Clinical and Treatment History of Patients with Partial DiGeorge Syndrome and Autoimmune Cytopenia at Multiple Centers.

BACKGROUND: Patients with partial DiGeorge syndrome (pDGS) can present with immune dysregulation, the most common being autoimmune cytopenia (AIC). There is a lack of consensus on the approach to type, combination, and timing of therapies for AIC in pDGS. Recognition of immune dysregulation early in pDGS clinical course may help individualize treatment and prevent adverse outcomes from chronic immune dysregulation. OBJECTIVES: Objectives of this study were to characterize the natural history, immune phenotype, and biomarkers in pDGS with AIC. METHODS: Data on clinical presentation, disease severity, immunological phenotype, treatment selection, and response for patients with pDGS with AIC were collected via retrospective chart review. Flow cytometric analysis was done to assess T and B cell subsets, including biomarkers of immune dysregulation. RESULTS: Twenty-nine patients with the diagnosis of pDGS and AIC were identified from 5 international institutions. Nineteen (62%) patients developed Evan's syndrome (ES) during their clinical course and twenty (69%) had antibody deficiency syndrome. These patients demonstrated expansion in T follicular helper cells, CD19hiCD21lo B cells, and double negative cells and reduction in CD4 naïve T cells and regulatory T cells. First-line treatment for 17/29 (59%) included corticosteroids and/or high-dose immunoglobulin replacement therapy. Other overlapping therapies included eltrombopag, rituximab, and T cell immunomodulators. CONCLUSIONS: AIC in pDGS is often refractory to conventional AIC treatment paradigms. Biomarkers may have utility for correlation with disease state and potentially even response to therapy. Immunomodulating therapies could be initiated early based on early immune phenotyping and biomarkers before the disease develops or significantly worsens.

The impact of active cytomegalovirus infection on donor-derived cell-free DNA testing in heart transplant recipients.

BACKGROUND: Little is known about the relationship between cytomegalovirus (CMV) infections and donor-derived cell-free DNA (dd-cfDNA) in heart transplant recipients. METHODS: In our study, CMV and dd-cfDNA results were prospectively collected on single-organ heart transplant recipients. If the CMV study was positive, a CMV study with dd-cfDNA was repeated 1-3 months later. The primary aim was to compare dd-cfDNA between patients with positive and negative CMV results. RESULTS: Of 44 patients enrolled between August 2022 and April 2023, 12 tested positive for CMV infections, 25 were included as controls, and seven patients with a viral infection without CMV were excluded. Baseline characteristics did not differ significantly between CMV-positive and CMV-negative patients with the exception of a later median time post-transplant in the CMV-positive group (253 days vs. 120 days, p = .03). Dd-cfDNA levels were significantly higher in patients with CMV infections compared to those without (p < .001) with more patients in the CMV positive group showing dd-cfDNA results ≥.12% (75% vs. 8%, p < .001) and ≥.20% (58% vs. 8%, p = .002). Each 1 log10 copy/ml reduction in CMV viral load from visit 1 to visit 2 was associated with a.23% reduction in log10 dd-cfDNA (p = .002). CONCLUSION: Our findings suggest that active CMV infections may raise dd-cfDNA levels in patients following heart transplantation. Larger studies are needed to validate these preliminary findings.

Gender Disparity in Surgical Device Patents: A Five-year Trend From Canada and the United States.

INTRODUCTION: Despite an increasing number of women pursuing careers in science, engineering, and medicine, gender disparities in patents persist. This study sought to analyze trends in inventor's gender for surgical device patents filed and granted in Canada and the United States from 2015 to 2019. METHODS: This study analyzed patents filed and granted by the Canadian Intellectual Property Office (CIPO) in the category of "Diagnosis; Surgery; Identification" and the United States Patent and Trademark Office (USPTO) in the category of "Surgery" from 2015 to 2019. The gender of the patent applicants was determined using a gender algorithm that predicts gender based on first names. Gender matches with names having a probability of less than 95% were excluded. RESULTS: We identified 14,312 inventors on patents filed and 12,737 inventors on patents granted by the CIPO for "Diagnosis; Surgery; Identification". In the USPTO category of "Surgery," we identified 75,890 inventors on patents filed and 44,842 inventors on patents granted. Female inventors accounted for 7%-10% of inventors from 2015 to 2019 for both patents filed and granted. The proportion of female inventors on patents granted was significantly lower than for patents filed for four of the 5 y analyzed for both the USPTO and CIPO. CONCLUSIONS: Female representation in surgical device patenting has stagnated, between 7 and 10%, from 2015 to 2019 in Canada and the United States. This underrepresentation of female inventors in surgical device patenting represents sizable gender disparity.

