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Solitary pulmonary nodules (SPNs) measuring 8 to 30 mm in diameter require further workup to determine the likelihood of malignancy.What is the diagnostic performance of a lung cancer prediction convolutional neural network (LCP-CNN) in SPNs using unenhanced and contrast-enhanced CT imaging compared with the current clinical workup?This was a post hoc analysis of the Single Pulmonary Nodule Investigation: Accuracy and Cost-Effectiveness of Dynamic Contrast Enhanced Computed Tomography in the Characterisation of Solitary Pulmonary Nodules trial, a prospective multicenter study comparing the diagnostic accuracy of dynamic contrast-enhanced (DCE) CT imaging with PET imaging in SPNs. The LCP-CNN was designed and validated in an external cohort. LCP-CNN-generated risk scores were created from the noncontrast and contrast-enhanced CT scan images from the DCE CT imaging. The gold standard was histologic analysis or 2 years of follow-up. The area under the receiver operating characteristic curves (AUC) were calculated using LCP-CNN score, maximum standardized uptake value, and DCE CT scan maximum enhancement and were compared using the DeLong test.Two hundred seventy participants (mean ± SD age, 68.3 ± 8.8 years; 49% women) underwent PET with CT scan imaging and DCE CT imaging with CT scan data available centrally for LCP-CNN analysis. The accuracy of the LCP-CNN on the noncontrast images (AUC, 0.83; 95% CI, 0.79-0.88) was superior to that of DCE CT imaging (AUC, 0.76; 95% CI, 0.69-0.82; P = .03) and equal to that of PET with CT scan imaging (AUC, 0.86; 95% CI, 0.81-0.90; P = .35). The presence of contrast resulted in a small reduction in diagnostic accuracy, with the AUC falling from 0.83 (95% CI, 0.79-0.88) on the noncontrast images to 0.80 to 0.83 after contrast (P .05 for 240 s after contrast only).An LCP-CNN algorithm provides an AUC equivalent to PET with CT scan imaging in the diagnosis of solitary pulmonary nodules.ClinicalTrials.gov Identifier; No.: NCT02013063.

Radiotherapy has proven efficacy in a wide range of cancers. There is growing interest in evaluating radiotherapy–novel agent combinations and a drive to initiate this earlier in the clinical development of the novel agent, where the scientific rationale and preclinical evidence for a radiotherapy combination approach are high. Optimal design, delivery, and interpretation of studies are essential. In particular, the design of phase I studies to determine safety and dosing is critical to an efficient development strategy. There is significant interest in early-phase research among scientific and clinical communities over recent years, at a time when the scrutiny of the trial methodology has significantly increased. To enhance trial design, optimize safety, and promote efficient trial conduct, this position paper reviews the current phase I trial design landscape. Key design characteristics extracted from 37 methodology papers were used to define a road map and a design selection process for phase I radiotherapy–novel agent trials. Design selection is based on single- or dual-therapy dose escalation, dose-limiting toxicity categorization, maximum tolerated dose determination, subgroup evaluation, software availability, and design performance. Fifteen of the 37 designs were identified as being immediately accessible and relevant to radiotherapy–novel agent phase I trials. Applied examples of using the road map are presented. Developing these studies is intensive, highlighting the need for funding and statistical input early in the trial development to ensure appropriate design and implementation from the outset. The application of this road map will improve the design of phase I radiotherapy–novel agent combination trials, enabling a more efficient development pathway.

Glacial cycles play important roles in determining the phylogeographic structure of terrestrial species, however, relatively little is known about their impacts on the distribution of marine biota. This study utilised modern (n = 350) and ancient (n = 26) mitochondrial genomes from Australasian snapper (Chrysophrys auratus) sampled in New Zealand to assess their demographic and phylogeographic history. We also tested for changes in genetic diversity using the up to 750-year-old mitochondrial genomes from pre-European archaeological sites to assess the potential impacts of human exploitation. Nucleotide diversity and haplotype diversity was high (π = 0.005, h = 0.972). There was no significant change in nucleotide diversity over the last 750 years (p = 0.343), with no detectable loss of diversity as a result of indigenous and industrial-scale fishing activity. While there was no evidence for contemporary population structure (AMOVA, p = 0.764), phylogeographic analyses identified two distinct mitochondrial clades that diverged approximately 650,000 years ago during the mid-Pleistocene, suggesting the species experienced barriers to gene flow when sea levels dropped over 120 m during previous glacial maxima. An exponential population increase was also observed around 8000 years ago consistent with a post-glacial expansion, which was likely facilitated by increased ocean temperatures and rising sea levels. This study demonstrates that glacial cycles likely played an important role in the demographic history of C. auratus and adds to our growing understanding of how dynamic climatic changes have influenced the evolution of coastal marine species.

This paper centralises visual artists in policymaking processes. It foregrounds the ways artists influence and determine the policies that affect their lives, practices, and careers through their higher art education in London (UK) art schools between 1986-2016. The uninvited and indirect processes by which artists are shaping policies using their education is captured through artsbased/informed methods developed for listening, analysing, and interpreting alongside grounded theory methodology. The practitionerled approach is key to noticing and raising the subtle agitations in the actions and inactions that underscore artists’ role as policy progenitors. Artists’ relationships with professional development and their experiences of structureless pedagogies, which are aligned to artistic myth are foregrounded. Their acceptances, rejections, and reframing of their fine art curricula is where their influence in shaping policy sits.

Peer reviewed: True, The aim of this study was to develop and validate an automated pipeline that could assist the diagnosis of active aortitis using radiomic imaging biomarkers derived from [18F]-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography (FDG PET-CT) images. The aorta was automatically segmented by convolutional neural network (CNN) on FDG PET-CT of aortitis and control patients. The FDG PET-CT dataset was split into training (43 aortitis:21 control), test (12 aortitis:5 control) and validation (24 aortitis:14 control) cohorts. Radiomic features (RF), including SUV metrics, were extracted from the segmented data and harmonized. Three radiomic fingerprints were constructed: A-RFs with high diagnostic utility removing highly correlated RFs; B used principal component analysis (PCA); C-Random Forest intrinsic feature selection. The diagnostic utility was evaluated with accuracy and area under the receiver operating characteristic curve (AUC). Several RFs and Fingerprints had high AUC values (AUC > 0.8), confirmed by balanced accuracy, across training, test and external validation datasets. Good diagnostic performance achieved across several multi-centre datasets suggests that a radiomic pipeline can be generalizable. These findings could be used to build an automated clinical decision tool to facilitate objective and standardized assessment regardless of observer experience.

The evolutionary history of Southern Hemisphere graylings (Retropinnidae) in Aotearoa New Zealand—including the number of colonisation events, the directionality and timing of dispersal, and their relationship to the Australian grayling—is poorly understood. The New Zealand grayling (Prototroctes oxyrhynchus) is the only known freshwater fish species to have gone extinct since human arrival in New Zealand. Despite its historical abundance, only 23 formalin-fixed specimens (both wet and dried) exist in museum collections globally, which were previously non-amenable to palaeogenetic analysis.Here, we used high-throughput DNA sequencing techniques, specifically designed for formalin-fixed specimens, to generate mitochondrial genomes of P. oxyrhynchus, and analysed these within a temporal phylogenetic framework of retropinnid and osmerid taxa.We recovered strong evidence for a sister relationship between the New Zealand and Australian grayling (P. mareana), with the two having a common ancestor around 13.8 Mya (95% HPD: 6.1–23.2 Mya), after the height of Oligocene marine inundation in New Zealand.Our temporal phylogenetic analysis suggests a single marine dispersal event between New Zealand and Australia, though the direction of dispersal is equivocal, followed by divergence into genetically and morphologically distinguishable species through isolation by distance.This study provides further insights into the possible drivers of the extinction of the New Zealand grayling, and highlights how advancements in palaeogenetic techniques can be used to test evolutionary hypotheses in extinct (and living) fish, which have been comparatively neglected in the field of ancient DNA.

Natural history collections worldwide contain a plethora of mollusc shells. Recent studies have detailed the sequencing of DNA extracted from shells up to thousands of years old and from various taphonomic and preservational contexts. However, previous approaches have largely addressed methodological rather than evolutionary research questions. Here, we report the generation of DNA sequence data from mollusc shells using such techniques, applied to Haliotis virginea Gmelin, 1791, a New Zealand abalone, in which morphological variation has led to the recognition of several forms and subspecies. We successfully recovered near-complete mitogenomes from 22 specimens including 12 dry-preserved shells up to 60 years old. We used a combination of palaeogenetic techniques that have not previously been applied to shell, including DNA extraction optimized for ultra-short fragments and hybridization-capture of single-stranded DNA libraries. Phylogenetic analyses revealed three major, well-supported clades comprising samples from: (1) The Three Kings Islands; (2) the Auckland, Chatham and Antipodes Islands; and (3) mainland New Zealand and Campbell Island. This phylogeographic structure does not correspond to the currently recognized forms. Critically, our nonreliance on freshly collected or ethanol-preserved samples enabled inclusion of topotypes of all recognized subspecies as well as additional difficult-to-sample populations. Broader application of these comparatively cost-effective and reliable methods to modern, historical, archaeological and palaeontological shell samples has the potential to revolutionize invertebrate genetic research.

Purpose To develop a machine learning (ML) model based on radiomic features (RF) extracted from whole prostate gland magnetic resonance imaging (MRI) for prediction of tumour hypoxia pre-radiotherapy. Material and methods Consecutive patients with high-grade prostate cancer and pre-treatment MRI treated with radiotherapy between 01/12/2007 and 1/08/2013 at two cancer centres were included. Cancers were dichotomised as normoxic or hypoxic using a biopsy-based 32-gene hypoxia signature (Ragnum signature). Prostate segmentation was performed on axial T2-weighted (T2w) sequences using RayStation (v9.1). Histogram standardisation was applied prior to RF extraction. PyRadiomics (v3.0.1) was used to extract RFs for analysis. The cohort was split 80:20 into training and test sets. Six different ML classifiers for distinguishing hypoxia were trained and tuned using five different feature selection models and fivefold cross-validation with 20 repeats. The model with the highest mean validation area under the curve (AUC) receiver operating characteristic (ROC) curve was tested on the unseen set, and AUCs were compared via DeLong test with 95% confidence interval (CI). Results 195 patients were included with 97 (49.7%) having hypoxic tumours. The hypoxia prediction model with best performance was derived using ridge regression and had a test AUC of 0.69 (95% CI: 0.14). The test AUC for the clinical-only model was lower (0.57), but this was not statistically significant (p = 0.35). The five selected RFs included textural and wavelet-transformed features. Conclusion Whole prostate MRI-radiomics has the potential to non-invasively predict tumour hypoxia prior to radiotherapy which may be helpful for individualised treatment optimisation.

