ABSTRACT
Innate vocal sounds such as laughing, screaming or crying convey one's feelings to others. In many species, including humans, scaling the amplitude and duration of vocalizations is essential for effective social communication1-3. In mice, female scent triggers male mice to emit innate courtship ultrasonic vocalizations (USVs)4,5. However, whether mice flexibly scale their vocalizations and how neural circuits are structured to generate flexibility remain largely unknown. Here we identify mouse neurons from the lateral preoptic area (LPOA) that express oestrogen receptor 1 (LPOAESR1 neurons) and, when activated, elicit the complete repertoire of USV syllables emitted during natural courtship. Neural anatomy and functional data reveal a two-step, di-synaptic circuit motif in which primary long-range inhibitory LPOAESR1 neurons relieve a clamp of local periaqueductal grey (PAG) inhibition, enabling excitatory PAG USV-gating neurons to trigger vocalizations. We find that social context shapes a wide range of USV amplitudes and bout durations. This variability is absent when PAG neurons are stimulated directly; PAG-evoked vocalizations are time-locked to neural activity and stereotypically loud. By contrast, increasing the activity of LPOAESR1 neurons scales the amplitude of vocalizations, and delaying the recovery of the inhibition clamp prolongs USV bouts. Thus, the LPOA disinhibition motif contributes to flexible loudness and the duration and persistence of bouts, which are key aspects of effective vocal social communication.
Subject(s)
Hypothalamus/physiology , Vocalization, Animal/physiology , Animals , Courtship , Estrogen Receptor alpha/metabolism , Female , Hypothalamus/cytology , Male , Mice , Mice, Inbred BALB C , Neurons/physiology , Periaqueductal Gray/cytology , Periaqueductal Gray/physiology , Preoptic Area/cytology , Preoptic Area/physiology , Synapses/metabolism , Time Factors , Ultrasonic WavesABSTRACT
Missing values are common in high-throughput mass spectrometry data. Two strategies are available to address missing values: (i) eliminate or impute the missing values and apply statistical methods that require complete data and (ii) use statistical methods that specifically account for missing values without imputation (imputation-free methods). This study reviews the effect of sample size and percentage of missing values on statistical inference for multiple methods under these two strategies. With increasing missingness, the ability of imputation and imputation-free methods to identify differentially and non-differentially regulated compounds in a two-group comparison study declined. Random forest and k-nearest neighbor imputation combined with a Wilcoxon test performed well in statistical testing for up to 50% missingness with little bias in estimating the effect size. Quantile regression imputation accompanied with a Wilcoxon test also had good statistical testing outcomes but substantially distorted the difference in means between groups. None of the imputation-free methods performed consistently better for statistical testing than imputation methods.
Subject(s)
Research Design , Bias , Cluster Analysis , Mass Spectrometry/methodsABSTRACT
Maternal immune dysregulation is a prenatal risk factor for autism spectrum disorder (ASD). Importantly, a clinically relevant connection exists between inflammation and metabolic stress that can result in aberrant cytokine signaling and autoimmunity. In this study we examined the potential for maternal autoantibodies (aAbs) to disrupt metabolic signaling and induce neuroanatomical changes in the brains of exposed offspring. To accomplish this, we developed a model of maternal aAb exposure in rats based on the clinical phenomenon of maternal autoantibody-related ASD (MAR-ASD). Following confirmation of aAb production in rat dams and antigen-specific immunoglobulin G (IgG) transfer to offspring, we assessed offspring behavior and brain structure longitudinally. MAR-ASD rat offspring displayed a reduction in pup ultrasonic vocalizations and a pronounced deficit in social play behavior when allowed to freely interact with a novel partner. Additionally, longitudinal in vivo structural magnetic resonance imaging (sMRI) at postnatal day 30 (PND30) and PND70, conducted in a separate cohort of animals, revealed sex-specific differences in total and regional brain volume. Treatment-specific effects by region appeared to converge on midbrain and cerebellar structures in MAR-ASD offspring. Simultaneously, in vivo 1H magnetic resonance spectroscopy (1H-MRS) data were collected to examine brain metabolite levels in the medial prefrontal cortex. Results showed that MAR-ASD offspring displayed decreased levels of choline-containing compounds and glutathione, accompanied by increased taurine compared to control animals. Overall, we found that rats exposed to MAR-ASD aAbs present with alterations in behavior, brain structure, and neurometabolites; reminiscent of findings observed in clinical ASD.
Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Prenatal Exposure Delayed Effects , Humans , Male , Pregnancy , Female , Rats , Animals , Autistic Disorder/metabolism , Autism Spectrum Disorder/metabolism , Autoantibodies , Prenatal Exposure Delayed Effects/metabolism , Brain/metabolism , Maternal ExposureABSTRACT
Solar photoexcitation of chromophoric groups in dissolved organic matter (DOM), when coupled to photoreduction of ubiquitous Fe(III)-oxide nanoparticles, can significantly accelerate DOM degradation in near-surface terrestrial systems, but the mechanisms of these reactions remain elusive. We examined the photolysis of chromophoric soil DOM coated onto hematite nanoplatelets featuring (001) exposed facets using a combination of molecular spectroscopies and density functional theory (DFT) computations. Reactive oxygen species (ROS) probed by electron paramagnetic resonance (EPR) spectroscopy revealed that both singlet oxygen and superoxide are the predominant ROS responsible for DOM degradation. DFT calculations confirmed that Fe(II) on the hematite (001) surface, created by interfacial electron transfer from photoexcited chromophores in DOM, can reduce dioxygen molecules to superoxide radicals (â¢O2-) through a one-electron transfer process. 1H nuclear magnetic resonance (NMR) and electrospray ionization Fourier-transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) spectroscopies show that the association of DOM with hematite enhances the cleavage of aromatic groups during photodegradation. The findings point to a pivotal role for organic matter at the interface that guides specific ROS generation and the subsequent photodegradation process, as well as the prospect of using ROS signatures as a forensic tool to help interpret more complicated field-relevant systems.
Subject(s)
Dissolved Organic Matter , Ferric Compounds , Reactive Oxygen Species , Superoxides , PhotolysisABSTRACT
This study aims to describe the perception of need for same-sex and same-race mentorship and role models at evolving stages of a medical career and to explore whether these differences affect career choices within the field of medicine. A total of 326 medical students, 309 resident physicians, and 200 faculty attending physicians at the University of California, Davis School of Medicine completed an online survey focused on their perceived value of same-sex and same-race mentorship throughout their stages of medical training and practice. The top three factors influencing specialty choice were lifestyle, time commitment, and supportive department. Although most respondents did not believe same-sex or same-race mentors or role models influenced their specialty choice, there were significant differences in the perceived importance and value of gender or race concordance between male versus female and white versus nonwhite populations. (Journal of Surgical Orthopaedic Advances 33(1):041-048, 2024).
Subject(s)
Career Choice , Mentors , Students, Medical , Humans , Male , Female , Students, Medical/psychology , Faculty, Medical/psychology , Surveys and Questionnaires , Internship and Residency , Adult , Attitude of Health PersonnelABSTRACT
OBJECTIVES: ABRUPT was a prospective, noninterventional, observational study of resuscitation practices at 21 burn centers. The primary goal was to examine burn resuscitation with albumin or crystalloids alone, to design a future prospective randomized trial. SUMMARY BACKGROUND DATA: No modern prospective study has determined whether to use colloids or crystalloids for acute burn resuscitation. METHODS: Patients ≥18 years with burns ≥ 20% total body surface area (TBSA) had hourly documentation of resuscitation parameters for 48 hours. Patients received either crystalloids alone or had albumin supplemented to crystalloid based on center protocols. RESULTS: Of 379 enrollees, two-thirds (253) were resuscitated with albumin and one-third (126) were resuscitated with crystalloid alone. Albumin patients received more total fluid than Crystalloid patients (5.2 ± 2.3 vs 3.7 ± 1.7 mL/kg/% TBSA burn/24 hours), but patients in the Albumin Group were older, had larger burns, higher admission Sequential Organ Failure Assessment (SOFA) scores, and more inhalation injury. Albumin lowered the in-to-out (I/O) ratio and was started ≤12 hours in patients with the highest initial fluid requirements, given >12 hours with intermediate requirements, and avoided in patients who responded to crystalloid alone. CONCLUSIONS: Albumin use is associated with older age, larger and deeper burns, and more severe organ dysfunction at presentation. Albumin supplementation is started when initial crystalloid rates are above expected targets and improves the I/O ratio. The fluid received in the first 24 hours was at or above the Parkland Formula estimate.
