Motor somatotopy impacts imagery strategy success in human intracortical brain-computer interfaces.

The notion of a somatotopically organized motor cortex, with movements of different body parts being controlled by spatially distinct areas of cortex, is well known. However, recent studies have challenged this notion and suggested a more distributed representation of movement control. This shift in perspective has significant implications, particularly when considering the implantation location of electrode arrays for intracortical brain-computer interfaces (iBCIs). We sought to evaluate whether the location of neural recordings from the precentral gyrus, and thus the underlying somatotopy, has any impact on the imagery strategies that can enable successful iBCI control. Three individuals with a spinal cord injury were enrolled in an ongoing clinical trial of an iBCI. Participants had two intracortical microelectrode arrays implanted in the arm and/or hand areas of the precentral gyrus based on presurgical functional imaging. Neural data were recorded while participants attempted to perform movements of the hand, wrist, elbow, and shoulder. We found that electrode arrays that were located more medially recorded significantly more activity during attempted proximal arm movements (elbow, shoulder) than did lateral arrays, which captured more activity related to attempted distal arm movements (hand, wrist). We also evaluated the relative contribution from the two arrays implanted in each participant to decoding accuracy during calibration of an iBCI decoder for translation and grasping tasks. For both task types, imagery strategy (e.g., reaching vs. wrist movements) had a significant impact on the relative contributions of each array to decoding. Overall, we found some evidence of broad tuning to arm and hand movements; however, there was a clear bias in the amount of information accessible about each movement type in spatially distinct areas of cortex. These results demonstrate that classical concepts of somatotopy can have real consequences for iBCI use, and highlight the importance of considering somatotopy when planning iBCI implantation.

Attachment and propensity for reporting compassionate opportunities and behavior in everyday life.

Introduction: Researchers have identified links between anxious and avoidant attachments and difficulties with self-compassion, giving others compassion, and receiving compassion. However, while compassion requires both awareness of opportunities for compassion and compassionate action, little is known about attachment-related differences in reporting compassionate opportunities. Further, most research relies on retrospective-reports that may not accurately assess compassionate behaviors in everyday life. Method: Consequently, we collected 2,757 experience sampling survey responses from 125 participants (95 women, 27 men, 3 non-binary, M age = 18.74, SD age = 1.66) to investigate whether attachment anxiety, avoidance, or their interaction were associated with differences in propensity for reporting compassionate opportunities, actions, and emotional responses to opportunities in everyday life across self-compassion, giving compassion, and receiving compassion. Results: Anxiety was associated with greater likelihood of reporting all types of compassionate opportunities and less positive responses to opportunities to receive compassion. Avoidance was associated with less likelihood of reporting opportunities to give and receive compassion and less positive responses to opportunities to give compassion. Those high in anxiety but simultaneously low in avoidance reported fewer self-compassionate actions, but we identified no further differences in compassionate action. Discussion: This study highlights the potential role of awareness of compassionate opportunities in attachment-related differences in compassion.

Estimating the Relationship Between Nurse Staffing and Medication Pass Workload Using National Barcode Data.

BACKGROUND: Measuring and assessing the relationship between inpatient nurse staffing and workload across a national health system is difficult due to challenges in systematically observing inpatient workload at the unit level. OBJECTIVE: The objective of this study was to apply a novel measure of inpatient nurse workload to estimate the relationship between inpatient nurse staffing and nurse workload at the unit level during a key nursing activity: the peak-time medication pass. METHODS: A retrospective observational study was conducted in the Veterans Health Administration, the largest employer of nurses in the U.S. The sample included all patients (n= 1,578,399 patient days) admitted to 311 non-intensive care unit inpatient acute care units in 112 hospitals in 2019 (104,588 unit days). Staffing was measured as the unit-level, nurse-to-patient ratio, and workload was measured using average time (duration) for RNs to complete the peak-time medication pass. RESULTS: We found a negative relationship between the RN-to-patient ratio and average peak time medication pass duration after adjusting for unit-level patient volume and average patient severity of illness and other unit-level factors. This relationship was non-linear: the marginal effect of staffing on workload decreased as staffing increased. DISCUSSION: As unit-level nurse staffing increased, average RN workload decreased. This result suggests that interventions to improve nurse staffing may have larger non-linear effects for units with lower staffing levels. Understanding the effect of differing staffing decisions on variations in nursing workload is critical for adopting models of care that effectively use scarce staffing resources and contribute to retaining nurses in the inpatient workforce. This work provides evidence that peak time medication pass duration is a valid process-based measure of workload and highlights the potential diminishing returns to increasing staffing.

