Commonly disrupted pathways in brain and kidney in a pig model of systemic endotoxemia.

Sepsis is a life-threatening state that arises due to a hyperactive inflammatory response stimulated by infection and rarely other insults (e.g., non-infections tissue injury). Although changes in several proinflammatory cytokines and signals are documented in humans and small animal models, far less is known about responses within affected tissues of large animal models. We sought to understand the changes that occur during the initial stages of inflammation by administering intravenous lipopolysaccharide (LPS) to Yorkshire pigs and assessing transcriptomic alterations in the brain, kidney, and whole blood. Robust transcriptional alterations were found in the brain, with upregulated responses enriched in inflammatory pathways and downregulated responses enriched in tight junction and blood vessel functions. Comparison of the inflammatory response in the pig brain to a similar mouse model demonstrated some overlapping changes but also numerous differences, including oppositely dysregulated genes between species. Substantial changes also occurred in the kidneys following LPS with several enriched upregulated pathways (cytokines, lipids, unfolded protein response, etc.) and downregulated gene sets (tube morphogenesis, glomerulus development, GTPase signal transduction, etc.). We also found significant dysregulation of genes in whole blood that fell into several gene ontology categories (cytokines, cell cycle, neutrophil degranulation, etc.). We observed a strong correlation between the brain and kidney responses, with significantly shared upregulated pathways (cytokine signaling, cell death, VEGFA pathways) and downregulated pathways (vasculature and RAC1 GTPases). In summary, we have identified a core set of shared genes and pathways in a pig model of systemic inflammation.

Modification in Applying Appendix D of 40 CFR Part 61 to Heated Solid Radionuclide Materials With High Melting and Boiling Points.

ABSTRACT: Appendix D of Title 40 Part 61 of the US Code of Federal Regulations (CFR) provides a procedure that US Department of Energy (US DOE) facility owners and operators can use to estimate radionuclide emissions to the atmosphere for dose calculations instead of measuring emissions for minor sources under the 40 CFR Part 61, Subpart H, National Emission Standards for Emissions of Radionuclides Other Than Radon From Department of Energy Facilities, regulation. The procedure assumes that any radioactive material heated above 100 °C is completely vaporized and emitted to the atmosphere. In 1991, the US DOE Oak Ridge Reservation (ORR) requested approval to use different release fractions (RFs) for uranium because of its high melting and boiling points. In response to the request, the US Environmental Protection Agency (US EPA) Region IV approved the use of modified RFs for elemental uranium provided no reaction had taken place to alter its chemical form. In 2015, the ORR requested approval to use different RFs for tungsten, again because of its high melting and boiling points. EPA Region IV approved the use of modified RFs for heated radioactive tungsten metal. In accordance with the two precedents set for heating uranium and radioactive tungsten metals, in 2016, the ORR requested approval to use modified RFs in a similar fashion for other radioactive solid metals and compounds with melting and boiling points above 500 °C that might be heated above 100 °C in future research projects and experiments. EPA Region IV again granted approval to use modified RFs for the list of compounds. This note discusses the proposed modified RFs and their development.

Radiological HEPA Filter 10-year Lifetime Evaluation in Research Facilities.

ABSTRACT: High-efficiency particulate air (HEPA) filters are widely employed by nuclear facilities to remove radiological particulate matter from their effluent exhaust streams. The purpose of this study is to evaluate the relationships between the 10-y HEPA filter lifetime deployment and its other performance indicators. This 10-y-long endeavor to collect and analyze data regarding the service life of HEPA filters at the Pacific Northwest National Laboratory began in 2010. A set of HEPA filters was selected, and the filters have been surveyed and analyzed at least annually to verify compliance with permit conditions. The study suggests the frequency of filter replacement should be based on the actual operational requirements, such as fume hood face velocity and/or efficiency test results, instead of on the prescribed filter "age limit" of 10 y from the date of manufacture (e.g., birth date) when operating under dry conditions. The study has now been completed, and over the past decade, all the HEPA filters have been replaced due to either technical issues as listed in this report or the previously recommended filter "age limit" of 10 y as prescribed by the oversight bodies. Experimentally determined failure rates are also determined from the data set and can be used to estimate the chances of HEPA filters surviving 15, 20, or even 30 y.

