Non-invasive venous waveform analysis (NIVA) for volume assessment in patients undergoing hemodialysis: an observational study.

BACKGROUND: Accurate assessment of volume status to direct dialysis remains a clinical challenge. Despite current attempts at volume-directed dialysis, inadequate dialysis and intradialytic hypotension (IDH) are common occurrences. Peripheral venous waveform analysis has recently been developed as a method to accurately determine intravascular volume status through algorithmic quantification of changes in the waveform that occur at different volume states. A noninvasive method to capture peripheral venous signals is described (Non-Invasive Venous waveform Analysis, NIVA). The objective of this proof-of-concept study was to characterize changes in NIVA signal with dialysis. We hypothesized that there would be a change in signal after dialysis and that the rate of intradialytic change in signal would be predictive of IDH. METHODS: Fifty subjects undergoing inpatient hemodialysis were enrolled. A 10-mm piezoelectric sensor was secured to the middle volar aspect of the wrist on the extremity opposite to the access site. Signals were obtained fifteen minutes before, throughout, and up to fifteen minutes after hemodialysis. Waveforms were analyzed after a fast Fourier transformation and identification of the frequencies corresponding to the cardiac rate, with a NIVA value generated based on the weighted powers of these frequencies. RESULTS: Adequate quality (signal to noise ratio > 20) signals pre- and post- dialysis were obtained in 38 patients (76%). NIVA values were significantly lower at the end of dialysis compared to pre-dialysis levels (1.203 vs 0.868, p < 0.05, n = 38). Only 16 patients had adequate signals for analysis throughout dialysis, but in this small cohort the rate of change in NIVA value was predictive of IDH with a sensitivity of 80% and specificity of 100%. CONCLUSIONS: This observational, proof-of-concept study using a NIVA prototype device suggests that NIVA represents a novel and non-invasive technique that with further development and improvements in signal quality may provide static and continuous measures of volume status to assist with volume directed dialysis and prevent intradialytic hypotension.

Soft Budget Constraints in Public Hospitals.

A soft budget constraint arises when a government is unable to commit to not 'bailout' a public hospital if the public hospital exhausts its budget before the end of the budget period. It is shown that if the political costs of a 'bailout' are relatively small, then the public hospital exhausts the welfare-maximising budget before the end of the budget period and a 'bailout' occurs. In anticipation, the government offers a budget to the public hospital that may be greater than or less than the welfare-maximising budget. In either case, the public hospital treats 'too many' elective patients before the 'bailout' and 'too few' after. The introduction of a private hospital reduces the size of any 'bailout' and increases welfare.

Testing odorants recovery from a novel metallized fluorinated ethylene propylene gas sampling bag.

UNLABELLED: Industry-standard Tedlar bags for odor sample collection from confined animal feeding operations (CAFOs) have been challenged by the evidence of volatile organic compound (VOC) losses and background interferences. Novel impermeable aluminum foil with a thin layer of fluorinated ethylene propylene (FEP) film on the surface that is in contact with a gas sample was developed to address this challenge. In this research, Tedlar and metallized FEP bags were compared for (a) recoveries of four characteristic CAFO odorous VOCs (ethyl mercaptan, butyric acid, isovaleric acid and p-cresol) after 30 min and 24 hr sample storage time and for (b) chemical background interferences. All air sampling and analyses were performed with solid-phase microextraction (SPME) followed by gas chromatography-mass spectroscopy (GC-MS). Mean target gas sample recoveries from metallized FEP bags were 25.9% and 28.0% higher than those in Tedlar bags, for 30 min and 24 hr, respectively. Metallized FEP bags demonstrated the highest p-cresol recoveries after 30-min and 24-hr storage, 96.1±44.5% and 44.8±10.2%, respectively, among different types of sampling bags reported in previous studies. However, a higher variability was observed for p-cresol recovery with metallized FEP bags. A 0% recovery of ethyl mercaptan was observed with Tedlar bags after 24-hr storage, whereas an 85.7±7.4% recovery was achieved with metallized FEP bags. Recoveries of butyric and isovaleric acids were similar for both bag types. Two major impurities in Tedlar bags' background were identified as N,N-dimethylacetamide and phenol, while backgrounds of metallized FEP bags were significantly cleaner. Reusability of metallized FEP bags was tested. IMPLICATIONS: Caution is advised when using polymeric materials for storage of livestock-relevant odorous volatile organic compounds. The odorants loss with storage time confirmed that long-term storage in whole-air form is ill advised. A focused short-term odor sample containment should be biased toward the most inert material available relative to the highest impact target odorant. Metallized FEP was identified as such a material to p-cresol as the highest impact odorant from confined animal feeding operations. Metallized FEP bags have much cleaner background than commercial Tedlar bags do. Significantly higher recoveries of methyl mercaptan and p-cresol were also observed with metallized FEP bags.

