Improving Accuracy of Administrative Data for Perforated Appendicitis Classification.

INTRODUCTION: Reliance on International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis codes may misclassify perforated appendicitis with resultant research, fiscal, and public health implications. We aimed to improve the accuracy of administrative data for perforated appendicitis classification relying on ICD-10-CM codes from 2015 to 2018. METHODS: We conducted a retrospective study of randomly sampled patients aged ≤18 years diagnosed with acute appendicitis from eight children's hospitals. Patients were identified using the Pediatric Health Information System, and true perforation status was determined by medical record review. We developed two algorithms by leveraging Pediatric Health Information System data elements and data mining (DM) approaches. The two developed algorithm performance was compared against algorithms that exclusively relied on ICD-10-CM codes using area under the curve and other measures. RESULTS: Of 1051 clinically validated encounters that were included, 383 (36.4%) patients were identified to have perforated appendicitis. The two algorithms developed using DM approaches primarily leveraged ICD-10-CM codes and length of stay. DM-developed algorithms had a significantly higher accuracy than algorithms relying exclusively on ICD-10-CM (P value < 0.01): sensitivity and specificity for DM-developed algorithms were 0.86-0.88 and 0.95-0.97, respectively, which were overall higher than algorithms that relied on only ICD-10-CM. CONCLUSIONS: This study provides an algorithm that can improve the accuracy of perforated appendicitis classification using commonly available elements in administrative data. We recommend that this algorithm is used in future appendicitis classification to ensure valid reporting, hospital-level benchmarking, and fiscal or public health assessments.

Environmental drivers of increased ecosystem respiration in a warming tundra.

Arctic and alpine tundra ecosystems are large reservoirs of organic carbon1,2. Climate warming may stimulate ecosystem respiration and release carbon into the atmosphere3,4. The magnitude and persistency of this stimulation and the environmental mechanisms that drive its variation remain uncertain5-7. This hampers the accuracy of global land carbon-climate feedback projections7,8. Here we synthesize 136 datasets from 56 open-top chamber in situ warming experiments located at 28 arctic and alpine tundra sites which have been running for less than 1 year up to 25 years. We show that a mean rise of 1.4 °C [confidence interval (CI) 0.9-2.0 °C] in air and 0.4 °C [CI 0.2-0.7 °C] in soil temperature results in an increase in growing season ecosystem respiration by 30% [CI 22-38%] (n = 136). Our findings indicate that the stimulation of ecosystem respiration was due to increases in both plant-related and microbial respiration (n = 9) and continued for at least 25 years (n = 136). The magnitude of the warming effects on respiration was driven by variation in warming-induced changes in local soil conditions, that is, changes in total nitrogen concentration and pH and by context-dependent spatial variation in these conditions, in particular total nitrogen concentration and the carbon:nitrogen ratio. Tundra sites with stronger nitrogen limitations and sites in which warming had stimulated plant and microbial nutrient turnover seemed particularly sensitive in their respiration response to warming. The results highlight the importance of local soil conditions and warming-induced changes therein for future climatic impacts on respiration.

Influence of solvent on cyclic polynorbornene tacticity.

Tacticity is critical to polymer properties. The influence of solvent on tacticity in the catalytic synthesis of cyclic polynorbornene (c-PNB) is reported. In toluene cis,syndiotactic c-PNB forms; in THF, cis,syn/iso c-PNB forms.

Controlled-Radical Polymerization of α-Lipoic Acid: A General Route to Degradable Vinyl Copolymers.

Here, we present the synthesis and characterization of statistical and block copolymers containing α-lipoic acid (LA) using reversible addition-fragmentation chain-transfer (RAFT) polymerization. LA, a readily available nutritional supplement, undergoes efficient radical ring-opening copolymerization with vinyl monomers in a controlled manner with predictable molecular weights and low molar-mass dispersities. Because lipoic acid diads present in the resulting copolymers include disulfide bonds, these materials efficiently and rapidly degrade when exposed to mild reducing agents such as tris(2-carboxyethyl)phosphine (Mn = 56 → 3.6 kg mol-1). This scalable and versatile polymerization method affords a facile way to synthesize degradable polymers with controlled architectures, molecular weights, and molar-mass dispersities from α-lipoic acid, a commercially available and renewable monomer.