Wastewater-based epidemiology in hazard forecasting and early-warning systems for global health risks.

With the advent of the SARS-CoV-2 pandemic, Wastewater-Based Epidemiology (WBE) has been applied to track community infection in cities worldwide and has proven succesful as an early warning system for identification of hotspots and changingprevalence of infections (both symptomatic and asymptomatic) at a city or sub-city level. Wastewater is only one of environmental compartments that requires consideration. In this manuscript, we have critically evaluated the knowledge-base and preparedness for building early warning systems in a rapidly urbanising world, with particular attention to Africa, which experiences rapid population growth and urbanisation. We have proposed a Digital Urban Environment Fingerprinting Platform (DUEF) - a new approach in hazard forecasting and early-warning systems for global health risks and an extension to the existing concept of smart cities. The urban environment (especially wastewater) contains a complex mixture of substances including toxic chemicals, infectious biological agents and human excretion products. DUEF assumes that these specific endo- and exogenous residues, anonymously pooled by communities' wastewater, are indicative of community-wide exposure and the resulting effects. DUEF postulates that the measurement of the substances continuously and anonymously pooled by the receiving environment (sewage, surface water, soils and air), can provide near real-time dynamic information about the quantity and type of physical, biological or chemical stressors to which the surveyed systems are exposed, and can create a risk profile on the potential effects of these exposures. Successful development and utilisation of a DUEF globally requires a tiered approach including: Stage I: network building, capacity building, stakeholder engagement as well as a conceptual model, followed by Stage II: DUEF development, Stage III: implementation, and Stage IV: management and utilization. We have identified four key pillars required for the establishment of a DUEF framework: (1) Environmental fingerprints, (2) Socioeconomic fingerprints, (3) Statistics and modelling and (4) Information systems. This manuscript critically evaluates the current knowledge base within each pillar and provides recommendations for further developments with an aim of laying grounds for successful development of global DUEF platforms.

Tonic Serotonin Measurements In Vivo Using N-Shaped Multiple Cyclic Square Wave Voltammetry.

Here, we present the development of a novel voltammetric technique, N-shaped multiple cyclic square wave voltammetry (N-MCSWV) and its application in vivo. It allows quantitative measurements of tonic extracellular levels of serotonin in vivo with mitigated fouling effects. N-MCSWV enriches the electrochemical information by generating high dimensional voltammograms, which enables high sensitivity and selectivity against 5-hydroindoleacetic acid (5-HIAA), dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), histamine, ascorbic acid, norepinephrine, adenosine, and pH. Using N-MCSWV, in combination with PEDOT:Nafion-coated carbon fiber microelectrodes, a tonic serotonin concentration of 52 ± 5.8 nM (n = 20 rats, ±SEM) was determined in the substantia nigra pars reticulata of urethane-anesthetized rats. Pharmacological challenges with dopaminergic, noradrenergic, and serotonergic synaptic reuptake inhibitors supported the ability of N-MCSWV to selectively detect tonic serotonin levels in vivo. Overall, N-MCSWV is a novel voltammetric technique for analytical quantification of serotonin. It offers continuous monitoring of changes in tonic serotonin concentrations in the brain to further our understanding of the role of serotonin in normal behaviors and psychiatric disorders.

Growth Curves of Subependymal Giant Cell Tumors in Tuberous Sclerosis Complex.

