Many-body theory of positron binding to polyatomic molecules.

Positron binding to molecules is key to extremely enhanced positron annihilation and positron-based molecular spectroscopy1. Although positron binding energies have been measured for about 90 polyatomic molecules1-6, an accurate ab initio theoretical description of positron-molecule binding has remained elusive. Of the molecules studied experimentally, ab initio calculations exist for only six; these calculations agree with experiments on polar molecules to at best 25 per cent accuracy and fail to predict binding in nonpolar molecules. The theoretical challenge stems from the need to accurately describe the strong many-body correlations including polarization of the electron cloud, screening of the electron-positron Coulomb interaction and the unique process of virtual-positronium formation (in which a molecular electron temporarily tunnels to the positron)1. Here we develop a many-body theory of positron-molecule interactions that achieves excellent agreement with experiment (to within 1 per cent in cases) and predicts binding in formamide and nucleobases. Our framework quantitatively captures the role of many-body correlations and shows their crucial effect on enhancing binding in polar molecules, enabling binding in nonpolar molecules, and increasing annihilation rates by 2 to 3 orders of magnitude. Our many-body approach can be extended to positron scattering and annihilation γ-ray spectra in molecules and condensed matter, to provide the fundamental insight and predictive capability required to improve materials science diagnostics7,8, develop antimatter-based technologies (including positron traps, beams and positron emission tomography)8-10, and understand positrons in the Galaxy11.

Intrawound Vancomycin Powder in Primary Total Hip Arthroplasty: A Prospective Quality Control Study.

BACKGROUND: The purpose of this retrospective analysis of a prospective quality control project was to determine whether the use of intrawound vancomycin powder (IVP) decreases the rate of periprosthetic joint infection (PJI) within 90 days following primary total hip arthroplasty (THA). METHODS: From October 2021 to September 2022, a prospective quality control project was undertaken in which 10 high-volume THA surgeons alternated between using and not using IVP each month while keeping other perioperative protocols unchanged. A retrospective analysis of the project was performed to compare the group of patients who received IVP to the group of patients who did not. The primary outcome was a culture positive infection within 90 days following primary THA. Secondary outcomes included gram-positive culture, overall reoperation rate, wound complications, readmission, and wound complications within 90 days post-operatively. A total of 1,193 primary THA patients were identified for analysis. There were 523 (43.8%) patients who received IVP and were included in the IVP group, while 670 (56.2%) did not and were included in the non-IVP group. Age, body mass index, and sex were similar between the 2 groups (P > .25). RESULTS: The IVP group had a higher rate of culture positive joint infections (1.7 [0.8, 3.2] versus 0.3% [0.04, 1.1], P = .01) than the non-IVP group. All PJI's were found to have gram positive bacteria in both groups. The IVP group had a higher overall reoperation rate than the non-IVP group (6.1 [4.2, 8.5] versus 2.4% [1.4, 3.9], P < .01). The IVP group had a higher reoperation rate for any wound complication compared to non-IVP patients (2.7 [1.5, 4.5] versus 0.7% [0.2, 1.7], P < .01). The overall readmission rate (6.1 [4.2, 8.5] versus 2.8% [1.7, 4.4], P < .01), as well as readmission for suspected infection (2.1 [1.1, 3.7] versus 0.6% [0.02, 1.5], P = .03), were higher in the IVP group. CONCLUSIONS: The use of IVP in primary THA was associated with a higher rate of PJI, overall reoperation, reoperation for wound complications, and readmission in a prospective quality control project. Until future prospective randomized studies determine the safety and efficacy of IVP in THA conclusively, we advocate against its utilization.

Improved Patient-reported Outcomes in Patients Aged 16 and Younger at Two Years After Anterior Cruciate Ligament Reconstruction Despite Relatively High Rates of Reinjury and Repeat Surgery.

BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) in adolescent patients, particularly those aged 16 and under, are increasingly common procedure that lacks robust clinical and patient-reported outcome (PRO) data. The purpose of this study was to report 2-year PROs of patients receiving ACLR aged 16 or younger using the single assessment numerical evaluation (SANE) and knee injury and osteoarthritis outcome score (KOOS). Secondary aims included characterizing treatment characteristics, return to sport (RTS), and clinical outcomes. METHODS: The institutional PRO database was queried for patients receiving ACLR from 2009 to 2020. Patients aged older than 16, revision procedures, concomitant ligament repairs/reconstructions, and patients without full outcome data at 2 years were excluded. Outcomes over 2 years after ACLR included SANE, KOOS, reinjuries, reoperations, and time to RTS. RESULTS: A total of 98 patients were included with an average age of 15.0 years. Most patients were females (77.6%). Bone-tendon-bone autograft (69.4%) was the most used. Average RTS was 8.7 months (range: 4.8 to 24.0 mo), with 90% of patients eventually returning to sport. A total of 23 patients (23.5%) experienced a reinjury and 24.5% (n = 24) underwent reoperation. Timing to RTS was not associated with reinjury, but patients who returned between 9.5 and 13.7 months did not sustain reinjuries. Mean KOOS and SANE scores at 2 years were 87.1 and 89.1, respectively, with an average improvement of +18.4 and +22.9, respectively. Change in KOOS was negatively impacted by reinjury to the anterior cruciate ligament graft and reoperation (anterior cruciate ligament failure: +10.0 vs 19.3, P = 0.081, respectively; reoperation: +13.2 vs +20.1, P = 0.051, respectively), though these did not reach statistical significance. CONCLUSION: Patients experienced improved SANE and KOOS scores after ACLR. Rates of reinjury and reoperation were relatively high and negatively impacted PRO scores but were not associated with the timing of RTS. Adolescent patients should be counseled regarding the risk of subsequent ipsilateral and contralateral knee injury after ACLR. LEVEL OF EVIDENCE: Level IV-case series.

Iatrogenic open humeral shaft fractures following functional bracing.

INTRODUCTION: The treatment of closed humeral shaft fractures tends to be successful with functional bracing. Treatment failure due to iatrogenic conversion to an open fracture has not been described in the literature. We present a case series of patients that experienced open humeral shaft fractures after initially being treated with functional bracing for closed humeral shaft fractures and describe what factors are associated with this complication. MATERIALS AND METHODS: This was a retrospective case series performed at three level 1 trauma centers across North America. All nonoperatively treated humeral shaft fractures were reviewed from 2001 to 2023. Patients were included if they sustained a humeral shaft fracture, > 18 years old, were initially treated non-operatively with functional bracing which subsequently converted to an open fracture. Eight patients met inclusion criteria. All included patients were eventually treated with irrigation, debridement, and open reduction and internal fixation. Outcomes assessed included mortality rate, time until the fracture converted from closed to open, need for further surgery, and bony union. Descriptive statistics were used in analysis. RESULTS: The eight included patients on average were 65 ± 21.4 years old and had a body mass index (BMI) of 25.6 ± 5.2. Six patients were initially injured due to a fall. Time until the fractures became open on average was 5.2 ± 3.6 weeks. Three patients (37.5%) died within 1.8 ± 0.6 years after initial injury. The average Charlson Comorbidity Index (CCI) score was 4.5 ± 3.4. Three patients (37.5%) had dementia. Common characteristics among this cohort included a history of visual disturbances (50.0%), cerebrovascular accident (50.0%), smoking (50.0%), and alcohol abuse (50.0%). CONCLUSION: Conversion from a closed to open humeral shaft fracture after functional bracing is a potentially devastating complication. Physicians should be especially cognizant of patients with a low BMI, history of falling or visual disturbance, dementia, age ≥ 65, decreased sensorimotor protection, and significant smoking or alcohol history when choosing to use functional bracing as the final treatment modality. LEVEL OF EVIDENCE: IV.