Building Tunable Degradation into High-Performance Poly(acrylate) Pressure-Sensitive Adhesives.

Pressure-sensitive adhesives (PSAs) based on poly(acrylate) chemistry are common in a wide variety of applications, but the absence of backbone degradability causes issues with recycling and sustainability. Here, we report a strategy to create degradable poly(acrylate) PSAs using simple, scalable, and functional 1,2-dithiolanes as drop-in replacements for traditional acrylate comonomers. Our key building block is α-lipoic acid, a natural, biocompatible, and commercially available antioxidant found in various consumer supplements. α-Lipoic acid and its derivative ethyl lipoate efficiently copolymerize with n-butyl acrylate under conventional free-radical conditions leading to high-molecular-weight copolymers (Mn > 100 kg mol-1) containing a tunable concentration of degradable disulfide bonds along the backbone. The thermal and viscoelastic properties of these materials are practically indistinguishable from nondegradable poly(acrylate) analogues, but a significant reduction in molecular weight is realized upon exposure to reducing agents such as tris (2-carboxyethyl) phosphine (e.g., Mn = 198 kg mol-1 → 2.6 kg mol-1). By virtue of the thiol chain ends produced after disulfide cleavage, degraded oligomers can be further cycled between high and low molecular weights through oxidative repolymerization and reductive degradation. Transforming otherwise persistent poly(acrylates) into recyclable materials using simple and versatile chemistry could play a pivotal role in improving the sustainability of contemporary adhesives.

Confronting racially exclusionary practices in the acquisition and analyses of neuroimaging data.

Across the brain sciences, institutions and individuals have begun to actively acknowledge and address the presence of racism, bias, and associated barriers to inclusivity within our community. However, even with these recent calls to action, limited attention has been directed to inequities in the research methods and analytic approaches we use. The very process of science, including how we recruit, the methodologies we utilize and the analyses we conduct, can have marked downstream effects on the equity and generalizability of scientific discoveries across the global population. Despite our best intentions, the use of field-standard approaches can inadvertently exclude participants from engaging in research and yield biased brain-behavior relationships. To address these pressing issues, we discuss actionable ways and important questions to move the fields of neuroscience and psychology forward in designing better studies to address the history of exclusionary practices in human brain mapping.

Statistics for quantifying aging in time transfer system delays.

Residual time delays in time transfer systems such as two-way satellite time and frequency transfer (TWSTFT), or GPS carrier phase (GPSCP) change over time. A double difference such as TWSTFT-GPSCP provides information on the changes in the relative time delays of the two systems. These changes are referred to as aging or time dispersion. A first difference statistic, RMS time interval error, TIERMS, provides the RMS time dispersion. The time deviation statistic (TDEV) or a variation on the Allan deviation (ADEV), referred to here as ADEVS, provide information on the nature of the random fluctuations in aging. This paper describes analytical and Monte Carlo techniques used to estimate the aging (time dispersion) from TDEV or ADEVS statistics, and finds that the aging can be more than a factor of four larger than TDEV or ADEVS. The use of ADEVS is recommended over TDEV since it is sensitive to time drift.

Safety of deep brain stimulation in pregnancy: A comprehensive review.