A theory of brain-computer interface learning via low-dimensional control.

A remarkable demonstration of the flexibility of mammalian motor systems is primates' ability to learn to control brain-computer interfaces (BCIs). This constitutes a completely novel motor behavior, yet primates are capable of learning to control BCIs under a wide range of conditions. BCIs with carefully calibrated decoders, for example, can be learned with only minutes to hours of practice. With a few weeks of practice, even BCIs with randomly constructed decoders can be learned. What are the biological substrates of this learning process? Here, we develop a theory based on a re-aiming strategy, whereby learning operates within a low-dimensional subspace of task-relevant inputs driving the local population of recorded neurons. Through comprehensive numerical and formal analysis, we demonstrate that this theory can provide a unifying explanation for disparate phenomena previously reported in three different BCI learning tasks, and we derive a novel experimental prediction that we verify with previously published data. By explicitly modeling the underlying neural circuitry, the theory reveals an interpretation of these phenomena in terms of biological constraints on neural activity.

Effect of TiC Nanoparticles on a Zn-Al-Cu System for Biodegradable Cardiovascular Stent Applications.

Despite being a weaker metal, zinc has become an increasingly popular candidate for biodegradable implant applications due to its suitable corrosion rate and biocompatibility. Previous studies have experimented with various alloy elements to improve the overall mechanical performance of pure Zn without compromising the corrosion performance and biocompatibility; however, the thermal stability of biodegradable Zn alloys has not been widely studied. In this study, TiC nanoparticles were introduced for the first time to a Zn-Al-Cu system. After hot rolling, TiC nanoparticles were uniformly distributed in the Zn matrix and effectively enabled phase control during solidification. The Zn-Cu phase, which was elongated and sharp in the reference alloy, became globular in the nanocomposite. The strength of the alloy, after introducing TiC nanoparticles, increased by 31% from 259.7 to 340.3 MPa, while its ductility remained high at 49.2% elongation to failure. Fatigue performance also improved greatly by adding TiC nanoparticles, increasing the fatigue limit by 47.6% from 44.7 to 66 MPa. Furthermore, TiC nanoparticles displayed excellent phase control capability during body-temperature aging. Without TiC restriction, Zn-Cu phases evolved into dendritic morphologies, and the Al-rich eutectic grew thicker at grain boundaries. However, both Zn-Cu and Al-rich eutectic phases remained relatively unchanged in shape and size in the nanocomposite. A combination of exceptional tensile properties, improved fatigue performance, better long-term stability with a suitable corrosion rate, and excellent biocompatibility makes this new Zn-Al-Cu-TiC material a promising candidate for biodegradable stents and other biodegradable applications.

Multi-modal Pulmonary Imaging: Using Complementary Information from CT and Hyperpolarized 129Xe MRI to Evaluate Lung Structure-Function.

Hyperpolarized 129Xe gas MRI is an emerging technique to evaluate and measure regional lung function including pulmonary gas distribution and gas exchange. Chest computed tomography (CT) still remains the clinical gold standard for imaging of the lungs, though, in part due to the rapid CT protocols that acquire high-resolution images in seconds and the widespread availability of CT scanners. Quantitative approaches have enabled the extraction of structural lung parenchymal, airway and vascular measurements from chest CT that have been evaluated in many clinical research studies. Together, CT and 129Xe MRI provide complementary information that can be used to evaluate regional lung structure and function, resulting in new insights into lung health and disease. 129Xe MR-CT image registration can be performed to measure regional lung structure-function to better understand lung disease pathophysiology, and to perform image-guided pulmonary interventions. Here, a method for 129Xe MRI-CT registration is outlined to support implementation in research or clinical settings. Registration methods and applications that have been employed to date in the literature are also summarized, and suggestions are provided for future directions that may further overcome technical challenges related to 129Xe MR-CT image registration and facilitate broader implementation of regional lung structure-function evaluation.