Net-Shaped DNA Nanostructures Designed for Rapid/Sensitive Detection and Potential Inhibition of the SARS-CoV-2 Virus.

We present a net-shaped DNA nanostructure (called "DNA Net" herein) design strategy for selective recognition and high-affinity capture of intact SARS-CoV-2 virions through spatial pattern-matching and multivalent interactions between the aptamers (targeting wild-type spike-RBD) positioned on the DNA Net and the trimeric spike glycoproteins displayed on the viral outer surface. Carrying a designer nanoswitch, the DNA Net-aptamers release fluorescence signals upon virus binding that are easily read with a handheld fluorimeter for a rapid (in 10 min), simple (mix-and-read), sensitive (PCR equivalent), room temperature compatible, and inexpensive (∼$1.26/test) COVID-19 test assay. The DNA Net-aptamers also impede authentic wild-type SARS-CoV-2 infection in cell culture with a near 1 × 103-fold enhancement of the monomeric aptamer. Furthermore, our DNA Net design principle and strategy can be customized to tackle other life-threatening and economically influential viruses like influenza and HIV, whose surfaces carry class-I viral envelope glycoproteins like the SARS-CoV-2 spikes in trimeric forms.

Capillary-Scale Hydrogel Microchannel Networks by Wire Templating.

Microvascular networks are essential for the efficient transport of nutrients, waste products, and drugs throughout the body. Wire-templating is an accessible method for generating laboratory models of these blood vessel networks, but it has difficulty fabricating microchannels with diameters of ten microns and narrower, a requirement for modeling human capillaries. This study describes a suite of surface modification techniques to  selectively control the interactions amongst wires, hydrogels, and world-to-chip interfaces. This wire templating method enables the fabrication of perfusable hydrogel-based rounded cross-section capillary-scale networks whose diameters controllably narrow at bifurcations down to 6.1 ± 0.3 microns in diameter. Due to its low cost, accessibility, and compatibility with a wide range of common hydrogels of tunable stiffnesses such as collagen, this technique may increase the fidelity of experimental models of capillary networks for the study of human health and disease.

Photonic-Plasmonic Coupling Enhanced Fluorescence Enabling Digital-Resolution Ultrasensitive Protein Detection.

Assays utilizing fluorophores are common throughout life science research and diagnostics, although detection limits are generally limited by weak emission intensity, thus requiring many labeled target molecules to combine their output to achieve higher signal-to-noise. We describe how the synergistic coupling of plasmonic and photonic modes can significantly boost the emission from fluorophores. By optimally matching the resonant modes of a plasmonic fluor (PF) nanoparticle and a photonic crystal (PC) with the absorption and emission spectrum of the fluorescent dye, a 52-fold improvement in signal intensity is observed, enabling individual PFs to be observed and digitally counted, where one PF tag represents one detected target molecule. The amplification can be attributed to the strong near-field enhancement due to the cavity-induced activation of the PF, PC band structure-mediated improvement in collection efficiency, and increased rate of spontaneous emission. The applicability of the method by dose-response characterization of a sandwich immunoassay for human interleukin-6, a biomarker used to assist diagnosis of cancer, inflammation, sepsis, and autoimmune disease is demonstrated. A limit of detection of 10 fg mL-1 and 100 fg mL-1 in buffer and human plasma respectively, is achieved, representing a capability nearly three orders of magnitude lower than standard immunoassays.

Rapid isothermal amplification and portable detection system for SARS-CoV-2.