Subject(s)
Albumins , Fluid Therapy , Humans , Isotonic Solutions/therapeutic use , Prospective Studies , Retrospective Studies , Treatment Outcome , Crystalloid Solutions/therapeutic use , Albumins/therapeutic use , North AmericaABSTRACT
His domain protein tyrosine phosphatase (HD-PTP; also known as PTPN23) collaborates with endosomal sorting complexes required for transport (ESCRTs) to sort endosomal cargo into intralumenal vesicles, forming the multivesicular body (MVB). Completion of MVB sorting is accompanied by maturation of the endosome into a late endosome, an event that requires inactivation of the early endosomal GTPase Rab5 (herein referring to generically to all isoforms). Here, we show that HD-PTP links ESCRT function with endosomal maturation. HD-PTP depletion prevents MVB sorting, while also blocking cargo from exiting Rab5-rich endosomes. HD-PTP-depleted cells contain hyperphosphorylated Rabaptin-5 (also known as RABEP1), a cofactor for the Rab5 guanine nucleotide exchange factor Rabex-5 (also known as RABGEF1), although HD-PTP is unlikely to directly dephosphorylate Rabaptin-5. In addition, HD-PTP-depleted cells exhibit Rabaptin-5-dependent hyperactivation of Rab5. HD-PTP binds directly to Rabaptin-5, between its Rabex-5- and Rab5-binding domains. This binding reaction involves the ESCRT-0/ESCRT-III binding site in HD-PTP, which is competed for by an ESCRT-III peptide. Jointly, these findings indicate that HD-PTP may alternatively scaffold ESCRTs and modulate Rabex-5-Rabaptin-5 activity, thereby helping to coordinate the completion of MVB sorting with endosomal maturation.
Subject(s)
Endosomal Sorting Complexes Required for Transport , Endosomes , ErbB Receptors , Vesicular Transport Proteins , Endosomal Sorting Complexes Required for Transport/genetics , Endosomal Sorting Complexes Required for Transport/metabolism , Endosomes/metabolism , ErbB Receptors/genetics , ErbB Receptors/metabolism , Lysosomes/metabolism , Protein Domains , Protein Transport , Protein Tyrosine Phosphatases/genetics , Protein Tyrosine Phosphatases/metabolismABSTRACT
AIM: To assess the accuracy, reliability, and discriminatory ability of a mobile app for measurement of migration percentage in hip surveillance radiographs of children with cerebral palsy (CP). METHOD: The free mobile app HipScreen (www.hipscreen.org) was utilized by a diverse group of users to measure the migration percentage of 40 hips at two time points after completing an online tutorial and competency test. The mean absolute error (MAE) was calculated against the reference standard obtained on a radiology workstation. Statistical analyses included linear regression, intraclass correlation coefficient (ICC), and area under receiver-operating characteristic curve (AUC). RESULTS: Thirty-seven users completed the study, with 30 having a healthcare professional background, but only 15 with x-ray interpretation expertise. The overall MAE of migration percentage measurement using the HipScreen app was 5.72% (95% confidence interval [CI]: 5.38-6.06), with good reliability between time points (ICC = 0.83). With a migration percentage less than 30% considered as a positive case, the HipScreen app had a sensitivity of 94% (95% CI: 87-97), specificity of 66% (95% CI: 61-77), and an AUC of 0.92 (95% CI: 0.88-0.96). INTERPRETATION: Users from a broad range of backgrounds can utilize the HipScreen app to measure hip surveillance radiographs with clinically acceptable accuracy, reliability, and discriminatory ability. WHAT THIS PAPER ADDS: The HipScreen app can accurately and reliably measure migration percentage. As a screening tool, HipScreen has excellent sensitivity and discriminatory ability. A broad range of HipScreen users achieve clinically acceptable performance.
