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Background Pre-resection biopsy (PRB) of large nonpedunculated colorectal polyps (LNPCPs, ≥ 20 mm) is often performed before referral for endoscopic mucosal resection (EMR). How this affects the EMR procedure is unknown. Methods This was a retrospective analysis of a prospectively collected cohort of patients with LNPCPs referred for EMR between 2013 to 2016 at an Australian tertiary center. Outcomes were differences between PRB and EMR histology, and effects of PRB on the EMR procedure. Results Among 586 LNPCPs, lesions that underwent PRB were larger (median 35 vs. 30 mm; P Conclusions Routine PRB of LNPCP did not reliably detect advanced histology and may have affected EMR complexity. PRB should be utilized with caution in guiding endoscopic management of LNPCPs.

Summary tiny-count is a highly flexible counting tool that allows for hierarchical classification and quantification of small RNA reads from high-throughput sequencing data. Selection rules can be used to filter reads by 5’ nucleotide, length, position of alignments in relation to reference features, and by the number of mismatches to reference sequences. tiny-count can quantify reads aligned to a genome or directly to small RNA or transcript sequences. With tiny-count, users can quantify a single class of small RNAs or multiple classes in parallel. tiny-count can resolve distinct classes of small RNAs, for example piRNAs and siRNAs, produced from the same locus. It can distinguish small RNAs variants, such as miRNAs and isomiRs, with single-nucleotide precision. tRNA, rRNA, and other RNA fragments can also be quantified. tiny-count can be run alone or as part of tinyRNA, a workflow that provides a basic all-in-one command line-based solution for small RNA-seq data analysis, with documentation and statistics generated at each step for accurate and reproducible results. Availability tiny-count and other tinyRNA tools are implemented in Python, C ++, Cython, and R, and the workflow is coordinated with CWL. tiny-count and tinyRNA are free and open-source software distributed under the GPLv3 license. tiny-count can be installed via Bioconda (https://anaconda.org/bioconda/tiny-count) and both tiny-count and tinyRNA documentation and software downloads are available at https://github.com/MontgomeryLab/tinyRNA. Supplementary information Reference data, including genome sequences and features tables, for certain species can be found at https://www.MontgomeryLab.org.

Introduction The frequency and severity of abdominal pain after endoscopic mucosal resection (EMR) of colonic laterally spreading lesions (LSLs) of ≥ 20 mm is unknown, as are the risk factors to predict its occurrence. We aimed to prospectively characterize pain after colonic EMR , determine the rapidity and frequency of its resolution after analgesia, and estimate the frequency of needing further intervention. Methods Procedural and lesion data on consecutive patients with LSLs who underwent EMR at a single tertiary referral center were prospectively collected. If pain after colonic EMR, graded using a visual analogue scale (VAS), lasted > 5 minutes, 1 g of paracetamol was administered. Pain lasting > 30 minutes lead to clinical review and upgrade to opiate analgesics. Investigations and interventions for pain were recorded. Results 67/336 patients (19.9 %, 95 %CI 16.0 %–24.5 %) experienced pain after colonic EMR (median VAS 5, interquartile range 3–7). Multivariable predictors of pain were: lesion size ≥ 40 mm, odds ratio [OR] 2.15 (95 %CI 1.22–3.80); female sex, OR 1.99 (95 %CI 1.14–3.48); and intraprocedural bleeding requiring endoscopic control, OR 1.77 (95 %CI 0.99–3.16). Of 67 patients with pain, 51 (76.1 %, 95 %CI 64.7 %–84.7 %) had resolution of their “mild pain” after paracetamol and were discharged without sequelae. The remaining 16 (23.9 %) required opiate analgesia (fentanyl), after which 11/16 patients (68.8 %; “moderate pain”) could be discharged. The 5/67 patients (7.5 %) with “severe pain” had no resolution despite fentanyl; all settled during hospital admission (median duration 2 days), intravenous analgesia, and antibiotics. Conclusion Pain after colonic EMR occurs in approximately 20 % of patients and resolves rapidly and completely in the majority with administration of intravenous paracetamol. Pain despite opiates heralds a more serious scenario and further investigation should be considered.

