Fasciola gigantica: Ultrastructural localisation of neoblast recruitment in somatic tissues during growth and development in the hepatic parenchyma of experimentally infected mice.

Application of 'omics' technology, and advances in in vitro methods for studying the growth of Fasciola hepatica, have highlighted the central role of migrating neoblasts in driving forward development and differentiation towards the adult-like form. Neoblast populations present molecular heterogeneity, morphological variation and changes associated with recruitment of these stem cells into their final tissue locations. However, terminal differentiation towards function, has received much less attention than has been the case for the free-living Platyhelminths. An actively replicating neoblast population, comprising cells with heterochromatic nuclei consistent with regulation of gene expression, has been identified in the parenchyma of juvenile Fasciola gigantica migrating in the liver of experimentally infected mice. In some of these cells, early cytoplasmic differentiation towards myocyte function was noted. Neoblasts have also been identified close to, and incorporated in, the subtegumental zone, the gastrodermis and the excretory ducts. In these locations, progressive morphological differentiation towards terminal function has been described. This includes the appearance of specific progenitors of type-1, type-2 and type-3 tegumental cells, the latter possibly contributing to tegumental spine development. 'Cryptic' surface molecular differentiation is postulated to account for recognition and 'docking' of migrating neoblasts with their final site for terminal differentiation.

Implementation and evaluation of a SARI surveillance system in a tertiary hospital in Scotland in 2021/2022.

OBJECTIVE: To set up and evaluate a new surveillance system for severe acute respiratory infection (SARI) in Scotland. STUDY DESIGN: Cross-sectional study and evaluation of surveillance system. METHODS: The SARI case definition comprised patients aged 16 years or over with an acute respiratory illness presentation requiring testing for influenza and SARS-CoV-2 and hospital admission. Data were collected from SARI cases by research nurses in one tertiary teaching hospital using a bespoke data collection tool from November 2021 to May 2022. Descriptive analyses of SARI cases were carried out. The following attributes of the surveillance system were evaluated according to Centers for Disease Control and Prevention (CDC) guidelines: stability, data quality, timeliness, positive predictive value, representativeness, simplicity, acceptability and flexibility. RESULTS: The final surveillance dataset comprised 1163 records, with cases peaking in ISO week 50 (week ending 19/12/2021). The system produced a stable stream of surveillance data, with the proportion of SARI records with sufficient information for effective surveillance increasing from 65.4% during the first month to 87.0% over time. Similarly, the proportion where data collection was completed promptly was low initially, but increased to 50%-65% during later periods. CONCLUSION: SARI surveillance was successfully established in one hospital, but for a national system, additional sentinel hospital sites across Scotland, with flexibility to ensure consistently high data completeness and timeliness are needed. Data collection should be automated where possible, and demands on clinicians minimised. SARI surveillance should be embedded and resourced as part of a national respiratory surveillance strategy.

Risk of Long-Term Ischemic Stroke in Patients With Traumatic Brain Injury and Incident Hypertension.

Traumatic brain injury (TBI) is independently associated with hypertension and ischemic stroke. The goal of this study was to determine the interplay between TBI and incident hypertension in the occurrence of post-TBI stroke. This prospective study used a hospital-based registry to identify patients without pre-existing comorbidities. TBI patients (n = 3664) were frequency matched on age, sex, and race to non-TBI patients (n = 1848). Follow-up started 6 months post-TBI or study entry and extended up to 10 years. To examine hypertension's role in post-TBI stroke, we used logistic regression models to calculate the effect estimates for stroke in four exposure categories that included TBI or hypertension in isolation and in combination. Second, we calculated the conditional direct effect (CDE) of TBI in models that considered hypertension as intermediary. Third, we examined whether TBI effect was modified by antihypertensive medication use. The 10-year cumulative incidence of stroke was higher in the TBI group (4.7%) than the non-TBI group (1.3%; p < 0.001). TBI patients who developed hypertension had the highest risk of stroke (odds ratio [OR] = 4.83, 95% confidence interval [CI] = 2.53-9.23, p < 0.001). The combined effect estimates were less than additive, suggesting an overlapping biological pathway. The total effect of TBI (OR = 3.16, 95% CI = 1.94-5.16, p < 0.001) was higher than the CDE that accounted for hypertension (OR = 2.45, 95% CI = 0.93-6.47, p = 0.06). Antihypertensives attenuated the TBI effect, suggesting that the TBI effect on stroke is partially mediated through hypertension. TBI is an independent risk factor for long-term stroke, and the underlying biological pathway may partly operate through TBI-precipitated hypertension. These findings suggest that screening for hypertension may mitigate stroke risk in TBI.

