Leveraging the Apple Ecosystem: Easy Viewing and Sharing of Three-dimensional Perforator Visualizations via iPad/iPhone-based Augmented Reality.

We introduce a novel technique using augmented reality (AR) on smartphones and tablets, making it possible for surgeons to review perforator anatomy in three dimensions on the go. Autologous breast reconstruction with abdominal flaps remains challenging due to the highly variable anatomy of the deep inferior epigastric artery. Computed tomography angiography has mitigated some but not all challenges. Previously, volume rendering and different headsets were used to enable better three-dimensional (3D) review for surgeons. However, surgeons have been dependent on others to provide 3D imaging data. Leveraging the ubiquity of Apple devices, our approach permits surgeons to review 3D models of deep inferior epigastric artery anatomy segmented from abdominal computed tomography angiography directly on their iPhone/iPad. Segmentation can be performed in common radiology software. The models are converted to the universal scene description zipped format, which allows immediate use on Apple devices without third-party software. They can be easily shared using secure, Health Insurance Portability and Accountability Act-compliant sharing services already provided by most hospitals. Surgeons can simply open the file on their mobile device to explore the images in 3D using "object mode" natively without additional applications or can switch to AR mode to pin the model in their real-world surroundings for intuitive exploration. We believe patient-specific 3D anatomy models are a powerful tool for intuitive understanding and communication of complex perforator anatomy and would be a valuable addition in routine clinical practice and education. Using this one-click solution on existing devices that is simple to implement, we hope to streamline the adoption of AR models by plastic surgeons.

Prognostic value of lateral lymph node metastasis in pretreatment MRI for rectal cancer in patients undergoing neoadjuvant chemoradiation followed by surgical resection without lateral lymph node dissection: A systemic review and meta-analysis.

PURPOSE: To systematically review and meta-analyze the prognostic significance of lateral lymph node metastasis (LLNM) on pretreatment MRI in patients with rectal cancer who undergo neoadjuvant chemoradiation followed by curative surgical resection without lateral lymph node dissection (LLND). METHODS: We searched the MEDLINE and EMBASE databases until September 27, 2023, utilizing the following search terms: (rectal OR rectum OR colorectal) AND (lateral OR sidewall) AND (lymph OR node). The QUIPS tool was employed to evaluate methodological quality. We pooled the association between LLNM on pretreatment MRI and outcomes such as local recurrence, distant metastasis, disease-free survival, and overall survival using hazard ratio (HR) and odds ratio (OR) based on random effects model. RESULTS: We included 9 studies, encompassing 3180 patients. LLNM on pretreatment MRI revealed a significant association with increased local recurrence rates (HR: 4.11; 95 % CI: [1.87, 9.02]) and elevated risks for both disease-free (HR: 1.70; 95 % CI: [1.42, 2.03]) and overall survival (HR: 1.76; 95 % CI: [1.44, 2.15]). As for distant metastasis, our analysis indicated a potential trend towards increased rates, though this did not reach statistical significance (HR: 1.67; 95 % CI: [0.85, 3.27]). CONCLUSIONS: Our findings underscore the relationship between LLNM and increased local recurrence and compromised disease-free and overall survival. This emphasizes the potential limitations of relying solely on neoadjuvant chemoradiation and highlights the potential need to intensify treatment in select patients.

Suture Packaging as a Marker for Intraoperative Image Alignment in Augmented Reality on Mobile Devices.

Preoperative vascular imaging has become standard practice in the planning of microsurgical breast reconstruction. Currently, translating perforator locations from radiological findings to a patient's abdomen is often not easy or intuitive. Techniques using three-dimensional printing or patient-specific guides have been introduced to superimpose anatomy onto the abdomen for reference. Augmented and mixed reality is currently actively investigated for perforator mapping by superimposing virtual models directly onto the patient. Most techniques have found only limited adoption due to complexity and price. Additionally, a critical step is aligning virtual models to patients. We propose repurposing suture packaging as an image tracking marker. Tracking markers allow quick and easy alignment of virtual models to the individual patient's anatomy. Current techniques are often complicated or expensive and limit intraoperative use of augmented reality models. Suture packs are sterile, readily available, and can be used to align abdominal models on the patients. Using an iPad, the augmented reality models automatically align in the correct position by using a suture pack as a tracking marker. Given the ubiquity of iPads, the combination of these devices with readily available suture packs will predictably lower the barrier to entry and utilization of this technology. Here, our workflow is presented along with its intraoperative utilization. Additionally, we investigated the accuracy of this technology.