Emergency Physician-performed Echocardiogram in Non-ST Elevation Acute Coronary Syndrome Patients Requiring Coronary Intervention.

Introduction: Identification of patients not meeting catheterization laboratory activation criteria by electrocardiogram (ECG) but who would benefit from early coronary intervention remains challenging in the emergency department (ED). The purpose of this study was to evaluate whether emergency physician (EP)-performed point-of-care transthoracic echocardiography (POC TTE) could help identify patients who required coronary intervention within this population. Methods: This was a retrospective observational cohort study of adult patients who presented to two EDs between 2018-2020. Patients were included if they received a POC TTE and underwent diagnostic coronary angiography within 72 hours of ED presentation. We excluded patients meeting catheterization laboratory activation criteria on initial ED ECG. Ultrasound studies were independently reviewed for presence of regional wall motion abnormalities (RWMA) by two blinded ultrasound fellowship-trained EPs. We then calculated test characteristics for coronary intervention. Results: Of the 221 patient encounters meeting inclusion criteria, 104 (47%) received coronary intervention or coronary artery bypass grafting (CABG) referral. Overall prevalence of RWMA on POC TTE was 35% (95% confidence interval [CI] 29-42%). Presence of RWMA had 38% (95% CI 29-49%) sensitivity and 68% (95% CI 58-76%) specificity for coronary intervention/CABG referral. Presence of "new" RWMA (presence on EP-performed POC TTE and prior normal echocardiogram) had 43% (95% CI 10-82%) sensitivity and 93% (95% CI 66-100%) specificity for coronary intervention/CABG referral. The EP-performed POC TTE interpretation of RWMA had 57% (95% CI 47-67%) sensitivity and 96% (95% CI 87-100%) specificity for presence of RWMA on subsequent cardiology echocardiogram during the same admission. Conclusion: Presence of RWMA on EP-performed POC TTE had limited sensitivity or specificity for coronary intervention or referral to CABG. The observed specificity appeared to trend higher in subjects with a prior echocardiogram demonstrating absence of RWMA, although a larger sample size will be required to confirm this finding. The EP-performed POC TTE RWMA had high specificity for presence of RWMA on subsequent cardiology echocardiogram. Further evaluation of the diagnostic performance of new RWMA on EP-performed POC TTE with a dedicated cohort is warranted.

Automated HEART score determination via ChatGPT: Honing a framework for iterative prompt development.

Objectives: This study presents a design framework to enhance the accuracy by which large language models (LLMs), like ChatGPT can extract insights from clinical notes. We highlight this framework via prompt refinement for the automated determination of HEART (History, ECG, Age, Risk factors, Troponin risk algorithm) scores in chest pain evaluation. Methods: We developed a pipeline for LLM prompt testing, employing stochastic repeat testing and quantifying response errors relative to physician assessment. We evaluated the pipeline for automated HEART score determination across a limited set of 24 synthetic clinical notes representing four simulated patients. To assess whether iterative prompt design could improve the LLMs' ability to extract complex clinical concepts and apply rule-based logic to translate them to HEART subscores, we monitored diagnostic performance during prompt iteration. Results: Validation included three iterative rounds of prompt improvement for three HEART subscores with 25 repeat trials totaling 1200 queries each for GPT-3.5 and GPT-4. For both LLM models, from initial to final prompt design, there was a decrease in the rate of responses with erroneous, non-numerical subscore answers. Accuracy of numerical responses for HEART subscores (discrete 0-2 point scale) improved for GPT-4 from the initial to final prompt iteration, decreasing from a mean error of 0.16-0.10 (95% confidence interval: 0.07-0.14) points. Conclusion: We established a framework for iterative prompt design in the clinical space. Although the results indicate potential for integrating LLMs in structured clinical note analysis, translation to real, large-scale clinical data with appropriate data privacy safeguards is needed.