C-STIM: Protocol for a randomized, single-blind, crossover study of cerebellar repetitive transcranial magnetic stimulation (rTMS) for postural instability in people with progressive supranuclear palsy (PSP).

Background: Methods for modulating the cerebellum with transcranial magnetic stimulation (TMS) are well established, and preliminary data from our group and others has shown evidence of transient improvements in balance after cerebellar repetitive transcranial magnetic stimulation (rTMS) in progressive suprancuclear palsy (PSP). This study examines extensive posturography measures before and after 10 sessions of cerebellar rTMS and sham TMS in PSP. Methods: Thirty subjects with PSP and postural instability will undergo cerebellar active and sham rTMS in a single-blind, crossover design with a randomized order of a 10-day intervention. Primary outcomes will be changes in sway area and medio-lateral range of sway with eyes open while standing on a stationary force-plate, and safety, tolerability, and blindedness. Secondary outcomes will include posturography and gait analysis with body-worn, triaxial inertial sensors, clinical balance scales and questionnaires, and a bedside test of vestibular function. Exploratory outcomes are changes in functional near infrared spectroscopy (fNIRS) signal over the prefrontal, supplementary motor, and primary motor cortices while standing and walking, and speech samples for future analysis. Discussion: The C-STIM crossover intervention study adds a longer duration of stimulation and extensive posturography measures to more finely measure the improvements in balance and exploratory functional near-infrared spectroscopy (fNIRS) over the prefronal, supplementary motor, and primary motor cortices during balance assessments before and after 10 sessions of cerebellar rTMS and 10 sessions of sham cerebellar TMS. This project will improve our understanding of the importance of the cerebellum for control of postural stability in PSP.

Venous thromboembolism in multiple myeloma: Increasing evidence in support of direct oral anticoagulants.

Venous thromboembolism (VTE) continues to cause significant morbidity and excess mortality in patients with multiple myeloma. The report by Costa and colleagues demonstrates superiority of direct oral anticoagulants over aspirin in terms of VTE prevention, without increased bleeding complications seen. Commentary on: Costa et al. Direct oral anticoagulants versus aspirin for primary thromboprophylaxis in patients with multiple myeloma undergoing outpatient therapy: A systematic review and updated meta-analysis. Br J Haematol 2023;203:395-403.

Machine learning can accurately predict risk factors for all-cause reoperation after ACLR: creating a clinical tool to improve patient counseling and outcomes.

