Novel penalised likelihood reconstruction of PET in the assessment of histologically verified small pulmonary nodules

OBJECTIVES: Investigate the effect of a novel Bayesian penalised likelihood (BPL) reconstruction algorithm on analysis of pulmonary nodules examined with 18F-FDG PET/CT, and to determine its effect on small, sub-10-mm nodules. METHODS: 18F-FDG PET/CTs performed for nodule evaluation in 104 patients (121 nodules) were retrospectively reconstructed using the new algorithm, and compared to time-of-flight ordered subset expectation maximisation (OSEM) reconstruction. Nodule and background parameters were analysed semi-quantitatively and visually. RESULTS: BPL compared to OSEM resulted in statistically significant increases in nodule SUV(max) (mean 5.3 to 8.1, p < 0.00001), signal-to-background (mean 3.6 to 5.3, p < 0.00001) and signal-to-noise (mean 24 to 41, p < 0.00001). Mean percentage increase in SUV(max) (%ΔSUV(max)) was significantly higher in nodules ≤10 mm (n = 31, mean 73 %) compared to >10 mm (n = 90, mean 42 %) (p = 0.025). Increase in signal-to-noise was higher in nodules ≤10 mm (224 %, mean 12 to 27) compared to >10 mm (165 %, mean 28 to 46). When applying optimum SUV(max) thresholds for detecting malignancy, the sensitivity and accuracy increased using BPL, with the greatest improvements in nodules ≤10 mm. CONCLUSION: BPL results in a significant increase in signal-to-background and signal-to-noise compared to OSEM. When semi-quantitative analyses to diagnose malignancy are applied, higher SUV(max) thresholds may be warranted owing to the SUV(max) increase compared to OSEM. KEY POINTS: • Novel Bayesian penalised likelihood PET reconstruction was applied for lung nodule evaluation. • This was compared to current standard of care OSEM reconstruction. • The novel reconstruction generated significant increases in lung nodule signal-to-background and signal-to-noise. • These increases were highest in small, sub-10-mm pulmonary nodules. • Higher SUV(max)thresholds may be warranted when using semi-quantitative analyses to diagnose malignancy

Marine Copepods, The Wildebeest of the Ocean

Copepods are amongst the most abundant animals on our planet. Who knew?! These small (typically 1–10 mm) crustaceans are found in all of the world’s oceans and play an important role in regulating Earth’s climate. Like wildebeest in the Serengeti graze on grasslands and are food for lions, herbivorous copepods represent a vital link in oceanic food chains between microscopic algae and higher predators, such as fish, birds, and whales. A group of copepods called Calanus are particularly important in the Northern Hemisphere. These tiny-but-mighty animals also share the wildebeest’s need to make a large annual migration—but in their case, they sink thousands of meters downwards to spend the winter in the deep, dark ocean. Understanding the lives of marine copepods, and how their populations will respond to climate change, is crucial for predicting the future health of the marine environment and how it helps our planet

18F-FDG PET/CT assessment of histopathologically confirmed mediastinal lymph nodes in non-small cell lung cancer using a penalised likelihood reconstruction

Purpose To investigate whether using a Bayesian penalised likelihood reconstruction (BPL) improves signal-to-background (SBR), signal-to-noise (SNR) and SUVmax when evaluating mediastinal nodal disease in non-small cell lung cancer (NSCLC) compared to ordered subset expectation maximum (OSEM) reconstruction. Materials and methods 18F-FDG PET/CT scans for NSCLC staging in 47 patients (112 nodal stations with histopathological confirmation) were reconstructed using BPL and compared to OSEM. Node and multiple background SUV parameters were analysed semi-quantitatively and visually. Results Comparing BPL to OSEM, there were significant increases in SUVmax (mean 3.2–4.0, p<0.0001), SBR (mean 2.2–2.6, p<0.0001) and SNR (mean 27.7–40.9, p<0.0001). Mean background SNR on OSEM was 10.4 (range 7.6–14.0), increasing to 12.4 (range 8.2–16.7, p<0.0001). Changes in background SUVs were minimal (largest mean difference 0.17 for liver SUVmean, p<0.001). There was no significant difference between either algorithm on receiver operating characteristic analysis (p=0.26), although on visual analysis, there was an increase in sensitivity and small decrease in specificity and accuracy on BPL. Conclusion BPL increases SBR, SNR and SUVmax of mediastinal nodes in NSCLC compared to OSEM, but did not improve the accuracy for determining nodal involvement

Can a key boreal Calanus copepod species now complete its life-cycle in the Arctic? Evidence and implications for Arctic food-webs

The changing Arctic environment is affecting zooplankton that support its abundant wildlife. We examined how these changes are influencing a key zooplankton species, Calanus finmarchicus, principally found in the North Atlantic but expatriated to the Arctic. Close to the ice-edge in the Fram Strait, we identified areas that, since the 1980s, are increasingly favourable to C. finmarchicus. Field-sampling revealed part of the population there to be capable of amassing enough reserves to overwinter. Early developmental stages were also present in early summer, suggesting successful local recruitment. This extension to suitable C. finmarchicus habitat is most likely facilitated by the long-term retreat of the ice-edge, allowing phytoplankton to bloom earlier and for longer and through higher temperatures increasing copepod developmental rates. The increased capacity for this species to complete its life-cycle and prosper in the Fram Strait can change community structure, with large consequences to regional food-webs