Liver Steatosis is Prevalent in Lean People With HIV and Associated With Exposure to Antiretroviral Treatment-A Cross-sectional Study.

Background: Steatotic liver disease is suggested to have a higher prevalence and severity in people with HIV (PHIV), including in those with a normal body mass index (BMI). In this study, we used data from the 2000HIV cohort to (1) assess the prevalence of liver steatosis and fibrosis in lean versus overweight/obese PHIV and (2) assess associations in these subgroups between steatosis and fibrosis with traditional risk factors and HIV-specific characteristics. Methods: The 2000HIV study cohort comprises 1895 virally suppressed PHIV that were included between 2019 and 2021 in 4 HIV treatment centers in the Netherlands. The majority (58.5%) underwent vibration-controlled transient elastography for the assessment of liver steatosis and fibrosis. The prevalence of steatosis (controlled attenuation parameter ≥263 dB/m) and fibrosis (liver stiffness measurement ≥7.0 kPa) was estimated. Multiple factors including HIV characteristics and antiretroviral drugs were tested in a logistic regression model for association with steatosis and fibrosis. Analyses were performed separately for lean (Asian descent: BMI < 23 kg/m2, other descent: BMI < 25 kg/m2) and overweight/obese (other BMI) participants. Results: Of 1050 PHIV including 505 lean and 545 overweight/obese PHIV, liver steatosis was observed in 37.7% of the overall study population, 19.7% of lean, and 54% of overweight/obese PHIV, whereas fibrosis was observed in 9.0% of the overall study population, 5.9% of lean, and 12.0% of overweight/obese PHIV.All associations with fibrosis and most associations with steatosis concerned metabolic factors such as type 2 diabetes mellitus (overall population: adjusted odds ratio [aOR] for steatosis: 2.3 [1.21-4.4], P = .011; aOR for fibrosis: 3.7 [1.82-7.53], P < .001). Furthermore, in lean PLHIV, liver steatosis was associated with CD4 and CD8 counts at enrollment, dual therapy, and history of treatment with raltegravir (aOR: 3.6 [1.53-8.47], P = .003), stavudine (aOR: 3.73 [1.69-8.2], P = .001), and indinavir (aOR: 3.86 [1.59-9.37], P = .003). These associations were not observed in overweight/obese PHIV. Conclusions: Liver steatosis was highly prevalent, affecting approximately one-fifth of lean PHIV and half of overweight/obese PHIV. Fibrosis was observed in a minority. Both steatosis and fibrosis were associated with traditional metabolic risk factors. In addition, (prior) exposure to specific antiretroviral drugs was associated liver steatosis in lean, but not in overweight/obese PHIV. Implementing increased screening protocols could enhance the identification of steatotic liver disease in lean PHIV.

Hepatic steatosis, metabolic dysfunction and risk of mortality: findings from a multinational prospective cohort study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are implicated in the aetiology of non-communicable diseases. Our study aimed to evaluate associations between NAFLD and MetS with overall and cause-specific mortality. METHODS: We used dietary, lifestyle, anthropometric and metabolic biomarker data from a random subsample of 15,784 EPIC cohort participants. NAFLD was assessed using the fatty liver index (FLI) and MetS using the revised definition. Indices for metabolic dysfunction-associated fatty liver disease (MAFLD) were calculated. The individual associations of these indices with overall and cause-specific mortality were assessed using multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs). As a subobjective, risk associations with adaptations of new classifications of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic and alcohol-related liver disease (MetALD) were also assessed. RESULTS: Among the 15,784 sub-cohort participants, a total of 1997 deaths occurred (835 due to cancer, 520 to CVD, 642 to other causes) over a median 15.6 (IQR, 12.3-17.1) years of follow-up. Compared to an FLI < 30, FLI ≥ 60 was associated with increased risks of overall mortality (HR = 1.44, 95%CI = 1.27-1.63), and deaths from cancer (HR = 1.32, 95%CI = 1.09-1.60), CVD (HR = 2.06, 95% CI = 1.61-2.63) or other causes (HR = 1.21, 95%CI = 0.97-1.51). Mortality risk associations were also elevated for individuals with MAFLD compared to those without. Individuals with MetS were at increased risk of all mortality endpoints, except cancer-specific mortality. MASLD and MetALD were associated with higher risk of overall mortality. CONCLUSIONS: Our findings based on a prospective cohort suggest that individuals with hepatic steatosis or metabolic dysfunction have a higher overall and cause-specific mortality risk.