The type species of Eucosma Hübner (Lepidoptera: Tortricidae: Eucosmini).

Eucosma Hübner is the largest genus in the Tortricidae with more than 290 named species. Historically, there has been confusion about the assignment of species to Eucosma and related genera, a problem which is perpetuated by the lack of a type specimen for the type species, E. circulana Hübner. Here we designate a neotype for E. circulana following analysis of eight North American species having similarities with that taxon. Eucosma circulana and E. gemellana Heinrich are redescribed, the latter being elevated from subspecies to species status. Eucosma paragemellana, new species, is described from specimens previously confused with E. gemellana, and E. fraudabilis Heinrich is reviewed.

Revised world catalogue of Eucopina, Eucosma, Pelochrista, and Phaneta (Lepidoptera: Tortricidae: Eucosmini).

A revised world catalogue of Eucopina, Eucosma, Pelochrista, and Phaneta is provided. Assignment to genus is based on generic redescriptions by Gilligan et al. (2013). A total of 709 names (including subspecies and synonyms) are listed, including 251 new combinations and 52 revised combinations.

"Skunky" Cannabis: Environmental Odor Troubleshooting and the "Need-for-Speed".

Although the "skunky" odor characteristic of cannabis has been widely referenced, its cause has been historically misassigned to unspecified "skunky terpenes". Recent reports from two independent research groups, the Koziel team (March and April 2021) and Oswald team (August and November 2021), have corrected this misassignment by linking the "skunky" character of industrial hemp and cannabis to 3-methyl-2-butene-1-thiol (321MBT). A recent USPTO patent application review clearly indicated that the Oswald team should take full credit for the discovery of this link with respect to cannabis. However, the August 19, 2021 publication of their patent application appears to be their formal public disclosure of 321MBT as the primary source odorant which is responsible for the targeted "skunky" odor. This date is well after the March and April 2021 public disclosures by the Koziel team for the 321MBT/"skunky" odor link relative to both cannabis and industrial hemp. This Viewpoint summarizes the investigative strategy leading to the public disclosure of this historically elusive link. It is presented from the perspective of the rapid multidimensional-gas chromatography-mass spectrometry-olfactometry (i.e., MDGC-MS-O) based odorant-prioritization "screening" approach, as applied by the Koziel team.

Qualitative Exploration of the 'Rolling Unmasking Effect' for Downwind Odor Dispersion from a Model Animal Source.

Solving environmental odor issues can be confounded by many analytical, technological, and socioeconomic factors. Considerable know-how and technologies can fail to properly identify odorants responsible for the downwind nuisance odor and, thereby, focus on odor mitigation strategies. We propose enabling solutions to environmental odor issues utilizing troubleshooting techniques developed for the food, beverage, and consumer products industries. Our research has shown that the odorant impact-priority ranking process can be definable and relatively simple. The initial challenge is the prioritization of environmental odor character from the perspective of the impacted citizenry downwind. In this research, we utilize a natural model from the animal world to illustrate the rolling unmasking effect (RUE) and discuss it more systematically in the context of the proposed environmental odorant prioritization process. Regardless of the size and reach of an odor source, a simplification of odor character and composition typically develops with increasing dilution downwind. An extreme odor simplification-upon-dilution was demonstrated for the prehensile-tailed porcupine (P.T. porcupine); its downwind odor frontal boundary was dominated by a pair of extremely potent character-defining odorants: (1) 'onion'/'body odor' and (2) 'onion'/'grilled' odorants. In contrast with the outer-boundary simplicity, the near-source assessment presented considerable compositional complexity and composite odor character difference. The ultimate significance of the proposed RUE approach is the illustration of naturally occurring phenomena that explain why some environmental odors and their sources can be challenging to identify and mitigate using an analytical-only approach (focused on compound identities and concentrations). These approaches rarely move beyond comprehensive lists of volatile compounds emitted by the source. The novelty proposed herein lies in identification of those few compounds responsible for the downwind odor impacts and requiring mitigation focus.

