescence (R2 = 0.11; P = 0.006). CONCLUSIONS: Higher skin autofluorescence is associated with retinopathy and cardiac autonomic dysfunction in adolescents with Type 1 diabetes. The relationship between skin autofluorescence and previous glycaemia may provide insight into metabolic memory. Longitudinal studies will determine the utility of skin autofluorescence as a non-invasive screening tool to predict future microvascular complications.