Functional capacities of microbial communities to carry out large scale geochemical processes are maintained during ex situ anaerobic incubation.

Mechanisms controlling CO2 and CH4 production in wetlands are central to understanding carbon cycling and greenhouse gas exchange. However, the volatility of these respiration products complicates quantifying their rates of production in the field. Attempts to circumvent the challenges through closed system incubations, from which gases cannot escape, have been used to investigate bulk in situ geochemistry. Efforts towards mapping mechanistic linkages between geochemistry and microbiology have raised concern regarding sampling and incubation-induced perturbations. Microorganisms are impacted by oxygen exposure, increased temperatures and accumulation of metabolic products during handling, storage, and incubation. We probed the extent of these perturbations, and their influence on incubation results, using high-resolution geochemical and microbial gene-based community profiling of anaerobically incubated material from three wetland habitats across a permafrost peatland. We compared the original field samples to the material anaerobically incubated over 50 days. Bulk geochemistry and phylum-level microbiota in incubations largely reflected field observations, but divergence between field and incubations occurred in both geochemistry and lineage-level microbial composition when examined at closer resolution. Despite the changes in representative lineages over time, inferred metabolic function with regards to carbon cycling largely reproduced field results suggesting functional consistency. Habitat differences among the source materials remained the largest driver of variation in geochemical and microbial differences among the samples in both incubations and field results. While incubations may have limited usefulness for identifying specific mechanisms, they remain a viable tool for probing bulk-scale questions related to anaerobic C cycling, including CO2 and CH4 dynamics.

An analysis of screen-detected invasive cancers by grade in the English breast cancer screening programme: are we failing to detect sufficient small grade 3 cancers?

OBJECTIVE: Randomised controlled trials have shown a reduction in breast cancer mortality from mammography screening and it is the detection of high-grade invasive cancers that is responsible for much of this effect. We determined the detection rates of invasive cancers by grade, size and type of screen and estimated relative sensitivities with emphasis on grade 3 detection. METHODS: This observational study analysed data from over 11 million screening episodes (67,681 invasive cancers) from the English NHS breast screening programme over seven screening years 2009/2010 to 2015/2016 for women aged 45-70. RESULTS: At prevalent (first) screens (which are unaffected by screening interval), the detection rate of small (< 15 mm) invasive cancers was 0.95 per 1000 for grade 1, but for grade 3 only 0.30 per 1000. The ratio of small (< 15 mm) to large (≥ 15 mm) cancers was 1.8:1 for grade 1 but reversed to 0.5:1 for grade 3. We estimated that the relative sensitivity for grade 3 invasive cancers was 52% of that for grade 1 and the relative sensitivity for small (< 15 mm) grade 3 only 26% of that for small (< 15 mm) grade 1 invasive cancers. CONCLUSIONS: Sensitivity for small grade 3 invasive cancers is poor compared with that for grade 1 and 2 invasive cancers and larger grade 3 malignancies. This observation is likely a limitation of the current technology related to the absence of identifiable mammographic features for small high-grade cancers. Future work should focus on technologies and strategies to improve detection of these clinically most significant cancers. KEY POINTS: • The detection of small high-grade invasive cancers is vital to reduce breast cancer mortality. • We estimate the sensitivity for small grade 3 invasive cancers may be only 26% of that of small grade 1 invasive cancers. This is likely to be associated with the non-specific mammographic features for these cancers. • New technologies and appropriate strategies using current technology are required to maximise the detection of small grade 3 invasive cancers.

Massive peatland carbon banks vulnerable to rising temperatures.