PURPOSE: Identifying predictive factors for all-cause reoperation after anterior cruciate ligament reconstruction could inform clinical decision making and improve risk mitigation. The primary purposes of this study are to (1) determine the incidence of all-cause reoperation after anterior cruciate ligament reconstruction, (2) identify predictors of reoperation after anterior cruciate ligament reconstruction using machine learning methodology, and (3) compare the predictive capacity of the machine learning methods to that of traditional logistic regression. METHODS: A longitudinal geographical database was utilized to identify patients with a diagnosis of new anterior cruciate ligament injury. Eight machine learning models were appraised on their ability to predict all-cause reoperation after anterior cruciate ligament reconstruction. Model performance was evaluated via area under the receiver operating characteristics curve. To explore modeling interpretability and radiomic feature influence on the predictions, we utilized a game-theory-based method through SHapley Additive exPlanations. RESULTS: A total of 1400 patients underwent anterior cruciate ligament reconstruction with a mean postoperative follow-up of 9 years. Two-hundred and eighteen (16%) patients experienced a reoperation after anterior cruciate ligament reconstruction, of which 6% of these were revision ACL reconstruction. SHapley Additive exPlanations plots identified the following risk factors as predictive for all-cause reoperation: diagnosis of systemic inflammatory disease, distal tear location, concomitant medial collateral ligament repair, higher visual analog scale pain score prior to surgery, hamstring autograft, tibial fixation via radial expansion device, younger age at initial injury, and concomitant meniscal repair. Pertinent negatives, when compared to previous studies, included sex and timing of surgery. XGBoost was the best-performing model (area under the receiver operating characteristics curve of 0.77) and outperformed logistic regression in this regard. CONCLUSIONS: All-cause reoperation after anterior cruciate ligament reconstruction occurred at a rate of 16%. Machine learning models outperformed traditional statistics and identified diagnosis of systemic inflammatory disease, distal tear location, concomitant medial collateral ligament repair, higher visual analog scale pain score prior to surgery, hamstring autograft, tibial fixation via radial expansion device, younger age at initial injury, and concomitant meniscal repair as predictive risk factors for reoperation. Pertinent negatives, when compared to previous studies, included sex and timing of surgery. These models will allow surgeons to tabulate individualized risk for future reoperation for patients undergoing anterior cruciate ligament reconstruction. LEVEL OF EVIDENCE: III.

A Deep Learning Tool for Automated Landmark Annotation on Hip and Pelvis Radiographs.

BACKGROUND: Automatic methods for labeling and segmenting pelvis structures can improve the efficiency of clinical and research workflows and reduce the variability introduced with manual labeling. The purpose of this study was to develop a single deep learning model to annotate certain anatomical structures and landmarks on antero-posterior (AP) pelvis radiographs. METHODS: A total of 1,100 AP pelvis radiographs were manually annotated by 3 reviewers. These images included a mix of preoperative and postoperative images as well as a mix of AP pelvis and hip images. A convolutional neural network was trained to segment 22 different structures (7 points, 6 lines, and 9 shapes). Dice score, which measures overlap between model output and ground truth, was calculated for the shapes and lines structures. Euclidean distance error was calculated for point structures. RESULTS: Dice score averaged across all images in the test set was 0.88 and 0.80 for the shape and line structures, respectively. For the 7-point structures, average distance between real and automated annotations ranged from 1.9 mm to 5.6 mm, with all averages falling below 3.1 mm except for the structure labeling the center of the sacrococcygeal junction, where performance was low for both human and machine-produced labels. Blinded qualitative evaluation of human and machine produced segmentations did not reveal any drastic decrease in performance of the automatic method. CONCLUSION: We present a deep learning model for automated annotation of pelvis radiographs that flexibly handles a variety of views, contrasts, and operative statuses for 22 structures and landmarks.

Evidence for a feeding related association between melanocortin in the NTS and Neuropeptide-Y in the PVN.

Melanocortin and neuropeptide-Y (NPY) are both involved in feeding and energy regulation, and they have opposite effects in the paraventricular nucleus of the hypothalamus (PVN). The present study examined an interaction between melanocortin in the nucleus of the solitary tract (NTS) and NPY in the PVN. Male Sprague-Dawley rats were implanted with cannulae in the injection sites of interest. In Experiment 1, subjects received either the melanocortin 3/4-receptor (MC3/4) antagonist SHU9119 (0, 10, 50 and 100 pmol/0.5 µl) or the MC3/4 agonist MTII (0, 10, 50, 100 and 200 pmol/0.5 µl) into the NTS. Food intake was measured at 1, 2, 4, 6 and 24-h post-injection. Administration of SHU9119 into the NTS significantly and dose-dependently increased food intake at 1, 2, 4, 6 and 6-24-h, and administration of MTII into the NTS significantly and dose-dependently decreased 24-h free feeding. In Experiment 2, subjects received the MC3/4 agonist MTII (0, 10, 50, 100 and 200 pmol/0.5 µl) into the NTS just prior to NPY (0 and 1µg/0.5 µl) in the PVN. PVN injection of NPY stimulated feeding, and administration of MTII (50, 100 and 200 pmol) into the NTS significantly and dose-dependently decreased NPY-induced feeding at 2, 4, 6 and 6-24-h. These data suggest that there could be a neuronal association between melanocortin in the NTS and NPY in the PVN, and that the melanocortin system in the NTS has an antagonistic effect on NPY-induced feeding in the PVN.