BACKGROUND AND PURPOSE: Growth of subependymal giant cell tumor and subependymal nodules has not been well-characterized. The purpose of this study was to determine whether growth curves can differentiate subependymal giant cell tumors from subependymal nodules. MATERIALS AND METHODS: Brain MR imaging of patients with tuberous sclerosis complex were retrospectively reviewed from 2002 to 2018. All lesions in the region of the foramen of Monro were measured. Lesions were categorized on the basis of maximal diameter at the most recent scan: small lesions (<1 cm), indeterminate lesions (>1 cm), and resected lesions (>1 cm and surgically resected). Growth velocity and acceleration on serial imaging were analyzed, and growth rates were calculated between 0 and 20 years of age and compared among the 3 categories. RESULTS: Forty-one patients were analyzed. The average age at the earliest scan was 5.9 (SD = 5.7) years. One hundred twenty-six small, 27 indeterminate, and 10 resected lesions were measured. Subependymal giant cell tumors grew faster than indeterminate lesions between 6 and 15 years of age. Indeterminate lesions grew faster than small lesions at 0-10 years of age. Resected lesions showed increased velocity and acceleration of growth compared with indeterminate lesions and small lesions on serial imaging. CONCLUSIONS: Growth differentiates subependymal nodules and subependymal giant cell tumors within the first 20 years of life, and the use of velocity and acceleration of growth may refine the diagnostic criteria of subependymal giant cell tumors. Additionally, 6-15 years of age may be an important period to monitor subependymal giant cell tumors at the foramen of Monro because increased growth may help to identify subependymal giant cell tumors that will continue to grow and result in obstructive hydrocephalus.

Pathology of grey seals Halichoerus grypus in southwest England including pups in early rehabilitation.

Few investigations have examined the pathology of grey seals Halichoerus grypus in southwest England, where it is the most abundant marine mammal. Here, primary pathological findings are presented from 107 post-mortem examinations of grey seals in southwest England between 2013 and 2020. Over three-quarters were pups in their first year of life; the origins of the carcasses reflected the known breeding season and breeding sites of grey seals in the region. Trauma was the most common primary pathological finding (n = 49), followed by infectious disease (n = 36). Traumatic findings included fisheries-related trauma (n = 15), other acute physical traumas (n = 15) and other chronic traumas (n = 19). Infectious disease findings included respiratory infections (n = 21) and gastrointestinal infections (n = 9). There was no difference in the primary pathological findings for seals found dead or that died or were euthanased on the day they were found compared to those dying in early rehabilitation, suggesting that it is appropriate to include findings from seals in early rehabilitation in studies of wild grey seal pathology. Seals that had not been frozen before post-mortem examination were nearly twice as likely to have a primary pathological finding of infectious disease or trauma than those that had been frozen, highlighting the need, wherever possible, to avoid freezing seals prior to post-mortem examination.

Local inhomogeneities resolved by scanning probe techniques and their impact on local 2DEG formation in oxide heterostructures.

Lateral inhomogeneities in the formation of two-dimensional electron gases (2DEG) directly influence their electronic properties. Understanding their origin is an important factor for fundamental interpretations, as well as high quality devices. Here, we studied the local formation of the buried 2DEG at LaAlO3/SrTiO3 (LAO/STO) interfaces grown on STO (100) single crystals with partial TiO2 termination, utilizing in situ conductive atomic force microscopy (c-AFM) and scattering-type scanning near-field optical microscopy (s-SNOM). Using substrates with different degrees of chemical surface termination, we can link the resulting interface chemistry to an inhomogeneous 2DEG formation. In conductivity maps recorded by c-AFM, a significant lack of conductivity is observed at topographic features, indicative of a local SrO/AlO2 interface stacking order, while significant local conductivity can be probed in regions showing TiO2/LaO interface stacking order. These results could be corroborated by s-SNOM, showing a similar contrast distribution in the optical signal which can be linked to the local electronic properties of the material. The results are further complemented by low-temperature conductivity measurements, which show an increasing residual resistance at 5 K with increasing portion of insulating SrO-terminated areas. Therefore, we can correlate the macroscopic electrical behavior of our samples to their nanoscopic structure. Using proper parameters, 2DEG mapping can be carried out without any visible alteration of sample properties, proving c-AFM and s-SNOM to be viable and destruction-free techniques for the identification of local 2DEG formation. Furthermore, applying c-AFM and s-SNOM in this manner opens the exciting prospect to link macroscopic low-temperature transport to its nanoscopic origin.

