Weightbearing Computed Tomography Can Accurately Detect Subtle Lisfranc Injury.

BACKGROUND: Early detection of Lisfranc injury is critical for improving clinical outcomes, but diagnosing subtle injury can be difficult. Weightbearing computed tomography (WBCT) allows evaluation of such injuries in 3 dimensions (3D) under physiologic load. This study aimed to assess the utility of 1-, 2-, and 3-dimensional measurements on WBCT to diagnose subtle injury in isolated ligamentous Lisfranc injuries. METHODS: Ten cadaveric specimens underwent WBCT evaluation of the Lisfranc joint complex in the intact state and subsequently with sequential sectioning of the dorsal Lisfranc ligament and interosseous Lisfranc ligament (IOL) to create subtle Lisfranc injury, and finally after transectioning of plantar Lisfranc ligament (PLL) to create the injury conditions for complete ligamentous Lisfranc injury. Measurements under static vertical tibial load of 80 kg were performed on WBCT images including (1) Lisfranc joint (medial cuneiform-base of second metatarsal) volume, (2) Lisfranc joint area, (3) C1-C2 intercuneiform area, (4) C1-M2 distance, (5) C1-C2 distance, (6) M1-M2 intermetatarsal distance, (7) first tarsometatarsal (TMT1) alignment, (8) second tarsometatarsal (TMT2) alignment, (9) TMT1 dorsal step-off distance, and (10) TMT2 dorsal step-off distance. RESULTS: In the subtle Lisfranc injury state, Lisfranc joint volume and area, C1-M2 distance, and M1-M2 distance measurements on WBCT significantly increased, when compared with the intact state (P values .001 to .014). Additionally, Lisfranc joint volume and area, C1-M2 distance, M1-M2 distance, TMT2 alignment, and TMT2 dorsal step-off measurements were increased in the complete Lisfranc injury state. Of all measurements, C1-M2 distance had the largest area under the curve (AUC) of 0.96 (sensitivity = 90%; specificity = 90%), followed by Lisfranc volume (AUC = 0.90; sensitivity = 80%; specificity = 80%) and Lisfranc area (AUC = 0.89; sensitivity = 80%; specificity = 100%). CONCLUSION: In a cadaveric model we found that WBCT scan can increase the diagnostic accuracy for subtle Lisfranc injury. Among the measurements, C1-M2 distance exhibited the highest level of accuracy. The 2D joint area and 3D joint volume also proved to be accurate, with 3D volume measurements of the Lisfranc joint displaying the most significant absolute difference between the intact state and increasing severity of Lisfranc injury. These findings suggest that 2D joint area and 3D joint volume may have potential as supplementary measurements to more accurately diagnose subtle Lisfranc injuries. CLINICAL RELEVANCE: WBCT may help surgeons detect subtle Lisfranc injuries.

Unit costs and cost-effectiveness of a device to improve TB treatment adherence in China.

BACKGROUND: Adherence to TB drugs is crucial for improving treatment outcomes. Digital adherence technologies can improve adherence; however, there is a lack of evidence on cost-effectiveness. This study aimed to explore the cost-effectiveness of medication event reminder monitors (MERM) in China compared with the standard of care, using results from a pragmatic, cluster-randomised superiority trial of an electronic MERM in China. METHODS: We collected primary unit cost data from the societal perspective, both at and above the health facility level. We estimated the incremental cost-effectiveness of MERM using a Markov model with a 20-year time horizon; a 3% discount rate was applied to costs and outcomes. We explored uncertainty through a series of sensitivity and scenario analyses. RESULTS: The incremental cost of MERM was $27.22 per patient. Probabilistic sensitivity analysis showed significant uncertainty about the intervention's cost-effectiveness. Changing assumptions around key parameters substantially affected our estimated incremental cost-effectiveness ratio. CONCLUSIONS: Although the incremental cost of the MERM box was low, current evidence does not indicate that the intervention would be cost-effective. However, the intervention's cost-effectiveness could improve if implemented as part of a broader strategy, including enhanced patient management.