Amplifying Curcumin's Antitumor Potential: A Heat-Driven Approach for Colorectal Cancer Treatment.

Introduction: Peritoneal metastases from colorectal cancer (CRC) present a significant clinical challenge with poor prognosis, often unresponsive to systemic chemotherapy. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment approach for select patients. The use of curcumin, a natural compound with antitumor properties, in HIPEC is of interest due to its lower side effects compared to conventional drugs and potential for increased efficacy through direct delivery to the peritoneal cavity. Methods: An in vitro hyperthermic model was developed to simulate clinical HIPEC conditions. Three colon cancer cell lines (SK-CO-1, COLO205, SNU-C1) representing different genetic mutations (p53, KRAS, BRAF) were treated with either curcumin (25 µM) or mitomycin-C (1 µM) for 1, 2, or 3 hours. Post-treatment, cells were incubated at 37°C (normothermia) or 42°C (hyperthermia). Cell viability and proliferation were assessed at 24, 48 and 72 hours post-treatment using Annexin V/PI, MTT assay, trypan blue exclusion, and Hoffman microscopy. Results: Hyperthermia significantly enhanced the antitumor efficacy of curcumin, evidenced by a two-fold reduction in cell viability compared to normothermia across all cell lines. In the SNU-C1 cell line, which harbors a p53 mutation, mitomycin-C failed to significantly impact cell viability, unlike curcumin, suggesting mutation-specific differences in treatment response. Discussion: The findings indicate that hyperthermia augments the antitumor effects of curcumin in vitro, supporting the hypothesis that curcumin could be a more effective HIPEC agent than traditional drugs like mitomycin-C. Mutation-associated differences in response to treatments were observed, particularly in p53 mutant cells. While further studies are needed, these preliminary results suggest that curcumin in HIPEC could represent a novel therapeutic strategy for CRC patients with peritoneal metastases. This approach may offer improved outcomes with fewer side effects, particularly in genetically distinct CRC subtypes.

Contextual factors influencing the association between the Affordable Care Act's Medicaid expansion and Veteran VA-Medicaid dual enrollment.

OBJECTIVE: To evaluate changes in dual enrollment after Affordable Care Act Medicaid expansion by VA priority group, (e.g., service connection), sex, and type of state expansion. STUDY SETTING: Our cohort was all Veterans ages 18-64 enrolled in VA and eligible for benefits due to military service-connection or low income from 2011 to 2016; the unit of analysis was person-year. STUDY DESIGN: Difference-in-difference and event-study analysis. The outcome was dual VA-Medicaid enrollment for at least 1 month annually. Medicaid expansion, VA priority status, whether a state expanded by a Section 1115 waiver, and sex were independent variables. We controlled for race, ethnicity, age, disease burden, distance to VA facilities, state, and year. DATA EXTRACTION METHODS: We used data from the VA Corporate Data Warehouse (CDW) regarding age and VA Priority Group to select our cohort of VA-enrolled individuals. We then took the cohort and crossed checked it with Medicaid Analytic Extract (MAX) and T-MSIS Analytic Files (TAF) to determine Medicaid enrollment status. PRINCIPAL FINDINGS: Service-connected Veterans experienced lower dual-enrollment increases across all sex and state-waiver groups (3.44 percentage points (95% CI: 1.83, 5.05 pp) for women, 3.93 pp (2.98, 4.98) for men, 4.06 pp (2.85, 5.27) for non-waiver states, and 3.00 pp (1.58 to 4.41) for waiver states) than Veterans who enrolled in the VA due to low income (8.19 pp (5.43, 10.95) for women, 9.80 pp (7.06, 12.54) for men, 10.21 pp (7.17, 13.25) for non-waiver states, and 7.39 pp (5.28, 9.50) for waiver states). CONCLUSIONS: Medicaid expansion is associated with dual enrollment. Dual-enrollment changes are greatest in those enrolled in the VA due to low income, but do not differ by sex or expansion type. Results can help VA identify groups disproportionately likely to have potential care-coordination issues due to usage of multiple health care systems.