Bubble bilevel ventilation facilitates gas exchange in anesthetized rabbits.

BACKGROUND: Bubble continuous positive airway pressure is an established therapy for infants in respiratory distress. In resource-limited settings, few treatment options exist for infants requiring further respiratory support. A bubble bilevel device has been developed to provide nonelectric, time-cycled, pressure-limited respiratory support. We compared the efficacy of bubble bilevel ventilation with conventional mechanical ventilation in sedated rabbits. METHODS: Six adult rabbits under inhaled isoflurane general anesthesia were ventilated by alternating intervals of conventional and bubble bilevel ventilation for three 10-15-min periods. During each period, interval arterial blood gas (ABG) measurements were obtained after at least 10 min on the respective mode of ventilation. RESULTS: The bubble bilevel system was able to deliver the following pressures: 20/7, 15/5, 12/5, 8/5 cm H2O. The estimated differences in arterial blood gas values on bubble bilevel vs. ventilator were as follows (normalized values): pH 7.41 vs. 7.40, pCO2 37.7 vs. 40, pO2 97.6 vs. 80. In addition, the bubble bilevel ventilation delivered consistent pressure waveforms without interruption for over 60 min on two rabbits. CONCLUSION: This study demonstrates promising in vivo results on the efficacy of a novel bubble bilevel device, which may prove useful for infants in respiratory distress. IMPACT: Given the lack of personnel, funds or infrastructure to provide neonatal mechanical ventilation in resource-limited settings, additional low-cost, low-tech treatments are necessary to save infant lives. Bubble bilevel ventilation reliably delivers two levels of airway pressure to anesthetized rabbits resulting in normalization of blood gases comparable to those achieved on a traditional ventilator. If proven effective, simple technologies like this device have the potential to significantly impact neonatal mortality due to respiratory distress globally.

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.

A compact stereotactic system for image-guided surgical intervention.

Objective. Stereotactic technology enables fine navigation to small structures in the human body. While current stereotactic systems facilitate accurate targeting, they are mechanically cumbersome and limited in scope. Here, we hypothesized that a stereotactic system could be developed with a reduced footprint while maintaining broad targeting capabilities in order to improve versatility in frame placement location and surgical workflow.Approach. We designed a stereotactic system around the center-of-arc principle, with mechanical properties that would enable a compact design and ample targeting and trajectory maneuverability. To examine the opportunity for a low-cost rapidly-deployable system we developed two fabrication variants, one using three dimensional (3D)-printing and the other using conventional machining. Mechanical and image-guided accuracies were tested in phantom studies using magnetic resonance imaging (MRI) and computed tomography. Using human cadaver head specimens, we assessed the system's surgical workflow and its ability to reliably and accurately implant electrodes in deep brain stimulation (DBS) surgery.Main results. We developed a small 7.7 × 5.4 cm2device platform that rigidly mounts to curvilinear bone and supports the attachment of surgical instrumentation. Attachment of two surgical instruments, an imaging localizer and a compact targeting device, demonstrated successful MRI-guided intervention in phantom studies with a vector error of 1.79 ± 0.41 mm. Evaluation of the 3D-printed system for DBS surgery confirmed ease of device platform attachment and instrument functionality, as well as demonstrated a surgical targeting accuracy of 1.83 ± 0.15 mm. In addition, we found the surgical time to be 78.3 ± 5.4 min for bilateral electrode implantation.Significance. We developed a light and compact stereotactic system whose accuracy is on par with those used clinically. This technology is suitable for clinical translation and its flexibility in positioning will seamlessly expand the capabilities for stereotaxy to treat a wide range of conditions, both within neurosurgery and beyond.

Validation of the British Society of Thoracic Imaging guidelines for COVID-19 chest radiograph reporting.