CONTEXTE: Il est crucial de respecter les médicaments antituberculeux pour améliorer les résultats du traitement. Les technologies numériques peuvent améliorer l'observance, mais il existe un manque de preuves sur leur rapport coût-efficacité. Cette étude a examiné le rapport coût-efficacité des moniteurs de rappel d'événements médicamenteux (MERM, pour l'anglais, « medication event reminder monitors ¼) en Chine par rapport aux soins standards, en se basant sur les résultats d'un essai pragmatique randomisé en grappes d'un MERM électronique en Chine. MÉTHODES: Les coûts unitaires primaires du point de vue de la société ont été collectés et analysés à la fois au niveau de l'établissement de santé et au-delà. Pour évaluer le rapport coût-efficacité différentiel du MERM, nous avons utilisé un modèle de Markov sur une période de 20 ans, en appliquant un taux d'actualisation de 3% aux coûts et aux résultats. Afin de prendre en compte les incertitudes, nous avons effectué plusieurs analyses de sensibilité et de scénarios. RÉSULTATS: Le coût supplémentaire du MERM s'élevait à 27,22 $ par patient. L'analyse de sensibilité probabiliste a révélé une incertitude importante concernant le rapport coût-efficacité de l'intervention. La variation des hypothèses liées aux paramètres clés a eu un impact significatif sur le rapport coût-efficacité différentiel estimé. CONCLUSIONS: Bien que le coût différentiel de la boîte MERM soit faible, les données actuelles n'indiquent pas que l'intervention serait rentable. Toutefois, le rapport coût-efficacité de l'intervention pourrait être amélioré si elle était mise en œuvre dans le cadre d'une stratégie plus large, comprenant une meilleure prise en charge des patients.

When and why is red blood cell genotyping applicable in transfusion medicine: a systematic review of the literature.

This review aims to provide a better understanding of when and why red blood cell (RBC) genotyping is applicable in transfusion medicine. Articles published within the last 8 years in peer-reviewed journals were reviewed in a systematic manner. RBC genotyping has many applications in transfusion medicine including predicting a patient's antigen profile when serologic methods cannot be used, such as in a recently transfused patient, in the presence of autoantibody, or when serologic reagents are not available. RBC genotyping is used in prenatal care to determine zygosity and guide the administration of Rh immune globulin in pregnant women to prevent hemolytic disease of the fetus and newborn. In donor testing, RBC genotyping is used for resolving ABO/D discrepancies for better donor retention or for identifying donors negative for high-prevalence antigens to increase blood availability and compatibility for patients requiring rare blood. RBC genotyping is helpful to immunohematology reference laboratory staff performing complex antibody workups and is recommended for determining the antigen profiles of patients and prospective donors for accurate matching for C, E, and K in multiply transfused patients. Such testing is also used to determine patients or donors with variant alleles in the Rh blood group system. Information from this testing aides in complex antibody identification as well as sourcing rare allele-matched RBC units. While RBC genotyping is useful in transfusion medicine, there are limitations to its implementation in transfusion services, including test availability, turn-around time, and cost.

Normal Fermi Surface in the Nodal Superconductor CeCoIn_{5} Revealed via Thermal Conductivity.

The thermal conductivity of heavy-fermion superconductor CeCoIn_{5} was measured with a magnetic field rotating in the tetragonal a-b plane, with the heat current in the antinodal direction, J|| [100]. We observe a sharp resonance in thermal conductivity for the magnetic field at an angle Θ≈12°, measured from the heat current direction [100]. This resonance corresponds to the reported resonance at an angle Θ^{'}≈33° from the direction of the heat current applied along the nodal direction, J||[110]. Both resonances, therefore, occur when the magnetic field is applied in the same crystallographic orientation in the two experiments, regardless of the direction of the heat current, proving conclusively that these resonances are due to the structure of the Fermi surface of CeCoIn_{5}. We argue that the uncondensed Landau quasiparticles, emerging with field, are responsible for the observed resonance. We support our experimental results with density-functional-theory model calculations of the density of states in a rotating magnetic field. Our calculations, using a model Fermi surface of CeCoIn_{5}, reveal several sharp peaks as a function of the field direction. Our study demonstrates that the thermal-conductivity measurement in rotating magnetic field can probe the normal parts of the Fermi surface deep inside the superconducting state.