Institutional variations in parathyroid adenoma localisation are largely dictated by local experience and availability of imaging investigations, with no consensus on the optimal approach. This review evaluates the role of multiple imaging techniques in primary hyperparathyroidism and highlights their advantages and limitations in different clinical contexts. A clinico-radiological review of parathyroid imaging techniques is illustrated with example cases and data from the literature. These include high-resolution ultrasound

Background and purpose Magnetic Resonance Imaging (MRI) exhibits scanner dependent contrast, which limits generalisability of radiomics and machine-learning for radiation oncology. Current deep-learning harmonisation requires paired data, retraining for new scanners and often suffers from geometry-shift which alters anatomical information. The aim of this study was to investigate style-blind auto-encoders for MRI harmonisation to accommodate unpaired training data, avoid geometry-shift and harmonise data from previously unseen scanners. Materials and methods A style-blind auto-encoder, using adversarial classification on the latent-space, was designed for MRI harmonisation. The public CC359 T1-w MRI brain dataset includes six scanners (three manufacturers, two field strengths), of which five were used for training. MRI from all six (including one unseen) scanner were harmonised to common contrast. Harmonisation extent was quantified via Kolmogorov-Smirnov testing of residual scanner dependence of 3D radiomic features, and compared to WhiteStripe normalisation. Anatomical content preservation was measured through change in structural similarity index on contrast-cycling (δSSIM). Results The percentage of radiomics features showing statistically significant scanner-dependence was reduced from 41% (WhiteStripe) to 16% for white matter and from 39% to 27% for grey matter. δSSIM < 0.0025 on harmonisation and de-harmonisation indicated excellent anatomical content preservation. Conclusions Our method harmonised MRI contrast effectively, preserved critical anatomical details at high fidelity, trained on unpaired data and allowed zero-shot harmonisation. Robust and clinically translatable harmonisation of MRI will enable generalisable radiomic and deep-learning models for a range of applications, including radiation oncology treatment stratification, planning and response monitoring.

Understanding how natural populations respond to climatic shifts is a fundamental goal of biological research in a fast-changing world. The Southern Ocean represents a fascinating system for assessing large-scale climate-driven biological change, as it contains extremely isolated island groups within a predominantly westerly, circumpolar wind and current system. Blue-eyed shags represent a paradoxical seabird radiation—a circumpolar distribution implies strong dispersal capacity yet their species-rich nature suggests local adaptation and isolation. Here we attempt to resolve this paradox in light of the history of repeated cycles of climate change in the Southern Ocean.

Objectives To assess the effectiveness of fluorine-18 fluorodeoxyglucose (FDG) positron-emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) for response assessment post curative-intent chemoradiotherapy (CRT) in anal squamous cell carcinoma (ASCC). Methods Consecutive ASCC patients treated with curative-intent CRT at a single centre between January 2018 and April 2020 were retrospectively identified. Clinical meta-data including progression-free survival (PFS) and overall survival (OS) outcomes were collated. Three radiologists evaluated PET-CT and MRI using qualitative response assessment criteria and agreed in consensus. Two-proportion z test was used to compare diagnostic performance metrics (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy). Kaplan-Meier analysis (Mantel-Cox log-rank) was performed. Results MRI (accuracy 76%, PPV 44.8%, NPV 95.7%) and PET-CT (accuracy 69.3%, PPV 36.7%, NPV 91.1%) performance metrics were similar; when combined, there were statistically significant improvements (accuracy 94.7%, PPV 78.9%, NPV 100%). Kaplan-Meier analysis demonstrated significant differences in PFS between responders and non-responders at PET-CT (p = 0.007), MRI (p = 0.005), and consensus evaluation (p < 0.001). Cox regression analysis of PFS demonstrated a lower hazard ratio (HR) and narrower 95% confidence intervals for consensus findings (HR = 0.093, p < 0.001). Seventy-five patients, of which 52 (69.3%) were females, with median follow-up of 17.8 months (range 5–32.6) were included. Fifteen of the 75 (20%) had persistent anorectal and/or nodal disease after CRT. Three patients died, median time to death 6.2 months (range 5–18.3). Conclusion Combined PET-CT and MRI response assessment post-CRT better predicts subsequent outcome than either modality alone. This could have valuable clinical benefits by guiding personalised risk-adapted patient follow-up. Key Points • MRI and PET-CT performance metrics for assessing response following chemoradiotherapy (CRT) in patients with anal squamous cell carcinoma (ASCC) were similar. • Combined MRI and PET-CT treatment response assessment 3 months after CRT in patients with ASCC was demonstrated to be superior to either modality alone. • A combined MRI and PET-CT assessment 3 months after CRT in patients with ASCC has the potential to improve accuracy and guide optimal patient management with a greater ability to predict outcome than either modality alone