Peatlands contain one-third of the world's soil carbon (C). If destabilized, decomposition of this vast C bank could accelerate climate warming; however, the likelihood of this outcome remains unknown. Here, we examine peatland C stability through five years of whole-ecosystem warming and two years of elevated atmospheric carbon dioxide concentrations (eCO2). Warming exponentially increased methane (CH4) emissions and enhanced CH4 production rates throughout the entire soil profile; although surface CH4 production rates remain much greater than those at depth. Additionally, older deeper C sources played a larger role in decomposition following prolonged warming. Most troubling, decreases in CO2:CH4 ratios in gas production, porewater concentrations, and emissions, indicate that the peatland is becoming more methanogenic with warming. We observed limited evidence of eCO2 effects. Our results suggest that ecosystem responses are largely driven by surface peat, but that the vast C bank at depth in peatlands is responsive to prolonged warming.

Correction to: An analysis of 11.3 million screening tests examining the association between recall and cancer detection rates in the English NHS breast cancer screening programme.

The original version of this article, published on 04 February 2019, unfortunately contained a mistake.

An analysis of 11.3 million screening tests examining the association between recall and cancer detection rates in the English NHS breast cancer screening programme.

OBJECTIVE: To develop methods to model the relationship between cancer detection and recall rates to inform professional standards. METHODS: Annual screening programme information for each of the 80 English NHSBSP units (totalling 11.3 million screening tests) for the seven screening years from 1 April 2009 to 31 March 2016 and some Dutch screening programme information were used to produce linear and non-linear models. The non-linear models estimated the modelled maximum values (MMV) for cancers detected at different grades and estimated how rapidly the MMV was reached (the modelled 'slope' (MS)). Main outcomes include the detection rate for combined invasive/micro-invasive and high-grade DCIS (IHG) detection rate and the low/intermediate grade DCIS (LIG) detection rate. RESULTS: At prevalent screens for IHG cancers, 99% of the MMV was reached at a recall rate of 7.0%. The LIG detection rate had no discernible plateau, increasing linearly at a rate of 0.12 per 1000 for every 1% increase in recall rate. At incident screens, 99% of the MMV for IHG cancer detection was 4.0%. LIG DCIS increased linearly at a rate of 0.18 per 1000 per 1% increase in recall rate. CONCLUSIONS: Our models demonstrate the diminishing returns associated with increasing recall rates. The screening programme in England could use the models to set recall rate ranges, and other countries could explore similar methodology. KEY POINTS: • Question: How can we determine optimum recall rates in breast cancer screening? • Findings: In this large observational study, we show that increases in recall rates above defined levels are almost exclusively associated with false positive recalls and a very small increase in low/intermediate grade DCIS. • Meaning: High recall rates are not associated with increases in detection of life-threatening cancers. The models developed in this paper can be used to help set recall rate ranges that maximise benefit and minimise harm.

Image processing can cause some malignant soft-tissue lesions to be missed in digital mammography images.

AIM: To investigate the effect of image processing on cancer detection in mammography. METHODS AND MATERIALS: An observer study was performed using 349 digital mammography images of women with normal breasts, calcification clusters, or soft-tissue lesions including 191 subtle cancers. Images underwent two types of processing: FlavourA (standard) and FlavourB (added enhancement). Six observers located features in the breast they suspected to be cancerous (4,188 observations). Data were analysed using jackknife alternative free-response receiver operating characteristic (JAFROC) analysis. Characteristics of the cancers detected with each image processing type were investigated. RESULTS: For calcifications, the JAFROC figure of merit (FOM) was equal to 0.86 for both types of image processing. For soft-tissue lesions, the JAFROC FOM were better for FlavourA (0.81) than FlavourB (0.78); this difference was significant (p=0.001). Using FlavourA a greater number of cancers of all grades and sizes were detected than with FlavourB. FlavourA improved soft-tissue lesion detection in denser breasts (p=0.04 when volumetric density was over 7.5%) CONCLUSIONS: The detection of malignant soft-tissue lesions (which were primarily invasive) was significantly better with FlavourA than FlavourB image processing. This is despite FlavourB having a higher contrast appearance often preferred by radiologists. It is important that clinical choice of image processing is based on objective measures.

Collective Excitations of Self-Bound Droplets of a Dipolar Quantum Fluid.