A modular approach to underexplored, unsymmetrical [1]benzothieno[3,2-b][1]benzothiophene (BTBT) scaffolds delivers a library of BTBT materials from readily available coupling partners by combining a transition-metal free Pummerer CH–CH-type cross-coupling and a Newman–Kwart reaction. This effective approach to unsymmetrical BTBT materials has allowed their properties to be studied. In particular, tuning the functional groups on the BTBT scaffold allows the solid-state assembly and molecular orbital energy levels to be modulated. Investigation of the charge transport properties of BTBT-containing small-molecule:polymer blends revealed the importance of molecular ordering during phase segregation and matching the highest occupied molecular orbital energy level with that of the semiconducting polymer binder, polyindacenodithiophene-benzothiadiazole (PIDTBT). The hole mobilities extracted from transistors fabricated using blends of PIDTBT with phenyl or methoxy functionalized unsymmetrical BTBTs were double those measured for devices fabricated using pristine PIDTBT. This study underscores the value of the synthetic methodology in providing a platform from which to study structure–property relationships in an underrepresented family of unsymmetrical BTBT molecular semiconductors., A modular approach to underexplored, unsymmetrical [1]benzothieno[3,2-b][1]benzothiophene (BTBT) scaffolds, combining a transition-metal free Pummerer CH–CH-type cross-coupling and a Newman–Kwart reaction, delivers a library of BTBT materials.

Isotropic phase de-wetting of discotic liquid crystals on a surface patterned with alternating ~5-10 μm wide wetting and de-wetting stripes results in the formation of long narrow droplets. On slow...

Background and Aims Laterally spreading lesions (LSLs) in the duodenum are conventionally treated by EMR. Recurrence is commonly encountered and can be difficult to treat safely due to the unique anatomic characteristics of the duodenum. Auxiliary techniques designed to prevent recurrence have not been described. Methods We sought to evaluate the effectiveness of thermal ablation of the defect margin after EMR (EMR-T) in reducing recurrence at first surveillance endoscopy (SE1, scheduled at 6 months) in a single tertiary referral center. All duodenal LSLs ≥10 mm referred for EMR were eligible. After successful EMR, thermal ablation was performed using snare-tip soft coagulation around the entire circumference of the resection defect. The primary outcome was the frequency of recurrence at SE1. A previous, well-characterized, prospective cohort of duodenal LSLs ≥10 mm treated by conventional EMR was the comparator. Results Over 43 months up to October 2019, 54 LSLs underwent EMR-T. One hundred twenty-five LSLs underwent conventional EMR in the comparator group. Patient and lesion characteristics were similar between the groups. Recurrence was significantly lower in the EMR-T group compared with the conventional EMR group (1 of 49 [2.3%] vs 19 of 108 [17.6%]; P = .01). No difference in technical success, EMR-related adverse outcomes, or referral to surgery were identified between the groups. Conclusions EMR-T significantly reduces the frequency of recurrence for duodenal LSLs. This technique is safe in the duodenum and has the potential to significantly improve the effectiveness of duodenal EMR. (Clinical trial registration number: NCT02306603.)

Background Gold nanocages have been widely used as multifunctional platforms for drug and gene delivery, as well as photothermal agents for cancer therapy. However, their potential as gene delivery systems for cancer treatment has been reported in combination with chemotherapeutics and photothermal therapy, but not in isolation so far. The purpose of this work was to investigate whether the conjugation of gold nanocages with the cancer targeting ligand lactoferrin, polyethylene glycol and polyethylenimine could lead to enhanced transfection efficiency on prostate cancer cells in vitro, without assistance of external stimulation. Methods Novel lactoferrin-bearing gold nanocages conjugated to polyethylenimine and polyethylene glycol have been synthesized and characterized. Their transfection efficacy and cytotoxicity were assessed on PC-3 prostate cancer cell line following complexation with a plasmid DNA. Results Lactoferrin-bearing gold nanocages, alone or conjugated with polyethylenimine and polyethylene glycol, were able to condense DNA at conjugate:DNA weight ratios 5:1 and higher. Among all gold conjugates, the highest gene expression was obtained following treatment with gold complex conjugated with polyethylenimine and lactoferrin, at weight ratio 40:1, which was 1.71-fold higher than with polyethylenimine. This might be due to the increased DNA cellular uptake observed with this conjugate, by up to 8.65-fold in comparison with naked DNA. Conclusion Lactoferrin-bearing gold nanocages conjugates are highly promising gene delivery systems to prostate cancer cells., Graphical Abstract