Mohs micrographic surgery for the treatment of invasive melanoma: A systematic review with meta-analyses.

BACKGROUND: The use of Mohs micrographic surgery (MMS) in melanoma treatment has divided opinion and evidence-based guidelines are lacking. OBJECTIVES: This systematic review aimed to analyse clinical outcomes for patients with invasive melanomas treated with Mohs rather than wide local excision (WLE). METHODS: Embase, MEDLINE and Cochrane databases (to 30 August 2023) were searched for studies using Mohs to treat invasive melanoma. Outcomes of interest were local recurrence and death from melanoma. RESULTS: Thirty-five articles involving 41,499 patients with invasive melanoma treated with Mohs were identified. Sixteen studies compared Mohs with WLE and 19 were Mohs-only, non-comparative studies. Patients treated with Mohs differed significantly from those undergoing WLE, in particular Mohs patients were older and had thinner melanomas. Two comparative studies using the same data source reported adjusted hazard ratios for melanoma-specific death and both showed no significant difference between Mohs and WLE-treated patients; 0.87 (95% CI 0.55-1.35) and 1.20 (95% CI 0.71-20.36). There was also no statistically significant difference in local recurrence risk; the unadjusted risk ratio for patients treated with Mohs was 0.46 (95% CI 0.14-1.51 p = 0.20) with moderate heterogeneity (I2 = 62%). No studies reported multivariable analyses for risk of local recurrence. Many studies generated from relatively few and often overlapping data sets have reported the use of Mohs to treat patients with invasive melanoma. Fewer studies were comparative between Mohs and WLE and these reported substantially different baseline risks of recurrence and death from melanoma between the groups. Mohs has generally been used for thinner melanomas in older patients; therefore, comparisons based on univariable analyses are likely to have been misleading. CONCLUSIONS: On the basis of currently available data, it is not possible to reliably assess whether outcomes differ if invasive melanomas with comparable features are treated with Mohs or WLE, and randomized trial evidence will be required for reliable conclusions to be reached.

A brief history of technical developments in intracytoplasmic sperm injection (ICSI). Dedicated to the memory of J.M. Cummins.

Intracytoplasmic sperm injection (ICSI) is an assisted reproductive technology for treatment of severe male infertility introduced into clinical practice in 1992. This review provides a brief history of the development of ICSI by acknowledging major developments in the field. The review addresses key developments in pre-clinical and early studies, how ICSI compares with in vitro fertilisation, long-term consequences, how the mechanistic approach to ICSI has changed in both manual and semi-automated approaches, and how sperm selection procedures are integrated into ICSI. From the beginnings using animal models in the 1960-1970s, the development of ICSI is a remarkable and transformative success story. Indeed, its broad use (70% of cycles globally) exceeds the need required for treating infertile males, and this remains a controversial issue. There remain questions around the long-term health impacts of ICSI. Furthermore, advances in automation of the ICSI procedure are occurring. An estimated 6million children have been born from the ICSI procedure. With further automation of sperm selection technologies, coupled with automation of the injection procedure, it is likely that the proportion of children born from ICSI will further increase.

Understanding quality of life issues in patients with advanced melanoma: Phase 1 and 2 in the development of the EORTC advanced melanoma module.