Determinants of referral network size for screening colonoscopies in the Veterans Health Administration after the implementation of the MISSION Act.

OBJECTIVE: To measure key characteristics of the Veterans Health Administration's (VHA) Community Care (CC) referral network for screening colonoscopy and identify market and institutional factors associated with network size. DATA SOURCES: VHA electronic health records, CC claim data, and National Plan and Provider Enumeration System. STUDY DESIGN: In this retrospective cross-sectional study, we measure the size of the VHA's CC referral networks over time and by VHA parent facility (n = 137). We used a multivariable linear regression to identify factors associated with network size at the market-year level. Network size was measured as the number of physicians who performed at least one VHA-purchased screening colonoscopy per 1000 enrollees at baseline. DATA EXTRACTION: Data were extracted for all Veterans (n = 102,119) who underwent a screening colonoscopy purchased by the VHA from a non-VHA physician from 2018 to 2021. PRINCIPAL FINDINGS: From 2018 to 2021, median network volume of screening colonoscopies per 1000 enrollees grew from 1.6 (IQR: 0.6, 4.6) to 3.6 (IQR: 1.6, 6.6). The median network size grew from 0.63 (IQR: 0.30, 1.26) to 0.92 (IQR: 0.57, 1.63). Finally, the median procedures per physician increased from 2.5 (IQR: 1.6, 4.2) to 3.2 (IQR: 2.4, 4.7). After adjusting for baseline market characteristics, volume of screening colonoscopies was positively related to network size (ß = 0.15, 95% CI: [0.10, 0.20]), negatively related to procedures per physician (ß = -0.12, 95% CI: [-0.18, -0.05]), and positively associated with the percent of rural enrollees (ß = 0.01, 95% CI: [0.00, 0.01]). CONCLUSIONS: VHA facilities with a higher volume of VHA-purchased screening colonoscopies and more rural enrollees had more non-VHA physicians providing care. Geographic variation in referral networks may also explain differences in the effects of the MISSION Act on access to care and patient outcomes.

Veterans Health Administration enrollees' choice of care setting relates to the expansion of care options: Evidence from screening colonoscopies before and after the MISSION Act.

OBJECTIVE: To estimate whether those enrolled in the Veterans Health Administration (VHA) were less likely to use VHA-delivered colorectal cancer screening colonoscopies after the MISSION Act. DATA SOURCES AND STUDY SETTING: Secondary data were collected on VHA-enrolled Veterans from FY2017-FY2021. STUDY DESIGN: This retrospective cross-sectional study measured the volume and share of screening colonoscopies that were VHA-delivered over time and by drive time eligibility-defined as living more than 60 min away from the nearest VHA specialty-care clinic. We used a multivariable logistic regression to adjust for patient and facility factors. DATA EXTRACTION: Data were extracted for VHA enrollees (n = 773,766) who underwent a screening colonoscopy either performed or purchased by the VHA from FY2017-FY2021. PRINCIPAL FINDINGS: In the 9 months after the implementation of the MISSION Act, and before the onset of the Covid-19 pandemic, the average monthly VHA-share of screening colonoscopies decreased by 3 percentage points (pp; 95% confidence interval [CI] = [-4 to -2 pp]) for the non-drive time eligible group and it decreased by 16 pp (95% CI = [-22 to -9 pp]) for the drive time eligible group. The total number of screening colonoscopies did not significantly change in either group during this time period. After adjusting for patient characteristics, a linear time trend, and parent facility fixed effects, implementation of the MISSION Act was associated with a reduction in the probability of a VHA-delivered screening colonoscopy (average marginal effect [AME]: -2.5 pp; 95% CI = [-5.1 to 0.0 pp]) for the non-drive time eligible group. The drive time eligible group (AME: -9.4 pp; 95% CI = [-13.2 to -5.5 pp]) experienced a larger change. CONCLUSIONS: The VHA-share of screening colonoscopies among VHA enrollees fell in the 9 months immediately after the passage of the MISSION Act. This decline was larger for VHA enrollees who were targeted for eligibility due to a longer drive time. These results suggest that the MISSION Act led to more VHA-purchased care among targeted VHA enrollees, though it is unclear whether total utilization increased.