Elevated levels of circulating cobalt ions have been linked with a wide range of systemic complications including neurological, endocrine, and cardiovascular symptoms. Case reports of patients with elevated blood cobalt ions have described significant cardiovascular complications including cardiomyopathy. However, correlation between the actual level of circulating cobalt and extent of cardiovascular injury has not previously been performed. This review examines evidence from the literature for a link between elevated blood cobalt levels secondary to metal-on-metal (MoM) hip arthroplasties and cardiomyopathy. Correlation between low, moderate, and high blood cobalt with cardiovascular complications has been considered. Elevated blood cobalt at levels over 250 µg/l have been shown to be a risk factor for developing systemic complications and published case reports document cardiomyopathy, cardiac transplantation, and death in patients with severely elevated blood cobalt ions. However, it is not clear that there is a hard cut-off value and cardiac dysfunction may occur at lower levels. Clinical and laboratory research has found conflicting evidence of cobalt-induced cardiomyopathy in patients with MoM hips. Further work needs to be done to clarify the link between severely elevated blood cobalt ions and cardiomyopathy. Cite this article: Bone Joint Res 2021;10(6):340–347.

Background and Purpose: The DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) randomized clinical trial demonstrated the efficacy of endovascular therapy in treating ischemic stroke 6 to 16 hours after onset, resulting in better functional outcomes than standard medical therapy alone. The objective of this secondary analysis is to analyze the effect of late-window endovascular treatment of ischemic stroke on quality of life (QoL) outcomes. Methods: Patients (n=182) who presented between 6 and 16 hours after they were last known to be well with acute anterior circulation ischemic stroke were randomized to endovascular thrombectomy plus standard medical therapy or standard medical therapy alone and followed-up through 90 days poststroke. QoL at day 90 was assessed with the QoL in Neurological Disorders measurement tool. Results: Of the 146 subjects alive at day 90, 136 (95%) filled out QoL in Neurological Disorders short forms. Patients treated with endovascular therapy had better QoL scores in each domain: mobility, social participation, cognitive function, and depression ( P 2 =0.82), a moderate proportion in social participation (Rs 2 =0.62), and a low proportion in cognition (Rs 2 =0.31) and depression (Rs 2 =0.19). Conclusions: Patients treated with endovascular therapy 6 to 16 hours after stroke have better QoL than patients treated with medical therapy alone, including better mobility, more social participation, superior cognition, and less depression. The modified Rankin Scale fails to capture patients’ outcomes in cognition and depression, which should therefore be assessed with dedicated QoL tools. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02586415.

Background and Aims Although sporadic duodenal and/or ampullary adenomas (DAs) are uncommon, they are increasingly diagnosed during upper endoscopy. These patients have a 3- to 7-fold increased risk of colonic neoplasia compared with the normal population. It is unknown, however, whether they also have an increased risk of additional small-bowel (SB) polyps. Our aim was to establish the prevalence of SB polyps in patients with DA. Methods In a single-center, prospective study, we used video capsule endoscopy (VCE) to investigate the prevalence of SB polyps in patients with a DA compared with patients undergoing VCE for obscure GI bleeding or iron deficiency anemia. Results Over 25 months, 201 patients were enrolled in the study; the mean age was 65 years and 47% were male. There were 101 control patients and 100 cases of DA cases (mean size, 30 mm (range, 10-80 mm)). We did not identify any SB polyps in either group. Colonic polyps were found more frequently in the DA group compared with controls (61% versus 37%, respectively (P =.002)). Advanced colonic adenoma (high-grade dysplasia, >10 mm, villous histology) were found in 18% of the DA group and 5% of the control group (P =.018). Conclusion Our data suggest that patients with a DA are not at risk for additional SB polyps and hence do not support screening with VCE. However, colonoscopy is mandatory due to the significantly higher risk of colonic polyps including advanced adenomas. (Clinical trial registration number: NCT02470416.)

