The stability of 65 biochemistry analytes in plasma, serum, and whole blood.

OBJECTIVES: The pre-analytical stability of various biochemical analytes requires careful consideration, as it can lead to the release of erroneous laboratory results. There is currently significant variability in the literature regarding the pre-analytical stability of various analytes. The aim of this study was to determine the pre-analytical stability of 65 analytes in whole blood, serum and plasma using a standardized approach. METHODS: Blood samples were collected from 30 healthy volunteers (10 volunteers per analyte) into five vacutainers; either SST, Li-heparin, K2-EDTA, or Na-fluoride/K-oxalate. Several conditions were tested, including delayed centrifugation with storage of whole blood at room temperature (RT) for 8 h, delayed centrifugation with storage of whole blood at RT or 4 °C for 24 h, and immediate centrifugation with storage of plasma or serum at RT for 24 h. Percent deviation (% PD) from baseline was calculated for each analyte and compared to the maximum permissible instability (MPI) derived from intra- and inter-individual biological variation. RESULTS: The majority of the analytes evaluated remained stable across all vacutainer types, temperatures, and timepoints tested. Glucose, potassium, and aspartate aminotransferase, among others, were significantly impacted by delayed centrifugation, having been found to be unstable in whole blood specimens stored at room temperature for 8 h. CONCLUSIONS: The data presented provides insight into the pre-analytical variables that impact the stability of routine biochemical analytes. This study may help to reduce the frequency of erroneous laboratory results released due to exceeded stability and reduce unnecessary repeat phlebotomy for analytes that remain stable despite delayed processing.

Stability and Analytical Characterization of Voriconazole as Measured by Immunoassay.

BACKGROUND: Voriconazole is a broad-spectrum triazole antifungal agent recommended for invasive fungal diseases, including invasive aspergillosis. Therapeutic drug monitoring via voriconazole target trough concentration is important to ensure efficacy while preventing toxicity. Our aim was to determine the stability of voriconazole as adapted and measured by an immunoassay. METHODS: Plasma from patient samples (n = 45) evaluated by a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was compared against an ARK immunoassay method, adapted and optimized on the Abbott Alinity c analyzer. Stability of voriconazole and analytical performance of ARK immunoassay was assessed, including functional sensitivity, limit of blank (LoB), limit of detection (LoD), and limit of quantification (LoQ), linearity, and precision. RESULTS: ARK voriconazole immunoassay was highly correlated (Pearson R = 0.988) to the LC-MS/MS method, with an average bias of 0.09 mg/L (2%). CV at LoQ of 0.5 mg/L was 3.7% while the functional sensitivity was established at 0.05 mg/L. Overall imprecision with liquid quality control material obtained from ARK was 5.0%, 6.3%, and 5.9% at 1 mg/L, 5 mg/L, and 10 mg/L, respectively. Limit of blank and LoD were 0.02 mg/L and 0.05 mg/L, respectively. Voriconazole in lithium heparin plasma separator tube declines over time, with a decrease that is more evident near or above toxic concentrations. CONCLUSION: Voriconazole collected in gel separation tubes declines over time, possibly due to absorptive properties. Voriconazole measurements by immunoassay and LC-MS/MS demonstrated acceptable comparability with sufficient level of sensitivity and precision.

An Integrated System of Braden Scale and Random Forest Using Real-Time Diagnoses to Predict When Hospital-Acquired Pressure Injuries (Bedsores) Occur.