In-Depth Review of Augmented Reality: Tracking Technologies, Development Tools, AR Displays, Collaborative AR, and Security Concerns.

Augmented reality (AR) has gained enormous popularity and acceptance in the past few years. AR is indeed a combination of different immersive experiences and solutions that serve as integrated components to assemble and accelerate the augmented reality phenomena as a workable and marvelous adaptive solution for many realms. These solutions of AR include tracking as a means for keeping track of the point of reference to make virtual objects visible in a real scene. Similarly, display technologies combine the virtual and real world with the user's eye. Authoring tools provide platforms to develop AR applications by providing access to low-level libraries. The libraries can thereafter interact with the hardware of tracking sensors, cameras, and other technologies. In addition to this, advances in distributed computing and collaborative augmented reality also need stable solutions. The various participants can collaborate in an AR setting. The authors of this research have explored many solutions in this regard and present a comprehensive review to aid in doing research and improving different business transformations. However, during the course of this study, we identified that there is a lack of security solutions in various areas of collaborative AR (CAR), specifically in the area of distributed trust management in CAR. This research study also proposed a trusted CAR architecture with a use-case of tourism that can be used as a model for researchers with an interest in making secure AR-based remote communication sessions.

Does CT scanning after pancreatoduodenectomy reduce readmission rates: an analysis of 900 resections at a high-volume center.

BACKGROUND: Pancreatoduodenectomy (PD) remains associated with significant complication and readmission rates. Infection constitutes a significant proportion of morbidity. We aim to evaluate whether CT scans performed prior to discharge for suspected infection prevents readmission. METHODS: A retrospective review of patients undergoing PD at a tertiary referral center from 2010 to 2018. RESULTS: A total of 982 patients underwent PD: 74% had no clinical infection at the index admission. Of the non-infected patients, 59% exhibited leukocytosis, 27% underwent a CT scan, and 33.6% were readmitted. Of the non-infected patients, 148 (20.3%) experienced major complications, and this was the strongest predictor of readmission (OR: 10.5, [95% CI: 6.5-17], p = 0.0001). In the non-infected patients who had major complications, CT scanning was predictive of lower risk of readmission (OR: 0.38, [95% CI: 0.17-0.83], p = 0.015). Leukocytosis was also found to be predictive of lower risk of readmission (OR: 0.42, [95% CI: 0.18-0.98], p = 0.044). These findings did not hold true for those who had yet to experience major complications on their index admission. CONCLUSION: CT scanning without evidence of infection was associated with reduction of readmission in the cohort with major complications and showed a trend towards preventing readmission in the overall cohort. Development of clinical algorithms to maximize the utility of this test is warranted.

North American urogynecology fellowship programs: value of program website content.

INTRODUCTION AND HYPOTHESIS: Urogynecology fellowship program websites are an important source of information to potential applicants, especially given the ongoing COVID-19 pandemic and resulting travel restrictions. Our study evaluated the publicly available information on American and Canadian urogynecology fellowship websites and present recommendations for website content development to promote the subspecialty of urogynecology. METHODS: Data were collected from all active American and Canadian urogynecology fellowship program websites between May and June 2020 against 72 criteria developed from previously published studies. The criteria included the following sections: Recruitment, Faculty Information, Current Fellows, Research and Education, Surgical Program, Clinical Work, Benefits and Career Planning, Wellness, and Environment. RESULTS: 54 American urogynecology program websites and 11 Canadian urogynecology program websites were analyzed. The mean score of American and Canadian websites was 46.46% (n = 33.45 ± 7.20 out of 72) and 27.40% (n = 19.73 ± 3.77 out of 72), respectively. American program websites scored significantly higher on available information than Canadian websites. The highest prevalence section across American websites was Wellness (64%, n = 1.92 ± 0.85 out of 3 criteria) while the lowest prevalence section was Clinical Work (15.17%, n = 0.91 ± 1.02 out of 6 criteria). Comparatively, Canadian websites scored highest in the Faculty Information section (43.12%, 3.45 ± 2.02) and lowest in the Clinical Work section (6%, n = 0.36 ± 0.67 out of 6 criteria). CONCLUSIONS: American and Canadian websites thoroughly covered the Wellness and Faculty Information sections, respectively. Program websites should consider adding details about Benefits and Career Planning and Clinical Work.