Dax-1 (dosage-sensitive sex reversal adrenal hypoplasia congenital region on X-chromosome gene 1) blocks 17β-estradiol biosynthesis and its knockdown would be expected to increase 17β-estradiol production. We hypothesized that knockdown of Dax-1 in a conditionally immortalized neural stem cell (NSC) line, MHP36, is a useful approach to increase 17β-estradiol production. Short hairpin (sh) RNA targeted to Dax-1 in NSCs, namely MHP36-Dax1KD cells, resulted in the degradation of Dax-1 RNA and attenuation of Dax-1 protein expression. In vitro, MHP36-Dax1KD cells exhibited overexpression of aromatase and increased 17β-estradiol secretion compared to MHP36 cells. As 17β-estradiol has been shown to promote the efficacy of cell therapy, we interrogated the application of 17β-estradiol-enriched NSCs in a relevant in vivo disease model. We hypothesized that MHP36-Dax1KD cells will enhance functional recovery after transplantation in a stroke model. C57BL/6 male adult mice underwent ischemia/reperfusion by left middle cerebral artery occlusion for 45 min using an intraluminal thread. Two days later male mice randomly received vehicle, MHP36 cells, MHP36-Dax1KD cells, and MHP36 cells suspended in 17β-estradiol (100 nm) or 17β-estradiol alone (100 nm) with serial behavioral testing over 28 days followed by post-mortem histology and blinded analysis. Recovery of sensorimotor function was accelerated and enhanced, and lesion volume was reduced by MHP36-Dax1KD transplants. Regarding mechanisms, immunofluorescence indicated increased synaptic plasticity and neuronal differentiation after MHP36-Dax1KD transplants. In conclusion, knockdown of Dax-1 is a useful target to increase 17β-estradiol biosynthesis in NSCs and improves functional recovery after stroke in vivo, possibly mediated through neuroprotection and improved synaptic plasticity. Therefore, targeting 17β-estradiol biosynthesis in stem cells may be a promising therapeutic strategy for enhancing the efficacy of stem cell-based therapies for stroke.

SummarytinyRNA performs precision analysis of small RNAs, including miRNAs, piRNAs, and siRNAs, from high-throughput sequencing experiments. At the core of tinyRNA is a highly flexible counting utility, tiny-count, that allows for hierarchical assignment of small RNA reads to features based on positional information, extent of feature overlap, 5’ nucleotide, length, and strandedness. tinyRNA provides an all-in-one solution for small RNA-seq data analysis, with documentation and statistics generated at each step for accurate, reproducible results.Availability and ImplementationtinyRNA tools are implemented in Python and R, and the pipeline workflow is coordinated with CWL. tinyRNA is free and open-source software distributed under the GPLv3 license. tinyRNA is available at https://github.com/MontgomeryLab/tinyRNA.Contacttai.montgomery@colostate.eduSupplementary informationReference data, including genome sequences and features tables, for certain species can be found at https://www.MontgomeryLab.org.