BACKGROUND AND OBJECTIVES: Bedsores/Pressure Injuries (PIs) are the second most common diagnosis in healthcare system billing records in the United States and account for 60,000 deaths annually. Hospital-Acquired Pressure Injuries (HAPIs) are one classification of PIs and indicate injuries that occurred while the patient was cared for within the hospital. Until now, all studies have predicted who will develop HAPI using classic machine algorithms, which provides incomplete information for the clinical team. Knowing who will develop HAPI does not help differentiate at which point those predicted patients will develop HAPIs; no studies have investigated when HAPI develops for predicted at-risk patients. This research aims to develop a hybrid system of Random Forest (RF) and Braden Scale to predict HAPI time by considering the changes in patients' diagnoses from admission until HAPI occurrence. METHODS: Real-time diagnoses and risk factors were collected daily for 485 patients from admission until HAPI occurrence, which resulted in 4619 records. Then for each record, HAPI time was calculated from the day of diagnosis until HAPI occurrence. Recursive Feature Elimination (RFE) selected the best factors among the 60 factors. The dataset was separated into 80% training (10-fold cross-validation) and 20% testing. Grid Search (GS) with RF (GS-RF) was adopted to predict HAPI time using collected risk factors, including Braden Scale. Then, the proposed model was compared with the seven most common algorithms used to predict HAPI; each was replicated for 50 different experiments. RESULTS: GS-RF achieved the best Area Under the Curve (AUC) (91.20 ± 0.26) and Geometric Mean (G-mean) (91.17 ± 0.26) compared to the seven algorithms. RFE selected 43 factors. The most dominant interactable risk factors in predicting HAPI time were visiting ICU during hospitalization, Braden subscales, BMI, Stimuli Anesthesia, patient refusal to change position, and another lab diagnosis. CONCLUSION: Identifying when the patient is likely to develop HAPI can target early intervention when it is needed most and reduces unnecessary burden on patients and care teams when patients are at lower risk, which further individualizes the plan of care.

Machine Learning Techniques, Applications, and Potential Future Opportunities in Pressure Injuries (Bedsores) Management: A Systematic Review.

Pressure Injuries (PI) are one of the most common health conditions in the United States. Most acute or long-term care patients are at risk of developing PI. Machine Learning (ML) has been utilized to manage patients with PI, in which one systematic review describes how ML is used in PI management in 32 studies. This research, different from the previous systematic review, summarizes the previous contributions of ML in PI from January 2007 to July 2022, categorizes the studies according to medical specialties, analyzes gaps, and identifies opportunities for future research directions. PRISMA guidelines were adopted using the four most common databases (PubMed, Web of Science, Scopus, and Science Direct) and other resources, which result in 90 eligible studies. The reviewed articles are divided into three categories based on PI time of occurrence: before occurrence (48%); at time of occurrence (16%); and after occurrence (36%). Each category is further broken down into sub-fields based on medical specialties, which result in sixteen specialties. Each specialty is analyzed in terms of methods, inputs, and outputs. The most relevant and potentially useful applications and methods in PI management are outlined and discussed. This includes deep learning techniques and hybrid models, integration of existing risk assessment tools with ML that leads to a partnership between provider assessment and patients' Electronic Health Records (EHR).

An Integrated System of Multifaceted Machine Learning Models to Predict If and When Hospital-Acquired Pressure Injuries (Bedsores) Occur.

Hospital-Acquired Pressure Injury (HAPI), known as bedsore or decubitus ulcer, is one of the most common health conditions in the United States. Machine learning has been used to predict HAPI. This is insufficient information for the clinical team because knowing who would develop HAPI in the future does not help differentiate the severity of those predicted cases. This research develops an integrated system of multifaceted machine learning models to predict if and when HAPI occurs. Phase 1 integrates Genetic Algorithm with Cost-Sensitive Support Vector Machine (GA-CS-SVM) to handle the high imbalance HAPI dataset to predict if patients will develop HAPI. Phase 2 adopts Grid Search with SVM (GS-SVM) to predict when HAPI will occur for at-risk patients. This helps to prioritize who is at the highest risk and when that risk will be highest. The performance of the developed models is compared with state-of-the-art models in the literature. GA-CS-SVM achieved the best Area Under the Curve (AUC) (75.79 ± 0.58) and G-mean (75.73 ± 0.59), while GS-SVM achieved the best AUC (75.06) and G-mean (75.06). The research outcomes will help prioritize at-risk patients, allocate targeted resources and aid with better medical staff planning to provide intervention to those patients.

Cervical Cancer Diagnosis Using an Integrated System of Principal Component Analysis, Genetic Algorithm, and Multilayer Perceptron.

