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Objectives To determine whether dental maturity (dental development) was delayed in patients with Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis, compared with a Dutch control group without syndromes. Materials and methods This study included 60 patients (38 patients with Muenke syndrome, 17 patients with Saethre-Chotzen syndrome, and 5 with TCF12-related craniosynostosis), aged 5.8–16.8 years that were treated at the Department of Oral Maxillofacial Surgery, Special Dental Care, and Orthodontics, in Sophia Children’s Hospital, Erasmus University Medical Center, Rotterdam, the Netherlands. Dental age was calculated according to Demirjian’s index of dental maturity. The control group included 451 children without a syndrome. Results Compared with the control group, dental development was delayed by an average of one year in 5- to 8-year-old patients with Muenke syndrome (P = 0.007) and in 8- to 10-year-old patients with Saethre-Chotzen syndrome (P = 0.044), but not in patients with TCF12-related craniosynostosis. Conclusions Our results indicated that dental development was delayed by one year, on average, in patients with Muenke syndrome and Saethre-Chotzen syndrome, compared with a Dutch control group without syndromes. Implications Our findings have improved the understanding of dental development in patients with Muenke and Saethre-Chotzen syndrome. These results can provide guidance on whether the orthodontist needs to consider growth disturbances related to dental development.

Introduction: The effect of pelvic fixation on postoperative medical complications, blood transfusion, length of hospital stay, and discharge disposition is poorly understood. Determining factors that predispose patients to increased complications after spinopelvic fusion will help surgeons to plan these complex procedures and optimize patients preoperatively. Methods: We conducted a retrospective cohort study using data from the ACS-NSQIP database between 2006 and 2016 of patients who underwent lumbar fusion with and without spinopelvic fixation. Data regarding demographics, complications, hospital stay, and discharge disposition were collected. Results: A total of 57,417 (98.5%) cases of lumbar fusion without spinopelvic fixation (LF) and 887 (1.5%) cases of lumbar fusion with spinopelvic fixation (SPF) were analyzed. The transfusion rate in the SPF group was 59.3% vs 13% in the LF group (p < 0.001). The mean length of stay (LOS) and discharge to skilled nursing facility (SNF) were significantly different (LOS: SPF 6.5 days vs LF 3.5 days p < 0.001; SNF: SPF 21.3% vs LF 10.4% p < 0.001). After controlling for demographic differences, the overall complication rates were not significantly different between the groups (p = 0.531). The odds ratio for transfusion in the SPF group was 2.9 (p < 0.001). The odds ratio for increased LOS and increased care discharge disposition were elevated in the SPF group (LOS OR: 1.3, p < 0.012, Discharge disposition OR: 1.8, p < 0.001). Conclusions: Patients who underwent SPF had increased complications, transfusion rate, LOS, and discharge to SNF or subacute rehab facilities as compared with patients who underwent LF. SPF remains an effective technique for achieving lumbosacral arthrodesis. Surgeons should consider the implications of the associated complication profile for SPF and the value of preoperative optimization in a select cohort of patients.

Spinal epidural abscess (SEA) is a rare condition associated with significant morbidity and mortality. Despite advances in diagnostic medicine, early recognition of SEAs remains elusive. The vague presentation of the disease, coupled with its numerous risk factors, the diagnostic requirement for obtaining advanced imaging, and the necessity of specialized care constitute extraordinary challenges to both diagnosis and treatment of SEA. Once diagnosed, SEAs require urgent or emergent medical and/or surgical management. As SEAs are a relatively rare pathology, high-quality data are limited and there is no consensus on their optimal management. This paper focuses on presenting the treatment modalities that have been successful in the management of SEAs and providing a critical assessment of how specific SEA characteristics may render one infection more amenable to primary surgical or medical interventions. This paper reviews the relevant history, epidemiology, clinical presentation, radiology, microbiology, and treatment of SEAs and concludes by addressing the medicolegal implications of delayed treatment of the disease.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a channelopathy which can lead to fatal ventricular arrhythmias. The diagnosis can be challenging due to a wide variety of clinical presentations. In this case, we describe the unusual presentation and subsequent workup of a young patient who was ultimately diagnosed with CPVT., Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a channelopathy which can lead to fatal ventricular arrhythmias. Diagnosis can be challenging due to a wide variety of clinical presentations. In this case, we describe the unusual presentation and subsequent workup of a young patient who was ultimately diagnosed with CPVT.