We calculate the collective excitations of a dipolar Bose-Einstein condensate in the regime where it self-binds into droplets stabilized by quantum fluctuations. We show that the filament-shaped droplets act as a quasi-one-dimensional waveguide along which low-angular-momentum phonons propagate. The evaporation (unbinding) threshold occurring as the atom number N is reduced to the critical value N_{c} is associated with a monopolelike excitation going soft as ε_{0}∼(N-N_{c})^{1/4}. Considering the system in the presence of a trapping potential, we quantify the crossover from a trap-bound condensate to a self-bound droplet.

Emergent equilibrium in many-body optical bistability.

Many-body systems constructed of quantum-optical building blocks can now be realized in experimental platforms ranging from exciton-polariton fluids to ultracold Rydberg gases, establishing a fascinating interface between traditional many-body physics and the driven-dissipative, nonequilibrium setting of cavity QED. At this interface, the standard techniques and intuitions of both fields are called into question, obscuring issues as fundamental as the role of fluctuations, dimensionality, and symmetry on the nature of collective behavior and phase transitions. Here, we study the driven-dissipative Bose-Hubbard model, a minimal description of numerous atomic, optical, and solid-state systems in which particle loss is countered by coherent driving. Despite being a lattice version of optical bistability, a foundational and patently nonequilibrium model of cavity QED, the steady state possesses an emergent equilibrium description in terms of a classical Ising model. We establish this picture by making new connections between traditional techniques from many-body physics (functional integrals) and quantum optics (the system-size expansion). To lowest order in a controlled expansion-organized around the experimentally relevant limit of weak interactions-the full quantum dynamics reduces to nonequilibrium Langevin equations, which support a phase transition described by model A of the Hohenberg-Halperin classification. Numerical simulations of the Langevin equations corroborate this picture, revealing that canonical behavior associated with the Ising model manifests readily in simple experimental observables.

Stability of peatland carbon to rising temperatures.

Peatlands contain one-third of soil carbon (C), mostly buried in deep, saturated anoxic zones (catotelm). The response of catotelm C to climate forcing is uncertain, because prior experiments have focused on surface warming. We show that deep peat heating of a 2 m-thick peat column results in an exponential increase in CH4 emissions. However, this response is due solely to surface processes and not degradation of catotelm peat. Incubations show that only the top 20-30 cm of peat from experimental plots have higher CH4 production rates at elevated temperatures. Radiocarbon analyses demonstrate that CH4 and CO2 are produced primarily from decomposition of surface-derived modern photosynthate, not catotelm C. There are no differences in microbial abundances, dissolved organic matter concentrations or degradative enzyme activities among treatments. These results suggest that although surface peat will respond to increasing temperature, the large reservoir of catotelm C is stable under current anoxic conditions.

Crystallization of high-strength nano-scale leucite glass-ceramics.

OBJECTIVES: Fine-grained, high strength, translucent leucite dental glass-ceramics are synthesized via controlled crystallization of finely milled glass powders. The objectives of this study were to utilize high speed planetary milling of an aluminosilicate glass for controlled surface crystallization of nano-scale leucite glass-ceramics and to test the biaxial flexural strength. METHODS: An aluminosilicate glass was synthesized, attritor or planetary milled and heat-treated. Glasses and glass-ceramics were characterized using particle size analysis, X-ray diffraction and scanning electron microscopy. Experimental (fine and nanoscale) and commercial (Ceramco-3, IPS Empress Esthetic) leucite glass-ceramics were tested using the biaxial flexural strength (BFS) test. Gaussian and Weibull statistics were applied. RESULTS: Experimental planetary milled glass-ceramics showed an increased leucite crystal number and nano-scale median crystal sizes (0.048-0.055 µm(2)) as a result of glass particle size reduction and heat treatments. Experimental materials had significantly (p<0.05) higher mean BFS and characteristic strength values than the commercial materials. Attritor milled and planetary milled (2h) materials showed no significant (p>0.05) strength difference. All other groups' mean BFS and characteristic strengths were found to be significantly different (p<0.05) to each other. The mean (SD) MPa strengths measured were: Attritor milled: 252.4 (38.7), Planetary milled: 225.4 (41.8) [4h milling] 255.0 (35.0) [2h milling], Ceramco-3: 75.7 (6.8) and IPS Empress: 165.5 (30.6). SIGNIFICANCE: Planetary milling enabled synthesis of nano-scale leucite glass-ceramics with high flexural strength. These materials may help to reduce problems associated with brittle fracture of all-ceramic restorations and give reduced enamel wear.