Use of Quantitative CT Imaging to Identify Bronchial Thermoplasty Responders.

BACKGROUND: Bronchial thermoplasty (BT) is a treatment for patients with poorly controlled, severe asthma. However, predictors of treatment response to BT are defined poorly. RESEARCH QUESTION: Do baseline radiographic and clinical characteristics exist that predict response to BT? STUDY DESIGN AND METHODS: We conducted a longitudinal prospective cohort study of participants with severe asthma receiving BT across eight academic medical centers. Participants received three separate BT treatments and were monitored at 3-month intervals for 1 year after BT. Similar to prior studies, a positive response to BT was defined as either improvement in Asthma Control Test results of ≥ 3 or Asthma Quality of Life Questionnaire of ≥ 0.5. Regression analyses were used to evaluate the association between pretreatment clinical and quantitative CT scan measures with subsequent BT response. RESULTS: From 2006 through 2017, 88 participants received BT, with 70 participants (79.5%) identified as responders by Asthma Control Test or Asthma Quality of Life Questionnaire criteria. Responders were less likely to undergo an asthma-related ICU admission in the prior year (3% vs 25%; P = .01). On baseline quantitative CT imaging, BT responders showed less air trapping percentage (OR, 0.90; 95% CI, 0.82-0.99; P = .03), a greater Jacobian determinant (OR, 1.49; 95% CI, 1.05-2.11), greater SD of the Jacobian determinant (OR, 1.84; 95% CI, 1.04-3.26), and greater anisotropic deformation index (OR, 3.06; 95% CI, 1.06-8.86). INTERPRETATION: To our knowledge, this is the largest study to evaluate baseline quantitative CT imaging and clinical characteristics associated with BT response. Our results show that preservation of normal lung expansion, indicated by less air trapping, a greater magnitude of isotropic expansion, and greater within-lung spatial variation on quantitative CT imaging, were predictors of future BT response. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01185275; URL: www. CLINICALTRIALS: gov.

The Lucy Thermal Emission Spectrometer (L'TES) Instrument.

The Lucy Thermal Emission Spectrometer (L'TES) will provide remote measurements of the thermophysical properties of the Trojan asteroids studied by the Lucy mission. L'TES is build-to-print hardware copy of the OTES instrument flown on OSIRIS-REx. It is a Fourier Transform spectrometer covering the spectral range 5.71-100 µm (1750-100 cm-1) with spectral sampling intervals of 8.64, 17.3, and 34.6 cm-1 and a 7.3-mrad field of view. The L'TES telescope is a 15.2-cm diameter Cassegrain telescope that feeds a flat-plate Michelson moving mirror mounted on a linear voice-coil motor assembly to a single uncooled deuterated l-alanine doped triglycine sulfate (DLATGS) pyroelectric detector. A significant firmware change from OTES is the ability to acquire interferograms of different length and spectral resolution with acquisition times of 0.5, 1, and 2 seconds. A single ∼0.851 µm laser diode is used in a metrology interferometer to provide precise moving mirror control and IR sampling at 772 Hz. The beamsplitter is a 38-mm diameter, 1-mm thick chemical vapor deposited diamond with an antireflection microstructure to minimize surface reflection. An internal calibration cone blackbody target, together with observations of space, provides radiometric calibration. The radiometric precision in a single spectrum is ≤2.2 × 10-8 W cm-2 sr-1 /cm-1 between 300 and 1350 cm-1. The absolute temperature error is <2 K for scene temperatures >75 K. The overall L'TES envelope size is 37.6 × 29.0 × 30.4 cm, and the mass is 6.47 kg. The power consumption is 12.6 W average. L'TES was developed by Arizona State University with AZ Space Technologies developing the electronics. L'TES was integrated, tested, and radiometrically calibrated on the Arizona State University campus in Tempe, AZ. Initial data from space have verified the instrument's radiometric and spatial performance.

