Three contrasts in 3 min: Rapid, high-resolution, and bone-selective UTE MRI for craniofacial imaging with automated deep-learning skull segmentation.

PURPOSE: Ultrashort echo time (UTE) MRI can be a radiation-free alternative to CT for craniofacial imaging of pediatric patients. However, unlike CT, bone-specific MR imaging is limited by long scan times, relatively low spatial resolution, and a time-consuming bone segmentation workflow. METHODS: A rapid, high-resolution UTE technique for brain and skull imaging in conjunction with an automatic segmentation pipeline was developed. A dual-RF, dual-echo UTE sequence was optimized for rapid scan time (3 min) and smaller voxel size (0.65 mm3). A weighted least-squares conjugate gradient method for computing the bone-selective image improves bone specificity while retaining bone sensitivity. Additionally, a deep-learning U-Net model was trained to automatically segment the skull from the bone-selective images. Ten healthy adult volunteers (six male, age 31.5 ± 10 years) and three pediatric patients (two male, ages 12 to 15 years) were scanned at 3 T. Clinical CT for the three patients were obtained for validation. Similarities in 3D skull reconstructions relative to clinical standard CT were evaluated based on the Dice similarity coefficient and Hausdorff distance. Craniometric measurements were used to assess geometric accuracy of the 3D skull renderings. RESULTS: The weighted least-squares method produces images with enhanced bone specificity, suppression of soft tissue, and separation from air at the sinuses when validated against CT in pediatric patients. Dice similarity coefficient overlap was 0.86 ± 0.05, and the 95th percentile Hausdorff distance was 1.77 ± 0.49 mm between the full-skull binary masks of the optimized UTE and CT in the testing dataset. CONCLUSION: An optimized MRI acquisition, reconstruction, and segmentation workflow for craniofacial imaging was developed.

Microglia either promote or restrain TRAIL-mediated excitotoxicity caused by Aß1-42 oligomers.

BACKGROUND: Alzheimer's disease (AD) features progressive neurodegeneration and microglial activation that results in dementia and cognitive decline. The release of soluble amyloid (Aß) oligomers into the extracellular space is an early feature of AD pathology. This can promote excitotoxicity and microglial activation. Microglia can adopt several activation states with various functional outcomes. Protective microglial activation states have been identified in response to Aß plaque pathology in vivo. However, the role of microglia and immune mediators in neurotoxicity induced by soluble Aß oligomers is unclear. Further, there remains a need to identify druggable molecular targets that promote protective microglial states to slow or prevent the progression of AD. METHODS: Hippocampal entorhinal brain slice culture (HEBSC) was employed to study mechanisms of Aß1-42 oligomer-induced neurotoxicity as well as the role of microglia. The roles of glutamate hyperexcitation and immune signaling in Aß-induced neurotoxicity were assessed using MK801 and neutralizing antibodies to the TNF-related apoptosis-inducing ligand (TRAIL) respectively. Microglial activation state was manipulated using Gi-hM4di designer receptor exclusively activated by designer drugs (DREADDs), microglial depletion with the colony-stimulating factor 1 receptor (CSF1R) antagonist PLX3397, and microglial repopulation (PLX3397 withdrawal). Proteomic changes were assessed by LC-MS/MS in microglia isolated from control, repopulated, or Aß-treated HEBSCs. RESULTS: Neurotoxicity induced by soluble Aß1-42 oligomers involves glutamatergic hyperexcitation caused by the proinflammatory mediator and death receptor ligand TRAIL. Microglia were found to have the ability to both promote and restrain Aß-induced toxicity. Induction of microglial Gi-signaling with hM4di to prevent pro-inflammatory activation blunted Aß neurotoxicity, while microglial depletion with CSF1R antagonism worsened neurotoxicity caused by Aß as well as TRAIL. HEBSCs with repopulated microglia, however, showed a near complete resistance to Aß-induced neurotoxicity. Comparison of microglial proteomes revealed that repopulated microglia have a baseline anti-inflammatory and trophic phenotype with a predicted pathway activation that is nearly opposite that of Aß-exposed microglia. mTORC2 and IRF7 were identified as potential targets for intervention. CONCLUSION: Microglia are key mediators of both protection and neurodegeneration in response to Aß. Polarizing microglia toward a protective state could be used as a preventative strategy against Aß-induced neurotoxicity.