Importance of spin-orbit interaction for the electron spin relaxation in organic semiconductors.

Despite the great interest organic spintronics has recently attracted, there is only a partial understanding of the fundamental physics behind electron spin relaxation in organic semiconductors. Mechanisms based on hyperfine interaction have been demonstrated, but the role of the spin-orbit interaction remains elusive. Here, we report muon spin spectroscopy and time-resolved photoluminescence measurements on two series of molecular semiconductors in which the strength of the spin-orbit interaction has been systematically modified with a targeted chemical substitution of different atoms at a particular molecular site. We find that the spin-orbit interaction is a significant source of electron spin relaxation in these materials.

Patient safety in developing countries: retrospective estimation of scale and nature of harm to patients in hospital.

OBJECTIVE: To assess the frequency and nature of adverse events to patients in selected hospitals in developing or transitional economies. DESIGN: Retrospective medical record review of hospital admissions during 2005 in eight countries. SETTING: Ministries of Health of Egypt, Jordan, Kenya, Morocco, Tunisia, Sudan, South Africa and Yemen; the World Health Organisation (WHO) Eastern Mediterranean and African Regions (EMRO and AFRO), and WHO Patient Safety. PARTICIPANTS: Convenience sample of 26 hospitals from which 15,548 patient records were randomly sampled. MAIN OUTCOME MEASURES: Two stage screening. Initial screening based on 18 explicit criteria. Records that screened positive were then reviewed by a senior physician for determination of adverse event, its preventability, and the resulting disability. RESULTS: Of the 15,548 records reviewed, 8.2% showed at least one adverse event, with a range of 2.5% to 18.4% per country. Of these events, 83% were judged to be preventable, while about 30% were associated with death of the patient. About 34% adverse events were from therapeutic errors in relatively non-complex clinical situations. Inadequate training and supervision of clinical staff or the failure to follow policies or protocols contributed to most events. CONCLUSIONS: Unsafe patient care represents a serious and considerable danger to patients in the hospitals that were studied, and hence should be a high priority public health problem. Many other developing and transitional economies will probably share similar rates of harm and similar contributory factors. The convenience sampling of hospitals might limit the interpretation of results, but the identified adverse event rates show an estimate that should stimulate and facilitate the urgent institution of appropriate remedial action and also to trigger more research. Prevention of these adverse events will be complex and involves improving basic clinical processes and does not simply depend on the provision of more resources.

Diagnostic quality of 50 and 100 µm computed radiography compared with screen-film mammography in operative breast specimens.

OBJECTIVE: To compare reader ratings of the clinical diagnostic quality of 50 and 100 µm computed radiography (CR) systems with screen-film mammography (SFM) in operative specimens. METHODS: Mammograms of 57 fresh operative breast specimens were analysed by 10 readers. Exposures were made with identical position and compression with three mammographic systems (Fuji 100CR, 50CR and SFM). Images were anonymised and readers blinded to the CR system used. A five-point comparative scoring system (-2 to +2) was used to assess seven quality criteria and overall diagnostic value. Statistical analysis was subsequently performed of reader ratings (n = 16,925). RESULTS: For most quality criteria, both CR systems were rated as equivalent to or better than SFM. The CR systems were significantly better at demonstrating skin edge and background tissue (p < 1 × 10(-5)). Microcalcification was best demonstrated on the CR50 system (p < 1 × 10(-5)). The overall diagnostic value of both CR systems was rated as being as good as or better than SFM (p < 1 × 10(-5)). CONCLUSION: In this clinical setting, the overall diagnostic performance of both CR systems was as good as or better than SFM, with the CR50 system performing better than the CR100.