Introduction: Deep brain stimulation (DBS) is increasingly used to treat the symptoms of various neurologic and psychiatric conditions. People can undergo the procedure during reproductive years but the safety of DBS in pregnancy remains relatively unknown given the paucity of published cases. We thus conducted a review of the literature to determine the state of current knowledge about DBS in pregnancy and to determine how eligibility criteria are approached in clinical trials with respect to pregnancy and the potential for pregnancy. Methods: A literature review was conducted in EMBASE to identify articles involving DBS and pregnancy. Two reviewers independently analyzed the articles to confirm inclusion. Data extracted for analysis included conditions treated, complications at all stages of pregnancy, neonatal/pediatric outcomes, and DBS target. A second search was then conducted using www.clinicaltrials.gov. The same two reviewers then assessed whether each trial excluded pregnant individuals, lactating individuals, or persons of childbearing age planning to conceive. Also assessed was whether contraception had to be deemed adequate prior to enrollment. Results: The literature search returned 681 articles. Following independent analysis and agreement of two reviewers, 8 pregnancy related DBS articles were included for analysis. These articles described 27 subjects, 29 pregnancies (2 with subsequent pregnancies), and 31 infants (2 twin pregnancies). There was 1 preterm birth at 35 weeks, and 3 patients who experienced discomfort from the DBS battery (i.e., impulse generator) placement site. All 27 patients had a DBS device implanted before they became pregnant, which remained in use throughout their pregnancy. There was exclusion of pregnant individuals from 68% of 135 interventional trials involving DBS. Approximately 44% of these trials excluded persons of childbearing age not on "adequate contraception" or wishing to conceive in the coming years. Finally, 22% excluded breastfeeding persons. Conclusion: The data from 29 pregnancies receiving DBS treatment during pregnancy was not associated with unexpected pregnancy or post-partum complication patterns. Many clinical trials have excluded pregnant individuals. Documentation of outcomes in larger numbers of pregnancies will help clarify the safety profile and will help guide study designs that will safely include pregnant patients.

RAFT Step-Growth Polymerization of Diacrylates.

RAFT step-growth polymerization was previously demonstrated with monomers that bear low rate of homopropagation to favor the chain transfer process; by contrast, acrylates are known to be fast homopropagating monomers, thereby posing serious challenges for RAFT step-growth. Here, we identified a chain transfer agent (CTA) that rapidly yields single unit monomer inserted (SUMI) CTA adducts with a model acrylate monomer. Using a bifunctional reagent of this CTA, we successfully demonstrated RAFT step-growth polymerization with diacrylates, yielding linear polymer backbones. Furthermore, we achieved inclusion of functionality (i.e., disulfide) into RAFT step-growth polymer via a disulfide incorporated bifunctional CTA. Grafting from this backbone resulted in molecular brush polymers with cleavable functionality in each repeat unit of the backbone, allowing selective degradation to afford well-defined unimolecular species of two polymeric side chains. Given the wide selection of commercially available diacrylates, RAFT step-growth polymerization of diacrylates will further enable facile synthesis of complex architectures with modular backbones.

Targeting the translational machinery in gastrointestinal stromal tumors (GIST): a new therapeutic vulnerability.

Although KIT-mutant GISTs can be effectively treated with tyrosine kinase inhibitors (TKIs), many patients develop resistance to imatinib mesylate (IM) as well as the FDA-approved later-line agents sunitinib, regorafenib and ripretinib. Resistance mechanisms mainly involve secondary mutations in the KIT receptor tyrosine kinase gene indicating continued dependency on the KIT signaling pathway. The fact that the type of secondary mutation confers either sensitivity or resistance towards TKIs and the notion that secondary mutations exhibit intra- and intertumoral heterogeneity complicates the optimal choice of treatment in the imatinib-resistant setting. Therefore, new strategies that target KIT independently of its underlying mutations are urgently needed. Homoharringtonine (HHT) is a first-in-class inhibitor of protein biosynthesis and is FDA-approved for the treatment of chronic myeloid leukemia (CML) that is resistant to at least two TKIs. HHT has also shown activity in KIT-mutant mastocytosis models, which are intrinsically resistant to imatinib and most other TKIs. We hypothesized that HHT could be effective in GIST through downregulation of KIT expression and subsequent decrease of KIT activation and downstream signaling. Testing several GIST cell line models, HHT led to a significant reduction in nascent protein synthesis and was highly effective in the nanomolar range in IM-sensitive and IM-resistant GIST cell lines. HHT treatment resulted in a rapid and complete abolishment of KIT expression and activation, while KIT mRNA levels were minimally affected. The response to HHT involved induction of apoptosis as well as cell cycle arrest. The antitumor activity of HHT was confirmed in a GIST xenograft model. Taken together, inhibition of protein biosynthesis is a promising strategy to overcome TKI resistance in GIST.