Detection of Ureaplasma diversum in the upper airways of Australian feedlot cattle.

Bovine respiratory disease (BRD) exerts a major impact on the beef cattle industry nationally and worldwide, with a range of aetiological factors impacting its pathogenesis. Previous research has focussed on an increasing number of bacteria and viruses that have been shown to play a role in eliciting disease. Recently, additional agents have been emerging as potential contributors to BRD, including the opportunistic pathogen Ureaplasma diversum. To determine if U. diversum was present in Australian feedlot cattle and if that presence was linked to BRD, nasal swabs were collected from a cohort of 34 hospital pen animals and compared to 216 apparently healthy animals sampled contemporaneously at feedlot induction and again after 14 days on feed at an Australian feedlot. All samples were subjected to a de novo polymerase chain reaction (PCR) assay targeting U. diversum in combination with other BRD agents. U. diversum was detected at a low prevalence in cattle at induction (Day 0: 6.9%, Day 14: 9.7%), but in a significantly greater proportion of cattle sampled from the hospital pen (58.8%). When considering the presence of other BRD-associated agents, co-detection of U. diversum and Mycoplasma bovis was most common in hospital pen animals receiving treatment for BRD. These findings suggest that U. diversum may be an opportunistic pathogen involved in the aetiology of BRD in Australian feedlot cattle, in combination with other agents, with further studies are warranted to identify if a causal relationship exists.

Frank Stinchfield Award: Creation of a Patient-Specific Total Hip Arthroplasty Periprosthetic Fracture Risk Calculator.

BACKGROUND: Many risk factors have been described for periprosthetic femur fracture (PPFFx) following total hip arthroplasty (THA), yet a patient-specific risk assessment tool remains elusive. The purpose of this study was to develop a high-dimensional, patient-specific risk-stratification nomogram that allows dynamic risk modification based on operative decisions. METHODS: We evaluated 16,696 primary nononcologic THAs performed between 1998 and 2018. During a mean 6-year follow-up, 558 patients (3.3%) sustained a PPFFx. Patients were characterized by individual natural language processing-assisted chart review on nonmodifiable factors (demographics, THA indication, and comorbidities), and modifiable operative decisions (femoral fixation [cemented/uncemented], surgical approach [direct anterior, lateral, and posterior], and implant type [collared/collarless]). Multivariable Cox regression models and nomograms were developed with PPFFx as a binary outcome at 90 days, 1 year, and 5 years, postoperatively. RESULTS: Patient-specific PPFFx risk based on comorbid profile was wide-ranging from 0.4-18% at 90 days, 0.4%-20% at 1 year, and 0.5%-25% at 5 years. Among 18 evaluated patient factors, 7 were retained in multivariable analyses. The 4 significant nonmodifiable factors included the following: women (hazard ratio (HR) = 1.6), older age (HR = 1.2 per 10 years), diagnosis of osteoporosis or use of osteoporosis medications (HR = 1.7), and indication for surgery other than osteoarthritis (HR = 2.2 for fracture, HR = 1.8 for inflammatory arthritis, HR = 1.7 for osteonecrosis). The 3 modifiable surgical factors were included as follows: uncemented femoral fixation (HR = 2.5), collarless femoral implants (HR = 1.3), and surgical approach other than direct anterior (lateral HR = 2.9, posterior HR = 1.9). CONCLUSION: This patient-specific PPFFx risk calculator demonstrated a wide-ranging risk based on comorbid profile and enables surgeons to quantify risk mitigation based on operative decisions. LEVEL OF EVIDENCE: Level III, Prognostic.

Shoulder arthroplasty after prior external beam radiation therapy: a matched cohort analysis.