Crystallization of high-strength fine-sized leucite glass-ceramics.

Manufacturing of leucite glass-ceramics often leads to materials with inhomogeneous microstructures. Crystal-glass thermal mismatches which produce microcracking around larger crystals-agglomerates are associated with reduced mechanical properties. The hypotheses were that fine (< 1 µm) crystal size and uniform microstructure in a thermally matched glass would increase the biaxial flexural strength (BFS). Glass was synthesized, attritor-milled, and heat-treated. Glasses and glass-ceramics were characterized by XRD, SEM, and Dilatometry. Experimental (A, M1A and M2A) and commercial glass-ceramics were tested by the BFS test. Experimental glass-ceramics showed an increased leucite crystal number and decreased crystal size with glass particle size reduction. Leucite glass-ceramics (< 1 µm) showed minimal matrix microcracking and BFS values of [mean (SD) MPa]: M1A = 253.8 (53.3); and M2A = 219.5 (54.1). Glass-ceramics M1A and M2A had higher mean BFS and characteristic strength than the IPS Empress Esthetic glass-ceramic (p < 0.05). Fine-grained, translucent leucite glass-ceramics were synthesized and produced high mean BFS.

Synthesis of triclinic calcium pyrophosphate crystals.

This paper presents a method for preparing crystals of triclinic calcium pyrophosphate (t-CPPD). A calcium pyrophosphate intermediate is first prepared by reaction of potassium pyrophosphate and calcium chloride. Samples of the intermediate are dissolved in hydrochloric acid and urea added. Upon heating to 95-100 degrees C, hydrolysis of the urea causes the pH to rise and t-CPPD crystallises out. Purity of the product was ascertained by chemical and physical analysis. Where large crystals are required an unstirred system is used, while smaller crystals are produced by stirring the reaction mixture.

Evaluation of computer-aided detection (CAD) devices.

We present a review of three major UK studies of computer-aided detection (CAD) for mammography. A short account of the motivation, methods and results is given for each of the three. A number of conclusions are drawn, particularly about the merits and difficulties of research in the field. The first two studies measured the impact of CAD on the sensitivity and specificity of film readers interpreting cases with known outcomes displayed on rollers with an artificially high frequency of cancers. In the first study 50 film readers each read 180 cases, including 60 cancers (40 screen-detected and 20 interval). In the second study 35 film readers viewed 120 cases including 44 cancers, of which 40 were selected to be difficult cases that CAD prompted correctly. The third study was carried out prospectively. 6111 films were independently double read by film readers who recorded a judgement before and after viewing CAD prompts. In addition to this, intraobserver measure of the impact of CAD, we compared the cancer detection rate in these cases with that in 1339 cases read over the same period without the benefit of CAD. None of the three studies showed a statistically significant effect attributable to CAD. There is evidence that a high proportion of missed cancers are prompted and that "emphasised" prompts, which have a greater positive predictive value, have a stronger impact on decision-making that other prompts.

The clinical importance of axillary lymphadenopathy detected on screening mammography: revisited.

AIM: The aim of this study was to re-evaluate our protocol for the management of isolated axillary lymphadenopathy (ALP) on mammographic screening. METHODS: In a retrospective review of 200,716 women screened at the South West London Breast Screening Service (SWLBSS) over 7 years, 72 women with ALP with an otherwise normal mammogram were identified. Thirteen patients were not recalled, nine of who had a known underlying diagnosis and the remainder had longstanding unchanged mammograms. Fifty-nine patients were recalled for further clinical assessment and investigations, including ultrasound, further mammographic views, fine-needle aspiration cytology (FNAC), blood tests and a chest radiograph. Those with a definite diagnosis were referred for appropriate management and those with benign reactive cytology on FNAC reviewed at 6 weeks with subsequent referral for excision of persisting abnormal nodes. RESULTS: The ultimate diagnosis was benign in 45 cases: 26 benign reactive changes, 11 arthritides, five with dermatological and viral conditions and three with tuberculosis. Malignancy was diagnosed in 13 cases: four with metastatic breast carcinoma and nine with lymphoma/leukaemia. The total number of newly diagnosed malignancies was 20% of women recalled. Another 5% of patients had active tuberculosis. Of the 22 patients with benign reactive cytology, one had significant pathology on excision biopsy: tuberculosis. Over 95% of the results from excision biopsy in these patients did not alter management. CONCLUSION: In the majority of patients, the FNAC results were representative of the final excision pathology. The present study suggests that excision biopsy could be omitted for those patients whose FNAC and culture are negative.