Rearing density and food variety impact growth, development, and survival of larvae in the declining amphibian, Pseudacris maculata.

Boreal chorus frogs (Pseudacris maculata Agassiz 1850) are a widespread amphibian in North America, but several populations are in decline. Specifically, we are developing captive breeding and reintroduction methods for the Great Lakes/St. Lawrence-Canadian Shield population. Here we present the effects of tadpole density, food variety, and addition of supplemental minerals to rearing water on the growth, development, and survival during the larval and metamorph/juvenile stages. We conducted two experiments using a factorial design. We found that low tadpole density (1 vs. 2 tadpoles/L) and high food variety (five food items vs. three food items) significantly increased tadpole body length and Gosner stage after 2 weeks (p < .001), increased survival to metamorphosis (p < .001), decreased time to metamorphosis (p < .001), and increased weight after metamorphosis (p < .001). On average, tadpoles in the high density/low food treatment, compared to the low density/high food, were 25% smaller after 2 weeks, had 3.9× lower survival to metamorphosis, took 1.25× longer to reach metamorphosis, and weighed 1.5× less after metamorphosis. In contrast, neither density (0.5 vs. 1 tadpole/L) nor mineral supplemented water affected growth and development, but tadpole survival was higher at 1 tadpole/L. Our findings demonstrate the feasibility of rearing boreal chorus frogs in captivity and provide guidelines for rearing this and similar species in a laboratory environment.

IGF-1 Mediated Neuroprotective Effects of Olfactory-Derived Mesenchymal Stem Cells on Auditory Hair Cells.

IMPORTANCE: Mesenchymal stem cells (MSCs) have the capability of providing ongoing paracrine support to degenerating tissues. Since MSCs can be extracted from a broad range of tissues, their specific surface marker profiles and growth factor secretions can be different. We hypothesized that MSCs derived from different sources might also have different neuroprotective potential. OBJECTIVE: In this study, we extracted MSCs from rodent olfactory mucosa and compared their neuroprotective effects on auditory hair cell survival with MSCs extracted from rodent adipose tissue. METHODS: Organ of Corti explants were dissected from 41 cochlea and incubated with olfactory mesenchymal stem cells (OMSCs) and adipose mesenchymal stem cells (AMSCs). After 72 hours, Corti explants were fixed, stained, and hair cells counted. Growth factor concentrations were determined in the supernatant and cell lysate using Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: Co-culturing of organ of Corti explants with OMSCs resulted in a significant increase in inner and outer hair cell stereocilia survival, compared to control. Comparisons between both stem cell lines, showed that co-culturing with OMSCs resulted in superior inner and outer hair cell stereocilia survival rates over co-culturing with AMSCs. Assessment of growth factor secretions revealed that the OMSCs secrete significant amounts of insulin-like growth factor 1 (IGF-1). Co-culturing OMSCs with organ of Corti explants resulted in a 10-fold increase in IGF-1 level compared to control, and their secretion was 2 to 3 times higher compared to the AMSCs. CONCLUSIONS: This study has shown that OMSCs may mitigate auditory hair cell stereocilia degeneration. Their neuroprotective effects may, at least partially, be ascribed to their enhanced IGF-1 secretory abilities compared to AMSCs.

Cost-Effectiveness Analysis of Early versus Late Debridement of Superficial Triangular Fibrocartilage Complex Tears.