AIM: To validate the British Society of Thoracic Imaging issued guidelines for the categorisation of chest radiographs for coronavirus disease 2019 (COVID-19) reporting regarding reproducibility amongst radiologists and diagnostic performance. MATERIALS AND METHODS: Chest radiographs from 50 patients with COVID-19, and 50 control patients with symptoms consistent with COVID-19 from prior to the emergence of the novel coronavirus were assessed by seven consultant radiologists with regards to the British Society of Thoracic Imaging guidelines. RESULTS: The findings show excellent specificity (100%) and moderate sensitivity (44%) for guideline-defined Classic/Probable COVID-19, and substantial interobserver agreement (Fleiss' k=0.61). Fair agreement was observed for the "Indeterminate for COVID-19" (k=0.23), and "Non-COVID-19" (k=0.37) categories; furthermore, the sensitivity (0.26 and 0.14 respectively) and specificity (0.76, 0.80) of these categories for COVID-19 were not significantly different (McNemar's test p=0.18 and p=0.67). CONCLUSION: An amalgamation of the categories of "Indeterminate for COVID-19" and "Non-COVID-19" into a single "not classic of COVID-19" classification would improve interobserver agreement, encompass patients with a similar probability of COVID-19, and remove the possibility of labelling patients with COVID-19 as "Non-COVID-19", which is the presenting radiographic appearance in a significant minority (14%) of patients.

The mental health impacts of climate change: Findings from a Pacific Island atoll nation.

BACKGROUND: Climate change is anticipated to have profound effects on mental health, particularly among populations that are simultaneously ecologically and economically vulnerable to its impacts. Various pathways through which climate change can impact mental health have been theorised, but the impacts themselves remain understudied. PURPOSE: In this article we applied psychological methods to examine if climate change is affecting individuals' mental health in the Small Island Developing State of Tuvalu, a Pacific Island nation regarded as exceptionally vulnerable to climate change. We determined the presence of psychological distress and associated impairment attributed to two categories of climate change-related stressors in particular: 1) local environmental impacts caused or exacerbated by climate change, and 2) hearing about global climate change and contemplating its future implications. METHODS: The findings draw on data collected in a mixed-method study involving 100 Tuvaluan participants. Data were collected via face-to-face structured interviews that lasted 45 min on average and were subjected to descriptive, correlational, and between-group analyses. RESULTS: The findings revealed participants' experiences of distress in relation to both types of stressor, and demonstrated that a high proportion of participants are experiencing psychological distress at levels that reportedly cause them impairment in one or more areas of daily life. CONCLUSIONS: The findings lend weight to the claim that climate change represents a risk to mental health and obliges decision-makers to consider these risks when conceptualizing climate-related harms or tallying the costs of inaction.

Pressure Induced Wetting and Dewetting of the Nonpolar Pocket of Deep-Cavity Cavitands in Water.

Hydrophobic interactions drive the binding of nonpolar ligands to the oily pockets of proteins and supramolecular species in aqueous solution. As such, the wetting of host pockets is expected to play a critical role in determining the thermodynamics of guest binding. Here we use molecular simulations to examine the impact of pressure on the wetting and dewetting of the nonpolar pockets of a series of deep-cavity cavitands in water. The portals to the cavitand pockets are functionalized with both nonpolar (methyl) and polar (hydroxyl) groups oriented pointing either upward or inward toward the pocket. We find wetting of the pocket is favored by the hydroxyl groups and dewetting is favored by the methyl groups. The distribution of waters in the pocket is found to exhibit a two-state-like equilibrium between wet and dry states with a free energy barrier between the two states. Moreover, we demonstrate that the pocket hydration of the cavitands can be collapsed onto a unified adsorption isotherm by assuming the effective pressures within each cavitand pocket differ by a shift pressure that depends on the chemical identity and number of functional groups placed about the portal. These observations support the development of a two-state capillary evaporation model that accurately describes the equilibrium between states and naturally gives rise to the effective shift pressures observed from simulation. This work demonstrates that the hydration of host pockets can be tuned following simple design rules that in turn are expected to impact the thermodynamics of guest complexation.