Tidal power lagoons have the potential to provide a reliable and long-term source of renewable power. The implementation of tidal lagoons will impact the tidal conditions and hydrodynamics of the surrounding coastal system. Impact assessments in the academic literature have generally investigated working proposals from industry of various shapes and sizes. As such, differences between the impacts arising from considered power plants in varying sites are in part influenced by the individual scheme characteristics, potentially masking the influence of site-specific factors. In this study, scheme design consistency is maintained, providing a basis to focus solely on the merits of the selected locations with regards to any associated impacts. The simulated tidal power lagoons are located in the Bristol Channel and Irish Sea, two distinct but tidally connected regions on the British coastline with contrasting marine environment characteristics. Results indicate that the more constrained geometry of the Bristol Channel contributes to higher individual and cumulative impacts than potential developments in the Irish Sea. This is in part facilitated by the higher degree of blockage introduced by tidal lagoon developments in the Bristol Channel. Furthermore, far-field impacts are found to be less pronounced compared to predictions reported in tidal barrage modelling studies.

This paper concerns the design and rigorous in silico evaluation of a closed-loop hemorrhage resuscitation algorithm with blood pressure (BP) as controlled variable. A lumped-parameter control design model relating volume resuscitation input to blood volume (BV) and BP responses was developed and experimentally validated. Then, three alternative adaptive control algorithms were developed using the control design model: (i) model reference adaptive control (MRAC) with BP feedback, (ii) composite adaptive control (CAC) with BP feedback, and (iii) CAC with BV and BP feedback. To the best of our knowledge, this is the first work to demonstrate model-based control design for hemorrhage resuscitation with readily available BP as feedback. The efficacy of these closed-loop control algorithms was comparatively evaluated as well as compared with an empiric expert knowledge-based algorithm based on 100 realistic virtual patients created using a well-established physiological model of cardiovascular (CV) hemodynamics. The in silico evaluation results suggested that the adaptive control algorithms outperformed the knowledge-based algorithm in terms of both accuracy and robustness in BP set point tracking: the average median performance error (MDPE) and median absolute performance error (MDAPE) were significantly smaller by >99% and >91%, and as well, their interindividual variability was significantly smaller by >88% and >94%. Pending in vivo evaluation, model-based control design may advance the medical autonomy in closed-loop hemorrhage resuscitation.