Eye and Head Movement Recordings Using Smartphones for Telemedicine Applications: Measurements of Accuracy and Precision.

Objective: Smartphones have shown promise in the assessment of neuro-ophthalmologic and vestibular disorders. We have shown that the head impulse test results recorded using our application are comparable with measurements from clinical video-oculography (VOG) goggles. The smartphone uses ARKit's capability to acquire eye and head movement positions without the need of performing a calibration as in most eye-tracking devices. Here, we measure the accuracy and precision of the eye and head position recorded using our application. Methods: We enrolled healthy volunteers and asked them to direct their eyes, their heads, or both to targets on a wall at known eccentricities while recording their head and eye movements with our smartphone application. We measured the accuracy as the error between the eye or head movement measurement and the location of each target and the precision as the standard deviation of the eye or head position for each of the target positions. Results: The accuracy of head recordings (15% error) was overall better than the accuracy of eye recordings (23% error). We also found that the accuracy for horizontal eye movements (17% error) was better than for vertical (27% error). Precision was also better for head movement (0.8 degrees) recordings than eye movement recordings (1.3 degrees) and variability tended to increase with eccentricity. Conclusion: Our results provide basic metrics evaluating the utility of smartphone applications in the quantitative assessment of head and eye movements. While the new method may not replace the more accurate dedicated VOG devices, they provide a more accessible quantitative option. It may be advisable to include a calibration recording together with any planned clinical test to improve the accuracy.

Oncologic Fidelity of Minimally Invasive Surgery to Resect Neoadjuvant-Treated Wilms Tumors.

BACKGROUND: The Children's Oncology Group recommends upfront resection of Wilms tumor (WT), however, unique scenarios warrant neoadjuvant chemotherapy and delayed resection. We hypothesized that in the context of neoadjuvant chemotherapy, minimally invasive surgery (MIS) to resect WT achieves equivalent oncologic fidelity and better maintains therapy schedules. METHODS: A retrospective analysis of WT treated between 2010-2021 at a free-standing children's hospital was performed. Patient and disease specific characteristics were collected, and pre-resection tumor volumes (TV) were calculated. Impact of MIS or open resection on oncologic fidelity and time to resume chemotherapy was analyzed. RESULTS: For the study period, 62 patients were treated for 65 WT, and 14 patients (22.6%) received neoadjuvant chemotherapy to treat 17 WT (26.2%): 7 Stage I (all predisposition syndromes), 2 stage III, 7 stage IV, and 1 stage V (bilateral). MIS was utilized to resect 6 WT from 5 patients. For partial nephrectomy, pre-resection TV was 0.38 ml if MIS and 10.38 ml if open (P = .025). For radical nephrectomy, pre-resection TV was 31.58 ml if MIS and 175.00 ml if open (P = .101). No significant differences between surgical approach were detected regarding pathologic variables or survival. Epidural use was significantly greater with open procedures (P = .001). Length of stay was 2.00 days after MIS compared to 6.00 for open resection (P = .004). Time to resume chemotherapy was 7.00 days after MIS versus 27.00 for open (P = .004). CONCLUSION: After neoadjuvant chemotherapy for WT, MIS partial and radical nephrectomies achieved equivalent oncologic fidelity, reduced epidural use and post-operative stays, and better maintained adjuvant therapy timelines when compared to open resections.

A gut microbiome tactile teaching tool and guided-inquiry activity promotes student learning.