The COVID-19 pandemic provides an urgent example where a gap exists between availability of state-of-the-art diagnostics and current needs. As assay protocols and primer sequences become widely known, many laboratories perform diagnostic tests using methods such as RT-PCR or reverse transcription loop mediated isothermal amplification (RT-LAMP). Here, we report an RT-LAMP isothermal assay for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and demonstrate the assay on clinical samples using a simple and accessible point-of-care (POC) instrument. We characterized the assay by dipping swabs into synthetic nasal fluid spiked with the virus, moving the swab to viral transport medium (VTM), and sampling a volume of the VTM to perform the RT-LAMP assay without an RNA extraction kit. The assay has a limit of detection (LOD) of 50 RNA copies per µL in the VTM solution within 30 min. We further demonstrate our assay by detecting SARS-CoV-2 viruses from 20 clinical samples. Finally, we demonstrate a portable and real-time POC device to detect SARS-CoV-2 from VTM samples using an additively manufactured three-dimensional cartridge and a smartphone-based reader. The POC system was tested using 10 clinical samples, and was able to detect SARS-CoV-2 from these clinical samples by distinguishing positive samples from negative samples after 30 min. The POC tests are in complete agreement with RT-PCR controls. This work demonstrates an alternative pathway for SARS-CoV-2 diagnostics that does not require conventional laboratory infrastructure, in settings where diagnosis is required at the point of sample collection.

A Target Recycling Amplification Process for the Digital Detection of Exosomal MicroRNAs through Photonic Resonator Absorption Microscopy.

Exosomal microRNAs (miRNAs) have considerable potential as pivotal biomarkers to monitor cancer development, dis-ease progression, treatment effects and prognosis. Here, we report an efficient target recycling amplification process (TRAP) for the digital detection of miRNAs using photonic resonator absorption microscopy. We achieve multiplex digital detection with sub-attomolar sensitivity in 20 minutes, robust selectivity for single nucleotide variants, and a broad dynamic range from 1 aM to 1 pM. Compared with traditional qRT-PCR, TRAP showed similar accuracy in profiling exosomal miRNAs derived from cancer cells, but also exhibited at least 31-fold and 61-fold enhancement in the limits of miRNA-375 and miRNA-21 detection, respectively. The TRAP approach is ideal for exosomal or circulating miRNA biomarker quantification, where the miRNAs are present in low concentrations or sample volume, with potentials for frequent, low-cost, and minimally invasive point-of-care testing.

Label-Free Digital Detection of Intact Virions by Enhanced Scattering Microscopy.

Several applications in health diagnostics, food, safety, and environmental monitoring require rapid, simple, selective, and quantitatively accurate viral load monitoring. Here, we introduce the first label-free biosensing method that rapidly detects and quantifies intact virus in human saliva with single-virion resolution. Using pseudotype SARS-CoV-2 as a representative target, we immobilize aptamers with the ability to differentiate active from inactive virions on a photonic crystal, where the virions are captured through affinity with the spike protein displayed on the outer surface. Once captured, the intrinsic scattering of the virions is amplified and detected through interferometric imaging. Our approach analyzes the motion trajectory of each captured virion, enabling highly selective recognition against nontarget virions, while providing a limit of detection of 1 × 103 copies/mL at room temperature. The approach offers an alternative to enzymatic amplification assays for point-of-collection diagnostics.

Smartphone clip-on instrument and microfluidic processor for rapid sample-to-answer detection of Zika virus in whole blood using spatial RT-LAMP.

