EMPOWER: Enacting Materials to Promote Ownership, Engagement, and Relevance.

Fostering locally relevant and community-centered forms of science learning that develop students' critical science agency problematizes a "one-size-fits-all" model of teacher learning; teachers must examine how community needs and resources, local inequities and justice issues, and curriculum materials can converge to design novel learning opportunities for science learners. This paper presents the core commitments of EMPOWER, a cross-institutional effort that aims to support teachers' sensemaking and adaptations of curriculum materials to promote student ownership, engagement, and relevance at multiple sites across the U.S.

"Driving the Ship" or Laying Buoys: Teachers' Use of Metaphor for Meaning-Making with Storylines.

Science curricula require new conceptualizations of how teachers relate to their materials. In this study of teacher learning, we analyze an experienced group of practicing Storylines teachers' use of metaphor to describe the roles and responsibilities of students and teachers in curriculum enactment. We found that every metaphor that teachers used to describe the uses of Storylines curriculum entailed a sort of wayfinding: a destination, a timeframe, a place, a journey, or the students' or teachers' respective position in that pursuit. These findings continue to indicate the usefulness of metaphor in foregrounding the central role that students play in NGSS-aligned instruction/materials, as well as the institutional forces that shape how curriculum materials get enacted inside the classroom. This study builds and contributes to current scholarship that aims to support teachers in reconceptualizing their role, relationship to students, and the institution of schooling, in the context of constructivist curricula.

Evaluating the Generalizability of Predictive Classifiers Built from DESI Imaging Lipid Data across Mass Spectrometry Platforms.

In this study, we evaluate the generalizability of predictive classifiers built from DESI lipid data for thyroid fine needle aspiration (FNA) biopsy analysis and classification using two high-performance mass spectrometers (time-of-flight and orbitrap) suited with different DESI imaging sources operated by different users. The molecular profiles obtained from thyroid samples with the different platforms presented similar trends, although specific differences in ion abundances were observed. When using a previously published statistical model built to discriminate thyroid cancer from benign thyroid tissues to predict on a new independent data set obtained, agreement for 24 of the 30 samples across the imaging platforms was achieved. We also tested the classifier on six clinical FNAs and obtained agreement between the predictive results and clinical diagnosis for the different conditions. Altogether, our results provide evidence that statistical classifiers generated from DESI lipid data are applicable across different high-resolution mass spectrometry platforms for thyroid FNA classification.

Advances and Emerging Medical Applications of Direct Mass Spectrometry Technologies for Tissue Analysis.

Offering superb speed, chemical specificity, and analytical sensitivity, direct mass spectrometry (MS) technologies are highly amenable for the molecular analysis of complex tissues to aid in disease characterization and help identify new diagnostic, prognostic, and predictive markers. By enabling detection of clinically actionable molecular profiles from tissues and cells, direct MS technologies have the potential to guide treatment decisions and transform sample analysis within clinical workflows. In this review, we highlight recent health-related developments and applications of direct MS technologies that exhibit tangible potential to accelerate clinical research and disease diagnosis, including oncological and neurodegenerative diseases and microbial infections. We focus primarily on applications that employ direct MS technologies for tissue analysis, including MS imaging technologies to map spatial distributions of molecules in situ as well as handheld devices for rapid in vivo and ex vivo tissue analysis.

Deeper Understanding of Solvent-Based Ambient Ionization Mass Spectrometry: Are Molecular Profiles Primarily Dictated by Extraction Mechanisms?

Solvent-based ambient ionization mass spectrometry (MS) techniques provide a powerful approach for direct chemical analysis and molecular profiling of biological tissues. While molecular profiling of tissues has been widely used for disease diagnosis, little is understood about how the interplay among solvent properties, matrix effects, and ion suppression can influence the detection of biological molecules. Here, we perform a systematic investigation of the extraction processes of lipids using an ambient ionization droplet microsampling platform to investigate how the physicochemical properties of the solvent systems and extraction time influence molecular extraction and detection. Direct molecular profiling and quantitative liquid chromatography-mass spectrometry (LC-MS) of discrete solvent droplets after surface sampling were investigated to provide insights into extraction and ionization mechanisms. The results of this study suggest that intermolecular interactions such as hydrogen bonding play a major role in extraction and detection of lipids using solvent-based ambient ionization techniques. In addition, extraction time was observed to impact the molecular profiles obtained, suggesting optimization of this parameter can be performed to favor detection of specific analytes.