Introduction/Background* Recently 3 Phase III first-line studies, PAOLA-1/ENGOT-ov25 (Ray-Coquard et al. NEJM 2019). PRIMA/ENGOT-ov26/GOG-3012 (Gonzales Martin et al. NEJM 2019) and VELIA/GOG-3005 (Coleman et al. NEJM 2019) have demonstrated that the addition of a PARP inhibitor (PARPi) to platinum-based therapy+/-bevacizumab improved progression-free survival (PFS) in advanced ovarian cancer (AOC) patients. The benefit was greater when the tumor was homologous recombination deficient (HRD) according to Myriad myChoice test, independently of BRCA status. The PAOLA-1 olaparib+bevacizumab maintenance regimen was approved in USA/Europe/Japan for HRD positive patients. The European initiative aims at evaluating various HRD tests on PAOLA-1 tumor samples to identify new reliable and feasible HRD tests Methodology The HRD initiative has 2 components; one based on artificial intelligence with various partners and the other, the European HRD ENGOT initiative (EHEI), is led by academic research laboratories (RL) from ENGOT groups. The HRD test evaluation protocol for the EHEI RL includes 3 phases. The phase 1 (2019/12) brought together European RL. Because non-BRCA Homologous Recombination Repair (HRR) mutations have not been found predictive of PARPi activity in PAOLA-1 (Pujade-Lauraine et al, SGO 2021)) RL tests based on these mutations were not selected for the next phases. Phase 2 evaluated the correlation between RL tests and the Myriad myChoice test on tumor samples from 85 PAOLA-1 BRCA wild type patients using the KAPPA statistics. Phase 3 is the final PFS evaluation on more than 350 additional patient samples. Result(s)* A total of 20 RL from 21 ENGOT groups participated to the EHEI phase 1. Half of them had a test mainly based on an HRR gene panel. Three RL did not pursue for various reasons (capacity, financial or regulatory). The remaining 7 RL from 6 countries (table 1) completed the phase 2 in May 2021 and may proceed to phase 3. Conclusion* The EHEI is a unique collaboration of European academic laboratories involved in gynecologic oncology translational research with the aim of providing a reliable biomarker (HRD) for selecting AOC patients who could benefit most from PARPi+/-bevacizumab in first-line therapy. HRD tests performance will be described after their phase 3 is completed.

Objective: To evaluate the effectiveness of the WhiteTeeth mobile app, a theory-based mobile health (mHealth) program for promoting oral hygiene in adolescent orthodontic patients. Methods: In this parallel randomized controlled trial, the data of 132 adolescents were collected during three orthodontic check-ups: at baseline (T0), at 6-week follow-up (T1) and at 12-week follow-up (T2). The intervention group was given access to the WhiteTeeth app in addition to usual care (n = 67). The control group received usual care only (n = 65). The oral hygiene outcomes were the presence and the amount of dental plaque (Al-Anezi and Harradine plaque index), and the total number of sites with gingival bleeding (Bleeding on Marginal Probing Index). Oral health behaviour and its psychosocial factors were measured through a digital questionnaire. We performed linear mixed-model analyses to determine the intervention effects. Results: At 6-week follow-up, the intervention led to a significant decrease in gingival bleeding (B = −3.74; 95% CI −6.84 to −0.65) and an increase in the use of fluoride mouth rinse (B = 1.93; 95% CI 0.36 to 3.50). At 12-week follow-up, dental plaque accumulation (B = −11.32; 95% CI −20.57 to −2.07) and the number of sites covered with plaque (B = −6.77; 95% CI −11.67 to −1.87) had been reduced significantly more in the intervention group than in the control group. Conclusions: The results show that adolescents with fixed orthodontic appliances can be helped to improve their oral hygiene when usual care is combined with a mobile app that provides oral health education and automatic coaching. Netherlands Trial Registry Identifier: NTR6206: 20 February 2017.

Introduction ‘Fluid creep’ or excessive fluid delivered to burn patients during early resuscitation has been suggested by several studies from individual burn centers. Methods We performed a Medline search from 1980 to 2015 in order to identify studies of burn patients predominantly resuscitated with lactated Ringers with infusion adjusted per urinary output. Data was abstracted for 48 publications (3196 patients) that met entry criteria. Results Higher resuscitation volumes compared to Parkland estimates were reported, but the trend of increasing resuscitation volumes over the last 30 years is not supported by regression of total fluid infused versus year of study. Mean 24 h fluid infused for all studies was 5.2 ± 1.1 mL/kg per %TBSA. The mean 24 h urinary output reported in 30 studies was 1.2 ± 0.5 mL/kg per hr. Burns with inhalation injuries (5 studies) received significantly more fluid than non-inhalation injured burn patients (5.0 ± 1.3 versus 3.9 ± 0.9 mL/kg per %TBSA). Fluid infused and urinary outputs were similar for adults and pediatric patients. The most striking finding of our analyses was the great ranges of the means and high standard deviations of volumes infused compared to the original Baxter publication that introduced the Parkland formula Conclusions These analyses suggest that burn units currently administer volumes larger than Parkland formula with great patient variability. Individual patient hourly data is needed to better understand the record of burn resuscitation and Fluid Creep.