Background: While initial nonoperative management is the conventional approach for superficial triangular fibrocartilage complex (TFCC) tears, a substantial portion of these cases go on to require surgery, and the optimal duration of nonoperative treatment is unknown. In this study, we evaluate the cost-effectiveness of early versus late arthroscopic debridement for the treatment of superficial TFCC tears without distal radioulnar joint (DRUJ) instability. Methods: We created a decision tree to compare the following strategies from a healthcare payer perspective: immediate arthroscopic debridement versus immobilization for 4 or 6 weeks with late debridement as needed. Costs were obtained from the Centers for Medicaid and Medicare Services and a national administrative claims database. Probabilities and health-related quality-of-life measures were obtained from published sources. We conducted sensitivity analyses on model inputs, including a probabilistic sensitivity analysis consisting of 10,000 Monte Carlo simulations. Results: Immobilization for 6 weeks while reserving arthroscopic debridement for refractory cases was both the least costly and most effective strategy. Immediate arthroscopic debridement became cost-effective when success rates of immobilization for 4 or 6 weeks were less than 7.7 or 10.5%, respectively. Our probabilistic sensitivity analysis showed that immobilization for 6 weeks was preferred 97.6% of the time, and immobilization for 4 weeks was preferred 2.4% of the time. Conclusion: Although various early and late debridement strategies can be used to treat superficial TFCC tears without DRUJ instability, immobilization for 6 weeks while reserving arthroscopic debridement for refractory cases is the optimal strategy from a cost-effectiveness standpoint.

Contrast-enhanced pelvic magnetic resonance imaging (MRI) for the prediction of treatment response in mucinous rectal cancer.

Background: In mucinous rectal cancer, it can be difficult to differentiate between cellular and acellular mucin. The purpose of this study was to evaluate, in patients with mucinous rectal cancer, the value of static enhancement (enh) and pharmacokinetic parameters of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in predicting pathologic complete response. Methods: This retrospective cross-sectional study performed at Memorial Sloan Kettering Cancer Center included 43 patients (24 males and 19 females; mean age, 57 years) with mucinous rectal cancer who underwent MRI at baseline as well as after neoadjuvant chemoradiotherapy but before surgical resection between 2008 and 2019. Two radiologists independently segmented tumors on contrast-enhanced axial 3D T1-weighted images and sagittal DCE magnetic resonance images. On contrast-enhanced axial T1-weighted images, the static parameters enh and relative enhancement (renh) were estimated. On DCE images, the pharmacokinetic parameters Ktrans, kep, relative Ktrans (rKtrans), and relative kep (rkep) were estimated. Associations between all parameters with pathologic complete response were tested using Wilcoxon signed-rank tests. Receiver operating characteristic (ROC) analysis was performed to assess the area under the curve (AUC) for each parameter. Results: Of the 43 patients who were included in the study, 42/43 (98%) had evaluable contrast-enhanced axial T1-weighted images and 35/43 (81%) had evaluable DCE images. Of the patients with evaluable contrast-enhanced axial T1-weighted images, 9/42 (21%) had pathologic complete response and 33/42 (79%) did not have pathologic complete response. For reader 1, enh(pre-neoadjuvant chemotherapy), enh(post-neoadjuvant chemotherapy), and renh were significant predictors of pathologic complete response [P=0.045 (AUC =0.73), 0.039 (AUC =0.74), and 0.0042, respectively]. For reader 2, enh(pre-neoadjuvant chemotherapy) and renh were significant predictors [P=0.021 (AUC =0.77) and 0.002, respectively]. For renh, the AUC was 0.83 for reader 1, and 0.82 for reader 2. Meanwhile, of those patients with evaluable DCE images, 9/35 (26%) had pathologic complete response and 26/35 (74%) did not have pathologic complete response. Ktrans(pre-neoadjuvant chemotherapy), kep(pre-neoadjuvant chemotherapy), and rkep were significant predictors [P=0.016 (AUC =0.73), 0.00057 (AUC =0.81), and 0.0096 (AUC =0.74), respectively]. Conclusions: Static and pharmacokinetic parameters of contrast-enhanced MRI show promise to predict neoadjuvant treatment response. Static enh parameters, which are simpler to assess, showed the strongest prediction.

Murine Progeria Model Exhibits Delayed Fracture Healing with Dysregulated Local Immune Response.