BACKGROUND: External beam radiation therapy (XRT) is a commonly used therapeutic modality for the treatment of various chest wall and axillary malignancies. Despite the known risk of local soft tissue dysfunction, and possibly compromised bone ingrowth for cementless implants, there remains limited data on the impact of prior XRT in a shoulder arthroplasty (SA) cohort. This study evaluated the outcomes of primary SA in patients with prior XRT compared to a matched cohort (MC). METHODS: Over a 27-year time period (1993-2020), 80 primary SAs (7 hemiarthroplasties [HAs], 29 anatomic total shoulder arthroplasties [aTSAs], and 44 reverse shoulder arthroplasties [rTSAs]) with previous XRT to the upper chest or axillary region and a minimum of 2-year follow-up were included. This cohort was matched (1:2) according to age, sex, body mass index (BMI), implant, and year of surgery with patients who had undergone HA or TSA for osteoarthritis or RSA for cuff tear arthropathy. Clinical outcomes including pain, active shoulder range of motion (ROM), strength, complications, and reoperations inclusive of revision surgery were assessed. RESULTS: The XRT cohort consisted of 71 (88.8%) women with a mean age of 70.9 (range, 43-87) years, BMI of 30.9 ± 7.6, and follow-up period of 6.6 years (range, 2.0-28.2). In these patients, SA led to substantial improvements in pain, ROM, and strength across the entire cohort. When compared to the MC, the XRT group demonstrated a lower final postoperative forward elevation (FE) (111° vs. 126°; P = .013) and less improvements in pain (5.3 vs. 6.2; P = .002), FE (34° vs. 54°; P = .002), and external rotation (13° vs. 24°; P < .001). There were 14 (17.5%) complications and 7 reoperations in the XRT group, with rotator cuff failure after HA or TSA (n = 4 of 36; 11.1%) as the most common complication and no instances of loose humeral components. The XRT group had a higher rate of complications (17.5% vs. 8.1%; P = .03) but not reoperations (8.8% vs. 3.1%; P = .059). When evaluated by implant, rTSA demonstrated the lowest rate of reoperations followed by aTSA and HA (2.3% vs. 10.3% vs. 42.9%; P = .002). CONCLUSIONS: Primary SA is an effective treatment modality for the improvement of pain, motion, and strength in patients with a history of prior XRT. However, when compared to patients without prior XRT, less clinical improvement and a higher rate of postoperative complications were observed.

Patient-specific Hip Arthroplasty Dislocation Risk Calculator: An Explainable Multimodal Machine Learning-based Approach.

Purpose: To develop a multimodal machine learning-based pipeline to predict patient-specific risk of dislocation following primary total hip arthroplasty (THA). Materials and Methods: This study retrospectively evaluated 17 073 patients who underwent primary THA between 1998 and 2018. A test set of 1718 patients was held out. A hybrid network of EfficientNet-B4 and Swin-B transformer was developed to classify patients according to 5-year dislocation outcomes from preoperative anteroposterior pelvic radiographs and clinical characteristics (demographics, comorbidities, and surgical characteristics). The most informative imaging features, extracted by the mentioned model, were selected and concatenated with clinical features. A collection of these features was then used to train a multimodal survival XGBoost model to predict the individualized hazard of dislocation within 5 years. C index was used to evaluate the multimodal survival model on the test set and compare it with another clinical-only model trained only on clinical data. Shapley additive explanation values were used for model explanation. Results: The study sample had a median age of 65 years (IQR: 18 years; 52.1% [8889] women) with a 5-year dislocation incidence of 2%. On the holdout test set, the clinical-only model achieved a C index of 0.64 (95% CI: 0.60, 0.68). The addition of imaging features boosted multimodal model performance to a C index of 0.74 (95% CI: 0.69, 0.78; P = .02). Conclusion: Due to its discrimination ability and explainability, this risk calculator can be a potential powerful dislocation risk stratification and THA planning tool.Keywords: Conventional Radiography, Surgery, Skeletal-Appendicular, Hip, Outcomes Analysis, Supervised Learning, Convolutional Neural Network (CNN), Gradient Boosting Machines (GBM) Supplemental material is available for this article. © RSNA, 2022.