Subject(s)
Cerebral Palsy , Hip Dislocation , Mobile Applications , Child , Humans , Cerebral Palsy/diagnosis , Reproducibility of Results , HipABSTRACT
PURPOSE: Forearm supination contractures occur in 7% of children with brachial plexus birth injuries (BPBI). Biceps rerouting is proposed when pronation has deteriorated but is passively correctable to at least 0° (neutral). The purpose of this investigation was to evaluate long-term outcomes of biceps rerouting for this indication, including magnitude and maintenance of correction, complications, and subsequent osteotomy. METHODS: We conducted a retrospective review of all children with BPBI and forearm supination contractures treated with biceps rerouting alone, for the above indications, from 1993 to 2017 with at least 2 years follow-up. Demographic information, BPBI characteristics, surgical details, and ranges of motion were obtained from medical records. Pre- and postoperative active pronation (AP) and supination (AS), elbow flexion contracture, and arc of forearm rotation (Arc) were analyzed using linear mixed-effect models. RESULTS: Twenty-five children (13 females; 13 left forearms; 15 global BPBI) underwent biceps rerouting at age 7 ± 3 years and were followed for 6 ± 3 years. Before surgery, the mean AP and AS were 6° ± 29° and 62° ± 27°, respectively. At the final follow-up, the mean AP, AS, and Arc were 39° ± 36°, 18° ± 34°, and 57° ± 42°, respectively. AP was significantly improved and AS was significantly decreased by 2 years after surgery and at the final follow-up. Neither Arc nor elbow flexion contracture changed significantly. Two of 25 (8%) children underwent subsequent forearm osteotomy. CONCLUSIONS: Biceps rerouting in children with BPBI improves the forearm position when pronation is deteriorating by shifting the arc from supination to pronation without decreasing the arc of motion or worsening elbow flexion contractures. There is a low risk of complications and a limited need for subsequent forearm osteotomy. These results are maintained over time. When performed before passive pronation is reduced beyond neutral, this procedure may prevent severe supination contractures and reduce the need for forearm osteotomy. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
Subject(s)
Birth Injuries , Brachial Plexus , Contracture , Female , Humans , Child , Child, Preschool , Supination , Contracture/surgery , Contracture/complications , Muscle, Skeletal/surgery , Forearm/surgery , Pronation , Birth Injuries/complications , Birth Injuries/surgeryABSTRACT
PURPOSE: This study examined the accuracy and reliability of measuring total motion of the fingers via telehealth using the following three different methods: (1) goniometry, (2) visual estimation, and (3) electronic protractor. Measurements were compared with in-person measurement, which was assumed to be the reference standard. METHODS: Thirty clinicians measured finger range of motion from prerecorded videos of a mannequin hand with articulating fingers, which was posed in extension and flexion that simulated a telehealth visit, using a goniometer with results blinded to the clinician (blinded goniometry), visual estimation, and an electronic protractor, in random order. Total motion was calculated for each finger and for all four fingers in sum. The experience level, familiarity with measuring finger range of motion, and opinions of measurement difficulty were assessed. RESULTS: Measurement with the electronic protractor was the only method equivalent to the reference standard within 20°. Remote goniometer and visual estimation did not fall within the acceptable error margin of equivalence, and both underestimated total motion. Electronic protractor also had the highest interrater reliability (intraclass correlation [upper limit, lower limit], 0.95 [0.92, 0.95]); goniometry (intraclass correlation, 0.94 [0.91, 0.97]) was nearly identical, whereas visual estimation (intraclass correlation, 0.82 [0.74, 0.89]) was much lower. Clinicians' experience and familiarity with range of motion measurements had no relationship with the findings. Clinicians reported visual estimation as the most difficult (80%) and electronic protractor as the easiest method (73%). CONCLUSIONS: This study showed that traditional in-person forms of measurement underestimate finger range of motion via telehealth; a new computer-based method (ie, electronic protractor) was found to be more accurate. CLINICAL RELEVANCE: The use of an electronic protractor can be beneficial to clinicians measuring range of motion in patients virtually.