Background: Bone fracture is one of the most globally prevalent injuries, with an estimated 189 million bone fractures occurring annually. Delayed union or nonunion occurs in up to 15% of fractures and involves the interruption or complete failure of bone continuity following fracture. Preclinical testing is essential to support the translation of novel strategies to promote improved fracture repair treatment, but there is a paucity of small animal models that recapitulate clinical attributes associated with delayed fracture healing. This study explores whether the Zmpste24 -/- (Z24 -/- ) knockout mouse model of Hutchinson-Gilford progeria syndrome presents with delayed fracture healing. Leveraging the previously characterized Z24 -/- phenotype of genomic instability, epigenetic changes, and fragility, we hypothesize that these underlying alterations will lead to significantly delayed fracture healing relative to age-matched wild type (WT) controls. Methods: WT and Z24 -/- mice received intramedullary fixed tibia fractures at ∼12 weeks of age. Mice were sacrificed throughout the time course of repair for the collection of organs that would provide information regarding the local (fracture callus, bone marrow, inguinal lymph nodes) versus peripheral (peripheral blood, contralateral tibia, abdominal organs) tissue microenvironments. Analyses of these specimens include histomorphometry, µCT, mechanical strength testing, protein quantification, gene expression analysis, flow cytometry for cellular senescence, and immunophenotyping. Results: Z24 -/- mice demonstrated a significantly delayed rate of healing compared to WT mice with consistently smaller fracture calli containing higher proportion of cartilage and less bone after injury. Cellular senescence and pro-inflammatory cytokines were elevated in the Z24 -/- mice before and after fracture. These mice further presented with a dysregulated immune system, exhibiting generally decreased lymphopoiesis and increased myelopoiesis locally in the bone marrow, with more naïve and less memory T cell but greater myeloid activation systemically in the peripheral blood. Surprisingly, the ipsilateral lymph nodes had increased T cell activation and other pro-inflammatory NK and myeloid cells, suggesting that elevated myeloid abundance and activation contributes to an injury-specific hyperactivation of T cells. Conclusion: Taken together, these data establish the Z24 -/- progeria mouse as a model of delayed fracture healing that exhibits decreased bone in the fracture callus, with weaker overall bone quality, immune dysregulation, and increased cellular senescence. Based on this mechanism for delayed healing, we propose this Z24 -/- progeria mouse model could be useful in testing novel therapeutics that could address delayed healing. The Translational Potential of this Article: This study employs a novel animal model for delayed fracture healing that researchers can use to screen fracture healing therapeutics to address the globally prevalent issue of aberrant fracture healing.

Circulating free insulin-like growth factor-I and prostate cancer: a case-control study nested in the European prospective investigation into cancer and nutrition.

BACKGROUND: Circulating total insulin-like growth factor-I (IGF-I) is an established risk factor for prostate cancer. However, only a small proportion of circulating IGF-I is free or readily dissociable from IGF-binding proteins (its bioavailable form), and few studies have investigated the association of circulating free IGF-I with prostate cancer risk. METHODS: We analyzed data from 767 prostate cancer cases and 767 matched controls nested within the European Prospective Investigation into Cancer and Nutrition cohort, with an average of 14-years (interquartile range = 2.9) follow-up. Matching variables were study center, length of follow-up, age, and time of day and fasting duration at blood collection. Circulating free IGF-I concentration was measured in serum samples collected at recruitment visit (mean age 55 years old; standard deviation = 7.1) using an enzyme-linked immunosorbent assay (ELISA). Conditional logistic regressions were performed to examine the associations of free IGF-I with risk of prostate cancer overall and subdivided by time to diagnosis (≤ 14 and > 14 years), and tumor characteristics. RESULTS: Circulating free IGF-I concentrations (in fourths and as a continuous variable) were not associated with prostate cancer risk overall (odds ratio [OR] = 1.00 per 0.1 nmol/L increment, 95% CI: 0.99, 1.02) or by time to diagnosis, or with prostate cancer subtypes, including tumor stage and histological grade. CONCLUSIONS: Estimated circulating free IGF-I was not associated with prostate cancer risk. Further research may consider other assay methods that estimate bioavailable IGF-I to provide more insight into the well-substantiated association between circulating total IGF-I and subsequent prostate cancer risk.

The Reconstructive Metaverse - Collaboration in Real-Time Shared Mixed Reality Environments for Microsurgical Reconstruction.