Efficiency-corrected PCR quantification for identification of prevalence and load of respiratory disease-causing agents in feedlot cattle.

Bovine respiratory disease (BRD) is the most prevalent disease in feedlot cattle worldwide with Bovine alphaherpesvirus 1 (BoAHV1), Histophilus somni, Mannheimia haemolytica, Mycoplasma bovis, Pasteurella multocida and Trueperella pyogenes accepted to be common etiological agents associated with BRD. Although these agents are common in the upper and lower airways in clinical BRD cases, some also exist as normal flora suggesting their presence in the upper airways alone is not necessarily informative with respect to disease status or risk. To determine the relationship between presence, load and disease status, we investigated the relationship between load in the upper airways at induction and active BRD cases in feedlot cattle using efficiency-corrected PCR quantification. By this approach, we were able to accurately determine the prevalence and load of the key BRD agents in the upper respiratory tract showing that cattle in the hospital pen had a higher prevalence, and load, of these agents both singly and in combination compared to cattle sampled at feedlot induction. A combination of agents was the most accurate indicator of BRD risk with cattle with four or more agents detected in the upper airway more likely to be undergoing treatment for BRD than non-BRD ailments. In addition, M. bovis was rarely detected at feedlot induction but was identified at high prevalence in cattle in the hospital pen. These findings present a potential new technological approach for the investigation, analysis and identification of BRD-associated viral and bacterial agents for Australian feedlot systems as well as for BRD disease management and treatment.

CyBorD-DARA in Newly Diagnosed Transplant-Eligible Multiple Myeloma: Results from the 16-BCNI-001/CTRIAL-IE 16-02 Study Show High Rates of MRD Negativity at End of Treatment.

The phase 1b 16-BCNI-001/CTRIAL-IE 16-02 CyBorD-DARA trial investigated the combination of Daratumumab with cyclophosphamide, bortezomib and dexamethasone in patients with newly diagnosed multiple myeloma (NDMM), followed by autologous stem cell transplantation and Daratumumab maintenance. CR/sCR rates were 50% after transplant and 62.5% at end of treatment. The overall percentage of patients achieving complete response or better was 77.8%. Progression-free survival rate at end of maintenance was 81.3% and estimated 2-year overall survival was 88.9%. 37.5% of patients demonstrated sustained MRD negativity to a level of 10-5 from transplant to analysis at EOT. In this phase 1b study, we have shown CyBorD-DARA to be an effective and well-tolerated immunomodulatory agent-free regiment in transplant-eligible NDMM.

Applying Deep Learning to Establish a Total Hip Arthroplasty Radiography Registry: A Stepwise Approach.

BACKGROUND: Establishing imaging registries for large patient cohorts is challenging because manual labeling is tedious and relying solely on DICOM (digital imaging and communications in medicine) metadata can result in errors. We endeavored to establish an automated hip and pelvic radiography registry of total hip arthroplasty (THA) patients by utilizing deep-learning pipelines. The aims of the study were (1) to utilize these automated pipelines to identify all pelvic and hip radiographs with appropriate annotation of laterality and presence or absence of implants, and (2) to automatically measure acetabular component inclination and version for THA images. METHODS: We retrospectively retrieved 846,988 hip and pelvic radiography DICOM files from 20,378 patients who underwent primary or revision THA performed at our institution from 2000 to 2020. Metadata for the files were screened followed by extraction of imaging data. Two deep-learning algorithms (an EfficientNetB3 classifier and a YOLOv5 object detector) were developed to automatically determine the radiographic appearance of all files. Additional deep-learning algorithms were utilized to automatically measure the acetabular angles on anteroposterior pelvic and lateral hip radiographs. Algorithm performance was compared with that of human annotators on a random test sample of 5,000 radiographs. RESULTS: Deep-learning algorithms enabled appropriate exclusion of 209,332 DICOM files (24.7%) as misclassified non-hip/pelvic radiographs or having corrupted pixel data. The final registry was automatically curated and annotated in <8 hours and included 168,551 anteroposterior pelvic, 176,890 anteroposterior hip, 174,637 lateral hip, and 117,578 oblique hip radiographs. The algorithms achieved 99.9% accuracy, 99.6% precision, 99.5% recall, and a 99.6% F1 score in determining the radiograph appearance. CONCLUSIONS: We developed a highly accurate series of deep-learning algorithms to rapidly curate and annotate THA patient radiographs. This efficient pipeline can be utilized by other institutions or registries to construct radiography databases for patient care, longitudinal surveillance, and large-scale research. The stepwise approach for establishing a radiography registry can further be utilized as a workflow guide for other anatomic areas. LEVEL OF EVIDENCE: Diagnostic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Underwater visibility constrains the foraging behaviour of a diving pelagic seabird.