Using A Disentangled Neural Network to Objectively Assess the Outcomes of Midfacial Surgery in Syndromic Craniosynostosis.

BACKGROUND: Advancements in artificial intelligence and the development of shape models that quantify normal head shape and facial morphology provide frameworks by which the outcomes of craniofacial surgery can be compared. In this work, we will demonstrate the use of the Swap Disentangled Variational Autoencoder (SD-VAE) to objectively assess changes following midfacial surgery. MATERIALS AND METHODS: Our model is trained on a dataset of 1405 3D meshes of healthy and syndromic patients which was augmented using a technique based on spectral interpolation. Patients with a diagnosis of Apert and Crouzon syndrome who had undergone sub- or trans-cranial midfacial procedures utilising rigid external distraction were then interpreted using this model as the point of comparison. RESULTS: A total of 56 patients met our inclusion criteria, 20 with Apert and 36 with Crouzon syndrome. By using linear discriminant analysis to project the high-dimensional vectors derived by SD-VAE onto a 2D space, the shape properties of Apert and Crouzon syndrome can be visualised in relation to the healthy population. In this way, we are able to show how surgery elicits global shape changes in each patient. To assess the regional movements achieved during surgery, we use a novel metric derived from the Malahanobis distance to quantify movements through the latent space. CONCLUSION: Objective outcome evaluation, which encourages in-depth analysis and enhances decision making, is essential for the progression of surgical practice. We have demonstrated how artificial intelligence has the ability to improve our understanding of surgery and its effect on craniofacial morphology.

Optic Nerve Sheath Diameter on Computed Tomography Scans Reflects Elevated Intracranial Pressure in Patients with Craniosynostosis.

INTRODUCTION: Assessment for elevated intracranial pressure (ICP) helps guide interventional decision-making to treat craniosynostosis. However, non-invasive techniques for measuring ICP are limited. This study assesses whether optic nerve sheath diameter (ONSD) on low-dose computed tomography (CT) scans is associated with ICP in patients with craniosynostosis. METHODS: Pediatric patients treated between 2014 and 2023 with craniosynostosis, intraoperative ICP measurements by direct subdural catheterization, and spectral domain-optical coherent tomography (SD-OCT) data were included. ONSD was retrospectively assessed on pre-operative CT scans by a masked neuroradiologist and compared to measures and proxies of ICP. RESULTS: Among 132 patients included, median age was 6.9 years (IQR 4.7-9.5) and 41 (31.1%) had a syndromic diagnosis. Maximum ONSD (ONSDmax) was increased in patients with ICP≥15mmHg (6.1mm vs. 5.5mm, p<0.01) and ICP≥20mmHg (6.3mm vs. 5.6mm, p<0.01). Maximum (r=0.32, p<0.001), minimum (r=0.26, p=0.003), and average (r=0.29, p<0.001) ONSD correlated with direct ICP measurements. ONSD and SD-OCT measurements were also correlated (RNFLmax: r=0.21, p=0.04; RTmax: r=0.24, p=0.02). An ONSDmax threshold of 5.75mm demonstrated 65% sensitivity and 64% specificity for detecting ICP≥15mmHg on optimized receiver operating characteristic curve analysis. Multivariable logistic regression generated an algorithm incorporating ONSDmax and age to detect ICP≥20mmHg with 64% sensitivity and 80% specificity. CONCLUSION: Optic nerve sheath diameter measured in low-dose CT scans detects elevated intracranial pressure with moderate accuracy, and precision increases when patient age is taken into consideration. Given the ease of accessing CT scan data, this may be a helpful ICP proxy for clinical decision-making.

Putting error bars on density functional theory.

Predicting the error in density functional theory (DFT) calculations due to the choice of exchange-correlation (XC) functional is crucial to the success of DFT, but currently, there are limited options to estimate this a priori. This is particularly important for high-throughput screening of new materials. In this work, the structure and elastic properties of binary and ternary oxides are computed using four XC functionals: LDA, PBE-GGA, PBEsol, and vdW-DF with C09 exchange. To analyze the systemic errors inherent to each XC functional, we employed materials informatics methods to predict the expected errors. The predicted errors were also used to better the DFT-predicted lattice parameters. Our results emphasize the link between the computed errors and the electron density and hybridization errors of a functional. In essence, these results provide "error bars" for choosing a functional for the creation of high-accuracy, high-throughput datasets as well as avenues for the development of XC functionals with enhanced performance, thereby enabling the accelerated discovery and design of new materials.