Program Website Evaluation of Canadian Obstetrics and Gynaecology Residency and Fellowship Programs.

OBJECTIVE: The purpose of our study was to assess the comprehensiveness of Canadian obstetrics and gynaecology residency and fellowship program websites to understand the quality of information available to prospective students and make recommendations, if needed. METHODS: All active residency and fellowship program websites (as of May 2020) were evaluated and compared using 72-point criteria in the following domains: Recruitment, Faculty, Current Residents/Fellows, Research and Education, Surgical Procedures, Clinical Work, Benefits and Incentives, Wellness, and Environment. Programs without websites were excluded from the study. Program website information availability was compared by geographic region. RESULTS: Out of the identified 80 residency and fellowship programs, 68.75% (55) were from central Canada, 6.25% (5) from Atlantic Canada, and 25% (20) from western Canada. The mean score for residency websites was 25.4 ± 7.59 (35.6% of criteria complete). The domains with the highest and lowest inclusion rates were Research and Education (46.3% criteria complete) and Current Residents (16.2% criteria complete). The mean score of fellowship websites was 27.9 ± 8.89 (38.8% criteria complete). For fellowship websites, Wellness had the highest inclusion rate (66.0% criteria complete), while Current Fellows had the lowest (13.2% criteria complete). Overall, fellowship websites scored higher than residency websites (27.9 ± 8.89 and 25.4 ± 7.59 out of 72 criteria, respectively). CONCLUSION: Overall, Canadian postgraduate obstetrics and gynaecology program websites include information on many topics relevant to prospective students, such as research, education, and wellness. Programs should provide more information about work hours, call schedules, and current trainees. Lastly, there is an opportunity for programs in western and Atlantic Canada to increase the comprehensiveness of their websites.

Resource recovery toward sustainability through nutrient removal from landfill leachate.

This study investigated the feasibility of integrated ammonium stripping and/or coconut shell waste-based activated carbon (CSWAC) adsorption in treating leachate samples. To valorize unused biomass for water treatment application, the adsorbent originated from coconut shell waste. To enhance its performance for target pollutants, the adsorbent was pretreated with ozone and NaOH. The effects of pH, temperature, and airflow rate on the removal of ammoniacal nitrogen (NH3-N) and refractory pollutants were studied during stripping alone. The removal performances of refractory compounds in this study were compared to those of other treatments previously reported. To contribute new knowledge to the field of study, perspectives on nutrients removal and recovery like phosphorus and nitrogen are presented. It was found that the ammonium stripping and adsorption treatment using the ozonated CSWAC attained an almost complete removal (99%) of NH3-N and 90% of COD with initial NH3-N and COD concentrations of 2500 mg/L and 20,000 mg/L, respectively, at optimized conditions. With the COD of treated effluents higher than 200 mg/L, the combined treatments were not satisfactory enough to remove target refractory compounds. Therefore, further biological processes are required to complete their biodegradation to meet the effluent limit set by environmental legislation. As this work has contributed to resource recovery as the driving force of landfill management, it is important to note the investment and operational expenses, engineering applicability of the technologies, and their environmental concerns and benefits. If properly managed, nutrient recovery from waste streams offers environmental and socio-economic benefits that would improve public health and create jobs for the local community.

Reforming MSWM in Sukunan (Yogjakarta, Indonesia): A case-study of applying a zero-waste approach based on circular economy paradigm.