Investigating the physiological ecology of mesopelagic zooplankton in the Scotia Sea (Southern Ocean) using lipid and stable isotope signatures

The mesopelagic zooplankton community plays an important role in the cycling and sequestration of carbon via the biological pump. However, little is known about the physiology and ecology of key taxa found within this region, hindering our understanding of their influence on the pathways of energy and organic matter cycling. We sampled the eight most abundant zooplankton (Calanoides acutus, Rhincalanus gigas, Paraeuchaeta spp., Chaetognatha, Euphausia triacantha, Thysanoessa spp., Themisto gaudichaudii and Salpa thompsoni) from within the mesopelagic zone in the Scotia Sea during a sinking diatom bloom and investigated their physiological ecology using lipid biomarkers and stable isotopic signatures of nitrogen. Data suggest that the large calanoid copepods, C. acutus and R. gigas, were in, or emerging from, a period of metabolic inactivity during the study period (November 15th – December 15th 2017). Abundant, but decreasing lipid reserves in the predominantly herbivorous calanoid copepods, suggest these animals may have been metabolising previously stored lipids at the time of sampling, rather than deriving energy solely from the diatom bloom. This highlights the importance of understanding the timing of diapause of overwintering species as their feeding is likely to have an impact on the turnover of particulate organic matter (POM) in the upper mesopelagic. The δ15N signatures of POM became enriched with increasing depth, whereas all species of zooplankton except T. gaudichaudii did not. This suggests that animals were feeding on fresher, surface-derived POM, rather than reworked particles at depth, likely influencing the quantity and quality of organic matter leaving the upper mesopelagic. Our study highlights the complexity of mesopelagic food webs and suggests that the application of broad trophic functional types may lead to an incorrect understanding of ecosystem dynamics

Evolutionary History of Rabies in Ghana

Rabies virus (RABV) is enzootic throughout Africa, with the domestic dog (Canis familiaris) being the principal vector. Dog rabies is estimated to cause 24,000 human deaths per year in Africa, however, this estimate is still considered to be conservative. Two sub-Saharan African RABV lineages have been detected in West Africa. Lineage 2 is present throughout West Africa, whereas Africa 1a dominates in northern and eastern Africa, but has been detected in Nigeria and Gabon, and Africa 1b was previously absent from West Africa. We confirmed the presence of RABV in a cohort of 76 brain samples obtained from rabid animals in Ghana collected over an eighteen-month period (2007–2009). Phylogenetic analysis of the sequences obtained confirmed all viruses to be RABV, belonging to lineages previously detected in sub-Saharan Africa. However, unlike earlier reported studies that suggested a single lineage (Africa 2) circulates in West Africa, we identified viruses belonging to the Africa 2 lineage and both Africa 1 (a and b) sub-lineages. Phylogeographic Bayesian Markov chain Monte Carlo analysis of a 405 bp fragment of the RABV nucleoprotein gene from the 76 new sequences derived from Ghanaian animals suggest that within the Africa 2 lineage three clades co-circulate with their origins in other West African countries. Africa 1a is probably a western extension of a clade circulating in central Africa and the Africa 1b virus a probable recent introduction from eastern Africa. We also developed and tested a novel reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay for the detection of RABV in African laboratories. This RT-LAMP was shown to detect both Africa 1 and 2 viruses, including its adaptation to a lateral flow device format for product visualization. These data suggest that RABV epidemiology is more complex than previously thought in West Africa and that there have been repeated introductions of RABV into Ghana. This analysis highlights the potential problems of individual developing nations implementing rabies control programmes in the absence of a regional programme

Erythroid-Specific Expression of β-globin from Sleeping Beauty-Transduced Human Hematopoietic Progenitor Cells

Gene therapy for sickle cell disease will require efficient delivery of a tightly regulated and stably expressed gene product to provide an effective therapy. In this study we utilized the non-viral Sleeping Beauty (SB) transposon system using the SB100X hyperactive transposase to transduce human cord blood CD34+ cells with DsRed and a hybrid IHK–β-globin transgene. IHK transduced cells were successfully differentiated into multiple lineages which all showed transgene integration. The mature erythroid cells had an increased β-globin to γ-globin ratio from 0.66±0.08 to 1.05±0.12 (p = 0.05), indicating expression of β-globin from the integrated SB transgene. IHK–β-globin mRNA was found in non-erythroid cell types, similar to native β-globin mRNA that was also expressed at low levels. Additional studies in the hematopoietic K562 cell line confirmed the ability of cHS4 insulator elements to protect DsRed and IHK–β-globin transgenes from silencing in long-term culture studies. Insulated transgenes had statistically significant improvement in the maintenance of long term expression, while preserving transgene regulation. These results support the use of Sleeping Beauty vectors in carrying an insulated IHK–β-globin transgene for gene therapy of sickle cell disease

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research