Objective: Individual physiological experiments typically provide useful but incomplete information about a studied physiological process. As a result, inferring the unknown parameters of a physiological model from experimental data is often challenging. The objective of this paper is to propose and illustrate the efficacy of a collective variational inference (C-VI) method, intended to reconcile low-information and heterogeneous data from a collection of experiments to produce robust personalized and generative physiological models. Methods: To derive the C-VI method, we utilize a probabilistic graphical model to impose structure on the available physiological data, and algorithmically characterize the graphical model using variational Bayesian inference techniques. To illustrate the efficacy of the C-VI method, we apply it to a case study on the mathematical modeling of hemorrhage resuscitation. Results: In the context of hemorrhage resuscitation modeling, the C-VI method could reconcile heterogeneous combinations of hematocrit, cardiac output, and blood pressure data across multiple experiments to obtain (i) robust personalized models along with associated measures of uncertainty and signal quality, and (ii) a generative model capable of reproducing the physiological behavior of the population. Conclusion: The C-VI method facilitates the personalized and generative modeling of physiological processes in the presence of low-information and heterogeneous data. Significance: The resulting models provide a solid basis for the development and testing of interpretable physiological monitoring, decision-support, and closed-loop control algorithms.

Existing burn resuscitation protocols exhibit large variability in treatment efficacy. Hence, they must be further optimized based on comprehensive knowledge of burn pathophysiology. A physics-based mathematical model that can replicate physiological responses in diverse burn patients can serve as an attractive basis to perform non-clinical testing of burn resuscitation protocols and to expand knowledge on burn pathophysiology. We intend to develop, optimize, validate, and analyze a mathematical model to replicate physiological responses in burn patients. Using clinical datasets collected from 233 burn patients receiving burn resuscitation, we developed and validated a mathematical model applicable to computer-aided in-human burn resuscitation trial and knowledge expansion. Using the validated mathematical model, we examined possible physiological mechanisms responsible for the cohort-dependent differences in burn pathophysiology between younger versus older patients, female versus male patients, and patients with versus without inhalational injury. We demonstrated that the mathematical model could replicate physiological responses in burn patients associated with wide demographic characteristics and injury severity and that an increased inflammatory response to injury may be a key contributing factor in increasing the mortality risk of older patients and patients with inhalation injury via an increase in the fluid retention. The mathematical model may provide an attractive platform to conduct non-clinical testing of burn resuscitation protocols and test new hypotheses on burn pathophysiology., 24 pages The final version of this paper has been accepted for publication in the IEEE Journal of Transactions on Biomedical Engineering (2021) and is available for early access at https://ieeexplore.ieee.org/document/9478222

This paper presents a mathematical model of blood volume kinetics and renal function in response to burn injury and resuscitation, which is applicable to the development and non-clinical testing of burn resuscitation protocols and algorithms. Prior mathematical models of burn injury and resuscitation are not ideally suited to such applications due to their limited credibility in predicting blood volume and urinary output observed in wide-ranging burn patients as well as in incorporating contemporary knowledge of burn pathophysiology. Our mathematical model consists of an established multi-compartmental model of blood volume kinetics, a hybrid mechanistic-phenomenological model of renal function, and novel lumped-parameter models of burn-induced perturbations in volume kinetics and renal function equipped with contemporary knowledge on burn-related physiology and pathophysiology. Using the dataset collected from 16 sheep, we showed that our mathematical model can be characterized with physiologically plausible parameter values to accurately predict blood volume kinetic and renal function responses to burn injury and resuscitation on an individual basis against a wide range of pathophysiological variability. Pending validation in humans, our mathematical model may serve as an effective basis for an in-depth understanding of complex burn-induced volume kinetic and renal function responses as well as development and non-clinical testing of burn resuscitation protocols and algorithms. Keywords: Mathematical Model, Burn Injury, Burn Resuscitation, Non-Clinical Testing, Burn Resuscitation Protocols, and Algorithms, Comment: Published in the Journal of Burns 24 Pages

