The homogenous alternative to biomineralization: Zn- and Mn-rich materials enable sharp organismal "tools" that reduce force requirements.

We measured hardness, modulus of elasticity, and, for the first time, loss tangent, energy of fracture, abrasion resistance, and impact resistance of zinc- and manganese-enriched materials from fangs, stings and other "tools" of an ant, spider, scorpion and nereid worm. The mechanical properties of the Zn- and Mn-materials tended to cluster together between plain and biomineralized "tool" materials, with the hardness reaching, and most abrasion resistance values exceeding, those of calcified salmon teeth and crab claws. Atom probe tomography indicated that Zn was distributed homogeneously on a nanometer scale and likely bound as individual atoms to more than » of the protein residues in ant mandibular teeth. This homogeneity appears to enable sharper, more precisely sculpted "tools" than materials with biomineral inclusions do, and also eliminates interfaces with the inclusions that could be susceptible to fracture. Based on contact mechanics and simplified models, we hypothesize that, relative to plain materials, the higher elastic modulus, hardness and abrasion resistance minimize temporary or permanent tool blunting, resulting in a roughly 2/3 reduction in the force, energy, and muscle mass required to initiate puncture of stiff materials, and even greater force reductions when the cumulative effects of abrasion are considered. We suggest that the sharpness-related force reductions lead to significant energy savings, and can also enable organisms, especially smaller ones, to puncture, cut, and grasp objects that would not be accessible with plain or biomineralized "tools".

Hydrogen isotopic analysis of nuclear reactor materials using ultrafast laser-induced breakdown spectroscopy.

Laser-induced breakdown spectroscopy is a promising method for rapidly measuring hydrogen and its isotopes, critical to a wide range of disciplines (e.g. nuclear energy, hydrogen storage). However, line broadening can hinder the ability to detect finely spaced isotopic shifts. Here, the effects of varying plasma generation conditions (nanosecond versus femtosecond laser ablation) and ambient environments (argon versus helium gas) on spectral features generated from Zircaloy-4 targets with varying hydrogen isotopic compositions were studied. Time-resolved 2D spectral imaging was employed to detail the spatial distribution of species throughout plasma evolution. Results highlight that hydrogen and deuterium isotopic shifts can be measured with minimal spectral broadening in a ∼ 10 Torr helium gas environment using ultrafast laser-produced plasmas.

Radiological-pathological correlation of negative CT biopsy results enables high negative predictive value for thoracic malignancy.

AIM: To evaluate multidisciplinary team (MDT) practice of radiological-pathological correlation of non-malignant biopsy results to examine the additive effect on the predictive values of computed tomography (CT) biopsy for malignancy and their subsequent management and outcomes. MATERIALS AND METHODS: A service evaluation of the MDT management of non-malignant lung biopsy results (May 2014- May 2017) was undertaken. RESULTS: Sixty patients had a non-malignant diagnosis on initial CT biopsy. Five patients were lost to follow-up leaving 55 in the final cohort. Forty-eight of the 55 patients had biopsy results classified as potentially non-specific, of which 26 were classified as concordant with radiology (e.g., organising pneumonia with compatible CT features), and 22 were classified as discordant (e.g., non-specific inflammation and yet sufficiently suspicious CT features). Patients with concordant negative pathology showed resolution (n=19) or stability (n=6) on imaging follow-up. One lesion demonstrated growth and was proven malignant on surgical resection. Discordant lesions were managed with repeat biopsy (n=8) or surgical resection (n=13), with 12 final benign diagnoses and nine malignancies. The negative predictive value of CT biopsy alone was 44/55 (80%), following repeat biopsy was 44/50 (88%), and following radiological-pathological assessment was 32/33 (97%). No patients underwent a shift in stage from time of biopsy to resection. CONCLUSION: Combining radiological-pathological interpretation of negative biopsy results offers superior negative predictive value for lung malignancy without delayed diagnosis of lung cancer.

Correlating work hardening with co-activation of stacking fault strengthening and transformation in a high entropy alloy using in-situ neutron diffraction.

Transformation induced plasticity (TRIP) leads to enhancements in ductility in low stacking fault energy (SFE) alloys, however to achieve an unconventional increase in strength simultaneously, there must be barriers to dislocation motion. While stacking faults (SFs) contribute to strengthening by impeding dislocation motion, the contribution of SF strengthening to work hardening during deformation is not well understood; as compared to dislocation slip, twinning induced plasticity (TWIP) and TRIP. Thus, we used in-situ neutron diffraction to correlate SF strengthening to work hardening behavior in a low SFE Fe40Mn20Cr15Co20Si5 (at%) high entropy alloy, SFE ~ 6.31 mJ m-2. Cooperative activation of multiple mechanisms was indicated by increases in SF strengthening and γ-f.c.c. → ε-h.c.p. transformation leading to a simultaneous increase in strength and ductility. The present study demonstrates the application of in-situ, neutron or X-ray, diffraction techniques to correlating SF strengthening to work hardening.