Wireless Measurements Using Electrical Impedance Spectroscopy to Monitor Fracture Healing.

There is an unmet need for improved, clinically relevant methods to longitudinally quantify bone healing during fracture care. Here we develop a smart bone plate to wirelessly monitor healing utilizing electrical impedance spectroscopy (EIS) to provide real-time data on tissue composition within the fracture callus. To validate our technology, we created a 1-mm rabbit tibial defect and fixed the bone with a standard veterinary plate modified with a custom-designed housing that included two impedance sensors capable of wireless transmission. Impedance magnitude and phase measurements were transmitted every 48 h for up to 10 weeks. Bone healing was assessed by X-ray, µCT, and histology. Our results indicated the sensors successfully incorporated into the fracture callus and did not impede repair. Electrical impedance, resistance, and reactance increased steadily from weeks 3 to 7-corresponding to the transition from hematoma to cartilage to bone within the fracture gap-then plateaued as the bone began to consolidate. These three electrical readings significantly correlated with traditional measurements of bone healing and successfully distinguished between union and not-healed fractures, with the strongest relationship found with impedance magnitude. These results suggest that our EIS smart bone plate can provide continuous and highly sensitive quantitative tissue measurements throughout the course of fracture healing to better guide personalized clinical care.

Reduced Hemoglobin Signal and Improved Detection of Endogenous Proteins in Blood-Rich Tissues for MALDI Mass Spectrometry Imaging.

Mass spectrometry imaging provides a powerful approach for the direct analysis and spatial visualization of molecules in tissue sections. Using matrix-assisted laser desorption/ionization mass spectrometry, intact protein imaging has been widely investigated for biomarker analysis and diagnosis in a variety of tissue types and diseases. However, blood-rich or highly vascular tissues present a challenge in molecular imaging due to the high ionization efficiency of hemoglobin, which leads to ion suppression of endogenous proteins. Here, we describe a protocol to selectively reduce hemoglobin signal in blood-rich tissues that can easily be integrated into mass spectrometry imaging workflows.

Return to Play and Recurrence After Calf Muscle Strain Injuries in Elite Australian Football Players.

BACKGROUND: Calf muscle strain injuries (CMSI) are prevalent in sport, but information about factors associated with time to return to play (RTP) and recurrence is limited. PURPOSE: To determine whether clinical and magnetic resonance imaging (MRI) data are associated with RTP and recurrence after CMSI. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Data of 149 CMSI reported to the Soft Tissue injury Registry of the Australian Football League were explored to evaluate the impact of clinical data and index injury MRI findings on RTP and recurrence. Clinical data included age, previous injury history, ethnicity, and the mechanism of injury. RESULTS: Irrespective of the anatomical location, players with CMSI with severe aponeurotic disruption (AD) took longer to RTP than players with CMSI with no AD: 31.3 ± 12.6 days vs 19.4 ± 10.8 days (mean ± SD; P = .003). A running-related mechanism of injury was associated with a longer RTP period for CMSI overall (adjusted hazard ratio [AHR], 0.59; P = .02). The presence of AD was associated with a longer RTP period for soleus injuries (AHR, 0.6; P = .025). Early recurrence (ie, ≤2 months of the index injury) was associated with older age (AHR, 1.3; P = .001) and a history of ankle injury (AHR, 3.9; P = .032). Older age (AHR, 1.1; P = .013) and a history of CMSI (AHR, 6.7; P = .002) increased the risk of recurrence within 2 seasons. The index injury MRI findings were not associated with risk of recurrence. CONCLUSION: A running-related mechanism of injury and the presence of AD on MRI were associated with a longer RTP period. Clinical rather than MRI data best indicate the risk of recurrent CMSI.