Changes in Ventricular Volume After Posterior Vault Distraction Osteogenesis in Patients With Syndromic and Nonsyndromic Craniosynostosis.

OBJECTIVE: Little is known about the response of the ventricular system to cranial vault surgery in patients with craniosynostosis. This study aims to evaluate the changes in the cerebral ventricular system in response to posterior vault distraction osteogenesis (PVDO) in patients with syndromic and nonsyndromic craniosynostosis. METHODS: A single-institution retrospective review of all patients with craniosynostosis undergoing PVDO from 2000 to 2022 was completed. Patients were included for analysis if they had pre and postoperative cranial computed tomography scans. Ventricular volume (VV) and intracranial volume (ICV) were calculated using segmentation software. RESULTS: Both patients with syndromic synostosis and nonsyndromic synostosis (NSS) experienced a significant increase in ICV after PVDO, but only patients with NSS experienced a significant VV change (P = 0.004). After normalization by ICV, total, lateral, and third VV changes retained significance with percentage increases of 114%, 117%, and 89%, respectively (P < 0.05 for all). CONCLUSION: The differing results between cohorts reinforce the concept that the intracranial milieu is different between patients with syndromic synostosis and NSS. The results of the NSS cohort suggest that these patients may exist in a compensated state in which a reduction in cerebral blood flow and VV allows for the maintenance of parenchymal health to prevent the development of intracranial hypertension. Further studies may explore VV as a surrogate marker of ICP elevation, and the utility of cranial vault remodeling on nonsynostotic pathologies with cephalocranial disproportion.

Evaluation of real-time fluorescence sensors and benchtop fluorescence for tracking and predicting sewage contamination in the Tijuana River Estuary at the US-Mexico border.

Cross-border flow of untreated sewage from Mexico into the USA via the Tijuana River is public health issue with negative consequences for coastal communities. Here we evaluate the potential application of fluorescence-based, submersible tryptophan-like (TRP) and humic-like (CDOM) fluorescence sensors for real-time tracking of wastewater pollution in an estuarine environment. Sonde fluorescence measurements were compared with benchtop fluorescence, fecal indicator bacteria (FIB) concentrations, and real-time specific conductivity measurements in the Tijuana River Estuary during dry and wet weather conditions, and with and without cross-border flow. TRP and CDOM fluorescence concentrations were low during times without cross-border flow and two-three orders of magnitude higher during storm events and after cross-border sewage flow events. Major deterioration in water quality, including hypoxic conditions, was observed after consistent, long-term cross-border sewage flow. Real-time TRP and CDOM fluorescence concentrations had a significant linear relationship with fecal indicator bacteria (FIB) concentrations during dry weather periods with cross-border flow (p < 0.001) but were poorly correlated during stormflow and during less polluted periods with no cross-border flow. TRP and CDOM fluorescence acquired on discrete samples using a benchtop fluorometer correlated significantly (p < 0.001) with FIB concentrations under all cross-border flow conditions. Based on relationships between benchtop TRP fluorescence and percent wastewater, the greatest amount of untreated wastewater in the estuary's surface layer during cross-border flow events was estimated at >80 % and occurred during neap tides, when concentrated, sewage-laden freshwater flowed over dense saline seawater due to stratification and lack of mixing in the estuary. These results are important because exposure to untreated sewage poses severe health risks for residents and visitors to adjacent coastal areas. While benchtop fluorescence was more effective for estimating the degree of wastewater pollution, submersible TRP and CDOM sensors provided a real-time alert of sewage contamination, which can be utilized in other sewage impacted estuarine environments.

Microbial reaction rate estimation using proteins and proteomes.

Microbes transform their environments using diverse enzymatic reactions. However, it remains challenging to measure microbial reaction rates in natural environments. Despite advances in global quantification of enzyme abundances, the individual relationships between enzyme abundances and their reaction rates have not been systematically examined. Using matched proteomic and reaction rate data from microbial cultures, we show that enzyme abundance is often insufficient to predict its corresponding reaction rate. However, we discovered that global proteomic measurements can be used to make accurate rate predictions of individual reaction rates (median R 2 = 0.78). Accurate rate predictions required only a small number of proteins and they did not need explicit prior mechanistic knowledge or environmental context. These results indicate that proteomes are encoders of cellular reaction rates, potentially enabling proteomic measurements in situ to estimate the rates of microbially mediated reactions in natural systems.