Over the past years, Indonesia, the world's fourth most populous country, has confronted environmental problems due to uncontrolled generation of municipal solid waste (MSW). While the integrated solid waste management (ISWM) represents a critical strategy for Indonesia to control its production, it is also recognized that economic approaches also need to be promoted to address the waste problem concertedly. In this case study, empirical approaches are developed to understand how a volume-based waste fee could be incorporated into MSW collection services and how to apply a zero-waste approach in Indonesia by adapting resource recovery initiatives, adapted from Germany's mature experiences in integrating the CE paradigm into the latter's MSWM practices. Currently, Sukunan village (Yogyakarta, Indonesia) promotes waste reduction at sources in the framework of community-based solid waste management (CBSWM) by mobilizing the local community for waste separation (organic and non-organic) and waste recycling. As a result, about 0.2 million Mt of CO2-eq emissions was avoided annually from local landfills. The economic benefits of recycling activities by the village's community also resulted in 30% reduction of the waste generated. This CBSWM scheme not only saves the government budget on waste collection, transport and disposal, but also extends the lifetime of local landfills as the final disposal sites. By integrating the CE paradigm into its MSWM practices through the implementation of economic instruments and adherence to the rule of law in the same way as Germany does, Indonesia could make positive changes to its environmental policy and regulation of MSW. A sound MSWM in Indonesia could play important roles in promoting the effectiveness of urban development with resource recovery approaches to facilitate its transition towards a CE nationwide in the long-term.

Mentorship and formal robotic proficiency skills curriculum improve subsequent generations' learning curve for the robotic distal pancreatectomy.

BACKGROUND: Minimally invasive distal pancreatectomy is the accepted standard of care. The robotic distal (RDP) learning curve is 20-40 surgeries with operating time (ORT) as the most significant factor. This study evaluates how formal mentorship and a robotic skills curriculum impact the learning curve for subsequent generation surgeons. METHODS: Consecutive RDP from 2008 to 2017 were evaluated. First Generation was two surgeons who started program without training or mentorship. Second Generation was the two surgeons who joined the program with mentorship. Third Generation was fellows who benefited from both formal training and mentorship. Multivariable models (MVA) were performed for ORT, clinically relevant pancreatic fistula (CR-POPF), and major complications (Clavien≥3). RESULTS: A total of 296 RDP were performed of which 187 did not include other procedures: First Generation (n = 71), Second Generation (n = 50), and Third Generation (n = 66). ORT decreased by generation (p < 0.001) without any differences in CR-POPF or Clavien≥3. On MVA, earlier generation (p = 0.019), pre-operative albumin (p = 0.001) and pancreatic adenocarcinoma (p = 0.019) were predictive of ORT. Increased BMI (p = 0.049) and neoadjuvant therapy (p = 0.046) were predictive of CR-POPF. Fellow participation at the console increased over time. CONCLUSION: Formal mentorship and a skills curriculum decreased the learning curve and complications were largely dependent on patient factors.

Sequential Localizing and Mapping: A Navigation Strategy via Enhanced Subsumption Architecture.

In this paper, we present a navigation strategy exclusively designed for social robots with limited sensors for applications in homes. The overall system integrates a reactive design based on subsumption architecture and a knowledge system with learning capabilities. The component of the system includes several modules, such as doorway detection and room localization via convolutional neural network (CNN), avoiding obstacles via reinforcement learning, passing the doorway via Canny edge's detection, building an abstract map called a Directional Semantic Topological Map (DST-Map) within the knowledge system, and other predefined layers within the subsumption architecture. The individual modules and the overall system are evaluated in a virtual environment using Webots simulator.

A Doorway Detection and Direction (3Ds) System for Social Robots via a Monocular Camera.

In this paper, we propose a novel algorithm to detect a door and its orientation in indoor settings from the view of a social robot equipped with only a monocular camera. The challenge is to achieve this goal with only a 2D image from a monocular camera. The proposed system is designed through the integration of several modules, each of which serves a special purpose. The detection of the door is addressed by training a convolutional neural network (CNN) model on a new dataset for Social Robot Indoor Navigation (SRIN). The direction of the door (from the robot's observation) is achieved by three other modules: Depth module, Pixel-Selection module, and Pixel2Angle module, respectively. We include simulation results and real-time experiments to demonstrate the performance of the algorithm. The outcome of this study could be beneficial in any robotic navigation system for indoor environments.

SLAM in Dynamic Environments: A Deep Learning Approach for Moving Object Tracking Using ML-RANSAC Algorithm.