Hoplodactylus tohu n. sp. Figures 2A, 3A–D, 4A–C; Supplementary Figures 5A–C. ZooBank registration of Hoplodactylus tohu n. sp.: urn:lsid:zoobank.org:pub: BC2A430C-D97C-4F45-9AFB-228379864926. Naultinus pacificus.– Gray 1843: 203 (in part, not Gray, 1842). Hoplodactylus duvaucelii [sic] McCann 1955: 39, fig. 3, pl. 4; McCann 1956a: 46; McCann 1956b: 15; Bustard 1963: 218; Sharell 1966: 49, pls. 28–31; Thoresen 1967: 197; Whitaker 1973: 122; Domrow et al. 1980: 295; Barwick 1982: 377; Bauer 1985: 90; Halliday & Verrell 1988: 260; Wilson & Freeman 1993: 1 – all in part (not Duméril & Bibron, 1836). Hoplodactylus duvaucelii.– Holder 1960: 302; Kluge 1967a: 25; Kluge 1967b: 1013; Werner et al. 1978: 378;7 Kennedy 1979: 1; Bauer 1986: 9; Worthy 1987b: 416; Bauer 1990: 108; Thompson et al. 1992: 123; Daugherty et al. 1993: 439; Bauer & Henle 1994: 139; Cree 1994: 352 Daugherty et al. 1994: 318; Towns & Daugherty 1994: 327; Worthy & Holdaway 1994: 326; East et al. 1995: 256; Worthy & Holdaway 1995: 350; Worthy & Holdaway 1996: 314; Hitchmough 1997: 1; Worthy 1997: 93; Bauer 1998: 43; Girling et al. 1998: 139, fig. 4; Worthy 1998: 448; Bannock et al. 1999: 102; Lukis 1999: 12; Flannagan 2000: 4; Jones 2000: 1, fig. 2.9; Towns & Ferreira 2001: 219; Towns et al. 2001: 4; Seligmann 2002: 277; Whitaker et al. 2002: 1; Hay et al. 2003: 16; Todd 2003: 17; Seligmann et al. 2003: 130; Holmes 2004: 4; Naish 2004: 18; Hare & Cree 2005: 137; Armstrong & Davidson 2006: 74; Hare et al. 2007: 89; Nielsen 2008: 5; Kelly & Sullivan 2010: 208; Miskelly 2010: 3; Wilson 2010: 6; Frank & Wilson 2011: 16; Nielsen et al. 2011: 17; Bell & Herbert 2012: 8; Str̂ckens et al. 2012: 542; Garcia-Porta & Ord 2013: 2667; Hitchmough et al. 2013: 10; Bell 2014: 8; Romijn et al. 2014: 111; Heath & Whitaker 2015: 751; Mockett 2015: 73; Chapple 2016b: 4; Chapple & Hitchmough 2016: 116; Cree & Hare 2016: 174; Hare et al. 2016: 140; Hare & Cree 2016: 246; Hitchmough et al. 2016a: 9; Hitchmough et al. 2016b: 89; Morgan-Richards et al. 2016: 77, fig. 2; Romijn and Hartley 2016: 196; Towns et al. 2016b: 308; Worthy 2016: 71; Bell and Herbert 2017: 38; Bowers 2017: 64; Knox et al. 2017: 490; Lozito & Tuan 2017: 148, fig. 2 Sion 2017: 131; Stancher et al. 2018: 36; van Winkel et al. 2018: 114, pls. 31, 40, 46, 128; Skipwith et al. 2019: 10; Florence-Bennett 2020: 13; Glynne et al. 2020: 804; Herbert 2020: 12; Price et al. 2020: 231; Scarsbrook 2021: 19, figs. 1.5, 2.1, 3.1, 3.3, 4.1; Scarsbrook et al. 2021: 2; Scarsbrook et al. 2022: 3, fig. 1 – all in part (not Duméril & Bibron, 1836). Naultinus duvaucelii.– Chrapliwy et al. 1961: 6 (in part, not Duméril & Bibron, 1836). Woodworthia duvaucelii.– Jewell 2008: 50 (in part, not Duméril & Bibron, 1836). Type material.— Holotype: New Zealand, Marlborough Sounds, Middle Trios Island, male, Y. M. McCann, February 1950, RE.000503. Paratypes: New Zealand, Marlborough Sounds, Middle Trios Island, 40°50.53′ S, 174°0.00′ E, both male, C. H. Daugherty, 22 November 1988, RE.006685, RE.006686 (tissue clips: FT2047, FT2048 respectively). Material examined.— The type material. Stephens Island (OMVT949). Trios Islands: Middle Trios Island (RE.000505,FT2046); South Trios Island (RE.006687). Sentinel Rock (RE.000948). Chetwode Island (RE.000949). Brothers Islands: North Brother Island (RE.002561, RE.005496, RE.006509, RE.006510, RE.007265, FT277, FT278). Northwest South Island (mainland): Gouland Downs, Holocene fossil (S.38813.2). Canterbury (mainland): Waikari, Holocene fossil (S.33501, S.33703.1, S.33703.7, S.33703.10, S.33703.11); Waitaki, Holocene fossil (OMVT719 a, OMVT807 a, OMVT807 b, OMVT3331, OMVT3332, OMVT3333). Diagnosis.— Hoplodactylus tohu may be distinguished from its only congener, H. duvaucelii, by several characters: H. tohu (generally) does not attain as great a size at maturity (Supp. Fig. 1), has a more pronounced brillar fold (Fig. 3A–B, E–F, 4C, F), and less often bears a median cleft in the mental scale (Supp. Table 3). An abrupt size decrease at the 5 th infralabial scale characterizing H. tohu is far less common in H. duvaucelii, with most individuals of the latter examined exhibiting a gradual size decrease in infralabial scales (Fig. 3B, F). H. tohu further differs from H. duvaucelii in generally having fewer subdigital lamellae on all digits of both the right manus and pes (Fig. 3C–D, G–H, Supp. Fig. 3). The first digit of the right manus in H. duvaucelii differs in having a consistently less emergent claw and, usually, a comparatively bulbous distal end (Fig. 3C, G). Previously reported differences (Morgan-Richards et al. 2016) in the coloration and extent of patterning between these taxa (Fig. 4) are generalizations and can be misleading given fluid overlap between the two species. Dorsal body coloration and patterning in H. tohu often resembles those of young H. duvaucelii in being relatively more strongly contrasting (Fig. 4A–B, D–E), with patterning generally becoming weaker at maturity. However, considerable variation in coloration and pattern (see Supp. Fig. 5) was observed throughout ontogeny in both species. Description.— Coloration on dorsal surface grey to grey-brown, sometimes with olive and dark brown blotches; patterning of well-developed, roughly symmetrical transverse bands from nape to tail base centered along spine, resembling chevrons or paired diamonds, less defined on tail and generally less defined on older individuals; often bearing irregular series of longitudinal rows of pale grey or white spots dorsolaterally, extending onto limbs; ventral surface buff, with occasional light brown speckling, speckles less frequent on head. Mouth lining and tongue pink. Body moderately large (SVL: 81.2–115.7 mm), robust, stout (TrK: 25.4–50.3 mm). Head large (HL: 26.1–33.8 mm; HW: 18.3–27 mm; HH: 12.2–16 mm), robust, subtriangular; inflated laterally between posterior edge of orbit and ear opening (EE: 7.7–11.8 mm), narrowing towards craniovertebral junction; neck clearly demarcated. Snout oviform (EN: 7.4–11.1 mm); slight indentation in medial nasal region, often blunt along anteriormost margin between nares (IN: 4–5.8 mm). Dorsum of occiput/nape covered in small granular scales that abruptly increase in size at level of anterior edge of orbit towards anterior margin of snout (2–3 times diameter of occipital granules); one row of enlarged, oval scales posterior to internasal(s) and dorsal to supralabials, broader than high; twice the diameter of adjacent loreal scales. Eyes approximately one fifth head length; varying in shade from pale olive-buff to dark greens or browns; pupils lenticular with weakly crenulated margin. Supraciliary scales elongate, conical, directed increasingly posterior posteriorly; brillar fold very pronounced; frontal narrowing anteriorly (IO: 7.8–11.8 mm), supraocular portion deeply furrowed. Ear opening moderate (EL: 2–4.1 mm), ovoid, twice as high as wide; oriented obliquely (widest posterodorsally to anteroventrally), skin fold covering dorsal limit. Rostral subpentagonal, much broader than high; contacted dorsally by 2 enlarged, oval supranasals and 1–3 smaller (homogenous), round internasals; medial rostral crease extending ventrally from upper margin ½ to ¾ length of rostral; usually terminating diffusely, but sometimes as an ovoid crease. Nares rounded, situated anterolaterally; bordered by rostral, supranasal, 3–5 small postnasals and first supralabial. Supralabials rectangular, rounded dorsally; slightly higher than broad; numbering 13–16 per side; gradually decreasing in size posteriorly; final 3–4 more narrowly convex; supralabials terminating beneath the posterior orbital margin (with 11 or 12 beneath orbit midline); posteriormost twice the size of loreal scales. Mental trapezoidal to subtriangular, with longest face along jaw margin, narrowing posteriorly; mental crease usually absent, extending ½ length of scale where present; mental shorter than laterally adjacent first infralabials; contacted posteriorly by 1 large or 2 smaller hexagonal postmentals, which separate infralabials. Infralabials numbering 9–14 per side; from the snout, infralabials 1–4 on each side are quadrate, more rounded ventrally, higher than broad; infralabial 5 usually marks commencement of a significant and discrete infralabial size decrease, sometimes on one side only, with subsequent infralabials becoming progressively smaller and increasingly circular in shape, terminating in-line with the posterior orbital margin. Anterior infralabials and postmental(s) bordered posteriorly by series of enlarged irregular chin shields; rows indistinct; anteriormost approximately ¾ diameter of postmental, with gradual transition to very small, rounded throat granules posteriorly. Dorsal scales small, mostly homogenous in size, bead-like, apically flattened, partially overlain; indistinct from scales of nape. Ventral scales roughly twice diameter of dorsal scales, circular, flattened, subimbricate, slightly enlarged in precloacal region, extending in rows onto thighs where they form a subtriangular patch; transition to granules at throat abrupt. Skin folds extending ventrolaterally along trunk; anteroposterior folds above fore- and hindlimb insertion. Limbs relatively short and robust, hindlimbs longer; scales on forelimb dorsum larger than dorsal body scales, subimbricate distally; ventral forelimb scales smaller than those dorsally; clear transition to enlarged scales of palm which resemble ventral body scales. Scales on preaxial surface of thigh enlarged, up to three times diameter of dorsal body scales at knee; circular, subimbricate; gradually decreasing in size both posteriorly and distally (along shin) to smaller granules; transition to scales of soles indistinct (resembling ventral body scales). 5–6 rows of precloacal pores in males, anteriormost 2 rows extending distally just over halfway along hind thigh; absent in females. Digits broad, with dilated pads on digits II–V that rapidly transition into slender distal extension, mostly of constant width but becoming narrowly tapered near distal end; digit I smallest on all feet, digit IV longest on manus, digit V longest on pes; angle at rest between digits IV and V greatest, greater on pes than manus; digits II–V of pes and I–IV of manus very weakly webbed; dorsal scales on digits large, especially on first digit; all digits bear recurved, mostly exposed claws. Basalmost 1–2 subdigital lamellae sometimes fragmented; unfragmented subdigital lamellae curved outwards, usually smoothly but sometimes more sharply curved medially; lamellar counts of right manus: 6–7 (I), 9–11 (II), 12–14 (III), 12–15 (IV), 9–11 (V), and pes: 6–9 (I), 10–13 (II), 14–16 (III), 14–18 (IV), 11–16 (V) digits. Tail (original) stout, shorter than SVL, gradually tapered to end, roughly circular in cross-section; often lost through autotomy and then regenerated. Regenerated tail demarcated by abrupt decrease in scale size and anteroposterior striations from point of detachment distally. Base of tail distinctly swollen (TW: 8.7–14.7), most notable in males at cloacal spurs, with enlarged hexagonal scales on underside roughly twice size of more anterior ventral scales. Caudal scales usually arranged in discrete, irregular rows, generally decreasing in size distally from the septum; autotomy septa visibly marked by one, sometimes two rows of large or smaller scales, separated by 9–11 scale rows; dorsal caudal scales approximately 1.5 times size of dorsal body scales, demarcating tail base; highly variable in both size and shape, circular to rounded rectangular; ventral caudal scales enlarged medially, twice as large as dorsal; rectangular to hexagonal, higher than broad, subimbricate. Cloacal spurs consisting of a set of greatly enlarged, conical scales, with most acute point orientated posterodorsally, situated adjacent to cloaca (laterally); often asymmetric in number: 2–5 (L) and 1–4 (R), first (largest) roughly twice size of ventral scales, decreasing in size posteriorly. Distribution.— New Zealand: formerly throughout the South Island (Holocene); presently restricted to some islands in the outer Marlborough Sounds and Cook Strait (Fig. 1). Remarks.— Hoplodactylus tohu has been recognized as distinct from H. duvaucelii for several years (MorganRichards et al. 2016; Hitchmough et al. 2021a). However, it has been unclear what rank to apply to this taxon. New Zealand diplodactylids frequently have highly conserved morphologies, and often greater intra- than inter-specific morphological variation (Hitchmough et al. 2016b). With both Hoplodactylus species recognized here having undergone recent major range contractions resulting in significant declines in morphological and genetic diversity (Scarsbrook et al. 2021; Scarsbrook et al. 2022), it is difficult to weight subtle character differences as these may have arisen, or increased in prevalence, recently, through chance, in relictual populations, and therefore not reflect deeper evolutionary divergences. That these taxa have been reported to produce viable cross-bred offspring in captive populations (Morgan-Richards et al. 2016) fails to meet the criteria of the Biological Species Concept (Mayr 1942). Reproductive isolation in the wild cannot be tested given their allopatric distributions. However, several pairings of lizard species that are widely recognized to be distinct (Brennan et al. 2016; Leaché & Cole 2006; Olave et al. 2011), including some other New Zealand diplodactylids (e.g., Naultinus sp.; Hitchmough et al. 2016b), have been shown to similarly produce viable hybrid offspring. Intergeneric hybrids have even been reported (RH pers. obs). Genetic distance (i.e., ~2.2% and ~4.0% across the mitochondrial genome and ND2 respectively) and estimated timing of lineage divergence of ~4.51 mya (Scarsbrook et al. 2022) between the two Hoplodactylus species recognized here are comparable with those of other recognized diplodactylid species pairings (e.g., 3.8% ND2 divergence between Mokopirirakau kahutarae Whitaker, 1985, and Mokopirirakau granulatus Gray, 1845; Knox et al. 2021). Their discrete (allopatric) distributions reflect commonly observed biogeographic patterns in other taxa (Baker et al. 1995; Efford et al. 2002; Greaves et al. 2007; Liggins et al. 2008; Lloyd 2003), which further influences our treatment of species-level distinction. Reports of interbreeding between H. tohu and H. duvaucelii in captivity makes careful management of both species essential to maintain species/genetic integrity. Individuals sourced for reintroduction or translocation purposes need to be of the correct species, and sourced from moderately large and stable populations (e.g. North Brother Island; Wilson 2010) to minimise impact on the source population. Further, source populations should be proximate (where practicable) to the site of translocation to ensure preservation of regional adaptations; a consideration more applicable to H. duvaucelii as extant populations are more numerous and occupy more ecologically varied habitats. It seems probable, for example, that H. duvaucelii rather than H. tohu, would have naturally occurred at Mana Island, off the southern North Island. However, the latter was translocated there from North Brother Island in 1998 through the release of 40 individuals (Miskelly 2010), with a self-sustaining population reported 15-years later (Bell & Herbert 2017). H. tohu has been recognized as a distinct management unit by the Department of Conservation since 2021 (Hitchmough et al. 2021a), listed as “nationally increasing” with the ‘Conservation Dependant’ and ‘Range Restricted’ qualifiers. H. tohu has a severely restricted distribution comprising a few islands (Fig. 1; Supp. Table 1) with highly anthropogenically modified habitats. The estimated total population size of the largest extant population, on the Brothers Islands, is between 583–677 (Wilson 2010). Based on this, the suggested IUCN Red List status of H. tohu is ‘Critically Endangered A1 (a, b, c, e)’: population reduction of>90% observed, estimated, inferred, or suspected in the past where the causes of the reduction are clearly reversible AND understood AND have ceased. Occurrence of H. tohu on several managed predator-free islands that already have conservation management strategies in place does at least render moderate security to this species from localized disturbances such as fire or predator incursions. However, additional protection through translocations to fenced and more distant mainland sanctuaries (e.g. Orokonui Ecosanctuary near Dunedin, and the Mokomoko Dryland Sanctuary in Central Otago) could be beneficial, given the increased vulnerability of small and sparsely forested islands to the effects of climate change (e.g. sea-level rise, coastal erosion, storm intensity; Macinnis-Ng et al. 2021). Such translocation may also facilitate the re-establishment of ‘lost’ ecological interactions and morphological diversity (e.g. Scarsbrook et al. 2021) specific to mainland and densely forested ecosystems. There is evidence of genetic sub-structuring (Scarsbrook et al. 2022) within the distribution of H. tohu, although this has been greatly reduced with the extinction of mainland South Island populations. Careful management, and possible further research should consider if individual populations are experiencing inbreeding depression and might benefit from genetic rescue – establishment of ‘new’ populations through interbreeding of individuals from different populations to increase genetic ‘fitness’ (i.e., adaptability). Conversely, continued maintenance of discrete lineages may also be appropriate if those lineages reflect local habitat adaptations or if pooled populations would comprise too few individuals to maintain the resulting genetic diversity due to genetic drift. Etymology.— The specific epithet was proposed by Dr Sharon Barcello-Gemmel, Rangatira of Te &Amacr;tiawa o Te Waka-a-M&amacr;ui Trust, in recognition of the tupuna [ancestor] Tohu K&amacr;kahi. Tohu K&amacr;kahi was one of the two Parihaka prophets with whakapapa [genealogical] connections to Te &Amacr;tiawa – the iwi [tribe] with mana whenua [authority] over Ng&amacr;whatu Kai Ponu [The Brothers], where the largest extant population occurs. Name used as noun in apposition.