Cervical cancer is one of the most dangerous diseases that affect women worldwide. The diagnosis of cervical cancer is challenging, costly, and time-consuming. Existing literature has focused on traditional machine learning techniques and deep learning to identify and predict cervical cancer. This research proposes an integrated system of Genetic Algorithm (GA), Multilayer Perceptron (MLP), and Principal Component Analysis (PCA) that accurately predicts cervical cancer. GA is used to optimize the MLP hyperparameters, and the MLPs act as simulators within the GA to provide the prediction accuracy of the solutions. The proposed method uses PCA to transform the available factors; the transformed features are subsequently used as inputs to the MLP for model training. To contrast with the PCA method, different subsets of the original factors are selected. The performance of the integrated system of PCA-GA-MLP is compared with nine different classification algorithms. The results indicate that the proposed method outperforms the studied classification algorithms. The PCA-GA-MLP model achieves the best accuracy in diagnosing Hinselmann, Biopsy, and Cytology when compared to existing approaches in the literature that were implemented on the same dataset. This study introduces a robust tool that allows medical teams to predict cervical cancer in its early stage.

Abuse of tropicamide eye drops: review of clinical data

Over the past 15 years, the increasing nonmedical use of tropicamide ophthalmic drops has been reported in Europe, coinciding with an increase in opioid addiction and drug-related mortality. Although tropicamide is generally known as a cheap alternative to heroin in Eastern Europe, it still appears to be a relatively new phenomenon that has arisen over the last decade. A narrative review was conducted of all the relevant sources published in more than five countries between January 1, 1975 and January 10, 2021. For bibliographic accuracy, the materials published in Russian and Italian were professionally translated to English. During the preparation of this report, we were able to interview five Russian-speaking patients who injected tropicamide in the past and we discuss another case of intravenous tropicamide use. This review was acknowledged by the institutional review board of the University of Missouri-Kansas City. All patients interviewed at the Unica Medical Center consented for their clinical information to be reported in a medical publication. We analyzed data from 50+ various sources and covered a variety of drug-related issues, including information on the extent, patterns, and trends in tropicamide use, its health consequences, and other clinical findings. The information provided in this article may help providers better detect tropicamide abuse and incorporate new rehabilitation strategies into the management of these patients.

Social connectedness of carers: An Australian national survey of carers.

Carers of people living with a disability, mental health problems, alcohol or drug dependency, chronic condition, terminal illness or who are frail due to age may experience negative caregiving impacts. Although carers' social isolation has been reported in many qualitative studies, it has largely been neglected in quantitative studies. Using data collected in the Carers NSW 2020 National Carer Survey, this large-scale quantitative study aimed to identify the extent of Australian carers' social connectedness and what factors may be related to their social well-being. The validated Friendship Scale was used to measure social connectedness of 5585 carers. More than half (56.2%) of these carers were socially isolated. Analysis found that a longer duration of caring, more time spent weekly caring, living with the care recipient, caring for a greater number of people, receiving no help from others, higher reported psychological distress and reporting perceived needs were all associated with greater social isolation. Identifying as female or nonbinary/gender diverse, identifying with a culturally and linguistically diverse background, and caring as a parent, former partner or young carer were also related to poorer social connectedness. Health and social services need to consider the needs of carers, identify carers who are socially isolated and provide resources to promote social connectedness. Greater attention in practice and research to focus on carers' social connectedness to address this crucial caregiving experience is required.

Abuse of tropicamide eye drops: review of clinical data.

Over the past 15 years, the increasing nonmedical use of tropicamide ophthalmic drops has been reported in Europe, coinciding with an increase in opioid addiction and drug-related mortality. Although tropicamide is generally known as a cheap alternative to heroin in Eastern Europe, it still appears to be a relatively new phenomenon that has arisen over the last decade. A narrative review was conducted of all the relevant sources published in more than five countries between January 1, 1975 and January 10, 2021. For bibliographic accuracy, the materials published in Russian and Italian were professionally translated to English. During the preparation of this report, we were able to interview five Russian-speaking patients who injected tropicamide in the past and we discuss another case of intravenous tropicamide use. This review was acknowledged by the institutional review board of the University of Missouri-Kansas City. All patients interviewed at the Unica Medical Center consented for their clinical information to be reported in a medical publication. We analyzed data from 50+ various sources and covered a variety of drug-related issues, including information on the extent, patterns, and trends in tropicamide use, its health consequences, and other clinical findings. The information provided in this article may help providers better detect tropicamide abuse and incorporate new rehabilitation strategies into the management of these patients.