The important problem of Simultaneous Localization and Mapping (SLAM) in dynamic environments is less studied than the counterpart problem in static settings. In this paper, we present a solution for the feature-based SLAM problem in dynamic environments. We propose an algorithm that integrates SLAM with multi-target tracking (SLAMMTT) using a robust feature-tracking algorithm for dynamic environments. A novel implementation of RANdomSAmple Consensus (RANSAC) method referred to as multilevel-RANSAC (ML-RANSAC) within the Extended Kalman Filter (EKF) framework is applied for multi-target tracking (MTT). We also apply machine learning to detect features from the input data and to distinguish moving from stationary objects. The data stream from LIDAR and vision sensors are fused in real-time to detect objects and depth information. A practical experiment is designed to verify the performance of the algorithm in a dynamic environment. The unique feature of this algorithm is its ability to maintain tracking of features even when the observations are intermittent whereby many reported algorithms fail in such situations. Experimental validation indicates that the algorithm is able to perform consistent estimates in a fast and robust manner suggesting its feasibility for real-time applications.

Psychosocial Stress Exposure Disrupts Mammary Gland Development.

Exposure to psychosocial stressors and ensuing stress physiology have been associated with spontaneous invasive mammary tumors in the Sprague-Dawley rat model of human breast cancer. Mammary gland (MG) development is a time when physiologic and environmental exposures influence breast cancer risk. However, the effect of psychosocial stress exposure on MG development remains unknown. Here, in the first comprehensive longitudinal study of MG development in nulliparous female rats (from puberty through young adulthood; 8-25 wks of age), we quantify the spatial gradient of differentiation within the MG of socially stressed (isolated) and control (grouped) rats. We then demonstrate that social isolation increased stress reactivity to everyday stressors, resulting in downregulation of glucocorticoid receptor (GR) expression in the MG epithelium. Surprisingly, given that chemical carcinogens increase MG cancer risk by preventing normal terminal end bud (TEB) differentiation, chronic isolation stress did not alter TEBs. Instead, isolation blunted MG growth and alveolobular differentiation and reduced epithelial cell proliferation in these structures. Social isolation also enhanced corpora luteal progesterone at all ages but reduced estrogenization only in early adulthood, a pattern that precludes modulated ovarian function as a sufficient mechanism for the effects of isolation on MG development. This longitudinal study of natural variation provides an integrated view of MG development and the importance of increased GR activation in nulliparous ductal growth and alveolobular differentiation. Thus, social isolation and its physiological sequelae disrupt MG growth and differentiation and suggest a contribution of stress exposure during puberty and young adulthood to the previously observed increase in invasive MG cancer observed in chronically socially-isolated adult Sprague-Dawley rats.

Investigation of the Dependence of the Flory-Huggins Interaction Parameter on Temperature and Composition in a Drug-Polymer System.

The Flory-Huggins (F-H) solubility equation has been widely used to describe the solubility of a small-molecule drug in a polymeric carrier and thus determine the design space available for formulating a stable amorphous solid dispersion. The F-H interaction parameter (χ) describes the thermodynamic properties of drug-polymer solutions and accounts for any enthalpic and entropic changes in solubility. Many studies have found that for a limited compositional range, χ varies proportionally to the inverse of the melting temperature of the drug. We explored this relationship using a highly sensitive DSC technique to detect remaining residual crystalline active pharmaceutical ingredients (APIs) following annealing of ball milled mixtures of crystalline itraconazole (ITZ) and either Soluplus or hydroxypropyl methylcellulose phthalate (HPMCP) at temperatures near the estimated solubility curve. Depending on the experimental approach taken, the measurement of drug-polymer solubility can be restricted to mixtures with a high proportion of drug, but in this study, solubility was experimentally determined for mixtures with API content as low as 10 wt %. Results suggest that the proposed linear relationship does not extend to compositions with smaller amounts of API, instead indicating that χ was both temperature- and composition-dependent for the systems studied. The feasibility of this technique to measure interactions in a ternary system containing itraconazole and both polymers was also determined; ITZ-HPMCP exhibited the most favorable values of χ, while ITZ-Soluplus and ITZ-Soluplus-HPMCP demonstrated similar interaction parameters.