Aims: This international study aimed to assess: 1) the prevalence of preoperative and postoperative COVID-19 among patients with hip fracture, 2) the effect on 30-day mortality, and 3) clinical factors associated with the infection and with mortality in COVID-19-positive patients. Methods: A multicentre collaboration among 112 centres in 14 countries collected data on all patients presenting with a hip fracture between 1st March-31st May 2020. Demographics, residence, place of injury, presentation blood tests, Nottingham Hip Fracture Score, time to surgery, management, ASA grade, length of stay, COVID-19 and 30-day mortality status were recorded. Results: A total of 7090 patients were included, with a mean age of 82.2 (range 50–104) years and 4959 (69.9%) being female. Of 651 (9.2%) patients diagnosed with COVID-19, 225 (34.6%) were positive at presentation and 426 (65.4%) were positive postoperatively. Positive COVID-19 status was independently associated with male sex (odds ratio (OR) 1.38, p = 0.001), residential care (OR 2.15, p < 0.001), inpatient fall (OR 2.23, p = 0.003), cancer (OR 0.63, p = 0.009), ASA grades 4 (OR 1.59, p = 0.008) or 5 (OR 8.28, p < 0.001), and longer admission (OR 1.06 for each increasing day, p < 0.001). Patients with COVID-19 at any time had a significantly lower chance of 30-day survival versus those without COVID-19 (72.7% versus 92.6%, p < 0.001). COVID-19 was independently associated with an increased 30-day mortality risk (hazard ratio (HR) 2.83, p < 0.001). Increasing age (HR 1.03, p = 0.028), male sex (HR 2.35, p < 0.001), renal disease (HR 1.53, p = 0.017), and pulmonary disease (HR 1.45, p = 0.039) were independently associated with a higher 30-day mortality risk in patients with COVID-19 when adjusting for confounders. Conclusion: The prevalence of COVID-19 in hip fracture patients during the first wave of the pandemic was 9%, and was independently associated with a three-fold increased 30-day mortality risk. Among COVID-19-positive patients, those who were older, male, with renal or pulmonary disease had a significantly higher 30-day mortality risk.

Peer reviewed: True, Acknowledgements: We are grateful for the invaluable contribution provided by patient representatives. HW is funded by The Urology Foundation and Pan London Cancer Alliance (Royal Marsden Partners, North Central London Cancer Alliance, North East London Cancer Alliance, South East London Cancer Alliance and the NIHR BRCs). VK receives funding from Prostate Cancer UK and the John Black Charitable Foundation. GDS and IAM are supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014) and GDS by the Cancer Research UK Cambridge Centre [C9685/A25177]. EP is supported by the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) North Thames at Bart’s Health NHS Trust. Mark Emberton receives research support from the United Kingdom’s National Institute of Health Research (NIHR) UCLH / UCL Biomedical Research Centre. He was conferred NIHR Senior Investigator Status in 2015. MGBT receives research funding from NIHR, St Peter’s Trust, Royal Free Charity, RCS, Facing up 2 Kidney Cancer and Kidney Cancer UK. The views expressed are those of the authors and not necessarily those of the funders., INTRODUCTION: The incidence of renal tumours is increasing and anatomic imaging cannot reliably distinguish benign tumours from renal cell carcinoma. Up to 30% of renal tumours are benign, with oncocytomas the most common type. Biopsy has not been routinely adopted in many centres due to concerns surrounding non-diagnostic rate, bleeding and tumour seeding. As a result, benign masses are often unnecessarily surgically resected. 99mTc-sestamibi SPECT/CT has shown high diagnostic accuracy for benign renal oncocytomas and other oncocytic renal neoplasms of low malignant potential in single-centre studies. The primary aim of MULTI-MIBI is to assess feasibility of a multicentre study of 99mTc-sestamibi SPECT/CT against a reference standard of histopathology from surgical resection or biopsy. Secondary aims of the study include obtaining estimates of 99mTc-sestamibi SPECT/CT sensitivity and specificity and to inform the design and conduct of a future definitive trial. METHODS AND ANALYSIS: A feasibility prospective multicentre study of participants with indeterminate, clinical T1 renal tumours to undergo 99mTc-sestamibi SPECT/CT (index test) compared with histopathology from biopsy or surgical resection (reference test). Interpretation of the index and reference tests will be blinded to the results of the other. Recruitment rate as well as estimates of sensitivity, specificity, positive and negative predictive value will be reported. Semistructured interviews with patients and clinicians will provide qualitative data to inform onward trial design and delivery. Training materials for 99mTc-sestamibi SPECT/CT interpretation will be developed, assessed and optimised. Early health economic modelling using a decision analytic approach for different diagnostic strategies will be performed to understand the potential cost-effectiveness of 99mTc-sestamibi SPECT/CT. ETHICS AND DISSEMINATION: Ethical approval has been granted (UK HRA REC 20/YH/0279) protocol V.5.0 dated 21/6/2022. Study outputs will be presented and published nationally and internationally. TRIAL REGISTRATION NUMBER: ISRCTN12572202.

The New Zealand endemic gecko genus Hoplodactylus is revised. Two species are recognized: Hoplodactylus duvaucelii (Duméril & Bibron, 1836) from the North Island and some near-shore islands, and H. tohu n. sp., which was formerly widespread throughout the South Island but is presently restricted to some islands in the Cook Strait region. H. delcourti (Bauer & Russell, 1986) is retained in Hoplodactylus sensu lato in the interest of taxonomic stability, pending further research, but is probably neither congeneric nor from New Zealand.