Long-term outcomes of nonsyndromic isolated unilateral lambdoid craniosynostosis.

This study combined qualitative and quantitative approaches to evaluate outcomes of isolated nonsyndromic unilateral lambdoid synostosis at the Children's Hospital of Philadelphia. Volumetric, linear, and angular analyses were performed on long-term postoperative and normal control scans. Preoperative and postoperative clinical photographs were evaluated for the presence of dysmorphic frontofacial features. Among 26 included patients, median age of surgery was 10 months and mean postoperative follow-up was 5.9 ± 5.7 years. Two (7.7%) patients underwent secondary cranial vault procedures. At most recent follow-up, 2 (7.7%) subjects reported intermittent headaches. Twenty (90.9%) of 22 patients were assigned Whitaker grade I. Among 9 subjects with long-term imaging at age 11.5 ± 5.3, posterior vault asymmetry, posterior fossa deflection angle, cranial base angle, and ear position asymmetry all remained greater than in the control group. Of subjects included in the frontofacial feature analysis (n = 10), 50% had resolution of all dysmorphic frontofacial features present preoperatively. Overall, most subjects who underwent PVR did not require revisional surgery and had good outcomes both aesthetically and functionally. Despite residual abnormalities in the cranial base and posterior vault, most had resolution of parietal bossing and facial scoliosis. Ear position asymmetry was the most common dysmorphic feature at long-term follow-up.

Salmonella re-engineers the intestinal environment to break colonization resistance in the presence of a compositionally intact microbiota.

The gut microbiota prevents harmful microbes from entering the body, a function known as colonization resistance. The enteric pathogen Salmonella enterica serovar (S.) Typhimurium uses its virulence factors to break colonization resistance through unknown mechanisms. Using metabolite profiling and genetic analysis, we show that the initial rise in luminal pathogen abundance was powered by a combination of aerobic respiration and mixed acid fermentation of simple sugars, such as glucose, which resulted in their depletion from the metabolome. The initial rise in the abundance of the pathogen in the feces coincided with a reduction in the cecal concentrations of acetate and butyrate and an increase in epithelial oxygenation. Notably, these changes in the host environment preceded changes in the microbiota composition. We conclude that changes in the host environment can weaken colonization resistance even in the absence of overt compositional changes in the gut microbiota.

Theileria orientalis Ikeda infection does not negatively impact growth performance or breeding soundness exam results in young beef bulls at bull test stations.

Introduction: Theileria orientalis Ikeda genotype is an emerging cattle disease in the US. Since 2017, when T. orientalis Ikeda was discovered in beef cattle in two counties in Virginia, cattle infections have risen to include ~67% of Virginia counties and 14 states. Consistent with New Zealand studies, many infected herds in Virginia were >90% positive upon initial testing without overt evidence of infection. Central bull tests present a unique opportunity to study the effects of T. orientalis Ikeda infections, as bulls from multiple source herds are consolidated. The objective of this study was to determine if infection with T. orientalis Ikeda affected the average daily gain (ADG), adjusted yearling weight (AYW) and breeding soundness of bulls at two test stations in Virginia over a period of years. Materials and methods: The bulls were fed and housed similarly to compare their growth performance and breeding soundness. For T. orientalis Ikeda testing, DNA was extracted from whole blood for quantitative polymerase chain reaction. Results: The number of bulls infected with T. orientalis Ikeda at initial delivery to the stations increased significantly over the years studied. Multivariable linear regression models, using Angus bulls from Virginia test stations, indicated no significant effect on ADG or AYW in bulls that became test positive during the test or were positive for the duration, compared to Angus bulls that were negative for the duration. At LOC A, the odds of passing a breeding soundness exam (BSE) were not significantly different for bulls that turned positive during the test or were positive for the duration, compared to bulls that were negative for the duration of the test. At LOC B, bulls that became positive during the test were 2.4 times more likely (95% CI: 1.165-4.995, p = 0.016) to pass their BSE compared to bulls that remained negative throughout the test. Discussion: We do not suppose that an obscured infection of T. orientalis Ikeda is protective for bulls to pass a BSE. However, this study demonstrates an obscured infection of T. orientalis Ikeda does not negatively affect weight gain or achievement of a satisfactory BSE rating at the central bull test stations in Virginia.