Calf muscle strain injuries in elite Australian Football players: A descriptive epidemiological evaluation.

BACKGROUND: Calf muscle strain injuries (CMSI) show consistent rates of prevalence and re-injury in elite Australian Football players. An epidemiological evaluation is warranted to better understand the clinical presentation and recovery of CMSI. PURPOSE: First, to describe the epidemiology of CMSI in elite Australian Football players. Second, to determine if recovery following injury is different according to: (a) injury type (index vs re-injury); (b) muscle injured (soleus vs gastrocnemius); and (c) mechanism of injury (running-related activity vs non running-related activity). STUDY DESIGN: Descriptive epidemiological. METHODS: Data retrieved from the Soft Tissue injury Registry of the Australian Football League were analyzed. Sixteen clubs submitted data on CMSI from 2014 to 2017. Data included: player characteristics, training and match history at the time of injury, MRI, and the time to reach recovery milestones. RESULTS: One hundred and eighty-four CMSI were included (149 index injuries; 35 re-injuries). Soleus injuries were most prevalent (84.6%). Soleus injuries took 25.4 ± 16.2 days to return to play, whereas gastrocnemius injuries took 19.1 ± 14.1 days (P = .097). CMSI sustained during running-related activities took approximately 12 days longer to recover than injuries sustained during non running-related activities (P = .001). Compared to index injuries, re-injuries involved older players (P = .03) and significantly more time was taken to run at >90% of maximum speed, return to full training, and return to play (P ≤ .001). Almost all of the observed re-injuries involved soleus (91.4%). CONCLUSION: Soleus injuries are more prevalent than gastrocnemius injuries in elite Australian Football players. Prognosis appears to be influenced by clinical factors, with CMSI sustained during running-related activities and re-injuries needing more time to recover.

Preoperative metabolic classification of thyroid nodules using mass spectrometry imaging of fine-needle aspiration biopsies.

Thyroid neoplasia is common and requires appropriate clinical workup with imaging and fine-needle aspiration (FNA) biopsy to evaluate for cancer. Yet, up to 20% of thyroid nodule FNA biopsies will be indeterminate in diagnosis based on cytological evaluation. Genomic approaches to characterize the malignant potential of nodules showed initial promise but have provided only modest improvement in diagnosis. Here, we describe a method using metabolic analysis by desorption electrospray ionization mass spectrometry (DESI-MS) imaging for direct analysis and diagnosis of follicular cell-derived neoplasia tissues and FNA biopsies. DESI-MS was used to analyze 178 tissue samples to determine the molecular signatures of normal, benign follicular adenoma (FTA), and malignant follicular carcinoma (FTC) and papillary carcinoma (PTC) thyroid tissues. Statistical classifiers, including benign thyroid versus PTC and benign thyroid versus FTC, were built and validated with 114,125 mass spectra, with accuracy assessed in correlation with clinical pathology. Clinical FNA smears were prospectively collected and analyzed using DESI-MS imaging, and the performance of the statistical classifiers was tested with 69 prospectively collected clinical FNA smears. High performance was achieved for both models when predicting on the FNA test set, which included 24 nodules with indeterminate preoperative cytology, with accuracies of 93% and 89%. Our results strongly suggest that DESI-MS imaging is a valuable technology for identification of malignant potential of thyroid nodules.

Image quality comparison between model-based iterative reconstruction and adaptive statistical iterative reconstruction chest computed tomography in cystic fibrosis patients.