Hoplodactylus tohu n. sp. Figures 2A, 3A–D, 4A–C; Supplementary Figures 5A–C. ZooBank registration of Hoplodactylus tohu n. sp.: urn:lsid:zoobank.org:pub: BC2A430C-D97C-4F45-9AFB-228379864926. Naultinus pacificus.– Gray 1843: 203 (in part, not Gray, 1842). Hoplodactylus duvaucelii [sic] McCann 1955: 39, fig. 3, pl. 4; McCann 1956a: 46; McCann 1956b: 15; Bustard 1963: 218; Sharell 1966: 49, pls. 28–31; Thoresen 1967: 197; Whitaker 1973: 122; Domrow et al. 1980: 295; Barwick 1982: 377; Bauer 1985: 90; Halliday & Verrell 1988: 260; Wilson & Freeman 1993: 1 – all in part (not Duméril & Bibron, 1836). Hoplodactylus duvaucelii.– Holder 1960: 302; Kluge 1967a: 25; Kluge 1967b: 1013; Werner et al. 1978: 378;7 Kennedy 1979: 1; Bauer 1986: 9; Worthy 1987b: 416; Bauer 1990: 108; Thompson et al. 1992: 123; Daugherty et al. 1993: 439; Bauer & Henle 1994: 139; Cree 1994: 352 Daugherty et al. 1994: 318; Towns & Daugherty 1994: 327; Worthy & Holdaway 1994: 326; East et al. 1995: 256; Worthy & Holdaway 1995: 350; Worthy & Holdaway 1996: 314; Hitchmough 1997: 1; Worthy 1997: 93; Bauer 1998: 43; Girling et al. 1998: 139, fig. 4; Worthy 1998: 448; Bannock et al. 1999: 102; Lukis 1999: 12; Flannagan 2000: 4; Jones 2000: 1, fig. 2.9; Towns & Ferreira 2001: 219; Towns et al. 2001: 4; Seligmann 2002: 277; Whitaker et al. 2002: 1; Hay et al. 2003: 16; Todd 2003: 17; Seligmann et al. 2003: 130; Holmes 2004: 4; Naish 2004: 18; Hare & Cree 2005: 137; Armstrong & Davidson 2006: 74; Hare et al. 2007: 89; Nielsen 2008: 5; Kelly & Sullivan 2010: 208; Miskelly 2010: 3; Wilson 2010: 6; Frank & Wilson 2011: 16; Nielsen et al. 2011: 17; Bell & Herbert 2012: 8; Str̂ckens et al. 2012: 542; Garcia-Porta & Ord 2013: 2667; Hitchmough et al. 2013: 10; Bell 2014: 8; Romijn et al. 2014: 111; Heath & Whitaker 2015: 751; Mockett 2015: 73; Chapple 2016b: 4; Chapple & Hitchmough 2016: 116; Cree & Hare 2016: 174; Hare et al. 2016: 140; Hare & Cree 2016: 246; Hitchmough et al. 2016a: 9; Hitchmough et al. 2016b: 89; Morgan-Richards et al. 2016: 77, fig. 2; Romijn and Hartley 2016: 196; Towns et al. 2016b: 308; Worthy 2016: 71; Bell and Herbert 2017: 38; Bowers 2017: 64; Knox et al. 2017: 490; Lozito & Tuan 2017: 148, fig. 2 Sion 2017: 131; Stancher et al. 2018: 36; van Winkel et al. 2018: 114, pls. 31, 40, 46, 128; Skipwith et al. 2019: 10; Florence-Bennett 2020: 13; Glynne et al. 2020: 804; Herbert 2020: 12; Price et al. 2020: 231; Scarsbrook 2021: 19, figs. 1.5, 2.1, 3.1, 3.3, 4.1; Scarsbrook et al. 2021: 2; Scarsbrook et al. 2022: 3, fig. 1 – all in part (not Duméril & Bibron, 1836). Naultinus duvaucelii.– Chrapliwy et al. 1961: 6 (in part, not Duméril & Bibron, 1836). Woodworthia duvaucelii.– Jewell 2008: 50 (in part, not Duméril & Bibron, 1836). Type material.— Holotype: New Zealand, Marlborough Sounds, Middle Trios Island, male, Y. M. McCann, February 1950, RE.000503. Paratypes: New Zealand, Marlborough Sounds, Middle Trios Island, 40°50.53′ S, 174°0.00′ E, both male, C. H. Daugherty, 22 November 1988, RE.006685, RE.006686 (tissue clips: FT2047, FT2048 respectively). Material examined.— The type material. Stephens Island (OMVT949). Trios Islands: Middle Trios Island (RE.000505,FT2046); South Trios Island (RE.006687). Sentinel Rock (RE.000948). Chetwode Island (RE.000949). Brothers Islands: North Brother Island (RE.002561, RE.005496, RE.006509, RE.006510, RE.007265, FT277, FT278). Northwest South Island (mainland): Gouland Downs, Holocene fossil (S.38813.2). Canterbury (mainland): Waikari, Holocene fossil (S.33501, S.33703.1, S.33703.7, S.33703.10, S.33703.11); Waitaki, Holocene fossil (OMVT719 a, OMVT807 a, OMVT807 b, OMVT3331, OMVT3332, OMVT3333). Diagnosis.— Hoplodactylus tohu may be distinguished from its only congener, H. duvaucelii, by several characters: H. tohu (generally) does not attain as great a size at maturity (Supp. Fig. 1), has a more pronounced brillar fold (Fig. 3A–B, E–F, 4C, F), and less often bears a median cleft in the mental scale (Supp. Table 3). An abrupt size decrease at the 5 th infralabial scale characterizing H. tohu is far less common in H. duvaucelii, with most individuals of the latter examined exhibiting a gradual size decrease in infralabial scales (Fig. 3B, F). H. tohu further differs from H. duvaucelii in generally having fewer subdigital lamellae on all digits of both the right manus and pes (Fig. 3C–D, G–H, Supp. Fig. 3). The first digit of the right manus in H. duvaucelii differs in having a consistently less emergent claw and, usually, a comparatively bulbous distal end (Fig. 3C, G). Previously reported differences (Morgan-Richards et al. 2016) in the coloration and extent of patterning between these taxa (Fig. 4) are generalizations and can be misleading given fluid overlap between the two species. Dorsal body coloration and patterning in H. tohu often resembles those of young H. duvaucelii in being relatively more strongly contrasting (Fig. 4A–B, D–E), with patterning generally becoming weaker at maturity. However, considerable variation in coloration and pattern (see Supp. Fig. 5) was observed throughout ontogeny in both species. Description.— Coloration on dorsal surface grey to grey-brown, sometimes with olive and dark brown blotches; patterning of well-developed, roughly symmetrical transverse bands from nape to tail base centered along spine, resembling chevrons or paired diamonds, less defined on tail and generally less defined on older individuals; often bearing irregular series of longitudinal rows of pale grey or white spots dorsolaterally, extending onto limbs; ventral surface buff, with occasional light brown speckling, speckles less frequent on head. Mouth lining and tongue pink. Body moderately large (SVL: 81.2–115.7 mm), robust, stout (TrK: 25.4–50.3 mm). Head large (HL: 26.1–33.8 mm; HW: 18.3–27 mm; HH: 12.2–16 mm), robust, subtriangular; inflated laterally between posterior edge of orbit and ear opening (EE: 7.7–11.8 mm), narrowing towards craniovertebral junction; neck clearly demarcated. Snout oviform (EN: 7.4–11.1 mm); slight indentation in medial nasal region, often blunt along anteriormost margin between nares (IN: 4–5.8 mm). Dorsum of occiput/nape covered in small granular scales that abruptly increase in size at level of anterior edge of orbit towards anterior margin of snout (2–3 times diameter of occipital granules); one row of enlarged, oval scales posterior to internasal(s) and dorsal to supralabials, broader than high; twice the diameter of adjacent loreal scales. Eyes approximately one fifth head length; varying in shade from pale olive-buff to dark greens or browns; pupils lenticular with weakly crenulated margin. Supraciliary scales elongate, conical, directed increasingly posterior posteriorly; brillar fold very pronounced; frontal narrowing anteriorly (IO: 7.8–11.8 mm), supraocular portion deeply furrowed. Ear opening moderate (EL: 2–4.1 mm), ovoid, twice as high as wide; oriented obliquely (widest posterodorsally to anteroventrally), skin fold covering dorsal limit. Rostral subpentagonal, much broader than high; contacted dorsally by 2 enlarged, oval supranasals and 1–3 smaller (homogenous), round internasals; medial rostral crease extending ventrally from upper margin ½ to ¾ length of rostral; usually terminating diffusely, but sometimes as an ovoid crease. Nares rounded, situated anterolaterally; bordered by rostral, supranasal, 3–5 small postnasals and first supralabial. Supralabials rectangular, rounded dorsally; slightly higher than broad; numbering 13–16 per side; gradually decreasing in size posteriorly; final 3–4 more narrowly convex; supralabials terminating beneath the posterior orbital margin (with 11 or 12 beneath orbit midline); posteriormost twice the size of loreal scales. Mental trapezoidal to subtriangular, with longest face along jaw margin, narrowing posteriorly; mental crease usually absent, extending ½ length of scale where present; mental shorter than laterally adjacent first infralabials; contacted posteriorly by 1 large or 2 smaller hexagonal postmentals, which separate infralabials. Infralabials numbering 9–14 per side; from the snout, infralabials 1–4 on each side are quadrate, more rounded ventrally, higher than broad; infralabial 5 usually marks commencement of a significant and discrete infralabial size decrease, sometimes on one side only, with subsequent infralabials becoming progressively smaller and increasingly circular in shape, terminating in-line with the posterior orbital margin. Anterior infralabials and postmental(s) bordered posteriorly by series of enlarged irregular chin shields; rows indistinct; anteriormost approximately ¾ diameter of postmental, with gradual transition to very small, rounded throat granules posteriorly. Dorsal scales small, mostly homogenous in size, bead-like, apically flattened, partially overlain; indistinct from scales of nape. Ventral scales roughly twice diameter of dorsal scales, circular, flattened, subimbricate, slightly enlarged in precloacal region, extending in rows onto thighs where they form a subtriangular patch; transition to granules at throat abrupt. Skin folds extending ventrolaterally along trunk; anteroposterior folds above fore- and hindlimb insertion. Limbs relatively short and robust, hindlimbs longer; scales on forelimb dorsum larger than dorsal body scales, subimbricate distally; ventral forelimb scales smaller than those dorsally; clear transition to enlarged scales of palm which resemble ventral body scales. Scales on preaxial surface of thigh enlarged, up to three times diameter of dorsal body scales at knee; circular, subimbricate; gradually decreasing in size both posteriorly and distally (along shin) to smaller granules; transition to scales of soles indistinct (resembling ventral body scales). 5–6 rows of precloacal pores in males, anteriormost 2 rows extending distally just over halfway along hind thigh; absent in females. Digits broad, with dilated pads on digits II–V that rapidly transition into slender distal extension, mostly of constant width but becoming narrowly tapered near distal end; digit I smallest on all feet, digit IV longest on manus, digit V longest on pes; angle at rest between digits IV and V greatest, greater on pes than manus; digits II–V of pes and I–IV of manus very weakly webbed; dorsal scales on digits large, especially on first digit; all digits bear recurved, mostly exposed claws. Basalmost 1–2 subdigital lamellae sometimes fragmented; unfragmented subdigital lamellae curved outwards, usually smoothly but sometimes more sharply curved medially; lamellar counts of right manus: 6–7 (I), 9–11 (II), 12–14 (III), 12–15 (IV), 9–11 (V), and pes: 6–9 (I), 10–13 (II), 14–16 (III), 14–18 (IV), 11–16 (V) digits. Tail (original) stout, shorter than SVL, gradually tapered to end, roughly circular in cross-section; often lost through autotomy and then regenerated. Regenerated tail demarcated by abrupt decrease in scale size and anteroposterior striations from point of detachment distally. Base of tail distinctly swollen (TW: 8.7–14.7), most notable in males at cloacal spurs, with enlarged hexagonal scales on underside roughly twice size of more anterior ventral scales. Caudal scales usually arranged in discrete, irregular rows, generally decreasing in size distally from the septum; autotomy septa visibly marked by one, sometimes two rows of large or smaller scales, separated by 9–11 scale rows; dorsal caudal scales approximately 1.5 times size of dorsal body scales, demarcating tail base; highly variable in both size and shape, circular to rounded rectangular; ventral caudal scales enlarged medially, twice as large as dorsal; rectangular to hexagonal, higher than broad, subimbricate. Cloacal spurs consisting of a set of greatly enlarged, conical scales, with most acute point orientated posterodorsally, situated adjacent to cloaca (laterally); often asymmetric in number: 2–5 (L) and 1–4 (R), first (largest) roughly twice size of ventral scales, decreasing in size posteriorly. Distribution.— New Zealand: formerly throughout the South Island (Holocene); presently restricted to some islands in the outer Marlborough Sounds and Cook Strait (Fig. 1). Remarks.— Hoplodactylus tohu has been recognized as distinct from H. duvaucelii for several years (MorganRichards et al. 2016; Hitchmough et al. 2021a). However, it has been unclear what rank to apply to this taxon. New Zealand diplodactylids frequently have highly conserved morphologies, and often greater intra- than inter-specific morphological variation (Hitchmough et al. 2016b). With both Hoplodactylus species recognized here having undergone recent major range contractions resulting in significant declines in morphological and genetic diversity (Scarsbrook et al. 2021; Scarsbrook et al. 2022), it is difficult to weight subtle character differences as these may have arisen, or increased in prevalence, recently, through chance, in relictual populations, and therefore not reflect deeper evolutionary divergences. That these taxa have been reported to produce viable cross-bred offspring in captive populations (Morgan-Richards et al. 2016) fails to meet the criteria of the Biological Species Concept (Mayr 1942). Reproductive isolation in the wild cannot be tested given their allopatric distributions. However, several pairings of lizard species that are widely recognized to be distinct (Brennan et al. 2016; Leaché & Cole 2006; Olave et al. 2011), including some other New Zealand diplodactylids (e.g., Naultinus sp.; Hitchmough et al. 2016b), have been shown to similarly produce viable hybrid offspring. Intergeneric hybrids have even been reported (RH pers. obs). Genetic distance (i.e., ~2.2% and ~4.0% across the mitochondrial genome and ND2 respectively) and estimated timing of lineage divergence of ~4.51 mya (Scarsbrook et al. 2022) between the two Hoplodactylus species recognized here are comparable with those of other recognized diplodactylid species pairings (e.g., 3.8% ND2 divergence between Mokopirirakau kahutarae Whitaker, 1985, and Mokopirirakau granulatus Gray, 1845; Knox et al. 2021). Their discrete (allopatric) distributions reflect commonly observed biogeographic patterns in other taxa (Baker et al. 1995; Efford et al. 2002; Greaves et al. 2007; Liggins et al. 2008; Lloyd 2003), which further influences our treatment of species-level distinction. Reports of interbreeding between H. tohu and H. duvaucelii in captivity makes careful management of both species essential to maintain species/genetic integrity. Individuals sourced for reintroduction or translocation purposes need to be of the correct species, and sourced from moderately large and stable populations (e.g. North Brother Island; Wilson 2010) to minimise impact on the source population. Further, source populations should be proximate (where practicable) to the site of translocation to ensure preservation of regional adaptations; a consideration more applicable to H. duvaucelii as extant populations are more numerous and occupy more ecologically varied habitats. It seems probable, for example, that H. duvaucelii rather than H. tohu, would have naturally occurred at Mana Island, off the southern North Island. However, the latter was translocated there from North Brother Island in 1998 through the release of 40 individuals (Miskelly 2010), with a self-sustaining population reported 15-years later (Bell & Herbert 2017). H. tohu has been recognized as a distinct management unit by the Department of Conservation since 2021 (Hitchmough et al. 2021a), listed as “nationally increasing” with the ‘Conservation Dependant’ and ‘Range Restricted’ qualifiers. H. tohu has a severely restricted distribution comprising a few islands (Fig. 1; Supp. Table 1) with highly anthropogenically modified habitats. The estimated total population size of the largest extant population, on the Brothers Islands, is between 583–677 (Wilson 2010). Based on this, the suggested IUCN Red List status of H. tohu is ‘Critically Endangered A1 (a, b, c, e)’: population reduction of>90% observed, estimated, inferred, or suspected in the past where the causes of the reduction are clearly reversible AND understood AND have ceased. Occurrence of H. tohu on several managed predator-free islands that already have conservation management strategies in place does at least render moderate security to this species from localized disturbances such as fire or predator incursions. However, additional protection through translocations to fenced and more distant mainland sanctuaries (e.g. Orokonui Ecosanctuary near Dunedin, and the Mokomoko Dryland Sanctuary in Central Otago) could be beneficial, given the increased vulnerability of small and sparsely forested islands to the effects of climate change (e.g. sea-level rise, coastal erosion, storm intensity; Macinnis-Ng et al. 2021). Such translocation may also facilitate the re-establishment of ‘lost’ ecological interactions and morphological diversity (e.g. Scarsbrook et al. 2021) specific to mainland and densely forested ecosystems. There is evidence of genetic sub-structuring (Scarsbrook et al. 2022) within the distribution of H. tohu, although this has been greatly reduced with the extinction of mainland South Island populations. Careful management, and possible further research should consider if individual populations are experiencing inbreeding depression and might benefit from genetic rescue – establishment of ‘new’ populations through interbreeding of individuals from different populations to increase genetic ‘fitness’ (i.e., adaptability). Conversely, continued maintenance of discrete lineages may also be appropriate if those lineages reflect local habitat adaptations or if pooled populations would comprise too few individuals to maintain the resulting genetic diversity due to genetic drift. Etymology.— The specific epithet was proposed by Dr Sharon Barcello-Gemmel, Rangatira of Te &Amacr;tiawa o Te Waka-a-M&amacr;ui Trust, in recognition of the tupuna [ancestor] Tohu K&amacr;kahi. Tohu K&amacr;kahi was one of the two Parihaka prophets with whakapapa [genealogical] connections to Te &Amacr;tiawa – the iwi [tribe] with mana whenua [authority] over Ng&amacr;whatu Kai Ponu [The Brothers], where the largest extant population occurs. Name used as noun in apposition., Published as part of Scarsbrook, Lachie, Walton, Kerry, Rawlence, Nicolas J. & Hitchmough, Rodney A., 2023, Revision of the New Zealand gecko genus Hoplodactylus, with the description of a new species, pp. 267-291 in Zootaxa 5228 (3) on pages 274-279, DOI: 10.11646/zootaxa.5228.3.3, http://zenodo.org/record/7532705, {"references": ["Gray, J. E. (1843) Descriptions of the reptiles and amphibians hitherto observed in New Zealand. In: Dieffenbach, E. (Ed.), Travels in New Zealand with contributions to the geography, geology, botany, and natural history of that country. Vol. 2. Murray, London, pp. 202 - 206.", "McCann, C. (1955) The lizards of New Zealand. Dominion Museum Bulletin, 17, 1 - 127.", "McCann, C. 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(2013) Key innovations and island colonization as engines of evolutionary diversification: a comparative test with the Australasian diplodactyloid geckos. Journal of Evolutionary Biology, 26, 2662 - 2680. https: // doi. org / 10.1111 / jeb. 12261", "Hitchmough, R., Anderson, P., Barr, B., Monks, J., Lettink, M., Reardon, J., Tocher, M. & Whitaker, T. (2013) Conservation status of New Zealand reptiles. 2012. In: New Zealand Threat Classification. Series 2. Department of Conservation, Wellington, pp. 1 - 16.", "Bell, T. (2014) Standardized common names for New Zealand reptiles. BioGecko, Wellington, 11 pp.", "Romijn, R. L., Nelson, N. J. & Monks, J. M. (2014) Forest geckos (Mokopirirakau ' Southern North Island') display diurno-nocturnal activity and are not reliant on retreats. New Zealand Journal of Zoology, 41, 103 - 113. https: // doi. org / 10.1080 / 03014223.2013.860041", "Heath, A. C. H. & Whitaker, A. H. (2015) Mites (Acari: Pterygosomatidae, Macronyssidae) taken from lizards intercepted at the New Zealand border. Systematic and Applied Acarology, 20, 739 - 756. https: // doi. org / 10.11158 / saa. 20.7.3", "Mockett, S. (2015) The evolution and diversity of parasites of New Zealand lizards. MSc thesis, University of Otago, Dunedin, 141 pp.", "Chapple, D. G. (2016 b) The future of New Zealand lizard research. In: Chapple, D. G. (Ed.), New Zealand Lizards. Springer, Cham, pp. 361 - 375. https: // doi. org / 10.1007 / 978 - 3 - 319 - 41674 - 8 _ 14", "Hitchmough, R. A., Patterson, G. B. & Chapple, D. G. (2016 b) Putting a name to diversity: Taxonomy of the New Zealand lizard fauna. In: Chapple, D. G. (Ed.), New Zealand Lizards. Springer, Cham, pp. 87 - 108. https: // doi. org / 10.1007 / 978 - 3 - 319 - 41674 - 8 _ 4", "Cree, A. & Hare, K. M. (2016) Reproduction and life history of New Zealand lizards. In: Chapple, D. G. (Ed.), New Zealand Lizards. 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Background: Incomplete response on FDG PET-CT following (chemo)radiotherapy (CRT) for head and neck squamous cell carcinoma (HNSCC) hinders optimal management. The study assessed the utility of an interval (second look) PET-CT. Methods: Patients with oropharyngeal squamous cell carcinoma cancer (OPSCC) treated with CRT at a single centre between 2013 and 2020 who underwent baseline, response, and second-look PET-CT were included. Endpoints were conversion rate to complete metabolic response (CMR) and test characteristics of second-look PET-CT. Results: In total, 714 patients with OPSCC underwent PET-CT post-radiotherapy. In total, 88 patients with incomplete response underwent second-look PET-CT a median of 13 weeks (interquartile range 10–15 weeks) after the initial response assessment. In total, 27/88 (31%) second-look PET-CTs showed conversion to CMR, primary tumour CMR in 20/60 (30%), and nodal CMR in 13/37 (35%). In total, 1/34 (3%) with stable tumour/nodal uptake at the second-look PET-CT relapsed. Sensitivity, specificity, positive (PPV), and negative predictive value (NPV) of second-look PET-CT were 95%, 49%, 50%, and 95% for tumour and 92%, 50%, 50%, and 92% for nodes, respectively. Primary tumour progression following CMR occurred in one patient, two patients with residual nodal uptake at second-look PET-CT progressed locoregionally, and one patient developed metastatic disease following CMR in residual nodes. Conclusion: Most patients undergoing second-look PET-CT converted to CMR or demonstrated stable PET signal. NPV was high, suggesting the potential to avoid unnecessary surgical intervention.