Rapid, simple, inexpensive, accurate, and sensitive point-of-care (POC) detection of viral pathogens in bodily fluids is a vital component of controlling the spread of infectious diseases. The predominant laboratory-based methods for sample processing and nucleic acid detection face limitations that prevent them from gaining wide adoption for POC applications in low-resource settings and self-testing scenarios. Here, we report the design and characterization of an integrated system for rapid sample-to-answer detection of a viral pathogen in a droplet of whole blood comprised of a 2-stage microfluidic cartridge for sample processing and nucleic acid amplification, and a clip-on detection instrument that interfaces with the image sensor of a smartphone. The cartridge is designed to release viral RNA from Zika virus in whole blood using chemical lysis, followed by mixing with the assay buffer for performing reverse-transcriptase loop-mediated isothermal amplification (RT-LAMP) reactions in six parallel microfluidic compartments. The battery-powered handheld detection instrument uniformly heats the compartments from below, and an array of LEDs illuminates from above, while the generation of fluorescent reporters in the compartments is kinetically monitored by collecting a series of smartphone images. We characterize the assay time and detection limits for detecting Zika RNA and gamma ray-deactivated Zika virus spiked into buffer and whole blood and compare the performance of the same assay when conducted in conventional PCR tubes. Our approach for kinetic monitoring of the fluorescence-generating process in the microfluidic compartments enables spatial analysis of early fluorescent "bloom" events for positive samples, in an approach called "Spatial LAMP" (S-LAMP). We show that S-LAMP image analysis reduces the time required to designate an assay as a positive test, compared to conventional analysis of the average fluorescent intensity of the entire compartment. S-LAMP enables the RT-LAMP process to be as short as 22 minutes, resulting in a total sample-to-answer time in the range of 17-32 minutes to distinguish positive from negative samples, while demonstrating a viral RNA detection as low as 2.70 × 102 copies per µl, and a gamma-irradiated virus of 103 virus particles in a single 12.5 µl droplet blood sample.

Overcoming the limitations of COVID-19 diagnostics with nanostructures, nucleic acid engineering, and additive manufacturing.

The COVID-19 pandemic revealed fundamental limitations in the current model for infectious disease diagnosis and serology, based upon complex assay workflows, laboratory-based instrumentation, and expensive materials for managing samples and reagents. The lengthy time delays required to obtain test results, the high cost of gold-standard PCR tests, and poor sensitivity of rapid point-of-care tests contributed directly to society's inability to efficiently identify COVID-19-positive individuals for quarantine, which in turn continues to impact return to normal activities throughout the economy. Over the past year, enormous resources have been invested to develop more effective rapid tests and laboratory tests with greater throughput, yet the vast majority of engineering and chemistry approaches are merely incremental improvements to existing methods for nucleic acid amplification, lateral flow test strips, and enzymatic amplification assays for protein-based biomarkers. Meanwhile, widespread commercial availability of new test kits continues to be hampered by the cost and time required to develop single-use disposable microfluidic plastic cartridges manufactured by injection molding. Through development of novel technologies for sensitive, selective, rapid, and robust viral detection and more efficient approaches for scalable manufacturing of microfluidic devices, we can be much better prepared for future management of infectious pathogen outbreaks. Here, we describe how photonic metamaterials, graphene nanomaterials, designer DNA nanostructures, and polymers amenable to scalable additive manufacturing are being applied towards overcoming the fundamental limitations of currently dominant COVID-19 diagnostic approaches. In this paper, we review how several distinct classes of nanomaterials and nanochemistry enable simple assay workflows, high sensitivity, inexpensive instrumentation, point-of-care sample-to-answer virus diagnosis, and rapidly scaled manufacturing.

Digital-resolution detection of microRNA with single-base selectivity by photonic resonator absorption microscopy.

Circulating exosomal microRNA (miR) represents a new class of blood-based biomarkers for cancer liquid biopsy. The detection of miR at a very low concentration and with single-base discrimination without the need for sophisticated equipment, large volumes, or elaborate sample processing is a challenge. To address this, we present an approach that is highly specific for a target miR sequence and has the ability to provide "digital" resolution of individual target molecules with high signal-to-noise ratio. Gold nanoparticle tags are prepared with thermodynamically optimized nucleic acid toehold probes that, when binding to a target miR sequence, displace a probe-protecting oligonucleotide and reveal a capture sequence that is used to selectively pull down the target-probe-nanoparticle complex to a photonic crystal (PC) biosensor surface. By matching the surface plasmon-resonant wavelength of the nanoparticle tag to the resonant wavelength of the PC nanostructure, the reflected light intensity from the PC is dramatically and locally quenched by the presence of each individual nanoparticle, enabling a form of biosensor microscopy that we call Photonic Resonator Absorption Microscopy (PRAM). Dynamic PRAM imaging of nanoparticle tag capture enables direct 100-aM limit of detection and single-base mismatch selectivity in a 2-h kinetic discrimination assay. The PRAM assay demonstrates that ultrasensitivity (<1 pM) and high selectivity can be achieved on a direct readout diagnostic.