The gut microbiome and its physiological impacts on human and animal health is an area of research emphasis. Microbes themselves are invisible and may therefore be abstract and challenging to understand. It is therefore important to infuse this topic into undergraduate curricula, including Anatomy and Physiology courses, ideally through an active learning approach. To accomplish this, we developed a novel tactile teaching tool with guided-inquiry (TTT-GI) activity where students explored how the gut microbiome ferments carbohydrates to produce short chain fatty acids (SCFAs). This activity was implemented in two sections of a large-enrollment Human Anatomy and Physiology course at a research intensive (R1) university in the Spring of 2022 that was taught using a hyflex format. Students who attended class in person used commonly available building toys to assemble representative carbohydrates of varying structural complexity, whereas students who attended class virtually made these carbohydrate structures using a digital learning tool. Students then predicted how microbes within the gut would ferment different carbohydrates into SCFAs, as well as the physiological implications of the SCFAs. We assessed this activity to address three research questions, with 182 students comprising our sample. First, we evaluated if the activity learning objectives were achieved through implementation of a pre-and post-assessment schema. Our results revealed that all three learning objectives of this activity were attained. Next, we evaluated if the format in which this TTT-GI activity was implemented impacted student learning. While we found minimal and nonsignificant differences in student learning between those who attended in-person and those who attended remotely, we did find significant differences between the two course sections, which differed in length and spacing of the activity. Finally, we evaluated if this TTT-GI approach was impactful for diverse students. We observed modest and nonsignificant positive learning gains for some populations of students traditionally underrepresented in STEM (first-generation students and students with one or more disabilities). That said, we found that the greatest learning gains associated with this TTT-GI activity were observed in students who had taken previous upper-level biology coursework.

Development and Characterization of an Electrocochleography-Guided Robotics-Assisted Cochlear Implant Array Insertion System.

OBJECTIVE: Electrocochleography (ECochG) is increasingly being used during cochlear implant (CI) surgery to detect and mitigate insertion-related intracochlear trauma, where a drop in ECochG signal has been shown to correlate with a decline in hearing outcomes. In this study, an ECochG-guided robotics-assisted CI insertion system was developed and characterized that provides controlled and consistent electrode array insertions while monitoring and adapting to real-time ECochG signals. STUDY DESIGN: Experimental research. SETTING: A research laboratory and animal testing facility. METHODS: A proof-of-concept benchtop study evaluated the ability of the system to detect simulated ECochG signal changes and robotically adapt the insertion. Additionally, the ECochG-guided insertion system was evaluated in a pilot in vivo sheep study to characterize the signal-to-noise ratio and amplitude of ECochG recordings during robotics-assisted insertions. The system comprises an electrode array insertion drive unit, an extracochlear recording electrode module, and a control console that interfaces with both components and the surgeon. RESULTS: The system exhibited a microvolt signal resolution and a response time <100 milliseconds after signal change detection, indicating that the system can detect changes and respond faster than a human. Additionally, animal results demonstrated that the system was capable of recording ECochG signals with a high signal-to-noise ratio and sufficient amplitude. CONCLUSION: An ECochG-guided robotics-assisted CI insertion system can detect real-time drops in ECochG signals during electrode array insertions and immediately alter the insertion motion. The system may provide a surgeon the means to monitor and reduce CI insertion-related trauma beyond manual insertion techniques for improved CI hearing outcomes.