Synchrotron x-ray microtomographic investigation of mineral concentrations at micrometre scale in sound and carious enamel.

Synchrotron X-ray microtomography (XMT) was used to measure the linear attenuation coefficient (LAC) for 1.9-microm sidelength voxels within approximal brown spot lesions and sound human enamel. XMT demonstrated three-dimensional features, notably sheets with approximately 30 microm periodicity having low LAC, identified as regions of demineralization corresponding to Retzius lines. Quantitative three-dimensional measurements of mineral concentration, derived from LAC with assumption of a single model composition, were consistent with previous measurements of sound and carious enamel from microradiographic projections. The uncertainty in measurements of mineral concentration and mineral fraction volume was investigated by modelling enamel with a range of composition and component densities. This analysis showed that, although mineral concentration can be determined from LAC with an error of <0.2 g cm(-3), the variation in pore fraction volume within caries lesions cannot be reliably determined from X-ray attenuation measurements alone.

Apparent solubility distributions of hydroxyapatite and enamel apatite.

Samples of human dental enamel and hydroxyapatite were equilibrated at 5 mg/40 ml for 9 days at 37 degrees C with acetate buffers adjusted to a range of saturations with respect to hydroxyapatite. Sigmoidal apparent solubility distributions, in which the fraction dissolved was plotted against--log(ion activity product for hydroxyapatite) (pIHA), were constructed. About 10% of the hydroxyapatite and 14% of the enamel was very soluble, dissolving even at pIHA 55. The apparent solubility distributions for both solids were invariant with pH (4.5, 5.0, 5.5), within experimental error, showing that solubility was controlled by a phase with the stoichiometry of hydroxyapatite, probably in the form of a surface layer or complex on the crystals, in agreement with other studies on carbonate-apatites and bone mineral. The pIHA at 50% dissolution was employed as an average value. The pIHA (50%) values for pooled data (58.76 for enamel and 60.17 for hydroxyapatite) were lower than the respective pIHA previously measured by conventional equilibration techniques. However, the average pIHA measured for enamel was higher than that obtained by the same technique in another study, possibly because of differences in specimen preparation and equilibration time. The possible implications of the findings for understanding the process of dental caries are discussed.

An evaluation of the impact of computer-based prompts on screen readers' interpretation of mammograms.

The NHS Breast Screening Programme is changing working practices in response to increased workload and manpower shortages. Radiographers are being trained as film readers. Computer aids are being considered. We have evaluated the impact of prompts placed by the R2 ImageChecker 1000 on the sensitivity and specificity of film readers, including non-radiologist film readers. 30 radiologists, 5 breast clinicians and 15 radiographers each read 180 films, including 60 cancers (20 false negative interval cases and 40 screen detected cancers). Each reader read each case twice, once with and once without computer prompts. The order in which the reading sessions were carried out was randomized separately for each reader. 36 out of 40 screen-detected cases were prompted by the ImageChecker, a sensitivity of 90%. Eight out of 20 interval cases were prompted, a sensitivity of 40%. No significant difference was found for readers' sensitivity or specificity between the prompted and unprompted conditions. No significant difference was found between the sensitivity and specificity of the different groups of film reader. No difference in impact of prompts was found for well or poorly performing film readers. The result suggests that this version of the ImageChecker would not have a significant impact on the UK screening programme.