State of Sweat: Emerging Wearable Systems for Real-Time, Noninvasive Sweat Sensing and Analytics.

Skin-interfaced wearable systems with integrated colorimetric assays, microfluidic channels, and electrochemical sensors offer powerful capabilities for noninvasive, real-time sweat analysis. This Perspective details recent progress in the development and translation of novel wearable sensors for personalized assessment of sweat dynamics and biomarkers, with precise sampling and real-time analysis. Sensor accuracy, system ruggedness, and large-scale deployment in remote environments represent key opportunity areas, enabling broad deployment in the context of field studies, clinical trials, and recent commercialization. On-body measurements in these contexts show good agreement compared to conventional laboratory-based sweat analysis approaches. These device demonstrations highlight the utility of biochemical sensing platforms for personalized assessment of performance, wellness, and health across a broad range of applications.

Taxonomic issues related to biological control prospects for the ragweed borer, Epiblema strenuana (Lepidoptera: Tortricidae).

The ragweed borer, Epiblema strenuana (Walker, 1863), has a long history of use as a biological control agent against important weed pests in the family Asteraceae. Recently, E. strenuana has been reported feeding on the invasive perennials Ambrosia confertiflora and A. tenuifolia in Israel. The geographic location of Israel has raised concern over the possibility that the moth may spread to areas such as Ethiopia where the oil-seed crop Guizotia abyssinica is cultivated, as this is a potential host for E. strenuana. However, the taxonomic status of E. strenuana and a current synonym, E. minutana (Kearfott, 1905) is unclear. These taxa have been treated as separate species in the past, and they potentially have different feeding habits and damage different parts of the plant. We analyzed DNA data and adult morphology and determined that E. minutana, stat. rev., is a valid species which we raise from synonymy with E. strenuana. Wing coloration, the shape of the female sterigma, and COI DNA barcodes are consistently different between the two species. We also determined that the species previously identified as E. strenuana in Israel is actually E. minutana. While detailed host range tests have been conducted on the E. strenuana populations released in Australia and China, the host range of E. minutana remains to be clarified. We discuss the history of biological control using E. strenuana and the implications for finding E. minutana in Israel. We also provide species redescriptions for E. strenuana and E. minutana and illustrate diagnostic characters.

A Feasibility Study Using a Machine Learning Suicide Risk Prediction Model Based on Open-Ended Interview Language in Adolescent Therapy Sessions.

BACKGROUND: As adolescent suicide rates continue to rise, innovation in risk identification is warranted. Machine learning can identify suicidal individuals based on their language samples. This feasibility pilot was conducted to explore this technology's use in adolescent therapy sessions and assess machine learning model performance. METHOD: Natural language processing machine learning models to identify level of suicide risk using a smartphone app were tested in outpatient therapy sessions. Data collection included language samples, depression and suicidality standardized scale scores, and therapist impression of the client's mental state. Previously developed models were used to predict suicidal risk. RESULTS: 267 interviews were collected from 60 students in eight schools by ten therapists, with 29 students indicating suicide or self-harm risk. During external validation, models were trained on suicidal speech samples collected from two separate studies. We found that support vector machines (AUC: 0.75; 95% CI: 0.69-0.81) and logistic regression (AUC: 0.76; 95% CI: 0.70-0.82) lead to good discriminative ability, with an extreme gradient boosting model performing the best (AUC: 0.78; 95% CI: 0.72-0.84). CONCLUSION: Voice collection technology and associated procedures can be integrated into mental health therapists' workflow. Collected language samples could be classified with good discrimination using machine learning methods.