New frontiers in atom probe tomography: a review of research enabled by cryo and/or vacuum transfer systems.

There has been a recent surge in the use of cryo and/or vacuum specimen preparation and transfer systems to broaden the scope of research enabled by the microscopy technique of atom probe tomography. This is driven by the fact that, as for many microscopes, the application of atom probes to air- and temperature-sensitive materials or wet biological specimens has previously been limited by transfer through air at room temperature. Here we provide an overview of areas of research that benefit from these new transfer and analysis protocols, as well as a review of current advances in transfer devices, environmental cells, and glove boxes for controlled specimen manipulation. This includes the study of catalysis and corrosion, biological samples, liquid-solid interfaces, natural aging, and the distribution of hydrogen in materials.

Impact of choice of volumetry software and nodule management guidelines on recall rates in lung cancer screening.

PURPOSE: Appropriate lung nodule management is essential to minimizing unnecessary patient recall in lung cancer screening. Two European guidelines provide differing recommendations in that participants with nodules ≥100 mm3 or ≥80 mm3 respectively should be recalled, at baseline. Nodule size estimation is known to vary between volumetry software packages (VSPs). The aim of this study was to examine the impact of choice of VSP on participant recall rates, when applying different European nodule management guidelines. An additional aim was to compare recall rates between 7 VSPs and manual diameter measurements. METHODS: 156 small-sized lung nodules (50-150 mm3) from the UK Lung Screening trial were measured using 7 different VSPs (VSP1-7) and also using manual diameter. The type of VSP used in the NELSON study (VSP1), on which European nodule management guidelines are based, provided the reference standard. Nodule size was compared using Bland Altman, and recall rates by Mcnemar's test. RESULTS: Compared to the reference standard, a 100 mm3 threshold for recall, resulted in no difference in recall rates only for VSP 5 & 7. Using an 80mm3 threshold resulted in no difference in recall rates for VSP2 & 6. Recall rates were significantly higher for VSP 4 regardless of threshold and when using manual diameter measurements. CONCLUSIONS: Appropriate nodule size thresholds for recall in screening depend on the type of volumetry software used. The results highlight the importance of benchmarking of volumetry packages.

Outstanding radiation resistance of tungsten-based high-entropy alloys.

A body-centered cubic W-based refractory high entropy alloy with outstanding radiation resistance has been developed. The alloy was grown as thin films showing a bimodal grain size distribution in the nanocrystalline and ultrafine regimes and a unique 4-nm lamella-like structure revealed by atom probe tomography (APT). Transmission electron microscopy (TEM) and x-ray diffraction show certain black spots appearing after thermal annealing at elevated temperatures. TEM and APT analysis correlated the black spots with second-phase particles rich in Cr and V. No sign of irradiation-created dislocation loops, even after 8 dpa, was observed. Furthermore, nanomechanical testing shows a large hardness of 14 GPa in the as-deposited samples, with near negligible irradiation hardening. Theoretical modeling combining ab initio and Monte Carlo techniques predicts the formation of Cr- and V-rich second-phase particles and points at equal mobilities of point defects as the origin of the exceptional radiation tolerance.

Mitochondrial DNA content of peripheral blood mononuclear cells in ART untreated & stavudine/zidovudine treated HIV-1-infected patients.

BACKGROUND & OBJECTIVES: Nucleoside reverse transcriptase inhibitors (NRTIs) are known to cause mitochondrial toxicity. This study was done to estimate mitochondrial DNA (mtDNA) content of peripheral blood mononuclear cells (PBMCs) among human immunodeficiency virus (HIV) infected, NRTI treated and antiretroviral therapy (ART)-naïve patients and evaluate the utility of mtDNA content as a biomarker of mitochondrial toxicity. METHODS: mtDNA content in PBMCs of 57 HIV-infected ART untreated and 30 ART treated with stavudine (d4T) or zidovudine (AZT) containing regimen were compared against 24 low-risk healthy controls (LoRHC). RESULTS: There was a significant (P=0.01) reduction in mtDNA content among HIV-infected (104; 80-135) compared to LoRHC (127; 110-167), and it was the same in both the treated (104.8; 88-130) and untreated patients (104.7; 78-142). mtDNA significantly (P=0.014) declined in ART treated patients symptomatic for toxicity (97; 74-111) than the asymptomatic patients (128; 103- 153). INTERPRETATION & CONCLUSIONS: mtDNA depletion in PBMCs was evident among HIV-infected individuals on ART. Moreover, as mtDNA content was reduced among the patients symptomatic for toxicity than the asymptomatic in both the HIV-infected groups, the current study supports mtDNA content of PBMCs to serve as a biomarker of mitochondrial dysfunction induced by NRTI and HIV. Longitudinal studies with a large sample need to be done to confirm these findings.