AIMS: We aimed to develop a European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) module tailored for patients with advanced (resectable or unresectable stage III/IV) melanoma receiving immune checkpoint inhibitors or targeted therapy. METHODS: Following the EORTC QoL Group module development guidelines, we conducted phases 1 and 2 of the development process. In phase 1, we generated a list of health-related (HR)QoL issues through a systematic literature review and semi-structured interviews with healthcare professionals (HCPs) and patients with advanced melanoma. In phase 2, these issues were converted into questionnaire items to create the preliminary module. RESULTS: Phase 1: we retrieved 8006 articles for the literature review, of which 35 were deemed relevant, resulting in 84 HRQoL issues being extracted to create the initial issue list. Semi-structured interviews with 18 HCPs and 28 patients with advanced melanoma resulted in 28 issues being added to the initial issue list. Following EORTC module development criteria, 26 issues were removed, and two issues were added after review by patient advocates. Phase 2: To ensure uniformity and avoid duplication, 16 issues were consolidated into eight items. Additionally, an independent expert contributed one new item, resulting in a preliminary module comprising 80 HRQoL items. CONCLUSION: We identified a range of HRQoL issues (dry skin, xerostomia, and arthralgia) relevant to patients with stage III/IV melanoma. Future module development phases will refine the questionnaire. Once completed, this module will enable standardized assessment of HRQoL in patients with (locally) advanced melanoma.

A phase II study (AARDVARC) of AZD4635 in combination with durvalumab and cabazitaxel in patients with progressive, metastatic, castration-resistant prostate cancer.

BACKGROUND: This phase II nonrandomized study evaluated the efficacy and safety of AZD4635 in combination with durvalumab (Arm A) or durvalumab plus cabazitaxel (Arm B) in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel and ≥1 novel hormonal agent. PATIENTS AND METHODS: The primary endpoint was radiographic progression-free survival (rPFS) per RECIST v1.1 (soft tissue) or the Prostate Cancer Clinical Trials Working Group 3 (bone). Secondary endpoints included safety, tolerability, overall survival, confirmed prostate-specific antigen (PSA50) response, pharmacokinetics, and objective response rate. Enrollment in Arm A was stopped following a sponsor decision unrelated to safety. The study was stopped based on the planned futility analysis due to low PSA50 response in Arm B. RESULTS: In the final analysis (1 November 2021), 30 patients were treated (Arm A, n = 2; Arm B, n = 28). The median rPFS in Arm B was 5.8 months (95% confidence interval 4.2-not calculable). Median rPFS was 5.8 months versus 4.2 months for patients with high versus low blood-based adenosine signature. The most common treatment-related adverse events in Arm B were nausea (50.0%), diarrhea (46.4%), anemia and neutropenia (both 35.7%), asthenia (32.1%), and vomiting (28.6%). Overall, AZD4635 in combination with durvalumab or AZD4635 in combination with cabazitaxel and durvalumab showed limited efficacy in patients with mCRPC. CONCLUSIONS: Although the safety profile of both combinations was consistent with known safety data of the individual agents, the results of this trial do not support further development of the combinations.

Five-year analysis of neoadjuvant dabrafenib and trametinib for stage III melanoma.