Genomics reveal the origins and current structure of a genetically depauperate freshwater species in its introduced Alaskan range.

Invasive species are a major threat to global biodiversity, yet also represent large-scale unplanned ecological and evolutionary experiments to address fundamental questions in nature. Here we analyzed both native and invasive populations of predatory northern pike (Esox lucius) to characterize landscape genetic variation, determine the most likely origins of introduced populations, and investigate a presumably postglacial population from Southeast Alaska of unclear provenance. Using a set of 4329 SNPs from 351 individual Alaskan northern pike representing the most widespread geographic sampling to date, our results confirm low levels of genetic diversity in native populations (average 𝝅 of 3.18 × 10-4) and even less in invasive populations (average 𝝅 of 2.68 × 10-4) consistent with bottleneck effects. Our analyses indicate that invasive northern pike likely came from multiple introductions from different native Alaskan populations and subsequently dispersed from original introduction sites. At the broadest scale, invasive populations appear to have been founded from two distinct regions of Alaska, indicative of two independent introduction events. Genetic admixture resulting from introductions from multiple source populations may have mitigated the negative effects associated with genetic bottlenecks in this species with naturally low levels of genetic diversity. Genomic signatures strongly suggest an excess of rare, population-specific alleles, pointing to a small number of founding individuals in both native and introduced populations consistent with a species' life history of limited dispersal and gene flow. Lastly, the results strongly suggest that a small isolated population of pike, located in Southeast Alaska, is native in origin rather than stemming from a contemporary introduction event. Although theory predicts that lack of genetic variation may limit colonization success of novel environments, we detected no evidence that a lack of standing variation limited the success of this genetically depauperate apex predator.

Reaction Time "Mismatch Costs" Change with the Likelihood of Stimulus-Response Compatibility.

Dyadic interactions require dynamic correspondence between one's own movements and those of the other agent. This mapping is largely viewed as imitative, with the behavioural hallmark being a reaction-time cost for mismatched actions. Yet the complex motor patterns humans enact together extend beyond direct-matching, varying adaptively between imitation, complementary movements, and counter-imitation. Optimal behaviour requires an agent to predict not only what is likely to be observed but also how that observed action will relate to their own motor planning. In 28 healthy adults, we examined imitation and counter-imitation in a task that varied the likelihood of stimulus-response congruence from highly predictable, to moderately predictable, to unpredictable. To gain mechanistic insights into the statistical learning of stimulus-response compatibility, we compared two computational models of behaviour: (1) a classic fixed learning-rate model (Rescorla-Wagner reinforcement [RW]) and (2) a hierarchical model of perceptual-behavioural processes in which the learning rate adapts to the inferred environmental volatility (hierarchical Gaussian filter [HGF]). Though more complex and hence penalized by model selection, the HGF provided a more likely model of the participants' behaviour. Matching motor responses were only primed (faster) in the most experimentally volatile context. This bias was reversed so that mismatched actions were primed when beliefs about volatility were lower. Inferential statistics indicated that matching responses were only primed in unpredictable contexts when stimuli-response congruence was at 50:50 chance. Outside of these unpredictable blocks the classic stimulus-response compatibility effect was reversed: Incongruent responses were faster than congruent ones. We show that hierarchical Bayesian learning of environmental statistics may underlie response priming during dyadic interactions.

Experimental study on novel biodegradable Zn-Fe-Si alloys.