In the midst of the SARS-CoV-2 pandemic, the US Association of American Medical Colleges (AAMC) required residency programme transition from in-person to virtual interviews for all applicants. The new virtual format upended a system that has relied on programmes and applicants balancing the likelihood of acceptance with the financial and time demands of cross-country travel. In this commentary, we address the history of residency interviewing in the USA and the emerging changes that are taking place in light of virtual interviews. We discuss the advantages of the new online format, including the reduced cost for applicants and programmes, as well as the decreased carbon footprint. We also discuss the inequities of virtual interviewing, involving a national maldistribution of interviews to only the top-tier candidates. We share previously unpublished data on the number of virtual interviews accepted by Stanford's 2020 residency applicants, compared with those conducted in person in 2019. We find Stanford applicants in all fields accepted more interviews: from a mean of 8 in 2019 to 14 in 2020, a change of 160% on average. Despite this, only half of Stanford 2020 applicants interviewing in the virtual format thought they had accepted more interviews than they would have in person. We comment on how transitions to online interviewing may be affecting medical schools and applicants disproportionately. Ultimately, we highlight the need and offer ideas for additional regulation on behalf of the AAMC to ensure a more equitable distribution of interview opportunities.

INTRODUCTION Endoscopic mucosal resection (EMR) is an effective therapy for naive large nonpedunculated colorectal polyps (N-LNPCPs). The best approach for the treatment of previously attempted LNPCPs (PA-LNPCPs) is undetermined. METHODS EMR performance for PA-LNPCPs was evaluated in a prospective observational cohort of LNPCPs ≥20 mm. Efficacy was measured by technical success (removal of all visible polypoid tissue during index EMR) and recurrence at first surveillance colonoscopy (SC1). Safety was assessed by clinically significant intraprocedural bleeding, deep mural injury types III-V, clinically significant post-EMR bleeding, and delayed perforation. RESULTS From January 2012 to October 2019, 158 PA-LNPCPs and 1,134 N-LNPCPs underwent EMR. Median PA-LNPCP size was 30 mm (interquartile range 25-46 mm). Technical success was 93.0% and increased to 95.6% after adjusting for 2-stage EMR. Cold-forceps avulsion with adjuvant snare-tip soft coagulation (CAST) was required for nonlifting polypoid tissue in 73 (46.2%). Median time to SC1 was 6 months (interquartile range 5-7 months). Recurrence occurred in 9 (7.8%). No recurrence was identified among 65 PA-LNPCPs which underwent margin thermal ablation at SC1 vs 9 (18.0%; P < 0.001) which did not. There were significant differences in resection duration (35 vs 25 minutes; P < 0.001), technical success (93.0% vs 96.6%; P = 0.026), and use of CAST (46.2% vs 7.6%; P < 0.001), between PA-LNPCPs and N-LNPCPs. When adjusting for 2-stage EMR, no difference in technical success was identified (95.6% vs 97.8%; P = 0.100). No differences in adverse events or recurrence were identified. DISCUSSION EMR, using auxillary techniques where necessary, can achieve high technical success and low recurrence frequencies for PA-LNPCPs.

The synthesis of donor–acceptor di-, tri- and tetrablock copolymers via sequential ROMP of electron rich and electron deficient paracyclophanediene monomers using Grubbs ruthenium carbene initiator, G3, is discussed. Block copolymers were initially formed with a cis/trans alkene geometry and these can be readily photoisomerised to the all trans forms. The optical and electrochemical properties of these block copolymers were examined by theory and experiment, and it was found that the HOMO and LUMO energy levels are localised on the donor and acceptor blocks, respectively.

ObjectiveLarge (≥20 mm) sessile serrated lesions (L-SSL) are premalignant lesions that require endoscopic removal. Endoscopic mucosal resection (EMR) is the existing standard of care but carries some risk of adverse events including clinically significant post-EMR bleeding and deep mural injury (DMI). The respective risk-effectiveness ratio of piecemeal cold snare polypectomy (p-CSP) in L-SSL management is not fully known.DesignConsecutive patients referred for L-SSL management were treated by p-CSP from April 2016 to January 2020 or by conventional EMR in the preceding period between July 2008 and March 2016 at four Australian tertiary centres. Surveillance colonoscopies were conducted at 6 months (SC1) and 18 months (SC2). Outcomes on technical success, adverse events and recurrence were documented prospectively and then compared retrospectively between the subsequent time periods.ResultsA total of 562 L-SSL in 474 patients were evaluated of which 156 L-SSL in 121 patients were treated by p-CSP and 406 L-SSL in 353 patients by EMR. Technical success was equal in both periods (100.0% (n=156) vs 99.0% (n=402)). No adverse events occurred in p-CSP, whereas delayed bleeding and DMI were encountered in 5.1% (n=18) and 3.4% (n=12) of L-SSL treated by EMR, respectively. Recurrence rates following p-CSP were similar to EMR at 4.3% (n=4) versus 4.6% (n=14) and 2.0% (n=1) versus 1.2% (n=3) for surveillance colonoscopy (SC)1 and SC2, respectively.ConclusionsIn a historical comparison on the endoscopic management of L-SSL, p-CSP is technically equally efficacious to EMR but virtually eliminates the risk of delayed bleeding and perforation. p-CSP should therefore be considered as the new standard of care for L-SSL treatment.