Understanding the sensory ecology of species is vital if we are to predict how they will function in a changing environment. Visual cues are fundamentally important for many predators when detecting and capturing prey. However, many marine areas have become more turbid through processes influenced by climate change, potentially affecting the ability of marine predators to detect prey. We performed the first study that directly relates a pelagic seabird species's foraging behaviour to oceanic turbidity. We collected biologging data from 79 foraging trips and 5472 dives of a visually dependent, pursuit-diving seabird, the Manx shearwater (Puffinus puffinus). Foraging behaviour was modelled against environmental variables affecting underwater visibility, including water turbidity, cloud cover and solar angle. Shearwaters were more likely to initiate area-restricted search and foraging dives in clearer waters. Underwater visibility also strongly predicted dive rate and depth, suggesting that fine-scale prey capture was constrained by the detectability of prey underwater. Our novel use of dynamic descriptors of underwater visibility suggests that visual cues are vital for underwater foraging. Our data indicate that climate change could negatively impact seabird populations by making prey more difficult to detect, compounded by the widely reported effects of reduced prey populations.

Aerosol delivery of star polymer-siRNA nanoparticles as a therapeutic strategy to inhibit lung tumor growth.

Lung cancer is a major contributor to cancer-related death worldwide. siRNA nanomedicines are powerful tools for cancer therapeutics. However, there are challenges to overcome to increase siRNA delivery to solid tumors, including penetration of nanoparticles into a complex microenvironment following systemic delivery while avoiding rapid clearance by the reticuloendothelial system, and limited siRNA release from endosomes once inside the cell. Here we characterized cell uptake, intracellular trafficking, and gene silencing activity of miktoarm star polymer (PDMAEMA-POEGMA) nanoparticles (star nanoparticles) complexed to siRNA in lung cancer cells. We investigated the potential of nebulized star-siRNA nanoparticles to accumulate into orthotopic mouse lung tumors to inhibit expression of two genes [ßIII-tubulin, Polo-Like Kinase 1 (PLK1)] which: 1) are upregulated in lung cancer cells; 2) promote tumor growth; and 3) are difficult to inhibit using chemical drugs. Star-siRNA nanoparticles internalized into lung cancer cells and escaped the endo-lysosomal pathway to inhibit target gene expression in lung cancer cells in vitro. Nebulized star-siRNA nanoparticles accumulated into lungs and silenced the expression of ßIII-tubulin and PLK1 in mouse lung tumors, delaying aggressive tumor growth. These results demonstrate a proof-of-concept for aerosol delivery of star-siRNA nanoparticles as a novel therapeutic strategy to inhibit lung tumor growth.

Relative perceptions of prevalence, impact and importance of photosensitisation in Australian livestock: A survey of veterinarians, livestock traders and livestock producers.

AIMS: To investigate the relative differences in the perceptions and awareness of outbreaks of photosensitisation in Australian livestock stakeholders, including veterinarians, livestock traders and producers. METHODS: A questionnaire was developed and circulated to livestock veterinarians, producers and traders in Australia via email addresses obtained from public access sources. The questionnaire was designed to evaluate participants' awareness and perception of health, welfare, and production issues associated with outbreaks of photosensitisation and towards the incidence and importance of photosensitisation in livestock. RESULTS: One hundred and twenty-eight online responses were received in total. Nearly half of the respondents (49.0%) indicated they would encounter 1-3 outbreaks annually. The majority of veterinarian and livestock producers stated that outbreaks of photosensitisation were common and economically important, with cattle and sheep being equally considered as susceptible species to this condition, and secondary (hepatogeneous) photosensitisation is the most common type. CONCLUSION: This survey confirms the anecdotal evidence that photosensitisation in livestock in Australia is commonly encountered by veterinarians and livestock producers. However, there is no industry-wide common acceptance of the issue, broader opinions should be canvassed when considering impacts on stakeholders regarding photosensitisation outbreaks in livestock in Australia or abroad in the future.