ABSTRACT
Thin film deposition from the vapor phase is a complex process involving adatom adsorption, movement, and incorporation into the growing film. Here, we present quantitative experimental data that reveals anion intermixing over long length scales during the deposition of epitaxial Fe2O3 and Cr2O3 films and heterostructures by oxygen-plasma-assisted molecular beam epitaxy. We track this diffusion by incorporating well-defined tracer layers containing 18O and/or 57Fe and measure their redistribution on the nanometer scale with atom probe tomography. Molecular dynamics simulations suggest potential intermixing events, which are then examined via nudged elastic band calculations. We reveal that adatoms on the film surface act to "pull up" subsurface O and Fe. Subsequent ring-like rotation mechanisms involving both adatom and subsurface anions then facilitate their mixing. In addition to film deposition, these intermixing mechanisms may be operant during other surface-mediated processes such as heterogeneous catalysis and corrosion.
ABSTRACT
Potomac horse fever (PHF) is a common cause of equine colitis in endemic areas. Until recently, the only causative agent known to cause PHF was Neorickettsia risticii. However, N. findlayensis has been isolated from affected horses. Horses typically become infected upon ingestion of Neorickettsia spp.-infected trematodes within aquatic insects. The most common clinical signs include diarrhea, fever, anorexia, lethargy and colic. The diagnostic test of choice for PHF is PCR of blood and feces. Tetracyclines remain an effective treatment. Supportive care, including fluid therapy, colloid administration, NSAID and anti-endotoxin medication, and digital cryotherapy, is also necessary in some cases.
Subject(s)
Anaplasmataceae Infections , Colitis , Horse Diseases , Neorickettsia risticii , Horses , Animals , Anaplasmataceae Infections/diagnosis , Anaplasmataceae Infections/microbiology , Anaplasmataceae Infections/veterinary , Horse Diseases/diagnosis , Colitis/veterinary , Diarrhea/veterinaryABSTRACT
The autocatalytic redox interaction between aqueous Fe(II) and Fe(III)-(oxyhydr)oxide minerals such as goethite and hematite leads to rapid recrystallization marked, in principle, by an atom exchange (AE) front, according to bulk iron isotopic tracer studies. However, direct evidence for this AE front has been elusive given the analytical challenges of mass-resolved imaging at the nanoscale on individual crystallites. We report successful isolation and characterization of the AE front in goethite microrods by 3D atom probe tomography (APT). The microrods were reacted with Fe(II) enriched in tracer 57Fe at conditions consistent with prior bulk studies. APT analyses and 3D reconstructions on cross-sections of the microrods reveal an AE front that is spatially heterogeneous, at times penetrating several nanometers into the lattice, in a manner consistent with defect-accelerated exchange. Evidence for exchange along microstructural domain boundaries was also found, suggesting another important link between exchange extent and initial defect content. The findings provide an unprecedented view into the spatial and temporal characteristics of Fe(II)-catalyzed recrystallization at the atomic scale, and substantiate speculation regarding the role of defects controlling the dynamics of electron transfer and AE interaction at this important redox interface.