Plastic surgeons routinely use 3D-models in their clinical practice, from 3D-photography and surface imaging to 3D-segmentations from radiological scans. However, these models continue to be viewed on flattened 2D screens that do not enable an intuitive understanding of 3D-relationships and cause challenges regarding collaboration with colleagues. The Metaverse has been proposed as a new age of applications building on modern Mixed Reality headset technology that allows remote collaboration on virtual 3D-models in a shared physical-virtual space in real-time. We demonstrate the first use of the Metaverse in the context of reconstructive surgery, focusing on preoperative planning discussions and trainee education. Using a HoloLens headset with the Microsoft Mesh application, we performed planning sessions for 4 DIEP-flaps in our reconstructive metaverse on virtual patient-models segmented from routine CT angiography. In these sessions, surgeons discuss perforator anatomy and perforator selection strategies whilst comprehensively assessing the respective models. We demonstrate the workflow for a one-on-one interaction between an attending surgeon and a trainee in a video featuring both viewpoints as seen through the headset. We believe the Metaverse will provide novel opportunities to use the 3D-models that are already created in everyday plastic surgery practice in a more collaborative, immersive, accessible, and educational manner.

Identifying proteomic risk factors for overall, aggressive, and early onset prostate cancer using Mendelian Randomisation and tumour spatial transcriptomics.

BACKGROUND: Understanding the role of circulating proteins in prostate cancer risk can reveal key biological pathways and identify novel targets for cancer prevention. METHODS: We investigated the association of 2002 genetically predicted circulating protein levels with risk of prostate cancer overall, and of aggressive and early onset disease, using cis-pQTL Mendelian randomisation (MR) and colocalisation. Findings for proteins with support from both MR, after correction for multiple-testing, and colocalisation were replicated using two independent cancer GWAS, one of European and one of African ancestry. Proteins with evidence of prostate-specific tissue expression were additionally investigated using spatial transcriptomic data in prostate tumour tissue to assess their role in tumour aggressiveness. Finally, we mapped risk proteins to drug and ongoing clinical trials targets. FINDINGS: We identified 20 proteins genetically linked to prostate cancer risk (14 for overall [8 specific], 7 for aggressive [3 specific], and 8 for early onset disease [2 specific]), of which the majority replicated where data were available. Among these were proteins associated with aggressive disease, such as PPA2 [Odds Ratio (OR) per 1 SD increment = 2.13, 95% CI: 1.54-2.93], PYY [OR = 1.87, 95% CI: 1.43-2.44] and PRSS3 [OR = 0.80, 95% CI: 0.73-0.89], and those associated with early onset disease, including EHPB1 [OR = 2.89, 95% CI: 1.99-4.21], POGLUT3 [OR = 0.76, 95% CI: 0.67-0.86] and TPM3 [OR = 0.47, 95% CI: 0.34-0.64]. We confirmed an inverse association of MSMB with prostate cancer overall [OR = 0.81, 95% CI: 0.80-0.82], and also found an inverse association with both aggressive [OR = 0.84, 95% CI: 0.82-0.86] and early onset disease [OR = 0.71, 95% CI: 0.68-0.74]. Using spatial transcriptomics data, we identified MSMB as the genome-wide top-most predictive gene to distinguish benign regions from high grade cancer regions that comparatively had five-fold lower MSMB expression. Additionally, ten proteins that were associated with prostate cancer risk also mapped to existing therapeutic interventions. INTERPRETATION: Our findings emphasise the importance of proteomics for improving our understanding of prostate cancer aetiology and of opportunities for novel therapeutic interventions. Additionally, we demonstrate the added benefit of in-depth functional analyses to triangulate the role of risk proteins in the clinical aggressiveness of prostate tumours. Using these integrated methods, we identify a subset of risk proteins associated with aggressive and early onset disease as priorities for investigation for the future prevention and treatment of prostate cancer. FUNDING: This work was supported by Cancer Research UK (grant no. C8221/A29017).

Towards electrophysiological measurement of presence in virtual reality through auditory oddball stimuli.