BACKGROUND: Neoadjuvant dabrafenib plus trametinib has a high pathological response rate and impressive short-term survival in patients with resectable stage III melanoma. We report 5-year outcomes from the phase II NeoCombi trial. PATIENTS AND METHODS: NeoCombi (NCT01972347) was a single-arm, open-label, single-centre, phase II trial. Eligible patients were adults (aged ≥18 years) with histologically confirmed, resectable, RECIST-measurable, American Joint Committee on Cancer seventh edition clinical stage IIIB-C BRAF V600E/K-mutant melanoma and Eastern Cooperative Oncology Group performance status ≤1. Patients received 52 weeks of treatment with dabrafenib 150 mg (orally twice per day) plus trametinib 2 mg (orally once per day), with complete resection of the pre-therapy tumour bed at week 12. RESULTS: Between 20 August 2014 and 19 April 2017, 35 patients were enrolled. At data cut-off (17 August 2021), the median follow-up was 60 months [95% confidence interval (CI) 56-72 months]. Overall, 21 of 35 (60%) patients recurred, including 12 (57%) with first recurrence in locoregional sites (followed by later distant recurrence in 6) and 9 (43%) with first recurrence in distant sites, including 3 in the brain. Most recurrences occurred within 2 years, with no recurrences beyond 3 years. At 5 years, recurrence-free survival (RFS) was 40% (95% CI 27% to 60%), distant metastasis-free survival (DMFS) was 57% (95% CI 42% to 76%), and overall survival was 80% (95% CI 67% to 94%). Five-year survival outcomes were stratified by pathological response: RFS was 53% with pathological complete response (pCR) versus 28% with non-pCR (P = 0.087), DMFS was 59% versus 55% (P = 0.647), and overall survival was 88% versus 71% (P = 0.205), respectively. CONCLUSIONS: Neoadjuvant dabrafenib plus trametinib has high pathological response rates in clinical stage III melanoma, but low rates of RFS, similar to those achieved with adjuvant targeted therapy alone. Patients with a pCR to dabrafenib plus trametinib still had a high risk of recurrence, unlike that seen with immunotherapy where recurrences are rare.

Histopathological diagnosis and surgical complications following bilateral anal sacculectomy for the treatment of unilateral canine apocrine gland anal sac adenocarcinoma: 35 cases (2019-2023).

OBJECTIVES: To report the histopathological diagnosis of both anal sacs in dogs undergoing bilateral anal sacculectomy for the treatment of unilateral apocrine gland anal sac adenocarcinoma and to compare the surgical complication rate associated with this procedure in this population with previously published literature. MATERIALS AND METHODS: Records were retrospectively reviewed for dogs that underwent bilateral anal sacculectomy for the treatment of apparently unilateral apocrine gland anal sac adenocarcinoma, at a single institute between 2019 and 2023. Clinical staging, surgical treatment, histological findings, intra- and postoperative complications were evaluated. RESULTS: Thirty-five dogs were included. Only five of 35 (14%) dogs were found to have histologically normal contralateral anal sacs. Non-neoplastic anal sac disease was found in 23 of 35 (66%) dogs and bilateral apocrine gland anal sac adenocarcinoma was seen in seven of 35 (20%) dogs. None of the dogs diagnosed with bilateral neoplasia had evidence of bilateral neoplasia before surgery despite a thorough work-up. Complications attributable to the primary tumour removal were seen in 9% of dogs intraoperatively and 14% of dogs postoperatively, commonly tumour capsule disruption and surgical site infection, respectively. CLINICAL SIGNIFICANCE: Bilateral anal sac disease was diagnosed histologically in the majority of presumed normal anal sacs, with 20% of cases being found to have bilateral apocrine gland anal sac adenocarcinoma. The surgical complication rates of this cohort were comparable to those reported for unilateral anal sacculectomy alone. These findings promote and encourage the use of bilateral anal sacculectomy in cases of suspected unilateral anal sac neoplasia.

Cleft Laterality Dental Arch Relationship Outcomes for Children with Unilateral Cleft Lip and Palate in New Zealand.

OBJECTIVES: To investigate cleft laterality dental arch relationship outcomes of children with non-syndromic complete unilateral cleft lip and palate (UCLP) in New Zealand. DESIGN: A retrospective nationwide study. SETTINGS: Virtual 3D orthodontic study models collected prior to undertaking secondary alveolar bone grafting. PARTICIPANTS: A total of 104 patients with UCLP (L = 80: R = 24). OUTCOME MEASURES: Four calibrated assessors used the GOSLON Yardstick and 100 mm Visual Analogue Scale (VAS) to score the randomised models on 2 separate assessment sessions. Weighted Kappa were used to determine the intra/inter-rater reliability for the GOSLON and correlations for the VAS. RESULTS: Intra-rater reliability ranged from 0.57-0.88 (GOSLON) and 0.45-0.93 (VAS). Inter-rater reliability ranged from 0.62-0.86 (GOSLON) and 0.64-0.93 (VAS).GOSLON scores for the left UCLP were 31.2% for good/very good; 26.3% for fair; 42.5% for poor/very poor while the right UCLP scored 8.3% for good/very good; 37.5% for fair; 54.2% for poor/very poor. The mean VAS for left and right UCLP were 53.4 (sd 22.5) and 44.6 (sd 17.1) respectively. Neither the GOSLON nor VAS differences reached statistical significance (both P = .08). CONCLUSIONS: From a clinical perspective right UCLP had worse dental arch relationship outcomes, however, these differences failed to reach statistical significance. Further studies using larger sample sizes are required to determine if cleft laterality is an important consideration when investigating UCLP dental arch outcomes.