ABSTRACT
BACKGROUND: Elderly (65 and older) fall-related injuries are a significant cause of morbidity and mortality. Although frailty predicts poor outcomes in geriatric trauma, literature comparing frailty scoring systems remains limited. Herein, we evaluated which frailty scoring system best predicts falls over time in the elderly. MATERIALS AND METHODS: Acute surgical patients 65 y and older were enrolled and prospectively observed. Demographics and frailty, assessed using the FRAIL Scale, Trauma Specific Frailty Index (TSFI), and Canadian Frailty Scale (CSHA-CFS), were collected at enrollment and 3 mo intervals following discharge for 1 y. Surveys queried the total number and timing of falls. Changes in frailty over time were assessed by logistic regression and area under the curve (AUC). RESULTS: Fifty-eight patients were enrolled. FRAIL Scale and CSHA-CFS scores did not change over time, but TSFI scores did (P ≤ 0.01). Worsening frailty was observed using TSFI at 6 (P ≤ 0.01) and 12 mo (P ≤ 0.01) relative to baseline. Mortality did not differ based on frailty using any frailty score. Increasing frailty scores and time postdischarge was associated with increased odds of a fall. AUC estimates with 95% CI were 0.72 [0.64, 0.80], 0.81 [0.74, 0.88], and 0.76 [0.68, 0.84] for the FRAIL Scale, TSFI, and CSHA-CFS, respectively. CONCLUSIONS: The risk of falls postdischarge were associated with increased age, time postdischarge, and frailty in our population. No scale appeared to significantly outperform the other by AUC estimation. Further study on the longitudinal effects of frailty is warranted.
Subject(s)
Accidental Falls/statistics & numerical data , Frailty , Health Status Indicators , Aged , Aged, 80 and over , Female , Humans , Male , Mortality , Prospective Studies , Risk AssessmentABSTRACT
Thiamine is a vital co-factor for several anti-inflammatory and antioxidant processes that are critical for mitigation of sepsis-associated inflammation, but pharmacokinetic (PK) analysis has not been reported in horses. We hypothesized that IV thiamine hydrochloride (TH) at increasing dosages would result in corresponding increases in plasma thiamine concentrations without causing adverse effects. A randomized cross-over study was performed in 9 healthy horses that each received TH at 5, 10, and 20 mg/kg IV. Blood was collected immediately prior to drug administration and at several time points thereafter. High-performance liquid chromatography with mass spectrometry was used to quantify thiamine concentrations at each time point. Non-compartmental PK methods showed that IV TH resulted in supraphysiologic plasma concentrations with a short half-life (0.77-1.12 h) and no adverse clinical signs were observed. The terminal rate constant decreased as the dosage increased (p < .0001) and clearance significantly decreased at the 20 mg/kg dosage (p = .0011). The area under the curve (AUC) increased in a non-linear fashion. These findings suggest that thiamine follows non-linear elimination kinetics in horses, which is likely due to saturation of renal elimination. Future studies are needed to identify therapeutic plasma concentrations and develop thiamine dosing recommendations for horses.
Subject(s)
Thiamine , Administration, Intravenous/veterinary , Animals , Area Under Curve , Cross-Over Studies , Half-Life , HorsesABSTRACT
Magnetic resonance imaging is the primary method used to diagnose canine glial cell neoplasia and noninfectious inflammatory meningoencephalitis. Subjective differentiation of these diseases can be difficult due to overlapping imaging characteristics. This study utilizes texture analysis (TA) of intra-axial lesions both as a means to quantitatively differentiate these broad categories of disease and to help identify glial tumor grade/cell type and specific meningoencephalitis subtype in a group of 119 dogs with histologically confirmed diagnoses. Fifty-nine dogs with gliomas and 60 dogs with noninfectious inflammatory meningoencephalitis were retrospectively recruited and randomly split into training (n = 80) and test (n = 39) cohorts. Forty-five of 120 texture metrics differed significantly between cohorts after correcting for multiple testing (false discovery rate < 0.05). After training the random forest algorithm, the classification accuracy for the test set was 85% (sensitivity 89%, specificity 81%). TA was only partially able to differentiate the inflammatory subtypes (granulomatous meningoencephalitis [GME], necrotizing meningoencephalitis [NME], and necrotizing leukoencephalitis [NLE]) (out-of-bag error rate of 35.0%) and was unable to identify metrics that could correctly classify glioma grade or cell type (out-of-bag error rate of 59.6% and 47.5%, respectively). Multiple demographic differences, such as patient age, sex, weight, and breed were identified between disease cohorts and subtypes which may be useful in prioritizing differential diagnoses. TA of MR images with a random forest algorithm provided classification accuracy of inflammatory and neoplastic brain disease approaching the accuracy of previously reported subjective radiologist evaluation.