Measurement of value in rotator cuff repair: patient-level value analysis for the 1-year episode of care.

BACKGROUND: Rotator cuff repair (RCR) is one of the most common elective orthopedic procedures, with predictable indications, techniques, and outcomes. As a result, this surgical procedure is an ideal choice for studying value. The purpose of this study was to perform patient-level value analysis (PLVA) within the setting of RCR over the 1-year episode of care. METHODS: Included patients (N = 396) underwent RCR between 2009 and 2016 at a single outpatient orthopedic surgery center. The episode of care was defined as 1-year following surgery. The Western Ontario Rotator Cuff index was collected at both the initial preoperative baseline assessment and the 1-year postoperative mark. The total cost of care was determined using time-driven activity-based costing (TDABC). Both PLVA and provider-level value analysis were performed. RESULTS: The average TDABC cost of care was derived at $5413.78 ± $727.41 (95% confidence interval, $5341.92-$5485.64). At the patient level, arthroscopic isolated supraspinatus tears yielded the highest value coefficient (0.82; analysis-of-variance F test, P = .01). There was a poor correlation between the change in the 1-year Western Ontario Rotator Cuff score and the TDABC cost of care (r2 = 0.03). Provider-level value analysis demonstrated significant variation between the 8 providers evaluated (P < .01). CONCLUSION: RCR is one of the most common orthopedic procedures, yet the correlations between cost of care and patient outcomes are unknown. PLVA quantifies the ratio of functional improvement to the TDABC-estimated cost of care at the patient level. This is the first study to apply PLVA over the first-year episode of care. With health care transitioning toward value-based delivery, PLVA offers a quantitative tool to measure the value of individual patient care delivery over the entire episode of care.

Microscopies Enabled by Photonic Metamaterials.

In recent years, the biosensor research community has made rapid progress in the development of nanostructured materials capable of amplifying the interaction between light and biological matter. A common objective is to concentrate the electromagnetic energy associated with light into nanometer-scale volumes that, in many cases, can extend below the conventional Abbé diffraction limit. Dating back to the first application of surface plasmon resonance (SPR) for label-free detection of biomolecular interactions, resonant optical structures, including waveguides, ring resonators, and photonic crystals, have proven to be effective conduits for a wide range of optical enhancement effects that include enhanced excitation of photon emitters (such as quantum dots, organic dyes, and fluorescent proteins), enhanced extraction from photon emitters, enhanced optical absorption, and enhanced optical scattering (such as from Raman-scatterers and nanoparticles). The application of photonic metamaterials as a means for enhancing contrast in microscopy is a recent technological development. Through their ability to generate surface-localized and resonantly enhanced electromagnetic fields, photonic metamaterials are an effective surface for magnifying absorption, photon emission, and scattering associated with biological materials while an imaging system records spatial and temporal patterns. By replacing the conventional glass microscope slide with a photonic metamaterial, new forms of contrast and enhanced signal-to-noise are obtained for applications that include cancer diagnostics, infectious disease diagnostics, cell membrane imaging, biomolecular interaction analysis, and drug discovery. This paper will review the current state of the art in which photonic metamaterial surfaces are utilized in the context of microscopy.

Immediate Weightbearing After Operative Treatment of Bimalleolar and Trimalleolar Ankle Fractures: Faster Return to Work for Patients with Nonsedentary Occupations.