Managing the risks associated with technological disruption in the road transport system: a control structure modelling approach.

Road transport is experiencing disruptive change from new first-of-a-kind technologies. While such technologies offer safety and operational benefits, they also pose new risks. It is critical to proactively identify risks during the design, development and testing of new technologies. The Systems Theoretic Accident Model and Processes (STAMP) method analyses the dynamic structure in place to manage safety risks. This study applied STAMP to develop a control structure model for emerging technologies in the Australian road transport system and identified control gaps. The control structure shows the actors responsible for managing risks associated with first-of-a-kind technologies and the existing control and feedback mechanisms. Gaps identified related to controls (e.g. legislation) and feedback mechanisms (e.g. monitoring for behavioural adaptation). The study provides an example of how STAMP can be used to identify control structure gaps requiring attention to support the safe introduction of new technologies.

This paper considers emerging risks associated with new technologies in the road transport system. It demonstrates a novel approach using STAMP to identify gaps in control and feedback mechanisms within the existing control structure which should be addressed to mitigate risk.

Suture Augmentation of a Four-Strand Semitendinosus Graft Improves Time-Zero Biomechanical Properties.

PURPOSE: To compare the time-zero biomechanical properties of hamstring graft preparations with or without suture augmentation for anterior cruciate ligament reconstruction (ACLR) in a full-construct cadaveric model. METHODS: Hamstring grafts were harvested from 24 fresh frozen human cadavers and prepared in 1 of 3 ways: quadrupled SemiTendinosus (SemiT), and quadrupled SemiT with suture augmentation (SemiT+2.0-mm tape or SemiT+1.3-mm tape; n = 8 per group). Adjustable loop suspensory implants and cortical buttons were used for fixation on a porcine tibia and acrylic block. Testing included force-controlled cyclic loading at 250 N and 400 N followed by load to failure. RESULTS: The 2 suture augmentation groups had less total elongation and increased stiffness compared to the nonsuture-augmented group (P = .025). The SemiT+2.0-mm tape group had 36% less total elongation and 34% increased stiffness compared to SemiT+1.3mm tape (P < .001). CONCLUSIONS: Suture augmentation improves construct biomechanics at time zero following hamstring tendon ACLR. Augmentation with 2.0-mm tape suture improves construct biomechanics compared to 1.3-mm tape suture. CLINICAL RELEVANCE: Independent suture augmentation of a quadrupled SemiT graft improves ACLR construct biomechanics. Outcomes were improved with augmentation using 2.0-mm tape suture compared to 1.3-mm tape suture.

Absence of Spontaneous Magnetic Fields due to Time-Reversal Symmetry Breaking in Bulk Superconducting UTe_{2}.

We have investigated the low-temperature local magnetic properties in the bulk of molten salt-flux (MSF)-grown single crystals of the candidate odd-parity superconductor UTe_{2} by zero-field muon spin relaxation (µSR). In contrast to previous µSR studies of UTe_{2} single crystals grown by a chemical vapor transport method, we find no evidence of magnetic clusters or electronic moments fluctuating slow enough to cause a discernible relaxation of the zero-field µSR asymmetry spectrum. Consequently, our measurements on MSF-grown single crystals rule out the generation of spontaneous magnetic fields in the bulk that would occur near impurities or lattice defects if the superconducting state of UTe_{2} breaks time-reversal symmetry. This result suggests that UTe_{2} is characterized by a single-component superconducting order parameter.