Purpose - To characterise and assess the quality of published research evaluating artificial intelligence (AI) methods for ovarian cancer diagnosis or prognosis using histopathology data. Methods - A search of PubMed, Scopus, Web of Science, CENTRAL, and WHO-ICTRP was conducted up to 19/05/2023. The inclusion criteria required that research evaluated AI on histopathology images for diagnostic or prognostic inferences in ovarian cancer. The risk of bias was assessed using PROBAST. Information about each model of interest was tabulated and summary statistics were reported. PRISMA 2020 reporting guidelines were followed. Results - 1573 records were identified, of which 45 were eligible for inclusion. There were 80 models of interest, including 37 diagnostic models, 22 prognostic models, and 21 models with other diagnostically relevant outcomes. Models were developed using 1-1375 slides from 1-776 ovarian cancer patients. Model outcomes included treatment response (11/80), malignancy status (10/80), stain quantity (9/80), and histological subtype (7/80). All models were found to be at high or unclear risk of bias overall, with most research having a high risk of bias in the analysis and a lack of clarity regarding participants and predictors in the study. Research frequently suffered from insufficient reporting and limited validation using small sample sizes. Conclusion - Limited research has been conducted on the application of AI to histopathology images for diagnostic or prognostic purposes in ovarian cancer, and none of the associated models have been demonstrated to be ready for real-world implementation. Key aspects to help ensure clinical translation include more transparent and comprehensive reporting of data provenance and modelling approaches, as well as improved quantitative performance evaluation using cross-validation and external validations.

TypeScript is a quickly evolving superset of JavaScript with active development of new features. Our paper seeks to understand how quickly these features are adopted by the developer community. Existing work in JavaScript shows the adoption of dynamic language features can be a major hindrance to static analysis. As TypeScript evolves the addition of features makes the underlying standard more and more difficult to keep up with. In our work we present an analysis of 454 open source TypeScript repositories and study the adoption of 13 language features over the past three years. We show that while new versions of the TypeScript compiler are aggressively adopted by the community, the same cannot be said for language features. While some experience strong growth others are rarely adopted by projects. Our work serves as a starting point for future study of the adoption of features in TypeScript. We also release our analysis and data gathering software as open source in the hope it helps the programming languages community.

New Zealand (NZ) has a diversity of large river ecosystems that provide essential ecosystem services but are impaired by multiple ecological impacts. River restoration is an active field worldwide and there is good potential for river restoration practitioners in NZ to draw on lessons from elsewhere, although there is also a need to tailor approaches to national and local contexts. Here, we provide a critical review of large floodplain river restoration to guide environmental management in NZ and inform research and management priorities. The review is structured using a driver-pressure-state-impact-response framework, with a focus on responses, i.e. large river restoration methods. Thirty-one river restoration methods aligned with 14 broad restoration goals were evaluated collaboratively and semi-quantitatively. Evaluation outcomes are presented to inform regional and national scale restoration planning. Recommendations were identified to address eight key knowledge or policy gaps: (1) understanding cumulative impacts facing large river systems, (2) prioritising restoration measures at the landscape-scale, (3) promoting lateral connectivity in large river floodplains, (4) incorporating knowledge of geomorphology into river management, (5) enhancing understanding of cultural priorities and community aspirations, (6) assessing how costs and benefits of river restoration vary among timescales, (7) understanding the feasibility of restoration methods that have received limited application in NZ and (8) improving protection of threatened native fish species.