INTRODUCTION: Cystic fibrosis (CF) predominantly affects young adults. Accurate radiological assessment of pulmonary disease is vital for predicting exacerbations, one of the leading causes of morbidity and mortality. We evaluated the image quality of model-based iterative reconstruction (MBIR) ultra-low-dose CT chest (ULD-CT) in CF evaluation. METHODS: We compared ULD-CT with standard adaptive statistical iterative reconstruction (ASIR) low-dose CT (LD-CT). Subjective assessment of contrast and noise were performed for each study. Background noise, signal to noise ratio (SNR) and contrast to noise ratio (CNR) were calculated and compared between the CT studies. Conspicuity of major structures was assessed. These aspects of image quality were compared to determine whether ULD-CT was superior to LD-CT in assessment of CF. RESULTS: The ULD-CT achieved median effective dose of 0.073 mSv, comparable to one standard chest radiograph and significantly lower than the median LD-CT dose of 1.22 mSv. ULD-CT had lower subjective contrast and higher subjective noise when compared to LD-CT. Objectively measured background noise was lower in ULD-CT (16.33 HU vs 38.53 HU, P < 0.0001) compared to LD-CT. ULD-CT had higher median CNR (52.65 vs 22.09, P < 0.0001) and SNR in lung (9.08 vs 7.29, P = 0.002) compared to LD-CT. ULD-CT was equal to LD-CT in identification of trachea, bronchi, pleural and pericardium. Interobserver reliability showed agreement of 80-92%. CONCLUSIONS: The image quality of ULD-CT is similar to LD-CT, at 1/16th the dose. MBIR constructed ULD-CT is an effective imaging modality for CF surveillance, with potential applications in other disease settings.

Smart bone plates can monitor fracture healing.

There are currently no standardized methods for assessing fracture healing, with physicians relying on X-rays which are only useful at later stages of repair. Using in vivo mouse fracture models, we present the first evidence that microscale instrumented implants provide a route for post-operative fracture monitoring, utilizing electrical impedance spectroscopy (EIS) to track the healing tissue with high sensitivity. In this study, we fixed mouse long bone fractures with external fixators and bone plates. EIS measurements taken across two microelectrodes within the fracture gap were able to track longitudinal differences between individual mice with good versus poor healing. We additionally present an equivalent circuit model that combines the EIS data to classify fracture repair states. Lastly, we show that EIS measurements strongly correlated with standard quantitative µCT values and that these correlations validate clinically-relevant operating frequencies for implementation of this technique. These results demonstrate that EIS can be integrated into current fracture management strategies such as bone plating, providing physicians with quantitative information about the state of fracture repair to guide clinical decision-making for patients.

Using impedance to track fracture healing rates in mice in vivo: A pilot study.

Fracture injuries are highly prevalent worldwide, with treatment of problematic fractures causing a significant burden on the U.S. healthcare system. Physicians typically monitor fracture healing by conducting physical examinations and taking radiographic images. However, nonunions currently take over 6 months to be diagnosed because these techniques are not sensitive enough to adequately assess fracture union. In this study, we display the utility of impedance spectroscopy to track different healing rates in a pilot study of an in vivo mouse tibia fracture model. We have developed small (56 µm) sensors and implanted them in an externally-stabilized fracture for twice-weekly measurement. We found that impedance magnitude increases steadily over time in healing mice but stalls in non-healing mice, and phase angle displays frequency-dependent behavior that also reflects the extent of healing at the fracture site. Our results demonstrate that impedance can track differences in healing rates early on, highlighting the potential of this technique as a method for early detection of fracture nonunion.

New opportunities for fracture healing detection: Impedance spectroscopy measurements correlate to tissue composition in fractures.

Accurate evaluation of fracture healing is important for clinical decisions on when to begin weight-bearing and when early intervention is necessary in cases of fracture nonunion. While the stages of healing involving hematoma, cartilage, trabecular bone, and cortical bone have been well characterized histologically, physicians typically track fracture healing by using subjective physical examinations and radiographic techniques that are only able to detect mineralized stages of bone healing. This exposes the need for a quantitative, reliable technique to monitor fracture healing, and particularly to track healing progression during the early stages of repair. The goal of this study was to validate the use of impedance spectroscopy to monitor fracture healing and perform comprehensive evaluation comparing measurements with histological evidence. Here, we show that impedance spectroscopy not only can distinguish between cadaver tissues involved throughout fracture repair, but also correlates to fracture callus composition over the middle stages of healing in wild-type C57BL/6 mice. Specifically, impedance magnitude has a positive relationship with % trabecular bone and a negative relationship with % cartilage, and the opposite relationships are found when comparing phase angle to these same volume fractions of tissues. With this information, we can quantitatively evaluate how far a fracture has progressed through the healing stages. Our results demonstrate the feasibility of impedance spectroscopy for detection of fracture callus composition and reveals its potential as a method for early detection of bone healing and fracture nonunion. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2620-2629, 2017.