Designing exceptional gas-separation polymer membranes using machine learning.

The field of polymer membrane design is primarily based on empirical observation, which limits discovery of new materials optimized for separating a given gas pair. Instead of relying on exhaustive experimental investigations, we trained a machine learning (ML) algorithm, using a topological, path-based hash of the polymer repeating unit. We used a limited set of experimental gas permeability data for six different gases in ~700 polymeric constructs that have been measured to date to predict the gas-separation behavior of over 11,000 homopolymers not previously tested for these properties. To test the algorithm's accuracy, we synthesized two of the most promising polymer membranes predicted by this approach and found that they exceeded the upper bound for CO2/CH4 separation performance. This ML technique, which is trained using a relatively small body of experimental data (and no simulation data), evidently represents an innovative means of exploring the vast phase space available for polymer membrane design.

Spontaneous drying of non-polar deep-cavity cavitand pockets in aqueous solution.

There are many open questions regarding the hydration of solvent-exposed non-polar tracts and pockets in proteins. Although water is predicted to de-wet purely repulsive surfaces and evacuate crevices, the extent of de-wetting is unclear when ubiquitous van der Waals interactions are in play. The structural simplicity of synthetic supramolecular hosts imbues them with considerable potential to address this issue. To this end, here we detail a combination of densimetry and molecular dynamics simulations of three cavitands, coupled with calorimetric studies of their complexes with short-chain carboxylates. Our results reveal the range of wettability possible within the ostensibly identical cavitand pockets-which differ only in the presence and/or position of the methyl groups that encircle the portal to their non-polar pockets. The results demonstrate the ability of macrocycles to template water cavitation within their binding sites and show how the orientation of methyl groups can trigger the drying of non-polar pockets in liquid water, which suggests new avenues to control guest complexation.

Novel Pulmonary Vasculitis with Splendore-Hoeppli Reaction in Grey Seals (Halichoerus grypus) Associated with Otostrongylus circumlitus Infection.

Lungworm infection in seals is an important cause of morbidity and mortality, inducing bronchopneumonia and affecting population dynamics in some areas of the world. We present a series of cases of lungworm infection in grey seals (Halichoerus grypus) associated with novel, significant and unusual pulmonary vascular changes. Grey seals (n = 180) that were stranded, in rehabilitation or in long-term captivity in the UK were subjected to post-mortem examination between 2012 and 2018. Lung tissue was collected from 47 individuals for histopathological examination. Polymerase chain reaction (PCR) on formalin-fixed and paraffin wax-embedded (FFPE) material was attempted for parasite identification on selected sections using lungworm-specific primers, and nematode morphology within sections was evaluated histologically. Fourteen of 47 (30%) of these grey seals showed evidence of segmental granulomatous and eosinophilic vasculitis with an intramural Splendore-Hoeppli reaction in medium to large pulmonary arteries. Intravascular nematodes suggestive of Otostrongylus circumlitus were seen in two cases. PCR on FFPE material was unable to detect a signal on selected tissue sections. Of the 14 affected seals, nine had concurrent bronchopneumonia and four had intra-alveolar/bronchiolar Parafilaroides spp. Thirteen of 14 animals with vasculitis lesions were weaned pups with only one adult affected. Previous pathological descriptions of lungworm infection in grey seals have dealt mainly with the bronchopneumonia. This case series has identified previously unrecorded vascular changes characterized by an intramural Splendore-Hoeppli reaction. Such change would impact on vascular integrity, increasing the likelihood of vascular rupture with pulmonary haemorrhage and increased risk of intravascular coagulation. A host-parasite relationship with the persistence of antigenic material following close contact with, or migration through, the blood vessel wall is suspected.

Pre-surgical lung biopsy in management of solitary pulmonary nodules: a cost effectiveness analysis.