Blood parasites can impact host fitness and can, thus, act as selective agents in their host’s evolution. The melanocortin system linked to colouration of vertebrates may infer higher parasite resistance via pleiotropic properties of the genes involved. Black Sparrowhawks (Accipiter melanoleucus) are colour polymorphic (dark and light morph adults) and distributed clinally in South Africa, with more dark morphs in the Southwest where the breeding season coincides with the rainy season. There, dark morphs have lower infections of haemosporidian parasites Haemoproteus nisi, suggesting a higher parasitic resistance. Thus, it is hypothesized that the morph distribution may be an adaptive response to coping with varying parasite prevalence associated with rainfall levels, which may regulate the parasites’ invertebrate vectors. This hypothesis assumes a fitness cost of high parasite burden, which could be specifically important during the energy-demanding breeding season. To explore this, we (1) quantified Black Sparrowhawk H. nisi infections across South Africa, and explored (2) breeding performance and apparent annual survival of adults, and (3) nestling body condition in Cape Town in relation to infection levels. In contrast to the predictions, we found that parasite prevalence did not vary across the country, we found no fitness costs of higher infection levels for breeding birds, and also nestling body condition was independent of infection levels. Thus, we found no support for our hypothesis. Black Sparrowhawk polymorphism is unlikely to be driven by an adaptive function linked to dealing with higher infections with H. nisi in regions with wetter breeding seasons.

Background Osteosarcoma (OSA) in dogs is an aggressive bone tumor with frequent chemotherapy failure and translational relevance for human health. Hypothesis/objectives We hypothesized that dogs with OSA could be treated safely by ex vivo activated T-cells that were generated by autologous cancer vaccination and supported by interleukin-2 (IL-2) treatment with survival more than twice that reported for amputation alone. Animals Osteosarcoma-bearing dogs (n = 14) were enrolled in a single-arm prospective trial after complete staging before amputation. Four healthy dogs also were treated in a safety study. Methods Autologous cancer cell vaccinations were administered intradermally and dogs underwent leukapheresis. Mononuclear cell products were stimulated ex vivo with a T-cell-activating agent. Activated product was transfused and 5 SC IL-2 injections were administered q48h. Dogs were monitored for metastasis by thoracic radiography every 3 months. Results Autologous cancer cell vaccine and activated cellular therapy (ACT) products were successfully generated. Toxicity was minimal after premedicants were instituted before ACT. With premedication, all toxicities were grade I/II. Median disease-free interval for all dogs was 213 days. One dog developed cutaneous metastasis but then experienced spontaneous complete remission. Median survival time for all dogs was 415 days. Five dogs survived >730 days. Conclusions and clinical importance This immunotherapy protocol without cytotoxic chemotherapy is safe and tolerable. Compared to historical amputation reports, survival was notably prolonged in this group of patients. Additional prospective studies are warranted to elucidate active immunologic mechanisms and further improve disease response and survival.