A Pivotal Study to Validate the Performance of a Novel Wearable Sensor and System for Biometric Monitoring in Clinical and Remote Environments.

BACKGROUND: Increasingly, drug and device clinical trials are tracking activity levels and other quality of life indices as endpoints for therapeutic efficacy. Trials have traditionally required intermittent subject visits to the clinic that are artificial, activity-intensive, and infrequent, making trend and event detection between visits difficult. Thus, there is an unmet need for wearable sensors that produce clinical quality and medical grade physiological data from subjects in the home. The current study was designed to validate the BioStamp nPoint® system (MC10 Inc., Lexington, MA, USA), a new technology designed to meet this need. OBJECTIVE: To evaluate the accuracy, performance, and ease of use of an end-to-end system called the BioStamp nPoint. The system consists of an investigator portal for design of trials and data review, conformal, low-profile, wearable biosensors that adhere to the skin, a companion technology for wireless data transfer to a proprietary cloud, and algorithms for analyzing physiological, biometric, and contextual data for clinical research. METHODS: A prospective, nonrandomized clinical trial was conducted on 30 healthy adult volunteers over the course of two continuous days and nights. Supervised and unsupervised study activities enabled performance validation in clinical and remote (simulated "at home") environments. System outputs for heart rate (HR), heart rate variability (HRV) (including root mean square of successive differences [RMSSD] and low frequency/high frequency ratio), activity classification during prescribed activities (lying, sitting, standing, walking, stationary biking, and sleep), step count during walking, posture characterization, and sleep metrics including onset/wake times, sleep duration, and respiration rate (RR) during sleep were evaluated. Outputs were compared to FDA-cleared comparator devices for HR, HRV, and RR and to ground truth investigator observations for activity and posture classifications, step count, and sleep events. RESULTS: Thirty participants (77% male, 23% female; mean age 35.9 ± 10.1 years; mean BMI 28.1 ± 3.6) were enrolled in the study. The BioStamp nPoint system accurately measured HR and HRV (correlations: HR = 0.957, HRV RMSSD = 0.965, HRV ratio = 0.861) when compared to ActiheartTM. The system accurately monitored RR (mean absolute error [MAE] = 1.3 breaths/min) during sleep when compared to a Capnostream35TM end-tidal CO2 monitor. When compared with investigator observations, the system correctly classified activities and posture (agreement = 98.7 and 92.9%, respectively), step count (MAE = 14.7, < 3% of actual steps during a 6-min walk), and sleep events (MAE: sleep onset = 6.8 min, wake = 11.5 min, sleep duration = 13.7 min) with high accuracy. Participants indicated "good" to "excellent" usability (average System Usability Scale score of 81.3) and preferred the BioStamp nPoint system over both the Actiheart (86%) and Capnostream (97%) devices. CONCLUSIONS: The present study validated the BioStamp nPoint system's performance and ease of use compared to FDA-cleared comparator devices in both the clinic and remote (home) environments.

Method comparison study of peripheral blood CD34+ count performed on an Abbott CELL-DYN Sapphire hematology analyzer versus flow cytometry reference procedure (modified ISHAGE).

INTRODUCTION: CD34+ cell enumeration is a critical parameter used to determine the timing of apheresis collections of hematopoietic progenitor cell products (HPC(A)). Automated hematology analyzers equipped with flow cytometry capabilities may be a solution to the problem of limited access to standard flow cytometry testing. METHODS: We compared CD34+ cell enumeration using a reference flow cytometry procedure employing modified International Society of Hematotherapy and Graft Engineering (ISHAGE) analysis with a hematology analyzer /flow cytometer hybrid (CELL DYN (CD)Sapphire) using a sequential gating analysis designed to emulate the ISHAGE gating strategy. RESULTS: CD34+ cell values obtained from the ISHAGE and CD Sapphire analysis were plotted and compared in a linear regression analysis which showed a high degree of correlation (R2=0.96). No statistically significant (p=0.53) differences in CD34+ cell enumeration values were observed between the flow cytometer and automated hematology analyzer using manual analysis schema. CONCLUSIONS: We have demonstrated that an automated hematology analyzer equipped with a flow module can provide CD34+ cell enumeration results in the peripheral blood for clinical decision algorithms without the need for a dedicated flow cytometry laboratory.