Large-Vessel Occlusion Is Associated with Poor Outcome in Stroke Patients Aged 80 Years or Older Who Underwent Intravenous Thrombolysis.

OBJECTIVE: We aimed to investigate the association between large-vessel occlusion (LVO) and functional outcome in elderly stroke patients treated with intravenous (IV) tissue plasminogen activator (tPA). METHODS: This was a retrospective study of acute ischemic stroke patients who received IV tPA within 4.5 hours after stroke onset between 2007 and 2013. Patients were categorized into 2 groups based on age (≥80 or < 80 years). LVO was evaluated by computed tomography angiography (CTA) before thrombolysis. Favorable outcome was defined as a modified Rankin Scale (mRS) score of 2 or lower at 3 months, or equal to the prestroke mRS score. RESULTS: Of 359 thrombolysis patients, 175 patients with CTA before a standard dose of IV tPA therapy (0.9 mg/kg body weight; maximum 90 mg) were included. Sixty-five patients were in the group aged 80 years or above with a median age of 84 (interquartile range: 82.5, 86) years. LVO was observed more often in the group with unfavorable outcome compared with the group with favorable outcome in older stroke patients (60.6% versus 21.9%, P = .002). The baseline National Institutes of Health Stroke Scale (NIHSS) score (odds ratio .864; 95% confidence interval [CI], .779-.959; P = .006) and LVO (odds ratio .233; 95% CI, .059-.930; P = .039) were independent associative factors for the unfavorable outcome in older patients treated with IV tPA after adjustment for patient characteristics. CONCLUSIONS: The baseline NIHSS score and LVO were independent predictors for functional outcome in elderly stroke patients received IV tPA.

Ultra-trace analysis of furanic compounds in transformer/rectifier oils with water extraction and high-performance liquid chromatography.

A novel approach for the determination of parts-per-billion level of 5-hydroxymethyl-2-furaldehyde, furfuryl alcohol, furfural, 2-furyl methyl ketone, and 5-methylfurfural in transformer or rectifier oils has been successfully innovated and implemented. Various extraction methods including solid-phase extraction, liquid-liquid extraction using methanol, acetonitrile, and water were studied. Water was by far the most efficient solvent for use as an extraction medium. Separation of the analytes was conducted using a 4.6 mm × 250 mm × 3.5 µm Agilent Zorbax column while detection and quantitation were conducted with a variable wavelength UV detector. Detection limits of all furans were at 1 ppb v/v with linear ranges range from 5 to 1000 ppb v/v with correlation coefficients of 0.997 or better. A relative standard deviation of at most 2.4% at 1000 ppb v/v and 7.3% at 5 ppb v/v and a recovery from 43% to 90% depending on the analyte monitored were obtained. The method was purposely designed to be environmental friendly with water as an extraction medium. Also, the method uses 80% water and 20% acetonitrile with a mere 0.2 mL/min of acetonitrile in an acetonitrile/water mixture as mobile phase. The analytical technique has been demonstrated to be highly reliable with low cost of ownership, suitable for deployment in quality control labs or in regions where available analytical resources and solvents are difficult to procure.

Impedance sensing device enables early detection of pressure ulcers in vivo.