Bioabsorbable metals are increasingly attracting attention for their potential use as materials for degradable implant devices. Zinc (Zn) alloys have shown great promises due to their good biocompatibility and favorable degradation rate. However, it has been difficult to maintain an appropriate balance among strength, ductility, biocompatibility, and corrosion rate for Zn alloys historically. In this study, the microstructure, chemical composition, mechanical properties, biocompatibility, and corrosion rate of a new ternary zinc-iron-silicon (Zn-Fe-Si) alloy system was studied as a novel material for potential biodegradable implant applications. The results demonstrated that the in situ formed Fe-Si intermetallic phases enhanced the mechanical strength of the material while maintaining a favorable ductility. With Fe-Si reinforcements, the microhardness of the Zn alloys was enhanced by up to 43%. The tensile strength was increased by up to 76% while elongation to failure remained above 30%. Indirect cytotoxicity testing showed the Zn-Fe-Si system had good biocompatibility. Immersion testing revealed the corrosion rate of Zn-Fe-Si system was not statistically different from pure Zn. To understand the underlying phase formation mechanism, the reaction process in this ternary system during the processing was also studied via phase evolution and Gibbs free energy analysis. The results suggest the Zn-Fe-Si ternary system is a promising new material for bioabsorbable metallic medical devices.

Imaging in Asthma Management.

Asthma is a heterogeneous disease characterized by chronic airway inflammation that affects more than 300 million people worldwide. Clinically, asthma has a widely variable presentation and is defined based on a history of respiratory symptoms alongside airflow limitation. Imaging is not needed to confirm a diagnosis of asthma, and thus the use of imaging in asthma has historically been limited to excluding alternative diagnoses. However, significant advances continue to be made in novel imaging methodologies, which have been increasingly used to better understand respiratory impairment in asthma. As a disease primarily impacting the airways, asthma is best understood by imaging methods with the ability to elucidate airway impairment. Techniques such as computed tomography, magnetic resonance imaging with gaseous contrast agents, and positron emission tomography enable assessment of the small airways. Others, such as optical coherence tomography and endobronchial ultrasound enable high-resolution imaging of the large airways accessible to bronchoscopy. These imaging techniques are providing new insights in the pathophysiology and treatments of asthma and are poised to impact the clinical management of asthma.

Analysis of Postoperative Gait, Hip Strength, and Patient-Reported Outcomes After OTA/AO 61-B and 61-C Pelvic Ring Injuries.

OBJECTIVES: To examine clinical gait parameters, hip muscle strength, pelvic functional outcomes, and psychological outcomes after surgical fixation of OTA/AO 61-B and 61-C pelvic ring injuries. DESIGN: Retrospective review identified 10 OTA/AO 61-B patients and 9 OTA/AO 61-C patients for recruitment who were between 1 and 5 years after pelvic fixation. Gait and strength assessments, and patient-reported outcome scores were performed/collected and analyzed. SETTING: Outpatient clinical motion performance laboratory. PATIENTS/PARTICIPANTS: Patients with OTA/AO 61-B and OTA/AO 61-C fractures who were between 1 and 5 years after pelvic fixation. MAIN OUTCOME MEASUREMENTS: Hip strength, kinetics, and spatial-temporal outcomes; Majeed Pelvic Outcome Score; Short Form 36; Hamilton Anxiety/Depression Rating Scales. RESULTS: There were no differences in age, body mass index, or time since definitive fixation between OTA/AO 61-B and 61-C groups. The OTA/AO 61-C group had higher median injury severity scores, longer length of stay, and greater postoperative pelvic fracture displacement. There was no difference in bilateral hip strength, bilateral peak hip moments, peak hip power, and walking speed between groups. Patients with OTA/AO 61-C fractures had lower scores on Short Form 36 General Health and Majeed Work, with a trend toward a lower Total Majeed score. There were no differences in self-reported total anxiety and depression symptoms. CONCLUSIONS: This study did not identify any gait, strength, or psychological differences between OTA/AO 61-B and 61-C injuries at 1-5 years of follow-up. However, increased injury severity in OTA/AO 61-C patients may have residual consequences on perceived general health and ability to work. This pilot study establishes a template for future research into functional recovery of patients with severe pelvic ring trauma. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Functionalizing Fibrin Hydrogels with Thermally Responsive Oligonucleotide Tethers for On-Demand Delivery.