Soft, stretchable, epidermal sensor with integrated electronics and photochemistry for measuring personal UV exposures.

Excessive ultraviolet (UV) radiation induces acute and chronic effects on the skin, eye and immune system. Personalized monitoring of UV radiation is thus paramount to measure the extent of personal sun exposure, which could vary with environment, lifestyle, and sunscreen use. Here, we demonstrate an ultralow modulus, stretchable, skin-mounted UV patch that measures personal UV doses. The patch contains functional layers of ultrathin stretchable electronics and a photosensitive patterned dye that reacts to UV radiation. Color changes in the photosensitive dyes correspond to UV radiation intensity and are analyzed with a smartphone camera. A software application has feature recognition, lighting condition correction, and quantification algorithms that detect and quantify changes in color. These color changes are then correlated with corresponding shifts in UV dose, and compared to existing UV dose risk levels. The soft mechanics of the UV patch allow for multi-day wear in the presence of sunscreen and water. Two evaluation studies serve to demonstrate the utility of the UV patch during daily activities with and without sunscreen application.

Specialist payment schemes and patient selection in private and public hospitals.

It has been observed that specialist physicians who work in private hospitals are usually paid by fee-for-service while specialist physicians who work in public hospitals are usually paid by salary. This paper provides an explanation for this observation. Essentially, fee-for-service aligns the interests of income preferring specialists with profit maximizing private hospitals and results in private hospitals treating a high proportion of short stay patients. On the other hand, salary aligns the interests of fairness preferring specialists with benevolent public hospitals that commit to admit all patients irrespective of their expected length of stay.

Intradural cranial chordoma: a rare presentation of an uncommon tumor. Surgical experience and review of the literature.

OBJECT: Intracranial intradural chordomas are extremely rare lesions, and only a few cases have been reported in the neurosurgical literature. The authors performed a retrospective analysis of cases treated at their institutions. They present an illustrative surgical scenario and discuss the published literature, pathogenesis, and histopathological features as well as available follow-up data on the clinical behavior of these intradural lesions. METHODS: The authors reviewed clinical, neuroimaging, operative and follow-up data from a series of 79 chordomas treated at their institutions over the last 17 years. They found that the tumors were confined exclusively to the intradural compartment in only three cases. Staining for MIB-1 was performed to support the differential diagnosis between ecchordosis physaliphora and intradural chordoma, and in all three patients the neoplastic nature of the lesions was confirmed. None of these three cases showed recurrence of the lesion at midterm follow up. CONCLUSIONS: Complete resection, followed by close clinical and neuroradiological follow up, is warranted in cases of intradural cranial chordoma.

Cranial nerve hemangioblastomas. Report of a rare case and review of literature.

BACKGROUND: Cranial nerve hemangioblastomas are exceedingly rare lesions. We review available literature and present the first surgical report on a solid hemangioblastoma arising from the trigeminal nerve and involving the Meckel cave that was successfully treated with selective embolization and successive surgical resection. CASE DESCRIPTION: A 54-year-old woman presented with an 8-month history of facial numbness associated with headache. An MRI revealed a highly vascularized supra- and infratentorial mass involving the right Meckel cave. A preoperative angiogram with selective embolization of tumoral feeders was performed, and the patient elected to undergo surgical treatment. A large solid lesion encasing the trigeminal nerve was resected without complications via a PLPA approach. Hystopathological examination revealed features consistent with the diagnosis of hemangioblastoma. Other stigmata or familiar history of VHL disease were absent. CONCLUSIONS: Review of the literature confirms that cranial nerve hemangioblastomas are very rare lesions that occur sporadically or in association with VHL disease. Surgical management of such lesions should be directed by clinical and radiological features as well as patient expectations.