When pressure is applied to a localized area of the body for an extended time, the resulting loss of blood flow and subsequent reperfusion to the tissue causes cell death and a pressure ulcer develops. Preventing pressure ulcers is challenging because the combination of pressure and time that results in tissue damage varies widely between patients, and the underlying damage is often severe by the time a surface wound becomes visible. Currently, no method exists to detect early tissue damage and enable intervention. Here we demonstrate a flexible, electronic device that non-invasively maps pressure-induced tissue damage, even when such damage cannot be visually observed. Using impedance spectroscopy across flexible electrode arrays in vivo on a rat model, we find that impedance is robustly correlated with tissue health across multiple animals and wound types. Our results demonstrate the feasibility of an automated, non-invasive 'smart bandage' for early detection of pressure ulcers.

Impedance sensing device for monitoring ulcer healing in human patients.

Chronic skin wounds affect millions of people each year and take billions of dollars to treat. Ulcers are a type of chronic skin wound that can be especially painful for patients and are tricky to treat because current monitoring solutions are subjective. We have developed an impedance sensing tool to objectively monitor the progression of healing in ulcers, and have begun a clinical trial to evaluate the safety and feasibility of our device to map damaged regions of skin. Impedance data has been collected on five patients with ulcers, and impedance was found to correlate with tissue health. A damage threshold was applied to effectively identify certain regions of skin as "damaged tissue".

Impedance spectroscopy to monitor fracture healing.

An estimated 7.9 million fracture injuries occur each year in the United States, of which a substantial fraction result in delayed or non-union. Current methods of monitoring fracture healing include taking x-rays and making clinical observations. However, x-ray confirmation of bone healing typically lags behind biologic healing, and physician assessment of healing is fraught with subjectivity. No standardized methods exist to assess the extent of healing that has taken place in a fracture. Without such knowledge, interventions to aid healing and prevent fracture non-union are often delayed, leading to increased morbidity and suffering to patients. We are developing an objective measurement tool that utilizes electrical impedance spectroscopy to distinguish between the various types of tissue present during the different stages of fracture healing. Preliminary measurements of cadaveric tissues reveal adequate spread in impedance measurements and differences in frequency response among different tissue types. Electrodes implanted in a simulated fracture created in an ex vivo cadaver model yield promising results for our system's ability to differentiate between the stages of fracture healing.

Does large vessel occlusion affect clinical outcome in stroke with mild neurologic deficits after intravenous thrombolysis?

BACKGROUND: Large vessel occlusion (LVO) is associated with poor functional outcome in acute ischemic stroke. Given the uncertainty whether LVO has the same significance in mild and severe stroke, we compared functional outcomes after intravenous thrombolysis, based on severity and LVO. METHODS: Ischemic stroke patients were thrombolyzed in less than 4.5 hours after onset between 2007 and 2013. LVO was defined as occlusion of one of the following arteries: internal carotid, middle cerebral (M1/M2), anterior cerebral (A1), posterior cerebral (P1), basilar, or vertebral (V4) arteries on prethrombolysis computed tomography angiography. Mild stroke was defined as baseline National Institutes of Health Stroke Scale (NIHSS) score 0-6. Favorable outcome was defined as modified Rankin Scale (mRS) score 0-1 at 3 months or equal to the prestroke mRS. RESULTS: There were 175 acute stroke patients, median age 74 years (interquartile range [IQR], 64-83), median baseline NIHSS = 11 (IQR, 5-16), and 63 of 175 patients (36%) with mild stroke. LVO was associated with worse outcome in severe stroke (age-adjusted odds ratio [OR] of favorable outcome, .42; 95% confidence interval [CI], .19-.93; P = .033) and mortality (age-adjusted OR, 3.52; 95% CI, 1.08-11.48; P = .037). Although the difference in favorable outcome between mild stroke patients with and without LVO was not significant (55.6% vs. 74.1%, P = .262; age-adjusted OR of favorable outcome, .42; 95% CI, .1-1.84; P = .251), the similarity of effects across both subgroups cannot be excluded (LVO-by-stroke severity interaction test, P = .906). CONCLUSIONS: LVO is associated with worse functional outcome and mortality in severe stroke after intravenous thrombolysis. Although significant association between LVO and outcome in mild stroke was not found, there were similar effects on outcome and a larger study might well confirm a relationship.