A coddling of the sagittal suture: inequality in spring-assisted expansion.

PURPOSE: We examined differences in long-term morphometric outcomes of spring-mediated cranioplasty (SMC) for various forms of isolated nonsyndromic sagittal craniosynostosis. METHODS: A retrospective review was performed of children who underwent SMC from 2011 to 2020 at the Children's Hospital of Philadelphia. Cephalic indices (CI), Whitaker grades, parietal bone thickness, and degree of suture fusion were assessed. Frontal bossing and vertex-nasion-opisthocranion (VNO) angles were compared to a normal control group. RESULTS: Fifty-four subjects underwent surgery at age 3.6 ± 1.0 months with follow-up of 6.3 ± 1.8 years. Mean CI was 75.2 ± 4.1 at 5.9 ± 2.0 years postoperatively. Mean CI were 75.8 ± 4.1 (n = 32), 76.4 ± 4.0 (n = 22), and 77.1 ± 4.8 (n = 11) at 5, 7, and 9+ years postoperatively, respectively. Three (5.6%) required reoperation for persistent scaphocephalic cranial deformity. Fifty-one (94.4%) were Whitaker Grade I. On physical examination, 12 (22.2%) demonstrated craniofacial abnormalities. At long-term follow-up, there were no differences in frontal bossing angle (102.7 ± 5.2 degrees versus 100.7 ± 5.6 degrees, p = .052) and VNO angle (44.9 ± 3.3 degrees versus 43.9 ± 2.2 degrees, p = .063) between study and control groups. Younger age at surgery predicted a lower Whitaker grade, more normalized VNO angle, and greater change in CI during active expansion. Increased percentage fused of the posterior sagittal suture predicted a higher Whitaker grade, while decreased anterior fusion was associated with frontal bossing and temporal hollowing. CONCLUSIONS: Overall, children undergoing spring-mediated cranioplasty for sagittal craniosynostosis demonstrated maintenance of CI, favorable cosmetic outcomes, and a low reoperation rate at mid-term follow-up. Early intervention is associated with improved aesthetic outcomes, and regional fusion patterns may influence long-term craniofacial dysmorphology.

A Comprehensive Integration and Synthesis of Methane Emissions from Canada's Oil and Gas Value Chain.

Methane emissions from the global oil and gas value chain are a major contributor to climate change, and their mitigation could avoid 0.1 °C of warming by 2050. Here, we synthesize nearly a decade of research encompassing thousands of multiscale methane measurements along the oil and gas value chain (production to end use) to better constrain estimates of methane emissions from Canada's energy sector and to identify research gaps contributing to uncertainty in current estimates. We find that total value chain methane emissions are 2,600 (2,100-3,700) kt, which broadly agrees with Canada's latest official inventory that now includes atmospheric measurement data in some of their oil and gas methane estimates. Accurate understanding of emission magnitudes is critical because Canada committed to a 75% reduction of oil and gas methane emissions by 2030. We also identify and discuss information gaps in both emissions and activity data, namely, from the midstream, downstream, and end-use sectors. While they make up a smaller portion of the total inventory, accurate quantification of these emissions is still important and could point to more cost-effective mitigation solutions. This work emphasizes the need for frequent, comprehensive measurements to better constrain the climate impacts of the oil and gas sector and to validate reductions and commitments pledged by industry and governments.

Prevalence of pelvic CT angiography (CTA) and angiographic embolization in geriatric patients with pelvic ring fractures presenting to two level I trauma centers.