A Hybrid System of Braden Scale and Machine Learning to Predict Hospital-Acquired Pressure Injuries (Bedsores): A Retrospective Observational Cohort Study.

Background: The Braden Scale is commonly used to determine Hospital-Acquired Pressure Injuries (HAPI). However, the volume of patients who are identified as being at risk stretches already limited resources, and caregivers are limited by the number of factors that can reasonably assess during patient care. In the last decade, machine learning techniques have been used to predict HAPI by utilizing related risk factors. Nevertheless, none of these studies consider the change in patient status from admission until discharge. Objectives: To develop an integrated system of Braden and machine learning to predict HAPI and assist with resource allocation for early interventions. The proposed approach captures the change in patients' risk by assessing factors three times across hospitalization. Design: Retrospective observational cohort study. Setting(s): This research was conducted at ChristianaCare hospital in Delaware, United States. Participants: Patients discharged between May 2020 and February 2022. Patients with HAPI were identified from Nursing documents (N = 15,889). Methods: Support Vector Machine (SVM) was adopted to predict patients' risk for developing HAPI using multiple risk factors in addition to Braden. Multiple performance metrics were used to compare the results of the integrated system versus Braden alone. Results: The HAPI rate is 3%. The integrated system achieved better sensitivity (74.29 ± 1.23) and detection prevalence (24.27 ± 0.16) than the Braden scale alone (sensitivity (66.90 ± 4.66) and detection prevalence (41.96 ± 1.35)). The most important risk factors to predict HAPI were Braden sub-factors, overall Braden, visiting ICU during hospitalization, and Glasgow coma score. Conclusions: The integrated system which combines SVM with Braden offers better performance than Braden and reduces the number of patients identified as at-risk. Furthermore, it allows for better allocation of resources to high-risk patients. It will result in cost savings and better utilization of resources. Relevance to clinical practice: The developed model provides an automated system to predict HAPI patients in real time and allows for ongoing intervention for patients identified as at-risk. Moreover, the integrated system is used to determine the number of nurses needed for early interventions. Reporting Method: EQUATOR guidelines (TRIPOD) were adopted in this research to develop the prediction model. Patient or Public Contribution: This research was based on a secondary analysis of patients' Electronic Health Records. The dataset was de-identified and patient identifiers were removed before processing and modeling.

Polypharmacy in Multiple Sclerosis: Current Knowledge and Future Directions.

Polypharmacy, or the daily use of five or more medications, is well documented in older adults and linked to negative outcomes such as medication errors, adverse drug reactions, and increased healthcare utilization. Like older adults, people with multiple sclerosis (PwMS) are susceptible to polypharmacy, owing to the variety of treatments used to address individual multiple sclerosis (MS) symptoms and other comorbidities. Between 15-65% of PwMS meet criteria for polypharmacy; in this population, polypharmacy is associated with increased reports of fatigue, subjective cognitive impairment, and reduced quality of life. Despite evidence of adverse outcomes, polypharmacy among PwMS remains a neglected area of research. This article examines the current literature regarding polypharmacy in MS, as well as implications for clinical practice and directions for future research.

Automated Quantification of Hydroxyl Reactivities: Prediction of Glycosylation Reactions.

The stereoselectivity and yield in glycosylation reactions are paramount but unpredictable. We have developed a database of acceptor nucleophilic constants (Aka) to quantify the nucleophilicity of hydroxyl groups in glycosylation influenced by the steric, electronic and structural effects, providing a connection between experiments and computer algorithms. The subtle reactivity differences among the hydroxyl groups on various carbohydrate molecules can be defined by Aka, which is easily accessible by a simple and convenient automation system to assure high reproducibility and accuracy. A diverse range of glycosylation donors and acceptors with well-defined reactivity and promoters were organized and processed by the designed software program "GlycoComputer" for prediction of glycosylation reactions without involving sophisticated computational processing. The importance of Aka was further verified by random forest algorithm, and the applicability was tested by the synthesis of a Lewis A skeleton to show that the stereoselectivity and yield can be accurately estimated.

COVID-19: A review of the proposed pharmacological treatments.