Subject(s)
Brain Neoplasms/veterinary , Dog Diseases/diagnostic imaging , Magnetic Resonance Imaging/veterinary , Meningoencephalitis/veterinary , Animals , Brain Neoplasms/pathology , Dog Diseases/pathology , Dogs , Granuloma/complications , Male , Meningoencephalitis/complications , Meningoencephalitis/diagnostic imaging , Retrospective StudiesABSTRACT
Bio-based production of industrial chemicals using synthetic biology can provide alternative green routes from renewable resources, allowing for cleaner production processes. To efficiently produce chemicals on-demand through microbial strain engineering, biomanufacturing foundries have developed automated pipelines that are largely compound agnostic in their time to delivery. Here we benchmark the capabilities of a biomanufacturing pipeline to enable rapid prototyping of microbial cell factories for the production of chemically diverse industrially relevant material building blocks. Over 85 days the pipeline was able to produce 17 potential material monomers and key intermediates by combining 160 genetic parts into 115 unique biosynthetic pathways. To explore the scale-up potential of our prototype production strains, we optimized the enantioselective production of mandelic acid and hydroxymandelic acid, achieving gram-scale production in fed-batch fermenters. The high success rate in the rapid design and prototyping of microbially-produced material building blocks reveals the potential role of biofoundries in leading the transition to sustainable materials production.
Subject(s)
Bacteria/metabolism , Industrial Microbiology/methods , Metabolic Engineering/methods , Benchmarking , Biosynthetic Pathways , Chemical Industry , Computer Simulation , Fermentation , Mandelic Acids/metabolism , StereoisomerismABSTRACT
BACKGROUND AND OBJECTIVES: Computed tomography (CT) measurements of sarcopenia have been proposed as biomarkers associated with outcomes in various cancers and have typically been evaluated at the L3 vertebral level. However, staging imaging for patients with extremity and truncal soft tissue sarcoma (STS) often only includes chest CT imaging which precludes evaluation at L3. Therefore, we sought to evaluate muscle metrics at T12 on standard staging chest CT scans and evaluate for correlation with overall and event-free survival in patients with STS. METHODS: CT chest imaging for 89 patients with intermediate and high-grade STS (53 male, 36 female; 58.5 ± 19.0 years old, follow-up 37.4 ± 27.1 months) was reviewed on PACS at T12 for skeletal muscle density (SMD) and skeletal muscle index (SMI). RESULTS: Overall survival increased with increased SMD on univariate (hazard ratio [HR] = 0.61 [0.43, 0.86]) and age-adjusted analysis (HR = 0.65 [0.42, 0.89]. Event-free survival also increased with increased SMD in univariate analyses (HR = 0.68 [0.49, 0.95]) but did not maintain significance after adjusting for age (HR = 0.68 [0.43, 1.07]). SMI was not a predictor of overall or event-free survival. CONCLUSIONS: Higher SMD measured on routinely obtained staging chest CTs in STS patients is associated with improved survival.