Cost comparison and complication profiles of superior capsular reconstruction, lower trapezius transfer, and reverse shoulder arthroplasty for irreparable rotator cuff tears.

BACKGROUND: Irreparable rotator cuff tears (IRCTs) pose treatment challenges both clinically and financially. As cost-effectiveness initiatives are prioritized, value-based health care delivery models are becoming increasingly common. The purpose of this study was to perform a comprehensive analysis of the cost, complications, and readmission rates of 3 common surgical treatment options for IRCTs: superior capsular reconstruction (SCR), arthroscopically assisted lower trapezius tendon transfer (LTTT), and reverse shoulder arthroplasty (RSA). METHODS: Between 2018 and 2020, 155 patients who underwent shoulder surgery at a single institution for IRCT with minimal to no arthritis were identified. Procedures performed included 20 SCRs, 47 LTTTs, and 88 RSAs. A cost analysis was designed to include a period of 60 days preoperatively, the index surgical hospitalization, and 90 days postoperatively, including costs of any readmission or reoperation. RESULTS: Mean standardized costs were as follows: preoperative evaluation SCR $507, LTTT $507, and RSA $730; index surgical hospitalization SCR $19,675, LTTT $15,722, and RSA $16,077; and postoperative care SCR $655, LTTT $686, and RSA $404. Significant differences were observed in the index surgical costs (P < .001), with SCR incurring an additional average cost of $3953 and $3598 compared with LTTT and RSA, respectively. The 90-day complication, reoperation, and readmission rates were 0%, 0%, and 0% in the SCR group; 2.1%, 0%, and 0% in the LTTT group; and 3.4%, 0%, and 1.1% in the RSA group, respectively. With the numbers available, differences among the 3 surgical procedures with respect to complication (P = .223), reoperation (P = .999), and readmission rates (P = .568) did not reach statistical significance. CONCLUSIONS: The mean standardized costs for the treatment of 3 common IRCT procedures inclusive of 60-day workup and 90-day postoperative recovery were $16,915, $17,210, and $20,837 for LTTT, RSA (average added cost $295), and SCR (average added cost $3922), respectively. This information may provide surgeons and institutions with cost-related information that will become increasingly relevant with the expansion of value-based surgical reimbursements.

Germline VHL Mutation Discovered in Association with EGFR-Positive Lung Cancer and Metachronous Hepatocellular Carcinoma: A Case Report.

VHL is a tumor suppressor gene located on chromosome 3 that is classically associated with tumors of the eye and CNS, renal cell carcinoma, and pheochromocytoma. We describe what appears to be the first report of an association between a germline VHL mutation and non-small cell lung cancer and metachronous hepatocellular carcinoma (HCC). Our case involves a 63-year-old nonsmoking male who was initially diagnosed with EGFR mutation-positive metastatic nonsquamous, non-small cell lung adenocarcinoma, who subsequently developed HCC and squamous cell carcinoma of the femur despite first-line treatment with EGFR-blocking osimertinib. Caris molecular profiling unexpectedly identified a shared underlying VHL mutation in all 3 lesions. Genetic mapping through a machine learning-based tool called Genomic Prevalence Score (GPSai™) helped determine that the femur tumor was a metastatic lesion as opposed to a separate primary and that the HCC was a distinct primary malignancy. We not only highlight the association between these tumors and a VHL mutation but also emphasize the value of next-generation sequencing and a molecular disease classifier in a patient with multiple primaries, how it helps guide therapy, and its value in guiding future studies.