Objectives: Tissue diagnosis prior to thoracic surgery with curative intent is vital in thoracic lesions concerning for lung cancer. Methods of obtaining tissue diagnosis are variable within the United Kingdom.Methods: We performed a model-based analysis to identify the most efficient method of diagnosis using both a health care perspective. Our analysis concerns adults in the UK presenting with a solitary pulmonary nodule suspicious for a primary lung malignancy, patients with more advanced disease (for example lymph node spread) were not considered. Model assumptions were derived from published sources and expert reviews, cost data were obtained from healthcare research group cost estimates (2016-17). Outcomes were measured in terms of costs experienced to healthcare trusts.Results: Our results show that CT guided percutaneous lung biopsy using an ambulatory approach, is the most cost-effective method of diagnosis. Indeed, using this approach, trust experience approximately half of the cost of an approach of surgical lung biopsy performed at the time of potential resection ('frozen section').Limitations and conclusions: Whilst this analysis is limited to the specific scenario of a solitary pulmonary nodule, these findings have implications for the implementation of lung cancer screening in the UK, which is likely to result in increased numbers of patients with such early disease.

Microplastics in marine mammals stranded around the British coast: ubiquitous but transitory?

Plastic pollution represents a pervasive and increasing threat to marine ecosystems worldwide and there is a need to better understand the extent to which microplastics (<5 mm) are ingested by high trophic-level taxa, such as marine mammals. Here, we perform a comprehensive assessment by examining whole digestive tracts of 50 individuals from 10 species whilst operating strict contamination controls. Microplastics were ubiquitous with particles detected in every animal examined. The relatively low number per animal (mean = 5.5) suggests these particles are transitory. Stomachs, however, were found to contain a greater number than intestines, indicating a potential site of temporary retention. The majority of particles were fibres (84%) while the remaining 16% was fragments. Particles were mainly blue and black (42.5% and 26.4%) in colour and Nylon was the most prevalent (60%) polymer type. A possible relationship was found between the cause of death category and microplastic abundance, indicating that animals that died due to infectious diseases had a slightly higher number of particles than those that died of trauma and other drivers of mortality. It is not possible, however, to draw any firm conclusions on the potential biological significance of this observation and further research is required to better understand the potential chronic effects of microplastic exposure on animal health, particularly as marine mammals are widely considered important sentinels for the implications of pollution for the marine environment.

Decreased staging of differentiated thyroid cancer in patients with chronic lymphocytic thyroiditis.

PURPOSE: The biological association between chronic lymphocytic thyroiditis (CLT) and differentiated thyroid cancer (DTC) has not been elucidated yet. The aim of the study was to assess whether the presence of CLT exerts any influence on clinical or histological presentation of DTC. METHODS: Nine hundred and seven consecutive patients with DTC treated in the years 1998-2016 were divided into two groups according to the presence or absence of concomitant CLT. The statistical differences were analysed. RESULTS: Out of 907 patients included in the study, 331 were diagnosed with DTC and CLT (studied group), while 576 patients with DTC but without CLT constituted a control group. The distribution of papillary and follicular thyroid cancer did not differ. In CLT group, the prevalence of pT1 was greater than for pT2-pT4 DTC (P = 0.0003; OR = 1.69, 95% CI 1.27-2.24) compared to controls (68.3 vs. 56.1%, respectively). The presence of multifocal lesions was similar. The thyroid capsule infiltration without extrathyroidal invasion (P < 0.0001; OR = 0.21, 95% CI 0.14-0.31) was more frequent in the studied group, unlike extracapsular invasion, which was significantly more often present in patients with DTC but without CLT (P = 0.004; OR = 1.66; 95% CI 1.17-2.34) as well as nodal involvement (P = 0.048; OR = 0.65, 95% CI 0.42-0.99). CONCLUSIONS: The collected data indicate a protective role of CLT in preventing the spread of the DTC. The presence of CLT might limit tumour growth to the primary site.