Subject(s)
Muscle, Skeletal/diagnostic imaging , Sarcoma/diagnostic imaging , Disease-Free Survival , Extremities/pathology , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Muscle, Skeletal/pathology , Neoplasm Staging , Retrospective Studies , Sarcoma/mortality , Sarcoma/pathology , Sarcopenia/diagnostic imaging , Sarcopenia/pathology , Survival Rate , Tomography, X-Ray Computed/methods , Torso/pathologyABSTRACT
OBJECTIVE. The purpose of this study was to determine dose-area product-to-effective dose (DAP/E) conversion coefficients for a five-view pelvic radiograph series. DAP/E conversion coefficients may be used for radiation dose optimization when designing institutional protocols for pelvic trauma evaluation. MATERIALS AND METHODS. We conducted a retrospective record review of 25 patients at a level 1 trauma center who had sustained pelvic fractures and required a five-view pelvic radiograph series during workup. E values given in International Commission on Radiological Protection Publication 103 were simulated with a PC-based Monte Carlo program in conjunction with anthropomorphic phantoms adjusted on the basis of patient height and weight. Inputs included tube voltage (in kV), tube filtration (in millimeters of aluminum), anode angle, x-ray beam collimation, geometric distances, and angle of projection for each radiograph in the series. An incident polychromatic x-ray spectrum was generated and matched to the corresponding DAP values of each radiograph, and regression analysis was performed for the DAP/E conversion coefficients. RESULTS.E was strongly correlated with DAP independent from body mass index, with a mean global DAP/E conversion coefficient of 0.0125 mSv/dGy · cm2 for all radiographs (R2 = 0.95). Mean DAP/E conversion coefficients were 0.0133, 0.0110, 0.0143, 0.0113, and 0.0101 mSv/dGy · cm2 for anteroposterior, inlet, outlet, Judet left, and Judet right views, respectively (all R2 ≥ 0.94). CONCLUSION. DAP/E conversion coefficients are provided for a five-view pelvic radiograph series to allow reliable estimation of E. Measurement of cumulative E may affirm protocol design changes for the management of pelvic trauma.
Subject(s)
Fractures, Bone/diagnostic imaging , Pelvic Bones/diagnostic imaging , Pelvic Bones/injuries , Radiation Dosage , Radiography, Abdominal , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Monte Carlo Method , Phantoms, Imaging , Retrospective Studies , Trauma CentersABSTRACT
OBJECTIVE: To describe the characteristics of patients who used the Royal Flying Doctor Service dental clinics and determine Royal Flying Doctor Service and non-Royal Flying Doctor Service dental service provision in mainland Australia. DESIGN: A prospective cohort study. SETTING: All Royal Flying Doctor Service dental clinics located throughout rural and remote Australia. PARTICIPANTS: All patients who accessed an Royal Flying Doctor Service dental clinic from April 2017 to September 2018. INTERVENTIONS: Royal Flying Doctor Service mobile dental clinics. MAIN OUTCOME MEASURES: Patient demographics and dental procedures conducted (by age, sex and Indigenous status); and the dental service provision and coverage (Royal Flying Doctor Service and non-Royal Flying Doctor Service) within mainland rural and remote Australia. RESULTS: There were 8992 patient episodes comprising 3407 individual patients with 27 897 services completed. There were 920 (27%) Indigenous and 1465 (43%) non-Indigenous patients (n = 1022 missing ethnicity data). The mean (SD) age was 31.5 (24.8) years; the age groups 5-9 years and 10-14 years received 17.6% and 15.1% of the services, respectively. There were 1124 (33%) men and 1295 (38%) women (n = 988 with missing sex data). Women were more likely (all P < .05) to receive preventive services, diagnostic services, restorative services, general services, endodontics and periodontics. Men were more likely (both P < .05) to receive oral surgery and prosthodontics. There are many rural and remote people required to travel more than 60 minutes by vehicle to access dental care. CONCLUSION: Without increasing dental provision and preventive services in rural areas, it seems likely that there are and will be unnecessary oral emergencies and hospitalisations.