Forecasting emergent risks in advanced AI systems: an analysis of a future road transport management system.

Artificial Intelligence (AI) is being increasingly implemented within road transport systems worldwide. Next generation of AI, Artificial General Intelligence (AGI) is imminent, and is anticipated to be more powerful than current AI. AGI systems will have a broad range of abilities and be able to perform multiple cognitive tasks akin to humans that will likely produce many expected benefits, but also potential risks. This study applied the EAST Broken Links approach to forecast the functioning of an AGI system tasked with managing a road transport system and identify potential risks. In total, 363 risks were identified that could have adverse impacts on the stated goals of safety, efficiency, environmental sustainability, and economic performance of the road system. Further, risks beyond the stated goals were identified; removal from human control, mismanaging public relations, and self-preservation. A diverse set of systemic controls will be required when designing, implementing, and operating future advanced technologies.Practitioner summary: This study demonstrated the utility of HFE methods for formally considering risks associated with the design, implementation, and operation of future technologies. This study has implications for AGI research, design, and development to ensure safe and ethical AGI implementation.

Molecular evidence of anteroposterior patterning in adult echinoderms.

The origin of the pentaradial body plan of echinoderms from a bilateral ancestor is one of the most enduring zoological puzzles1,2. Because echinoderms are defined by morphological novelty, even the most basic axial comparisons with their bilaterian relatives are problematic. To revisit this classical question, we used conserved anteroposterior axial molecular markers to determine whether the highly derived adult body plan of echinoderms masks underlying patterning similarities with other deuterostomes. We investigated the expression of a suite of conserved transcription factors with well-established roles in the establishment of anteroposterior polarity in deuterostomes3-5 and other bilaterians6-8 using RNA tomography and in situ hybridization in the sea star Patiria miniata. The relative spatial expression of these markers in P. miniata ambulacral ectoderm shows similarity with other deuterostomes, with the midline of each ray representing the most anterior territory and the most lateral parts exhibiting a more posterior identity. Strikingly, there is no ectodermal territory in the sea star that expresses the characteristic bilaterian trunk genetic patterning programme. This finding suggests that from the perspective of ectoderm patterning, echinoderms are mostly head-like animals and provides a developmental rationale for the re-evaluation of the events that led to the evolution of the derived adult body plan of echinoderms.

Harold Gillies, pioneer of modern plastic surgery, and Donald Morton, pioneer of modern surgical oncology: Master problem-solvers and surgical role models.

Harold Gillies, plastic surgeon, and Donald Morton, surgical oncologist, were iconic pioneers in their respective fields. Both of them made their mark by identifying crucial practical problems and finding innovative ways of solving them. Gillies grappled with the challenge of restoring form and function to British military personnel injured in World War I, and he set up a dedicated facility for performing this work. He introduced many new reconstructive techniques that became the foundation of the modern specialty of plastic and reconstructive surgery, which he established and nurtured. Morton, in the United States, applied his problem-solving skills to the long-debated question of the best way to manage regional lymph nodes in patients with melanoma. He developed the innovative technique of sentinel lymph node biopsy and initiated large-scale international clinical trials to establish its validity and clinical value. This and other important contributions to the emerging field of surgical oncology earned Morton his reputation as a pioneer and leader of that specialty. The problems that confronted Gillies and Morton were completely different, but both demonstrated remarkable skills as master problem-solvers in their respective fields and made extraordinary contributions to the body of knowledge and welfare of patients. All surgeons must be problem-solvers because every patient who presents for surgical management represents a new problem (or set of problems) to be addressed. As surgeons, we would do well to consider individuals such as Gillies and Morton as role models for our own problem-solving activities in day-to-day clinical practice.