OBJECTIVES: Hemorrhage in osteoporotic pelvic ring fractures is a rare, but serious complication. Most bleeding comes from the bone or venous plexuses, but arterial injury does occur. The purpose of this study was to characterize a large geriatric pelvic fracture cohort and determine the prevalence of pelvic CT angiography (CTA) and subsequent need for arterial embolization. METHODS: A cohort of geriatric pelvic fracture patients at two level 1 trauma centers was reviewed. Many epidemiologic and patient factors were collected for cohort characterization. The primary outcome was if patients underwent a CTA of the pelvis and subsequently underwent arterial embolization. RESULTS: There were 457 patients included and mean age was 83.1 years (range 65-100). Most patients had a low energy mechanism (91.4 %). In-hospital mortality was recorded for 30 cases (6.6 %). Of these deaths, two received a pelvic CTA and two had an embolization procedure. Pelvic CTA was performed on 33 patients (7.2 %). Fourteen patients (3.0 %) had an arterial embolization procedure. A high energy mechanism of injury was associated with receiving a pelvic CTA (p = 0.0067). Mechanism of injury was not associated with undergoing an embolization procedure (p = 0.685). DISCUSSION: In the geriatric population, even patients with stable pelvic fractures can present with life-threatening arterial bleeding. A non-insignificant percentage of patients will require CTA for suspected bleeding (7.2 %) and embolization to treat confirmed arterial bleeding (3.0 %). CONCLUSIONS: Bleeding events in geriatric pelvic ring injuries is a previously under researched area of orthopedic trauma. Further research is needed to elucidate the exact pathomechanisms of arterial injury and what patients or injury patterns are most significantly associated. Specifically, larger cohort sizes and evaluating our existing cohort with different injury classification systems may yield useful results.

A novel Nav1.5-dependent feedback mechanism driving glycolytic acidification in breast cancer metastasis.

Solid tumours have abnormally high intracellular [Na+]. The activity of various Na+ channels may underlie this Na+ accumulation. Voltage-gated Na+ channels (VGSCs) have been shown to be functionally active in cancer cell lines, where they promote invasion. However, the mechanisms involved, and clinical relevance, are incompletely understood. Here, we show that protein expression of the Nav1.5 VGSC subtype strongly correlates with increased metastasis and shortened cancer-specific survival in breast cancer patients. In addition, VGSCs are functionally active in patient-derived breast tumour cells, cell lines, and cancer-associated fibroblasts. Knockdown of Nav1.5 in a mouse model of breast cancer suppresses expression of invasion-regulating genes. Nav1.5 activity increases ATP demand and glycolysis in breast cancer cells, likely by upregulating activity of the Na+/K+ ATPase, thus promoting H+ production and extracellular acidification. The pH of murine xenograft tumours is lower at the periphery than in the core, in regions of higher proliferation and lower apoptosis. In turn, acidic extracellular pH elevates persistent Na+ influx through Nav1.5 into breast cancer cells. Together, these findings show positive feedback between extracellular acidification and the movement of Na+ into cancer cells which can facilitate invasion. These results highlight the clinical significance of Nav1.5 activity as a potentiator of breast cancer metastasis and provide further evidence supporting the use of VGSC inhibitors in cancer treatment.

Mystery of the Muenke midface: spheno-occipital synchondrosis fusion and craniofacial skeletal patterns.

PURPOSE: The spheno-occipital synchondrosis (SOS) is an important site of endochondral ossification in the cranial base that closes prematurely in Apert, Crouzon, and Pfeiffer syndromes, which contributes to varying degrees of midface hypoplasia. The facial dysmorphology of Muenke syndrome, in contrast, is less severe with low rates of midface hypoplasia. We thus evaluated the timing of SOS fusion and cephalometric landmarks in patients with Muenke syndrome compared to normal controls. METHODS: Patients with Muenke syndrome who had at least one fine-cut head computed tomography scan performed from 2000 to 2020 were retrospectively reviewed. A case-control study was performed of patient scans and age- and sex-matched control scans. SOS fusion status was evaluated as open, partially closed, or closed. RESULTS: We included 28 patients and compared 77 patient scans with 77 control scans. Kaplan-Meier analysis demonstrated an insignificantly earlier timeline of SOS fusion in Muenke syndrome (p = 0.300). Mean sella-orbitale (SO) distance was shorter (44.0 ± 6.6 vs. 47.7 ± 6.7 mm, p < 0.001) and mean sella-nasion-Frankfort horizontal (SN-FH) angle was greater (12.1° ± 3.8° vs. 10.1° ± 3.2°, p < 0.001) in the Muenke group, whereas mean sella-nasion-A point (SNA) angle was similar and normal (81.1° ± 5.7° vs. 81.4° ± 4.7°, p = 0.762). CONCLUSION: Muenke syndrome is characterized by mild and often absent midfacial hypoplasia, with the exception of slight retropositioning of the infraorbital rim. Interestingly, SOS fusion patterns in these patients are not significantly different from age- and sex-matched controls despite an increased odds of fusion. It is possible that differences in timing of SOS fusion may manifest phenotypically at the infraorbital rim rather than at the maxilla.