There are a limited number of stimuli-responsive biomaterials that are capable of delivering customizable dosages of a therapeutic at a specific location and time. This is especially true in tissue engineering and regenerative medicine applications, where it may be desirable for the stimuli-responsive biomaterial to also serve as a scaffolding material. Therefore, the purpose of this study was to engineer a traditionally non-stimuli responsive scaffold biomaterial to be thermally responsive so it could be used for on-demand drug delivery applications. Fibrin hydrogels are frequently used for tissue engineering and regenerative medicine applications, and they were functionalized with thermally labile oligonucleotide tethers using peptides from substrates for factor XIII (FXIII). The alpha 2-plasmin inhibitor peptide had the greatest incorporation efficiency out of the FXIII substrate peptides studied, and conjugates of the peptide and oligonucleotide tethers were successfully incorporated into fibrin hydrogels via enzymatic activity. Single-strand complement oligo with either a fluorophore model drug or platelet-derived growth factor-BB (PDGF-BB) could be released on demand via temperature increases. These results demonstrate a strategy that can be used to functionalize traditionally non-stimuli responsive biomaterials suitable for on-demand drug delivery systems (DDS).

Binder Jetting of Custom Silicone Powder for Direct Three-Dimensional Printing of Maxillofacial Prostheses.

Recent advances in digital workflow have transformed clinician's ability to offer patient-specific devices for medical and dental applications. However, the digital workflow of patient-specific maxillofacial prostheses (MFP) remains incomplete, and several steps in the manufacturing process are still labor-intensive and are costly in both time and resources. Despite the high demand for direct digital MFP manufacturing, three-dimensional (3D) printing of colored silicone MFP is limited by the processing routes of medical-grade silicones and biocompatible elastomers. In this study, a binder jetting 3D printing process with polyvinyl butyral (PVB)-coated silicone powder was developed for direct 3D printing of MFP. Nanosilica-treated silicone powder was spray dried with PVB by controlling the Ohnesorge number and processing parameters. After printing, the interconnected pores were infused with silicone and hexamethyldisiloxane (HMDS) by pressure-vacuum sequential infiltration to produce the final parts. Particle size, coating composition, surface treatment, and infusion conditions influenced the mechanical properties of the 3D-printed preform, and of the final infiltrated structure. In addition to demonstrating the feasibility of using silicone powder-based 3D printing for MFP, these results can be used to inform the modifications required to accommodate the manufacturing of other biocompatible elastomeric materials.

Inotersen to Treat Polyneuropathy Associated with Hereditary Transthyretin (hATTR) Amyloidosis.

Background: Amyloidosis is a group of diseases with the common pathophysiology of protein misfolding and aberrant deposition in tissue. There are both acquired and hereditary forms of this disease, and this review focuses on the latter hereditary transthyretin-mediated (hATTR). hATTR affects about 50,000 individuals globally and mostly appears as one of three syndromes - cardiac, polyneuropathy, and oculoleptomeningeal. Polyneuropathy is the most common form, and there is usually some overlap in individual patients. Results: Recently, novel therapeutic options emerged in the form of groundbreaking drugs, Patisiran and Inotersen, small interfering RNA molecules that target TTR and reduce the production of this protein. By targeting TTR mRNA transcripts, Inotersen decreases protein translation and production, reducing the deposition of misfolded proteins. It was shown to be both effective and safe for use and specifically formulated to concentrate in the liver - where protein production takes place. Conclusion: hATTR is a rare, progressive, and debilitating disease. Its most common presentation is that of polyneuropathy, and it carries a very poor prognosis and a natural history conveying a median survival of < 12 years. Novel therapeutic options are groundbreaking by providing disease-modifying specific, targeted therapies against TTR production and deposition. The use of RNA interference (RNAi) opens the door to the treatment of hereditary diseases by targeting them at the genetic level.