The emerging pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge for healthcare systems globally. The clinical course of COVID-19 and its ability to rapidly create widespread infection has major implications, warranting vigorous infection prevention and control measures. As the confirmed number of cases has surpassed 5.6 million worldwide and continues to grow, the potential severity of the disease and its deadly complications requires urgent development of novel therapeutic agents to both prevent and treat COVID-19. Although vaccines and specific drug therapies have yet to be discovered, ongoing research and clinical trials are being conducted to investigate the efficacy of repurposed drugs for treating COVID-19. In the present review, the drug candidates that have been suggested to treat COVID-19 will be discussed. These include anti-viral agents (remdesivir, ribavirin, lopinavir-ritonavir, favipiravir, chloroquine, hydroxychloroquine, oseltamivir, umifenovir), immunomodulatory agents (tocilizumab, interferons, plasma transfusions), and adjunctive agents (azithromycin, corticosteroids), among other miscellaneous agents. The mechanisms of action and further pharmacological properties will be explored, with a particular focus on the evidence-based safety and efficacy of each agent.

Tumor volume reduction evaluated by cone beam computed tomography during stereotactic body radiotherapy for early stage non-small cell lung cancer.

BACKGROUND: We hypothesized that significant tumor volume reduction (TVR) occurs over the course of stereotactic body radiotherapy (SBRT) for early stage non-small cell lung cancer (NSCLC), and that TVR correlates with clinical outcomes. METHODS: We conducted a retrospective review of patients treated with SBRT for early stage NSCLC across two academic centers. For each patient, we contoured the tumor volume (TV) on cone beam computed tomography (CBCT) images obtained before each treatment fraction. We then calculated TVR based on the TV from the first and last days of treatment. We used log-rank tests to quantify differences in overall survival (OS), progression-free survival (PFS) and recurrence based on TVR. RESULTS: Data from 69 patients and a total of 73 treated tumors were analyzed. The median follow-up for survivors was 51.8 months (range, 6.9 to 80.0 months). The median TVR for the cohort was 10.1% (range, -5.7% to 43.5%). There was no significant difference in either OS (median 33.4 vs. 29.1 months, P=0.79) or PFS (median 26.3 vs. 12.3 months, P=0.43) for those with high TVRs (≥10.1%) vs. low TVRs (<10.1%), respectively. There was a trend toward superior 2-year PFS in the high TVR group (52.2% vs. 36.7%, P=0.062), but this effect diminished on longer follow-up (4-year PFS 31.9% vs. 26.7%, P=0.15). No associations were observed between TVR and local, regional or distant recurrence. CONCLUSIONS: We were not able to demonstrate that TVR is a reliable predictive imaging marker for stage I/II NSCLC treated with SBRT. Future studies with larger sample sizes are needed to clarify a potential relationship between TVR and early outcomes.

Direct Dehydrative Glycosylation Catalyzed by Diphenylammonium Triflate.

Methods for direct dehydrative glycosylations of carbohydrate hemiacetals catalyzed by diphenylammonium triflate under microwave irradiation are described. Both armed and disarmed glycosyl-C1-hemiacetal donors were efficiently glycosylated in moderate to excellent yields without the need for any drying agents and stoichiometric additives. This method has been successfully applied to a solid-phase glycosylation.

Establishment of Guidelines for the Control of Glycosylation Reactions and Intermediates by Quantitative Assessment of Reactivity.

Stereocontrolled chemical glycosylation remains a major challenge despite vast efforts reported over many decades and so far still mainly relies on trial and error. Now it is shown that the relative reactivity value (RRV) of thioglycosides is an indicator for revealing stereoselectivities according to four types of acceptors. Mechanistic studies show that the reaction is dominated by two distinct intermediates: glycosyl triflates and glycosyl halides from N-halosuccinimide (NXS)/TfOH. The formation of glycosyl halide is highly correlated with the production of α-glycoside. These findings enable glycosylation reactions to be foreseen by using RRVs as an α/ß-selectivity indicator and guidelines and rules to be developed for stereocontrolled glycosylation.

Clinical Outcomes of the HIV Protease Inhibitor Nelfinavir With Concurrent Chemoradiotherapy for Unresectable Stage IIIA/IIIB Non-Small Cell Lung Cancer: A Phase 1/2 Trial.