The aim of this thesis is to evaluate the effect of collaborative work on primary-age children’s reasoning about shape, space and measure. Children’s early development in these areas of mathematics has been well researched but the difficulties older children experience are less well charted. Method: An intervention study was carried out with two Year 5 classes in a South London primary school using a naturalistic experimental design with two parallel classes as the intervention and control groups. The intervention class undertook two iterations of group work while the control class worked individually across the two sessions. An innovative pre- to post-test measure was developed using the Rasch Analysis partial credit model. This consisted of two sets of six similar and overlapping think-aloud tasks. The design of the group work was informed by both sociocultural and socio-cognitive conflict theory: ground rules for talk were used in the intervention class and the children were grouped in triads with differing ideas (elicited from their pre-test responses). Novel features were included to increase the likelihood of all children encountering challenge to their initial ideas: a) the children were prompted to reflect on the certainty of their joint or individual answers at the end of the first session; b) the children all had the chance to consult written clues in the second session, at the cost of a point per clue. Analysis: Quantitative comparison of the children’s progress from pre- to post-test was complemented with qualitative analysis of the children’s use of language across the study. Transcripts of the children talking about the shape, space and measurement tasks were coded for imaginative expressions to explore whether imaginative forms were associated with more sophisticated reasoning about shape, space and measure. The children’s group talk was coded for exploratory features of language to evaluate the impact on the children’s reasoning of the prompt to reflect on the certainty of their joint responses. Findings: The children working in groups made significantly more progress than the children working alone from pre- to post-test, as hypothesised, and they were more effective in their decisions about whether to seek help in the form of written clues than children working alone. Following the prompt to reflect on their group answers, there were changes in the observed language of the intervention groups. While the overall use of exploratory features: “because”, “I think”, “I agree/disagree” and modal verbs remained similar from session one to session two, there was a significant increase in the use of modal verbs following the prompt (p < .05). Swift surface-level agreements were probed further after a group consensus had been reached. Using a grounded approach, the children’s imaginative expressions across the study were coded and three categories identified: movement, manipulation or decomposition. Children working with peers made more progress and increased their use of imaginative expressions from pre- to post-test by comparison with the children working alone. Temporal analysis of the children’s talk across the study revealed common examples of imaginative work that supported the development of more sophisticated reasoning. For example, imagining “splitting” and “halving” objects served as a heuristic bridge towards inferring length and finding the difference. Similarly, by imagining “turning” and “squashing” familiar shapes, children began to create axioms about the properties of shape beyond iconic examples and orientations. The partial credit model used to measure children’s progress in this study increases our knowledge about the incremental steps that children make in their understanding about geometry and measurement in the upper primary years. By revealing the imaginative language tools the children used to probe their existing reasoning models, this study highlights the importance of children articulating their imaginative work in maths with peers.

Background: Data on the accuracy of response assessment 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography-computed tomography (PET-CT) following (chemo)radiotherapy in patients with oropharynx squamous cell carcinoma (OPSCC) is predominantly based on HPV-positive disease. There is a paucity of data for HPV-negative disease, which has a less favourable prognosis. Methods: 96 patients treated with (chemo)radiotherapy for HPV-negative OPSCC with baseline and response assessment FDG PET-CT between 2013–2020, were analysed. PET-CT response was classified as negative, equivocal, or positive based on qualitative reporting. PET-CT response categories were analysed with reference to clinicopathological outcomes. Test characteristics were evaluated, comparing negative results to equivocal and positive results together. Post-test probabilities were calculated separately for positive and equivocal or negative results. Results: Median follow-up was 26 months. The negative predictive value of a negative scan was 93.7 and 93.2%, respectively, for primary tumour and nodal disease. For a negative scan, the post-test probability was 0.06 for primary and 0.07 for nodal disease. The post-test probability of an equivocal scan was 0.51 and 0.72 for primary and lymph node, respectively. The post-test probability of a positive scan approached 1. For patients with/without a negative scan, two-year overall survival and progression-free survival were 83% versus 30% and 79% versus 17% (p < 0.001), respectively. Conclusion: The NPV of a negative response assessment PET-CT in HPV-negative OPSCC is high, supporting a strategy of clinical monitoring. Contrasting with the published literature for HPV-positive OPSCC, an equivocal response scan was associated with a moderate rate of residual disease.

The atomCAT2 project will analyse retrospective data from anal cancer patients treated with (chemo)radiotherapy across institutions in the UK and internationally. The study aims to develop and validate outcome prediction models using baseline patient characteristics and simple treatment-related factors. It will use distributing learning methodology, which facilitates multi-centre data analysis without individual patient data leaving the local data repository. This will allow us to examine which factors predict for effect of radiotherapy on the primary cancer, and which factors predict for metastatic spread. Ultimately, this could aid in the design of better trials for anal cancer as well as improve treatment for future patients.

Objectives Relapse occurs in ~20% of patients with classical Hodgkin lymphoma (cHL) despite treatment adaption based on 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography response. The objective was to evaluate pre-treatment FDG PET/CT–derived machine learning (ML) models for predicting outcome in patients with cHL. Methods All cHL patients undergoing pre-treatment PET/CT at our institution between 2008 and 2018 were retrospectively identified. A 1.5 × mean liver standardised uptake value (SUV) and a fixed 4.0 SUV threshold were used to segment PET/CT data. Feature extraction was performed using PyRadiomics with ComBat harmonisation. Training (80%) and test (20%) cohorts stratified around 2-year event-free survival (EFS), age, sex, ethnicity and disease stage were defined. Seven ML models were trained and hyperparameters tuned using stratified 5-fold cross-validation. Area under the curve (AUC) from receiver operator characteristic analysis was used to assess performance. Results A total of 289 patients (153 males), median age 36 (range 16–88 years), were included. There was no significant difference between training (n = 231) and test cohorts (n = 58) (p value > 0.05). A ridge regression model using a 1.5 × mean liver SUV segmentation had the highest performance, with mean training, validation and test AUCs of 0.82 ± 0.002, 0.79 ± 0.01 and 0.81 ± 0.12. However, there was no significant difference between a logistic model derived from metabolic tumour volume and clinical features or the highest performing radiomic model. Conclusions Outcome prediction using pre-treatment FDG PET/CT–derived ML models is feasible in cHL patients. Further work is needed to determine optimum predictive thresholds for clinical use. Key points • A fixed threshold segmentation method led to more robust radiomic features. • A radiomic-based model for predicting 2-year event-free survival in classical Hodgkin lymphoma patients is feasible. • A predictive model based on ridge regression was the best performing model on our dataset.

Background A systematic literature review of the performance of 18Fluorine-fluciclovine PET/CT for imaging of men with recurrent prostate cancer was performed. Methods Scientific literature databases (MEDLINE, ScienceDirect and Cochrane Libraries) were searched systematically during Oct 2020 using PRISMA criteria. No limit was put on the date of publication. Prospective studies reporting a patient-level 18F-fluciclovine detection rate (DR) from ≥25 patients with recurrent prostate cancer were sought. Proceedings of relevant meetings held from 2018 through Oct 2020 were searched for abstracts meeting criteria. Results Searches identified 321 unique articles. In total, nine articles (six papers and three conference abstracts), comprising a total of 850 patients met inclusion criteria. Most studies (n = 6) relied on ASTRO-Phoenix Criteria, EAU-ESTRO-SIOG, and/or ASTRO-AUA guidelines to identify patients with biochemical recurrence. Patients’ PSA levels ranged from 0.02–301.7 ng/mL (median level per study, 0.34–4.10 ng/mL [n = 8]). Approximately 64% of patients had undergone prostatectomy, but three studies focused solely on post-prostatectomy patients. Adherence to imaging protocol guidelines was heterogeneous, with variance seen in administered activity, uptake and scan times. Overall patient-level DR varied between studies from 26% to 83%, with 78% of studies reporting a DR > 50%. DR was proportional to PSA, but even at PSA n = 7) ranged from 18% to 78% and extra-prostatic rates (n = 6) from 8% to 72%. Pelvic node and bone lesion DR ranged from 8% to 47% and 0% to 26%, respectively (n = 5). 18F-Fluciclovine PET/CT was shown to impact patient management and outcomes. Two studies reported 59–63% of patients to have a management change post-scan. A further study showed significant increase in failure-free survival following 18F-fluciclovine-guided compared with conventional imaging-guided radiotherapy planning. Conclusions 18F-Fluciclovine PET/CT shows good performance in patients with recurrent prostate cancer leading to measurable clinical benefits. Careful adherence to recommended imaging protocols may help optimize DR.

Background Radiological and pathological studies in severe COVID‐19 pneumonia (SARS‐CoV‐2) have demonstrated extensive pulmonary immunovascular thrombosis and infarction. This study investigated whether these focal changes may present with chest pain mimicking pulmonary emoblism (PE) in ambulant patients. Methods CTPAs from outpatients presenting with chest pain to Leeds Teaching Hospital NHS Trust 1st March to 31 May 2020 (n = 146) and 2019 (n = 85) were compared. Regions of focal ground glass opacity (GGO), consolidation and/or atelectasis (parenchymal changes) were determined, and all scans were scored using British Society for Thoracic Imaging (BSTI) criteria for COVID‐19, and the 2020 cohort was offered SARS‐CoV‐2 antibody testing. Results Baseline demographic and clinical data were similar between groups with absence of fever, normal lymphocytes and marginally elevated CRP and D‐Dimer values. Evidence of COVID‐19 or parenchymal changes was observed in 32.9% (48/146) of cases in 2020 compared to 16.5% (14/85) in 2019 (P = 0.007). 11/146 (7.5%) patients met BSTI criteria for COVID‐19 in 2020 compared with 0/14 in 2019 (P = 0.008). 3/39 patients tested had detectable COVID‐19 antibodies (2 with parenchymal changes and 1 with normal parenchyma) however 0/6 patients whose CTPA met BSTI criteria “likely/suspicious for COVID‐19” and attended antibody testing were SARS‐CoV‐2 antibody positive. Conclusions 32.8% ambulatory patients with suspected PE in 2020 had parenchymal changes with 7.5% diagnosed as COVID‐19 infection by imaging criteria, despite the absence of other COVID‐19 symptoms. These findings suggest that localized COVID‐19 pneumonitis with immunothrombosis occurs distal to the bronchiolar arteriolar circulation, causing pleural irritation and chest pain without viraemia, accounting for the lack of fever and systemic symptoms.

Since December 2019, coronavirus SARS-CoV-2 (COVID-19) has rapidly developed into a global epidemic, with millions of patients affected worldwide. As part of the diagnostic pathway, computed tomography (CT) scans are used to help patient management. However, parenchymal imaging findings in COVID-19 are non-specific and can be seen in other diseases. In this work, we propose to first segment lesions from CT images, and further, classify COVID-19 patients from healthy persons and common pneumonia patients. In detail, a novel Dynamic Fusion Segmentation Network (DFSN) that automatically segments infection-related pixels is first proposed. Within this network, low-level features are aggregated to high-level ones to effectively capture context characteristics of infection regions, and high-level features are dynamically fused to model multi-scale semantic information of lesions. Based on DFSN, Dynamic Transfer-learning Classification Network (DTCN) is proposed to distinguish COVID-19 patients. Within DTCN, a pre-trained DFSN is transferred and used as the backbone to extract pixel-level information. Then the pixel-level information is dynamically selected and used to make a diagnosis. In this way, the pre-trained DFSN is utilized through transfer learning, and clinical significance of segmentation results is comprehensively considered. Thus DTCN becomes more sensitive to typical signs of COVID-19. Extensive experiments are conducted to demonstrate effectiveness of the proposed DFSN and DTCN frameworks. The corresponding results indicate that these two models achieve state-of-the-art performance in terms of segmentation and classification.