The goal of this study was to compare immediate weightbearing (IWB) and traditional weightbearing (TWB) postoperative protocols in unstable ankle fractures, as this has not been compared in prior works. We hypothesize that an immediate weightbearing protocol after ankle fracture fixation will lead to an earlier return to work. An ankle fracture registry was reviewed for operatively treated unstable bimalleolar and trimalleolar ankle fractures at an ambulatory surgery center and followed up at associated outpatient clinics. All fracture cases reviewed occurred from 2009 to 2015. Immediate weightbearing patients were placed into a controlled ankle motion (CAM) boot and allowed to fully bear weight the day of surgery. Traditional weightbearing patients were placed into a CAM boot with 6 weeks of non-weightbearing. Demographics, fixation technique, and injury characteristics were surveyed. Physical job demand was stratified for 69 patients meeting the inclusion criteria (34 IWB and 35 TWB). The main outcome of this study was measured as the time to return to work. Subgroup analysis of patients with nonsedentary jobs demonstrated a significantly earlier return to work for the IWB group (5.7 versus 10.0 weeks, p = .04). Multivariate regression analysis identified a statistically significant 2.25-week (p = .05) earlier return to work for the IWB group after adjustment for occupational physical demand, demographics, fracture characteristics, and participation in a light work period before full work return. In patients with nonsedentary jobs, an IWB protocol after operative management of bimalleolar and trimalleolar ankle fractures resulted in an earlier return to work compared with traditional protocols.

Corridor-diameter-dependent angular tolerance for safe transiliosacral screw placement: an anatomic study of 433 pelves.

BACKGROUND: The purpose of this study was to determine the angular tolerance of the S1 and S2 segments to accommodate a transiliosacral screw across both sacroiliac joints. HYPOTHESIS: We hypothesized that the angular tolerance for transiliosacral screw placement would be more constrained than the angular tolerance for iliosacral fixation in pelves where a safe osseous corridor was measured. MATERIALS AND METHODS: The cortical boundaries of the S1 and S2 sacral segments in 433 pelvic CTs were digitally mapped. A straight-line path was placed within each osseous corridor and extended across both SI joints past the outer iliac cortices. The diameter of the path was increased until it breached the cortex, geometrically determining maximum diameter (Dmax). Angular tolerance for screw placement was calculated with trigonometric analysis of the Dmax value of the corridor, and the average distance from the termination of the osseous corridor to the site of percutaneous insertion. Gender, age, and BMI were evaluated as independent predictors using binomial logistic regression. RESULTS: The transiliosacral angular tolerance for the S1 and S2 osseous corridors was 1.53 ± 0.57 degrees and 1.02 ± 0.33 degrees, respectively. 68.9% of S1 corridors and 81.1% of S2 corridors had a safe zone (corridor diameter ≥ 10 mm) for transiliosacral placement, 48.3% of the pelves had a safe zone for both corridors, while 5.1% had no safe zones. Females had a less frequent Dmax ≥ 10 mm at S1, 52% vs 67% (p = 0.001), and at S2, 64% vs 86% (p < 0.001). DISCUSSION: In conclusion, the angular tolerance of 1.53 and 1.03 degrees for the S1 and S2 segments, respectively, creating a narrow interval for safe passage of the trans-iliac and trans-sacral, with approximately 31.1% of patients not having a viable corridor for screw passage. A correlation exist between S1 and S2 corridors with Dmax ≥ 10 mm and the resulting increase in angular tolerance for safe passage of a transilioscral screw. LEVEL OF EVIDENCE IV: Level Retrospective Cohort.

Immediate weight bearing as tolerated (WBAT) correlates with a decreased length of stay post intramedullary fixation for subtrochanteric fractures: a multicenter retrospective cohort study.