Dental Public Health In Action: Barriers to oral healthcare provision for older people in residential and nursing care homes: A mixed method evaluation and strategy development in County Durham, North East England.

This paper presents a case study on the use of mixed methods in research into practice to inform policy. The study was undertaken as part of a review of oral healthcare for older people in residential and nursing care homes in County Durham, North East England. The findings highlighted challenges in the provision of good quality oral healthcare to older people in residential and nursing care homes and informed the county's oral health strategy (Durham County Council DCC, 2016). Key recommendations include the need to develop and implement a minimum set of best practice oral health standards within care home contracts and train care home staff in oral healthcare. The paper relates to two key dental public health competencies: (i) designing and using mixed method studies to address gaps in evidence and triangulating the findings from quantitative and qualitative methods; (ii) the development of evidence based policies. The research is relevant to: care home staff; commissioners in local authority adult and social care; public health practitioners; oral health improvement teams; domiciliary and special care dentists, dental commissioners, researchers and academics.

The TEMPO Trial at 5 Years: Transoral Fundoplication (TIF 2.0) Is Safe, Durable, and Cost-effective.

BACKGROUND: Questions remain about the therapeutic durability of transoral incisionless fundoplication (TIF). In this study, clinical outcomes were evaluated at 5 years post-TIF 2.0. METHODS: A total of 63 chronic gastroesophageal reflux disease (GERD) sufferers with troublesome symptoms refractory to proton pump inhibitor (PPI) therapy, absent or ≤2 cm hiatal hernia, and abnormal esophageal acid exposure were randomized to the TIF group or PPI group. Following the 6-month evaluation, all patients in the PPI group elected for crossover to TIF; therefore, all 63 patients underwent TIF 2.0 with EsophyX2 device. Primary outcome was elimination of daily troublesome regurgitation and atypical symptoms at the 5-year follow-up. Secondary outcomes were improvement in symptom scores, PPI use, reoperations, and patient health satisfaction. The cost-effectiveness of TIF 2.0 was also estimated. RESULTS: Of 63 patients, 60 were available at 1 year, 52 at 3 years, and 44 at 5 years for evaluation. Troublesome regurgitation was eliminated in 88% of patients at 1 year, 90% at 3 years, and 86% at 5 years. Resolution of troublesome atypical symptoms was achieved in 82% of patients at 1 year, 88% at 3 years, and 80% at 5 years. No serious adverse events occurred. There were 3 reoperations by the end of the 5-year follow-up. At the 5-year follow-up, 34% of patients were on daily PPI therapy as compared with 100% of patients at screening. The total GERD Health-related quality-of-life score improved by decreasing from 22.2 to 6.8 at 5 years ( P < .001). CONCLUSION: In this patient population, the TIF 2.0 procedure provided safe and sustained long-term elimination of troublesome GERD symptoms.

Removal of acetaminophen from synthetic wastewater in a fixed-bed column adsorption using low-cost coconut shell waste pretreated with NaOH, HNO3, ozone, and/or chitosan.

Acetaminophen (Ace) is a trace pollutant widely found in sewage treatment plant (STP) wastewater. We test the feasibility of coconut shell waste, a low cost adsorbent from coconut industry, for removing Ace from synthetic solution in a fixed-bed column adsorption. To enhance its performance, the surface of granular activated carbon (GAC) was pre-treated with NaOH, HNO3, ozone, and/or chitosan respectively. The results show that the chemical modification of the GAC's surface with various chemicals has enhanced its Ace removal during the column operations. Among the modified adsorbents, the ozone-treated GAC stands out for the highest Ace adsorption capacity (38.2 mg/g) under the following conditions: 40 mg/L of Ace concentration, 2 mL/min of flow rate, 45 cm of bed depth. Both the Thomas and the Yoon-Nelson models are applicable to simulate the experimental results of the column operations with their adsorption capacities: ozone-treated GAC (20.88 mg/g) > chitosan-coated GAC (16.67 mg/g) > HNO3-treated GAC (11.09 mg/g) > NaOH-treated GAC (7.57 mg/g) > as-received GAC (2.84 mg/g). This suggests that the ozone-treated GAC is promising and suitable for Ace removal in a fixed-bed reactor.