A survey of UK percutaneous lung biopsy practice: current practices in the era of early detection, oncogenetic profiling, and targeted treatments.

AIM: To ascertain current percutaneous lung biopsy practices around the UK. MATERIALS AND METHODS: A web-based survey was sent to all British Society of Thoracic Imaging (BSTI) and British Society of Interventional Radiology (BSIR) members (May 2017) assessing all aspects of lung biopsy practice. Responses were collected anonymously. RESULTS: Two hundred and thirty-nine completed responses were received (28.8% response rate). Of the respondents, 48.5% worked in a teaching hospital and 51.5% in a district general hospital, while 32.6% (78/239) were specialist thoracic radiologists, 29.2% (70/239) "general" radiologists with a thoracic subspecialty interest, and 28% (67/239) interventional radiologists. Of the respondents, 30.1% (72/239) did not require pre-biopsy lung function tests (PFTs); 45.6% (108/237) stopped aspirin before the procedure; 97.5% primarily use computed tomography (CT) guidance for biopsy and 88.7% (212/239) perform core needle biopsy (CNB); and 86.6% of radiologists use a co-axial technique. There was wide variation in the number of samples routinely taken with most radiologists performing 1-2 passes (55.9%) or 3-4 passes (40.8%). Sixty-four percent reported using chest drain prevention techniques to minimise the impact of iatrogenic pneumothorax, with needle aspiration most frequent (43.9%). Timing of post-biopsy chest radiography (CXR), performed by 95.8% (228/239), also varied greatly: most commonly at either 1 hour (23%), 2 hours (24.7%), or 4 hours (22.6%). Moreover, the time of patient discharge after uncomplicated biopsy was variable, although the majority (66.1%) discharge patients after ≥4 hours. CONCLUSION: There are striking variations among surveyed UK radiologists performing lung biopsy in decision-making, pre-biopsy work-up, post-biopsy monitoring, management of pneumothorax, and discharge. The results suggest a need for new updated national percutaneous lung biopsy guidelines.

The influence of inspiratory effort and emphysema on pulmonary nodule volumetry reproducibility.

AIM: To evaluate the impact of inspiratory effort and emphysema on reproducibility of pulmonary nodule volumetry. MATERIALS AND METHODS: Eighty-eight nodules in 24 patients with emphysema were studied retrospectively. All patients had undergone volumetric inspiratory and end-expiratory thoracic computed tomography (CT) for consideration of bronchoscopic lung volume reduction. Inspiratory and expiratory nodule volumes were measured using commercially available software. Local emphysema extent was established by analysing a segmentation area extended circumferentially around each nodule (quantified as percent of lung with density of -950 HU or less). Lung volumes were established using the same software. Differences in inspiratory and expiratory nodule volumes were illustrated using the Bland-Altman test. The influences of percentage reduction in lung volume at expiration, local emphysema extent, and nodule size on nodule volume variability were tested with multiple linear regression. RESULTS: The majority of nodules (59/88 [67%]) showed an increased volume at expiration. Mean difference in nodule volume between expiration and inspiration was +7.5% (95% confidence interval: -24.1, 39.1%). No relationships were demonstrated between nodule volume variability and emphysema extent, degree of expiration, or nodule size. CONCLUSION: Expiration causes a modest increase in volumetry-derived nodule volumes; however, the effect is unpredictable. Local emphysema extent had no significant effect on volume variability in the present cohort.

A bacterial-biofilm-induced oral osteolytic infection can be successfully treated by immuno-targeting an extracellular nucleoid-associated protein.

Periodontal disease exemplifies a chronic and recurrent infection with a necessary biofilm component. Mucosal inflammation is a hallmark response of the host seen in chronic diseases, such as colitis, gingivitis, and periodontitis (and the related disorder peri-implantitis). We have taken advantage of our recently developed rat model of human peri-implantitis that recapitulates osteolysis, the requirement of biofilm formation, and the perpetuation of the bona fide disease state, to test a new therapeutic modality with two novel components. First we used hyperimmune antiserum directed against the DNABII family of proteins, now known to be a critical component of the extracellular matrix of bacterial biofilms. Second we delivered the antiserum as cargo in biodegradable microspheres to the site of the biofilm infection. We demonstrated that delivery of a single dose of anti-DNABII in poly(lactic-co-glycolic acid) (PLGA) microspheres induced significant resolution of experimental peri-implantitis, including marked reduction of inflammation. These data support the continued development of a DNABII protein-targeted therapeutic for peri-implantitis and other chronic inflammatory pathologies of the oral cavity in animals and humans.