IMPORTANCE: Local failure after chemoradiotherapy (CT-RT) significantly contributes to mortality in patients with locally advanced non-small cell lung cancer (LA-NSCLC). One approach to improve local control is through targeted radiosensitization of the tumor. OBJECTIVE: To evaluate the dose-limiting toxic effects, maximally tolerated dose, and recommended phase 2 dose of the protease inhibitor nelfinavir mesylate, administered concurrently with CT-RT in patients with LA-NSCLC, and, in the phase 2 portion of the study, to estimate the objective response rate, local and distant failure rates, and overall survival. DESIGN, SETTING, AND PARTICIPANTS: This prospective, open-label, single-group, single-institution phase 1/2 trial tested the oral protease inhibitor nelfinavir in combination with concurrent CT-RT in 35 patients aged 18 to 89 years with biopsy-confirmed unresectable stage IIIA/IIIB LA-NSCLC and a minimum Karnofsky performance status from June 29, 2007, to February 22, 2012, with an analysis date of May 9, 2017. Median follow-up for all patients was 6.8 years, with a minimum 5 years of follow-up for all survivors. INTERVENTIONS: Oral nelfinavir mesylate, 625 mg, twice daily or 1250 mg, twice daily was administered for 7 to 14 days before and during concurrent CT-RT. MAIN OUTCOMES AND MEASURES: Graded toxic effects, overall survival, local failure, distant failure, objective response rate, and progression-free survival as measured by Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS: Thirty-five patients (16 women and 19 men; median age, 60 years [range, 39-79 years]) enrolled and met protocol-specified criteria for adherence, with 5 at a dose of 625 mg twice daily and 30 at a dose of 1250 mg twice daily. No dose-limiting toxic effects were observed. No grade 4 or higher nonhematologic toxic effects were observed. Thirty-three of the 35 patients had evaluable posttreatment computed tomographic scans, with an objective response rate of 94% (31 of 33; 95% CI, 86%-100%). The cumulative incidence of local failure was 39% (95% CI, 30.5%-47.5%). Median progression-free survival was 11.7 months (95% CI, 6.2-17.1 months). Median overall survival for all patients was 41.1 months (95% CI, 19.0-63.1 months); the 5-year mean (SE) overall survival rate was 37.1% (8.2%). CONCLUSIONS AND RELEVANCE: This study suggests that nelfinavir administered with concurrent CT-RT is associated with acceptable toxic effects and a promising objective response rate, local failure, progression-free survival, and overall survival in unresectable LA-NSCLC. These data suggest that nelfinavir may enhance the efficacy of standard CT-RT in this disease. Additional testing in the randomized phase 3 setting should be conducted to establish the improvement associated with nelfinavir with concurrent CT-RT. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00589056.

Four-Year Outcomes From a Prospective Phase II Clinical Trial of Moderately Hypofractionated Proton Therapy for Localized Prostate Cancer.

PURPOSE: Moderately hypofractionated radiation therapy represents an effective treatment for localized prostate cancer (PC). Although large randomized trials have reported the efficacy of photon-based hypofractionated therapy, hypofractionated proton therapy (HFPT) has not been extensively studied. This study was performed to determine the clinical and patient-reported outcomes for patients with PC treated with HFPT. METHODS AND MATERIALS: Between 2010 and 2017, 184 men were enrolled on a trial of 70 Gy in 28 fractions of HFPT for low- to intermediate-risk PC. Acute and late toxicity was evaluated using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Patient-reported outcomes were measured by International Prostate Symptom Score, International Index of Erectile Function Questionnaire, and Expanded Prostate Cancer Index Composite scores. RESULTS: Median follow-up was 49.2 months. Enrolled patients had low-risk (n = 18), favorable intermediate-risk (n = 78), and unfavorable intermediate-risk (n = 88) PC. Four-year rates of biochemical-clinical failure-free survival were 93.5% (95% confidence interval, 89%-98%), 94.4% (89%-100%), 92.5% (86%-100%), and 93.8% (88%-100%) in the overall group and the low-risk, favorable intermediate-risk, and unfavorable intermediate-risk cohorts, respectively (log-rank P > .4). The incidence of acute grade 2 or higher gastrointestinal (GI) and urologic toxicities were 3.8% and 12.5%, respectively. The 4-year incidence of late grade 2 or higher urologic and GI toxicity was 7.6% (4%-13%) and 13.6% (9%-20%), respectively. One late grade 3 GI toxicity was reported. All late toxicities were transient. Patient-reported International Prostate Symptom, International Index of Erectile Function, and Expanded Prostate Cancer Index Composite scores had no significant long-term changes after completion of HFPT (Supplementary Table 1, available at https://doi.org/10.1016/j.ijrobp.2019.05.069). CONCLUSIONS: HFPT is associated with low rates of toxicity and does not appear to negatively affect 4-year patient reported urinary and bowel health. Further comparative analyses are warranted to better understand differences between proton and photon HFRT.