Waterbirds in stochastic environments exhibit nomadism in order to cater for the unpredictable availability of water resources. Lesser flamingos Phoeniconaias minor have long been thought to be nomadic waterbirds. In southern Africa, conservation efforts for lesser flamingos are hampered by a lack of knowledge about their movement trajectories. To investigate their movement ecology in southern Africa, we fitted GPS–GSM transmitters to 12 adults and tracked their movements over four years, from March 2016 to February 2020. Net squared displacement (NSD) was used in nonlinear least squares models classifying trajectories as nomadic, migratory, mixed-migratory, home range restricted or dispersal movement types. Data from eight of the 12 birds met the criteria for the NSD analysis. Model success was good; only 8 out of 120 (6.7%) movement type models failed to reach convergence. Goodness of fit statistics from the NSD models supported migratory and mixed migratory movement types (concordance criteria coefficient (CC) = 0.78) for more than half of the annual trajectories investigated (57.2%). Dispersal, home range-restricted and nomadic movements best described 28.6, 9.5 and 4.8% of annual trajectories, respectively, but all resulted in a mean CC of < 0.4 and thus did not fit observed NSD patterns as well as the migratory movement types. We then used nonlinear mixed effects models to account for annual and individual differences in migration parameters. Variation in the timing and duration of all migrations were more important than variation in migration distance, indicating well-established summer and winter ‘ranges’ and routes between Kamfers Dam (South Africa) and Sua Pan (Botswana). We propose that lesser flamingos in central southern Africa may be partial migrants, not true nomads, as most of their movements followed a regular, repeated pattern between two primary locations.

Disassortative mating in color-polymorphic raptors is a proposed mechanism for the maintenance of color polymorphism in populations. Selection for such a mating system may occur if there are fitness advantages of mating with a contrasting morph. In the black sparrowhawk (Accipiter melanoleucus), mixed-morph pairs may have a selective advantage because they produce offspring that have higher survival rates. Two hypotheses, which may explain the mechanism, are the “avoidance-image” and “complementarity” hypotheses. The first suggests that, within a predator’s territory, prey develop a search image for the more commonly encountered parental morph, for example, the male morph during incubation and brooding. Females of a contrasting morph to their partner would then have higher capture rates once they commence hunting in the later nestling phase. Thus, the “avoidance-image” hypothesis predicts higher provisioning rates for mixed-morph pairs. Alternatively, the “complementarity” hypothesis posits that different color morphs exploit different environmental conditions, allowing mixed-morph pairs to hunt under a wider range of conditions and predicts that food is delivered more consistently. We test these hypotheses using nest cameras to record prey delivery rates during the late nestling phase when both parents are hunting. We found support for the “complementarity” hypothesis, with mixed-morph pairs delivering food more consistently but not at a higher rate. This higher consistency in prey deliveries may explain the improved survival of the offspring of mixed-morph pairs and could, therefore, play a role in maintaining the stability of color polymorphism in this system.

Background The IDEAL (Idea, Development, Evaluation, Assessment, Long‐term study) framework is a scheme of investigation for innovative surgical therapeutic interventions. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a procedure based on laparoscopy to deliver intraperitoneal chemotherapy for peritoneal metastases, introduced in 2011. The aim of this article was to review literature on PIPAC and assess whether development of the technique has followed the IDEAL framework. Methods A search of MEDLINE and Embase was carried out to identify scientific reports on PIPAC published between January 2000 and February 2019. The studies were categorized according to the IDEAL stages. Results Eighty‐six original research papers on PIPAC were identified. There were 23 stage 0, 18 stage 1, 25 stage 2a and six stage 2b studies. Protocol papers for stage 1, 2b and 3 studies, and trial registrations for stage 2a studies, were also identified. The number of centres publishing reports and the number of publications has increased each year. Overall, there has been progression through the IDEAL stages; however, about 60 per cent of clinical reports published in 2018 were stage 1 Idea‐type studies. Conclusion Since its introduction, studies investigating PIPAC have progressed in line with the IDEAL framework. However, the majority of studies reported recently were stage 0 and 1 studies., This review assesses whether the introduction of pressurized intraperitoneal aerosol chemotherapy has followed the IDEAL (Innovation, Development, Evaluation, Assessment, Long‐term use) framework, and whether the problems with surgical innovation have been addressed. Pipac and review