UK Lung Cancer RCT Pilot Screening Trial: baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening.

BACKGROUND: Lung cancer screening using low-dose CT (LDCT) was shown to reduce lung cancer mortality by 20% in the National Lung Screening Trial. METHODS: The pilot UK Lung Cancer Screening (UKLS) is a randomised controlled trial of LDCT screening for lung cancer versus usual care. A population-based questionnaire was used to identify high-risk individuals. CT screen-detected nodules were managed by a pre-specified protocol. Cost effectiveness was modelled with reference to the National Lung Cancer Screening Trial mortality reduction. RESULTS: 247 354 individuals aged 50-75 years were approached; 30.7% expressed an interest, 8729 (11.5%) were eligible and 4055 were randomised, 2028 into the CT arm (1994 underwent a CT). Forty-two participants (2.1%) had confirmed lung cancer, 34 (1.7%) at baseline and 8 (0.4%) at the 12-month scan. 28/42 (66.7%) had stage I disease, 36/42 (85.7%) had stage I or II disease. 35/42 (83.3%) had surgical resection. 536 subjects had nodules greater than 50 mm(3) or 5 mm diameter and 41/536 were found to have lung cancer. One further cancer was detected by follow-up of nodules between 15 and 50 mm(3) at 12 months. The baseline estimate for the incremental cost-effectiveness ratio of once-only CT screening, under the UKLS protocol, was £8466 per quality adjusted life year gained (CI £5542 to £12 569). CONCLUSIONS: The UKLS pilot trial demonstrated that it is possible to detect lung cancer at an early stage and deliver potentially curative treatment in over 80% of cases. Health economic analysis suggests that the intervention would be cost effective-this needs to be confirmed using data on observed lung cancer mortality reduction. TRIAL REGISTRATION: ISRCTN 78513845.

CT screening for lung cancer: Is the evidence strong enough?

The prevailing questions at this time in both the public mind and the clinical establishment is, do we have sufficient evidence to implement lung cancer Computed Tomography (CT) screening in Europe? If not, what is outstanding? This review addresses the twelve major areas, which are critical to any decision to implement CT screening and where we need to assess whether we have sufficient evidence to proceed to a recommendation for implementation in Europe. The readiness level of these twelve categories in 2015 have been with colour coded, where green indicates we have sufficient evidence, amber is borderline evidence and red requires further evidence. Recruitment from the 'Hard to Reach' community still remains at red, while mortality data, cost effectiveness and screening interval are all categorised as amber. The integration of smoking cessation into CT screening programmes is still considered to be category amber. The US Preventive Services Task Force have recommended that CT screening is implemented in the USA utilising the NLST criteria, apart from continuing screening to 80 years of age. The cost effectiveness of the NLST was calculated to be $81,000/QALY, however, its well recognised that the costs of medical care in the USA, is far higher than that of Europe. Medicare have agreed to cover the cost of screening but have stipulated a number of stringent requirements for inclusion. To date we do not have good CT screening mortality data available in Europe and eagerly await the publication of the NELSON trial data in 2016 and then the pooled UKLS and NELSON data thereafter. However in the meantime we should start planning for implementation in Europe, especially in the areas of the radiological service provision and accreditation, as well as identifying novel mechanisms to recruit from the hardest to reach communities.

Visualizing nanoscale 3D compositional fluctuation of lithium in advanced lithium-ion battery cathodes.

The distribution of cations in Li-ion battery cathodes as a function of cycling is a pivotal characteristic of battery performance. The transition metal cation distribution has been shown to affect cathode performance; however, Li is notoriously challenging to characterize with typical imaging techniques. Here laser-assisted atom probe tomography (APT) is used to map the three-dimensional distribution of Li at a sub-nanometre spatial resolution and correlate it with the distribution of the transition metal cations (M) and the oxygen. As-fabricated layered Li1.2Ni0.2Mn0.6O2 is shown to have Li-rich Li2MO3 phase regions and Li-depleted Li(Ni0.5Mn0.5)O2 regions. Cycled material has an overall loss of Li in addition to Ni-, Mn- and Li-rich regions. Spinel LiNi0.5Mn1.5O4 is shown to have a uniform distribution of all cations. APT results were compared to energy dispersive spectroscopy mapping with a scanning transmission electron microscope to confirm the transition metal cation distribution.