Speaker gaze increases information coupling between infant and adult brains.

When infants and adults communicate, they exchange social signals of availability and communicative intention such as eye gaze. Previous research indicates that when communication is successful, close temporal dependencies arise between adult speakers' and listeners' neural activity. However, it is not known whether similar neural contingencies exist within adult-infant dyads. Here, we used dual-electroencephalography to assess whether direct gaze increases neural coupling between adults and infants during screen-based and live interactions. In experiment 1 (n = 17), infants viewed videos of an adult who was singing nursery rhymes with (i) direct gaze (looking forward), (ii) indirect gaze (head and eyes averted by 20°), or (iii) direct-oblique gaze (head averted but eyes orientated forward). In experiment 2 (n = 19), infants viewed the same adult in a live context, singing with direct or indirect gaze. Gaze-related changes in adult-infant neural network connectivity were measured using partial directed coherence. Across both experiments, the adult had a significant (Granger) causal influence on infants' neural activity, which was stronger during direct and direct-oblique gaze relative to indirect gaze. During live interactions, infants also influenced the adult more during direct than indirect gaze. Further, infants vocalized more frequently during live direct gaze, and individual infants who vocalized longer also elicited stronger synchronization from the adult. These results demonstrate that direct gaze strengthens bidirectional adult-infant neural connectivity during communication. Thus, ostensive social signals could act to bring brains into mutual temporal alignment, creating a joint-networked state that is structured to facilitate information transfer during early communication and learning.

Persistence of fimbrial tissue on the ovarian surface after salpingectomy.

BACKGROUND: Salpingectomy is recommended as a risk-reducing strategy for epithelial tubo-ovarian cancer. The gold standard procedure is complete tubal excision. OBJECTIVE: The purpose of this study was to assess the presence of residual fimbrial/tubal tissue on ovarian surfaces after salpingectomy. STUDY DESIGN: Prospective analysis of patients who underwent salpingo-oophorectomy with or without hysterectomy for benign indications, early cervical cancer, or low-risk endometrial cancer at a UK National Health Service Trust. Salpingectomy with or without hysterectomy was performed initially, followed by oophorectomy within the same operation. Separately retrieved tubes and ovaries were sectioned serially and examined completely histologically. The main outcome measure was histologically identified fimbrial/ tubal tissue on ovarian surface. Chi-square/Fisher's exact tests were used to evaluate categoric variables. RESULTS: Twenty-five consecutive cases (mean age, 54.8 ± 5.0 years) that comprised 41 adnexae (unilateral, 9; bilateral, 16) were analyzed. Seventeen (68.0%), 5 (20.0%), and 3 (12.0%) procedures were performed by consultant gynecologists, subspecialty/specialist trainees, and consultant gynecologic oncologists, respectively. Twelve of 25 procedures (48.0%) were laparoscopic, and 13 of 25 procedures (52.0%) involved laparotomy. Four of 25 patients (16.0%; 95% confidence interval, 4.5-36.1%) or 4 of 41 adnexae (9.8%; 95% confidence interval, 2.7-23.1%) showed residual microscopic fimbrial tissue on the ovarian surface. Tubes/ovaries were free of adhesions in 23 cases. Two cases had dense adnexal adhesions, but neither had residual fimbrial tissue on the ovary. Residual fimbrial tissue was not associated significantly with surgical route or experience (consultant, 3/20 [15%]; trainee, 1/5 [20%]; P=1.0). CONCLUSION: Residual fimbrial tissue remains on the ovary after salpingectomy in a significant proportion of cases and could impact the level of risk-reduction that is obtained.