OBJECTIVE: Presence is an important aspect of user experience in virtual reality. It corresponds to the illusion of being physically located in a virtual environment. This feeling is usually measured through questionnaires that disrupt presence, are subjective and do not allow for real-time measurement. Electroencephalography (EEG), which measures brain activity, is increasingly used to monitor the state of users, especially while immersed in virtual reality. APPROACH: In this paper, we present a way of evaluating presence, through the measure of the attention dedicated to the real environment via an EEG oddball paradigm. Using breaks in presence (BiP), this experimental protocol constitutes an ecological method for the study of presence, as different levels of presence are experienced in an identical virtual environment. MAIN RESULTS: Through analyzing the EEG data of 18 participants, a significant increase in the neurophysiological reaction to the oddball, i.e., the P300 amplitude, was found in low presence condition compared to high presence condition. This amplitude was significantly correlated with the self-reported measure of presence. Using Riemannian geometry to perform single-trial classification, we present a classification algorithm with 79% accuracy in detecting between two presence conditions. SIGNIFICANCE: Taken together our results promote the use of EEG and oddball stimuli to monitor presence offline or in real-time without interrupting the user in the virtual environment.

Watch and Wait in Rectal Cancer Patients with Residual Mucin on MRI following Neoadjuvant Therapy.

BACKGROUND: Neoadjuvant therapy (NAT) leads to a clinical complete response (cCR) in a significant proportion of patients with locally advanced rectal cancer (LARC), allowing for possible nonoperative management. The presence of mucin on MRI after NAT leads to uncertainty about residual disease and appropriateness of a watch-and-wait (WW) strategy in patients with no evidence of disease on proctoscopy (endoscopic cCR). METHODS: MRI reports for LARC patients seen between July 2016 and January 2020 at Memorial Sloan Kettering Cancer Center were queried for presence of mucin in the tumor bed on MRI following NAT. Clinicodemographic, pathologic, and outcome data were compiled and analyzed. RESULTS: Of 71 patients with mucin on post-treatment MRI, 20 had a cCR and 51 had abnormalities on endoscopy and/or physical exam. One patient with a cCR opted out of WW; thus, 19 patients (27%) entered WW and 52 patients (73%) were planned for surgery (Non-WW). Of the 19 WW patients, 15 (79%) have had no local regrowth with median follow-up of 50 months (range, 29-76 months), while 4 (21%) experienced regrowth between 9 and 29 months after neoadjuvant therapy. Of the 52 patients who were planned to have surgery (Non-WW), 49 underwent resection while 3 developed metastatic disease that precluded curative-intent surgery. Five (10%) of the 49 patients who underwent surgery, including the one with an endoscopic cCR, had a pathologic complete response. CONCLUSIONS: The presence of mucin after NAT for LARC does not preclude WW management in otherwise appropriate candidates who achieve an endoscopic cCR.

Determinants of Systemic SARS-CoV-2-Specific Antibody Responses to Infection and to Vaccination: A Secondary Analysis of Randomised Controlled Trial Data.

SARS-CoV-2 infections elicit antibodies against the viral spike (S) and nucleocapsid (N) proteins; COVID-19 vaccines against the S-protein only. The BCG-Corona trial, initiated in March 2020 in SARS-CoV-2-naïve Dutch healthcare workers, captured several epidemic peaks and the introduction of COVID-19 vaccines during the one-year follow-up. We assessed determinants of systemic anti-S1 and anti-N immunoglobulin type G (IgG) responses using trial data. Participants were randomised to BCG or placebo vaccination, reported daily symptoms, SARS-CoV-2 test results, and COVID-19 vaccinations, and donated blood for SARS-CoV-2 serology at two time points. In the 970 participants, anti-S1 geometric mean antibody concentrations (GMCs) were much higher than anti-N GMCs. Anti-S1 GMCs significantly increased with increasing number of immune events (SARS-CoV-2 infection or COVID-19 vaccination): 104.7 international units (IU)/mL, 955.0 IU/mL, and 2290.9 IU/mL for one, two, and three immune events, respectively (p < 0.001). In adjusted multivariable linear regression models, anti-S1 and anti-N log10 concentrations were significantly associated with infection severity, and anti-S1 log10 concentration with COVID-19 vaccine type/dose. In univariable models, anti-N log10 concentration was also significantly associated with acute infection duration, and severity and duration of individual symptoms. Antibody concentrations were not associated with long COVID or long-term loss of smell/taste.

One hundred fifty years of total laryngectomies.