Surgical outcomes and complications of bedside tracheostomy in the ICU for patients on ECMO.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is increasingly employed in the management of patients with severe cardiac and pulmonary dysfunction. Patients commonly require tracheostomy for ventilator liberation. Though bedside percutaneous tracheostomy is commonly performed, it has the potential for increased complications, both surgical and with the ECMO circuit. We examined surgical outcomes of bedside percutaneous tracheostomy in the ECMO population. METHODS: Patients were identified from an institutional database for bedside procedures. Demographics and data on complications were recorded. Descriptive statistics were calculated. RESULTS: 37 patients on ECMO at the time of tracheostomy were identified. Median age and BMI were 43.2 and 28.0, respectively. 33 patients (89%) were on VV ECMO, and 4 (11%) were on VA ECMO. All were on anticoagulation prior to tracheostomy, which was held for 4 h before and after the procedure in all cases. There were no procedure-related deaths or airway losses. No patients experienced periprocedural clotting events of their ECMO circuit or oxygenator within 24 h. 3 patients (8%) required reintervention (re-exploration or bronchoscopy) for bleeding. Four other patients (10%) had minor bleeding controlled with packing. One patient had pneumomediastinum which resolved without intervention, and one had an occlusion of their tracheostomy which was treated with tracheostomy exchange. CONCLUSIONS: Bedside percutaneous tracheostomy is feasible for patients on ECMO. Further study is needed to determine specific risk factors for complications and means to mitigate these. Bedside percutaneous tracheostomy may be considered as part of the management of patients on ECMO to help facilitate liberation from mechanical support.

Proof of Concept for an "eyePhone" App to Measure Video Head Impulses.

OBJECTIVE: Differentiating benign from dangerous causes of dizziness or vertigo presents a major diagnostic challenge for many clinicians. Bedside presentations of peripheral vestibular disorders and posterior fossa strokes are often indistinguishable other than by a few subtle vestibular eye movements. The most challenging of these to interpret is the head impulse test (HIT) of vestibulo-ocular reflex (VOR) function. There have been major advances in portable video-oculography (VOG) quantification of the video HIT (vHIT), but these specialized devices are not routinely available in most clinical settings. As a first step towards smartphone-based diagnosis of strokes in patients presenting vestibular symptoms, we sought proof of concept that we could use a smartphone application ("app") to accurately record the vHIT. METHODS: This was a cross-sectional agreement study comparing a novel index test (smartphone-based vHIT app) to an accepted reference standard test (VOG-based vHIT) for measuring VOR function. We recorded passive (examiner-performed) vHIT sequentially with both methods in a convenience sample of patients visiting an otoneurology clinic. We quantitatively correlated VOR gains (ratio of eye to head movements during the HIT) from each side/ear and experts qualitatively assessed the physiologic traces by the two methods. RESULTS: We recruited 11 patients; 1 patient's vHIT could not be reliably quantified with either device. The novel and reference test VOR gain measurements for each ear (n = 20) were highly correlated (Pearson's r = 0.9, p = 0.0000001) and, qualitatively, clinically equivalent. CONCLUSIONS: This preliminary study provides proof of concept that an "eyePhone" app could be used to measure vHIT and eventually developed to diagnose vestibular strokes by smartphone.

Evaluation of Selfies and Filtered Selfies and Effects on First Impressions.

BACKGROUND: Selfies and filtered selfies are becoming more prevalent throughout society and in the facial plastic surgery clinic. The term "Snapchat dysmorphia" has been used to describe patients seeking procedures to look like their selfie or filtered selfie. This is particularly frequent in the Millennial population, aged 22 to 37 years. OBJECTIVES: The authors sought to determine the effects on first impression from different photograph types: selfies, filtered selfies, a rear-facing smartphone camera, and a digital camera (DC). We hypothesize that the DC photographs will have the highest rated first impressions among evaluators despite the popularity of selfies and filtered selfies. METHODS: This study included 240 evaluators and 4 patients each completing the 4 different photograph types. The evaluators completed a survey rating first impression on various measures of success for each photograph type. RESULTS: A total of 960 first impressions were recorded for each of the 8 subscales, yielding 7680 individual assessments of first impression. The DC photograph was found to have the highest first impression scores among the 4 photograph types. There was no statistical difference between selfies and filtered selfies. The rear-facing smartphone camera received the lowest first impression scores. CONCLUSIONS: Our findings indicate that the standard DC photograph taken during a preoperative consultation has higher first impressions than selfies or filtered selfies. Although "Snapchat dysmorphia" may continue to be a growing trend in the near future, our findings provide important information to discuss with patients in the preoperative visit to set realistic expectations.