BACKGROUND: Subtrochanteric femur fractures associate with a relatively high complication rate and are traditionally treated operatively with a period of limited weight bearing. Transitioning from extramedullary to intramedullary implants, there are increasing biomechanical and clinical data to support early weight bearing. This multicenter retrospective study examines the effect of postoperative weight bearing as tolerated (WBAT) for subtrochanteric femur fractures. We hypothesize that WBAT will result in a decreased length of stay (LOS) without increasing the incidence of re-operation. METHODS: This study assesses total LOS and postoperative LOS after intramedullary fixation for subtrochanteric fractures between postoperative weight bearing protocols across 6 level I trauma centers (n = 441). Analysis techniques consisted of multivariable linear regression and nonparametric comparative tests. Additional subanalyses were performed, targeting mechanism of injury (MOI), Winquist-Hansen fracture comminution, 20-year age strata, and injury severity score (ISS). RESULTS: Total LOS was shorter in WBAT protocol within the overall sample (7.4 vs 9.7 days; p < 0.01). Rates of re-operation were similar between the two groups (10.6% vs 10.5%; p = 0.99). Stratified analysis identified patients between ages 41-80, WH comminution 2-3, high MOI, and ISS between 6-15 and 21-25 to demonstrate a significant reduction in LOS as a response to WBAT. CONCLUSION: An immediate postoperative weight bearing as tolerated protocol in patients with subtrochanteric fractures reduced length of hospital stay with no significant difference in reoperation and complication rates. If no contraindication exists, immediate weight bearing as tolerated should be considered for patients with subtrochanteric femur fractures treated with statically locked intramedullary nails. LEVEL OF EVIDENCE: Therapeutic Level III.

Development of a Linker-Mediated Immunoassay Using Chemically Transitioned Nanosensors.

Sensitive and specific quantification of protein biomarkers is important in medical diagnostics, academic research, and pharmaceutical development. However, multiple binding steps in conventional sandwich immunoassay protocols result in high assay hands-on-time and delayed results. This is particularly relevant for medical diagnostics, where assay turn-around-time can have an immense impact on patient outcomes. To address this limitation, we report the assembly of nanosensors prepared using DNA-antibody conjugates, which combine capture and detection antibody binding steps by facilitating rapid antigen capture. Following antigen binding, detection antibodies are released using chemically induced complex rearrangement. A panel of 12 chemical additives are characterized to identify melting point depressants capable of rapidly denaturing double stranded DNA (dsDNA) linkers, and 8 compounds are demonstrated to be capable of disrupting dsDNA while maintaining the integrity of protein binding. This technique is then validated for the measurement of the heart attack indicator cardiac troponin I and is shown to successfully combine antigen binding steps while also increasing detection sensitivity 42×. Linker-mediated immunoassays are also demonstrated to provide robust quantification in human serum and are shown to be compatible with each of the most commonly used immunoassay detection modalities.

Efficient ab initio calculation of electronic stopping in disordered systems via geometry pre-sampling: Application to liquid water.

Knowledge of the electronic stopping curve for swift ions, Se(v), particularly around the Bragg peak, is important for understanding radiation damage. Experimentally, however, the determination of such a feature for light ions is very challenging, especially in disordered systems such as liquid water and biological tissue. Recent developments in real-time time-dependent density functional theory (rt-TDDFT) have enabled the calculation of Se(v) along nm-sized trajectories. However, it is still a challenge to obtain a meaningful statistically averaged Se(v) that can be compared to observations. In this work, taking advantage of the correlation between the local electronic structure probed by the projectile and the distance from the projectile to the atoms in the target, we devise a trajectory pre-sampling scheme to select, geometrically, a small set of short trajectories to accelerate the convergence of the averaged Se(v) computed via rt-TDDFT. For protons in liquid water, we first calculate the reference probability distribution function (PDF) for the distance from the proton to the closest oxygen atom, ϕR(rp→O), for a trajectory of a length similar to those sampled experimentally. Then, short trajectories are sequentially selected so that the accumulated PDF reproduces ϕR(rp→O) to increasingly high accuracy. Using these pre-sampled trajectories, we demonstrate that the averaged Se(vp) converges in the whole velocity range with less than eight trajectories, while other averaging methods using randomly and uniformly distributed trajectories require approximately ten times the computational effort. This allows us to compare the Se(vp) curve to experimental data and assess widely used empirical tables based on Bragg's rule.