The inaugural total laryngectomy in history was conducted by Billroth in 1873. Nevertheless, significant enhancements to the technique were achieved through the contributions of Gluck, Sorensen, and various other surgeons. Throughout the twentieth century, advancements in anesthesia, infectious disease, hospital hygiene, antibiotic therapy, resuscitation, and the expertise of numerous laryngologists elevated total laryngectomy to a pivotal surgical intervention in head and neck surgery. The latter half of the twentieth century witnessed a paradigm shift with the emergence of organ preservation protocols. Total laryngectomy became the preferred choice for patients experiencing radiotherapy failure. However, the widespread use of laryngeal conservative treatments appears to be correlated with a decline in overall survival rates in the United States and Europe. The evolution of new minimally invasive surgical approaches in the twenty-first century may usher in a revolutionary era in the management of laryngeal carcinoma, offering the potential for improved survival and functional outcomes.

Harnessing ecological theory to enhance ecosystem restoration.

Ecosystem restoration can increase the health and resilience of nature and humanity. As a result, the international community is championing habitat restoration as a primary solution to address the dual climate and biodiversity crises. Yet most ecosystem restoration efforts to date have underperformed, failed, or been burdened by high costs that prevent upscaling. To become a primary, scalable conservation strategy, restoration efficiency and success must increase dramatically. Here, we outline how integrating ten foundational ecological theories that have not previously received much attention - from hierarchical facilitation to macroecology - into ecosystem restoration planning and management can markedly enhance restoration success. We propose a simple, systematic approach to determining which theories best align with restoration goals and are most likely to bolster their success. Armed with a century of advances in ecological theory, restoration practitioners will be better positioned to more cost-efficiently and effectively rebuild the world's ecosystems and support the resilience of our natural resources.

Long-term data reveal that grazer density mediates climatic stress in salt marshes.

Understanding how climate and local stressors interact is paramount for predicting future ecosystem structure. The effects of multiple stressors are often examined in small-scale and short-term field experiments, limiting understanding of the spatial and temporal generality of the findings. Using a 22-year observational dataset of plant and grazer abundance in a southeastern US salt marsh, we analyzed how changes in drought and grazer density combined to affect plant biomass. We found: (1) increased drought severity and higher snail density both correlated with lower plant biomass; (2) drought and snail effects interacted additively; and, (3) snail effects had a threshold, with additive top-down effects only occurring when snails were present at high densities. These results suggest that the emergence of multiple stressor effects can be density dependent, and they validate short-term experimental evidence that consumers can augment environmental stress. These findings have important implications for predicting future ecosystem structure and managing natural ecosystems.

Peroperative administration of tranexamic acid in Roux-en-Y and one-anastomosis gastric bypass to reduce haemorrhage in patients with morbid obesity: protocol for randomised controlled trial (PATRY trial).

INTRODUCTION: By implementation of Enhanced Recovery After Bariatric Surgery protocols and day-care surgery, early discharge poses a challenge if excessive bleeding occurs after bariatric surgery. Tranexamic acid (TXA) has demonstrated efficacy in other surgical fields and in bariatric pilot studies. This trial aims to assess the efficacy of peroperative administration of TXA in reducing haemorrhage in patients undergoing gastric bypass surgery. METHOD AND ANALYSIS: This is a multicentre, phase III, double-blind randomised controlled trial in six high-volume bariatric centres in the Netherlands. A total of 1524 eligible patients, aged 18 years or older, undergoing primary gastric bypass surgery (either Roux-en-Y gastric bypass or one-anastomosis gastric bypass) will be randomised between TXA and placebo (1:1, variable block, stratified for centre, day-care/overnight stay and type of surgery) after obtaining informed consent (2.5% less haemorrhage, power 80%, 2-sided-α 0.05 and 10% dropout). Exclusion criteria are pregnancy, amedical history of acute bleeding (without cause), venous thrombotic events (VTEs), epilepsy, anticoagulant use and iatrogenic bleeding during surgery (aside from staple line). The primary outcome is postoperative haemorrhage requiring intervention within 30 days postoperatively. Secondary outcome measures are staple line reinforcement, blood loss, duration of surgery, postoperative haemoglobin, vital parameters, minor and major complications, side effects of TXA (nausea, hypotension and VTE), length of hospital stay and directly made costs. ETHICS AND DISSEMINATION: Written informed consent will be obtained from all participants. The protocol has been approved by the Medical Research Ethics Committees United, Nieuwegein, on 7 February 2023 (registration number: R22.102). Results will be disseminated through peer-reviewed publications and conferences. TRIAL REGISTRATION NUMBER: NCT05464394.