Highly Uncertain Methane Leakage from Oil and Gas Wells in Canada Despite Measurement and Reporting.

Leakage of fluids from oil and gas wells is a source of the key greenhouse gas methane, and presents environmental risks, including groundwater contamination. A loss of well integrity can result in fluid leakage into the annular space between subsequent well casings (which is often vented to the atmosphere) or into the surrounding subsurface. In Canada, industry reporting on well integrity is often incomplete, leading government inventories to disagree on emission magnitudes. In this study, we model wellbore methane emissions using industry data in British Columbia and Alberta, Canada, finding that differing model assumptions to handle unclear/missing data have a strong influence on estimated emissions. Considering estimates derived from industry reporting and from independent measurement, wellbore emissions in the two provinces range anywhere from 23 to 176 kt of methane, representing 1.7-11.4% of their upstream sector methane emissions. Further, finding over 130 examples of measured leaks seemingly missing from industry reporting, we conclude that wellbore emissions, groundwater contamination, and broader environmental risks are underestimated. We provide recommendations to improve well integrity tracking through data quality assurance measures and increased testing. Finally, we find that ongoing optical gas imaging camera surveys could be an effective tool to augment wellbore testing requirements to minimize industry burden.

Identification of Alpha-Gal glycolipids in saliva of Lone-Star Tick (Amblyomma americanum).

Alpha-Gal Syndrome (AGS) is a delayed allergic reaction triggered by IgE antibodies targeting galactose-α-1,3-galactose (α-gal), prevalent in red meat. Its global significance has increased, with over 450,000 estimated cases in the United States alone. AGS is linked to tick bites, causing sensitization and elevated α-gal specific IgE levels. However, the precise mechanisms and tick intrinsic factors contributing to AGS development post-tick bites remain unclear. This study aims to characterize the alpha-gal conjugated lipid antigens in Amblyomma americanum (Am. americanum) salivary glands and saliva. Nanospray ionization mass spectrometry (NSI-MS) analysis revealed the identification of α-gal bound lipid antigens in Am. americanum saliva. Additionally, the activation of basophils by extracted alpha-gal bound lipids and proteins provides evidence of their antigenic capabilities.

Genetic Heterogeneity, Craniofacial Surgical Burden, and Surgical Techniques in Patients With Saethre-Chotzen Syndrome.

OBJECTIVE: While genotype correlates with phenotype in patients with many forms of syndromic craniosynostosis, the relationship between molecular diagnosis and craniofacial surgical history in patients with Saethre-Chotzen syndrome (SCS) is more variable. This manuscript characterizes that relationship and evaluates operative trends in these patients over the past 3 decades. METHODS: Demographic information, molecular diagnosis, and craniofacial surgical history in patients born with SCS between 1989 and 2023 were compared with appropriate statistics, including t tests and analysis of variance. RESULTS: Thirty-five patients with SCS were included, and there was no difference in total craniofacial procedures among those with TWIST1 substitutions (2.1 ± 1.6), duplications (3.0 ± 4.2), insertions (3.5 ± 0.7), or deletions (2.4 ± 1.9; P = 0.97). Cranial expansion rates were also similar across all genetic diagnoses (P>0.05), and surgical incidence was similar across patients with unicoronal, bicoronal, and multisuture involvement (P > 0.05). Those with an initial fronto-orbital advancement had a lower incidence of secondary cranial vault procedures compared with those with an initial posterior vault distraction osteogenesis (29% versus 71%, P < 0.05), though this did not control for phenotypic severity. On average, total cranial vault surgical burden (1.35 ± 0.67 versus 1.75 ± 0.46) and cranial expansion surgical burden (1.40 ± 0.68 versus 1.88 ± 0.64) between the fronto-orbital advancement-first and posterior vault distraction osteogenesis-first cohorts were similar (P = 0.11, P = 0.17, respectively). CONCLUSION: While SCS is molecularly and phenotypically heterogeneous, genetic diagnosis does not appear associated with rates of craniofacial surgery. Additional prospective study of correlations between genotype, severity of craniofacial manifestations, and treatment algorithms is warranted; but, in the end, it may be that this highly variable form of syndromic craniosynostosis warrants tailored, expectant management.