Anti-1-amino-3

Purpose There is increasing use of radical prostatectomy to treat patients with high-risk prostate cancer. This has contributed toward a pathologic stage migration, and a greater number of patients are subsequently being diagnosed with biochemical failure. There is increasing use of advanced imaging techniques in the setting of biochemical failure, including positron emission tomography-computed tomography (PET-CT). Methods and Materials This critical literature review highlights the evidence for PET-CT in postprostatectomy biochemical failure and identifies sites of pelvic lymph node relapse in the setting of biochemical failure and the potential implications that the locations of these relapses may have for salvage therapies. Potential future directions are then considered. Results The optimal PET-CT tracer remains uncertain but there is increasing use of prostate-specific membrane antigen PET-CT for investigating sites of nodal metastasis at low prostate-specific antigen levels, and this is leading to a blurring of the biochemical and radiologic recurrence phases. The optimal therapeutic approach remains undefined, with current trials investigating postoperative radiation therapy to the whole pelvis in addition to the prostatic fossa, the use of PET-CT in the setting of biochemical recurrence to guide delivery of salvage radiation therapy, and, for patients with node-only relapsed prostate cancer, the addition of whole pelvis radiation therapy to metastasis-directed therapies such as stereotactic ablative radiotherapy. Conclusions The most appropriate target volume for salvage radiation therapy remains uncertain, and the findings of studies using PET-CT to map nodal recurrences suggest that there could be a role for extending whole pelvis radiation therapy volumes to increase coverage of superior nodal regions. The emerging fields of radiomics and radiogenomics could provide important prognostic information and aid decision making for patients with relapsed prostate cancer.

Purpose\ud\udEarly and accurate localization of lesions in patients with biochemical recurrence (BCR) of prostate cancer may guide salvage therapy decisions. The present study, 18F-Fluciclovine PET/CT in biochemicAL reCurrence Of Prostate caNcer (FALCON; NCT02578940), aimed to evaluate the effect of 18F-fluciclovine on management of men with BCR of prostate cancer.\udMethods and Materials\ud\udMen with a first episode of BCR after curative-intent primary therapy were enrolled at 6 UK sites. Patients underwent 18F-fluciclovine positron emission tomography/computed tomography (PET/CT) according to standardized procedures. Clinicians documented management plans before and after scanning, recording changes to treatment modality as major and changes within a modality as other. The primary outcome measure was record of a revised management plan postscan. Secondary endpoints were evaluation of optimal prostate specific antigen (PSA) threshold for detection, salvage treatment outcome assessment based on 18F-fluciclovine-involvement, and safety.\udResults\ud\ud18F-Fluciclovine was well tolerated in the 104 scanned patients (median PSA = 0.79 ng/mL). Lesions were detected in 58 out of 104 (56%) patients. Detection was broadly proportional to PSA level; ≤1 ng/mL, 1 out of 3 of scans were positive, and 93% scans were positive at PSA >2.0 ng/mL. Sixty-six (64%) patients had a postscan management change (80% after a positive result). Major changes (43 out of 66; 65%) were salvage or systemic therapy to watchful waiting (16 out of 66; 24%); salvage therapy to systemic therapy (16 out of 66; 24%); and alternative changes to treatment modality (11 out of 66, 17%). The remaining 23 out of 66 (35%) management changes were modifications of the prescan plan: most (22 out of 66; 33%) were adjustments to planned brachytherapy/radiation therapy to include a 18F-fluciclovine-guided boost. Where 18F-fluciclovine guided salvage therapy, the PSA response rate was higher than when 18F-fluciclovine was not involved (15 out of 17 [88%] vs 28 out of 39 [72%]).\udConclusions\ud\ud18F-Fluciclovine PET/CT located recurrence in the majority of men with BCR, frequently resulting in major management plan changes. Incorporating 18F-fluciclovine PET/CT into treatment planning may optimize targeting of recurrence sites and avoid futile salvage therapy.

Objectives Radiomics is a promising avenue in non-invasive characterisation of diffuse glioma. Clinical translation is hampered by lack of reproducibility across centres and difficulty in standardising image intensity in MRI datasets. The study aim was to perform a systematic review of different methods of MRI intensity standardisation prior to radiomic feature extraction. Methods MEDLINE, EMBASE, and SCOPUS were searched for articles meeting the following eligibility criteria: MRI radiomic studies where one method of intensity normalisation was compared with another or no normalisation, and original research concerning patients diagnosed with diffuse gliomas. Using PRISMA criteria, data were extracted from short-listed studies including number of patients, MRI sequences, validation status, radiomics software, method of segmentation, and intensity standardisation. QUADAS-2 was used for quality appraisal. Results After duplicate removal, 741 results were returned from database and reference searches and, from these, 12 papers were eligible. Due to a lack of common pre-processing and different analyses, a narrative synthesis was sought. Three different intensity standardisation techniques have been studied: histogram matching (5/12), limiting or rescaling signal intensity (8/12), and deep learning (1/12)—only two papers compared different methods. From these studies, histogram matching produced the more reliable features compared to other methods of altering MRI signal intensity. Conclusion Multiple methods of intensity standardisation have been described in the literature without clear consensus. Further research that directly compares different methods of intensity standardisation on glioma MRI datasets is required. Key Points • Intensity standardisation is a key pre-processing step in the development of robust radiomic signatures to evaluate diffuse glioma. • A minority of studies compared the impact of two or more methods. • Further research is required to directly compare multiple methods of MRI intensity standardisation on glioma datasets.

Background The aim of this study was to explore the feasibility of assisted diagnosis of active (peri-)aortitis using radiomic imaging biomarkers derived from [18F]-Fluorodeoxyglucose Positron Emission Tomography–Computed Tomography (FDG PET–CT) images. Methods The aorta was manually segmented on FDG PET–CT in 50 patients with aortitis and 25 controls. Radiomic features (RF) (n = 107), including SUV (Standardized Uptake Value) metrics, were extracted from the segmented data and harmonized using the ComBat technique. Individual RFs and groups of RFs (i.e., signatures) were used as input in Machine Learning classifiers. The diagnostic utility of these classifiers was evaluated with area under the receiver operating characteristic curve (AUC) and accuracy using the clinical diagnosis as the ground truth. Results Several RFs had high accuracy, 84% to 86%, and AUC scores 0.83 to 0.97 when used individually. Radiomic signatures performed similarly, AUC 0.80 to 1.00. Conclusion A methodological framework for a radiomic-based approach to support diagnosis of aortitis was outlined. Selected RFs, individually or in combination, showed similar performance to the current standard of qualitative assessment in terms of AUC for identifying active aortitis. This framework could support development of a clinical decision-making tool for a more objective and standardized assessment of aortitis.

Methodological and technological improvements are continually revolutionizing the field of ancient DNA. Most ancient DNA extraction methods require the partial (or complete) destruction of finite museum specimens, which disproportionately impacts small or fragmentary subfossil remains, and future analyses. We present a minimally destructive ancient DNA extraction method optimized for small vertebrate remains. We applied this method to detect lost mainland genetic diversity in the large New Zealand diplodactylid gecko genus Hoplodactylus, which is presently restricted to predator-free island and mainland sanctuaries. We present the first mitochondrial genomes for New Zealand diplodactylid geckos, recovered from 19 modern, six historical/archival (1898-2011) and 16 Holocene Hoplodactylus duvaucelii sensu latu specimens, and one modern Woodworthia sp. specimen. No obvious damage was observed in post-extraction micro-computed tomography reconstructions. All "large gecko" specimens examined from extinct populations were found to be conspecific with extant Hoplodactylus species, suggesting their large relative size evolved only once in the New Zealand diplodactylid radiation. Phylogenetic analyses of Hoplodactylus samples recovered two genetically (and morphologically) distinct North and South Island clades, probably corresponding to distinct species. Finer phylogeographical structuring within Hoplodactylus spp. highlighted the impacts of Late Cenozoic biogeographical barriers, including the opening and closure of Pliocene marine straits, fluctuations in the size and suitability of glacial refugia, and eustatic sea-level change. Recent mainland extinction obscured these signals from the modern tissue-derived data. These results highlight the utility of minimally destructive DNA extraction in genomic analyses of less well studied small vertebrate taxa, and the conservation of natural history collections.

Objectives Imaging options to localize biochemical recurrence (BCR) of prostate cancer after radical prostatectomy (RP) are limited, especially at low prostate-specific antigen (PSA) levels. The FALCON study evaluated the impact of 18F-fluciclovine PET/CT on management plans for patients with BCR. Here, we evaluate salvage radiotherapy decisions in patients post-RP. Methods We conducted a subgroup analysis of post-RP patients enrolled in FALCON who had a prescan plan for salvage radiotherapy (± androgen-deprivation therapy). Patients’ treatment plans post-18F-fluciclovine PET/CT were compared with their prescan plans. Fisher exact test was used to determine the impact of PSA and Gleason sum on positivity and anatomical patterns of uptake. Results Sixty-five (63%) FALCON patients had undergone RP. Of these, 62 (median PSA, 0.32 ng/mL) had a prescan plan for salvage radiotherapy. Twenty-one (34%) had 18F-fluciclovine-avid lesions. Disease was confined to the prostate bed in 11 patients (52%) and to the pelvis in a further 5 (24%), while 5 (24%) had extrapelvic findings. Trends towards more disseminated disease with increasing PSA or Gleason sum were observed but did not reach statistical significance. Postscan, 25 (40%) patients had a management change; 17 (68%) were changed to the treatment modality (8 to systemic therapy, 8 to active surveillance, 1 other) and 8 (32%) were radiotherapy field modifications. Conclusions Incorporating 18F-fluciclovine PET/CT into treatment planning may help identify patients suitable for salvage radiotherapy, help augment planned radiotherapy to better target lesions and support the clinician to optimise patient management.

Objectives Imaging options to localize biochemical recurrence (BCR) of prostate cancer after radical prostatectomy (RP) are limited, especially at low prostate-specific antigen (PSA) levels. The FALCON study evaluated the impact of 18F-fluciclovine PET/CT on management plans for patients with BCR. Here, we evaluate salvage radiotherapy decisions in patients post-RP. Methods We conducted a subgroup analysis of post-RP patients enrolled in FALCON who had a prescan plan for salvage radiotherapy (± androgen-deprivation therapy). Patients’ treatment plans post-18F-fluciclovine PET/CT were compared with their prescan plans. Fisher exact test was used to determine the impact of PSA and Gleason sum on positivity and anatomical patterns of uptake. Results Sixty-five (63%) FALCON patients had undergone RP. Of these, 62 (median PSA, 0.32 ng/mL) had a prescan plan for salvage radiotherapy. Twenty-one (34%) had 18F-fluciclovine-avid lesions. Disease was confined to the prostate bed in 11 patients (52%) and to the pelvis in a further 5 (24%), while 5 (24%) had extrapelvic findings. Trends towards more disseminated disease with increasing PSA or Gleason sum were observed but did not reach statistical significance. Postscan, 25 (40%) patients had a management change; 17 (68%) were changed to the treatment modality (8 to systemic therapy, 8 to active surveillance, 1 other) and 8 (32%) were radiotherapy field modifications. Conclusions Incorporating 18F-fluciclovine PET/CT into treatment planning may help identify patients suitable for salvage radiotherapy, help augment planned radiotherapy to better target lesions and support the clinician to optimise patient management.