Objectives The objective of this study was to compare maxillary dimensions and growth in newborns with Complete Unilateral Cleft Lip and Palate (UCLP) to healthy newborns before and after cheiloplasty. Additionally, a palatal growth curve is constructed to give more information about the natural growth before surgical intervention. Methods Twenty-eight newborns with complete UCLP were enrolled in this study. Multiple plaster-casts of each child during their first year were collected and grouped in before and after cheiloplasty. A previous developed semi-automatic segmentation tool was used to assess the maxillary dimensions and were compared to a healthy control group. Z-scores were calculated to indicate differences between the two populations and if cheiloplasty had influence on maxillary growth. Furthermore, the prediction model created in a previous study was used to indicate differences between predictions and the outcome in UCLP measurements. The analysis was tested for inter- and intra-observer variability. Results Results show differences in alveolar and palatal shape in UCLP patients in comparison with healthy controls. Prior to cheiloplasty an increased width and alveolar length was observed while the palatal depth was decreased. After cheiloplasty the widths moved towards normal but were still significantly larger. Conclusion Infants with unilateral cleft lip and palate show a wider maxillary arch in comparison with the control population. Initial treatment has most influence on the width of the arch, which decreased towards normal.

The aim of this study was to develop an accurate and intuitive semi-automatic segmentation technique to calculate an average maxillary arch and palatal growth profile for healthy newborns in their first year of life. Seventy babies born between 1985 and 1988 were included in this study. Each child had five impressions made in the first year after birth that were digitalized. A semi-automatic segmentation tool was developed and used to assess the maxillary dimensions. Finally, random effect models were built to describe the growth and build a simulation population of 10,000 newborns. The segmentation was tested for inter- and intra-observer variability. The Pearson correlation coefficient for each of the variables was between 0.94 and 1.00, indicating high inter-observer agreement. The paired sample t test showed that, except for the tuberosity distance, there were small, but significant differences in the landmark placements between observers. Intra-observer repeatability was high, with Pearson correlation coefficients ranging from 0.87 to 1.00 for all measurements, and the mean differences were not significant. A third or second degree growth curve could be successfully made for each parameter. These findings indicated this method could be used for objective clinical evaluation of maxillary growth. The resulting growth models can be used for growth studies in healthy newborns and for growth and treatment outcome studies in children with cleft lip and palate or other craniofacial anomalies.

In this paper we describe a data set of multivariate physiological measurements recorded from conscious sheep (N = 8; 37.4 ± 1.1 kg) during hemorrhage. Hemorrhage was experimentally induced in each animal by withdrawing blood from a femoral artery at two different rates (fast: 1.25 mL/kg/min; and slow: 0.25 mL/kg/min). Data, including physiological waveforms and continuous/intermittent measurements, were transformed to digital file formats (European Data Format [EDF] for waveforms and Comma-Separated Values [CSV] for continuous and intermittent measurements) as a comprehensive data set and stored and publicly shared here (Appendix A). The data set comprises experimental information (e.g., hemorrhage rate, animal weight, event times), physiological waveforms (arterial and central venous blood pressure, electrocardiogram), time-series records of non-invasive physiological measurements (SpO2, tissue oximetry), intermittent arterial and venous blood gas analyses (e.g., hemoglobin, lactate, SaO2, SvO2) and intermittent thermodilution cardiac output measurements. A detailed explanation of the hemodynamic and pulmonary changes during hemorrhage is available in a previous publication (Scully et al., 2016) [1] .

Intra-atrial reentrant tachycardia (IART) is a common sequela in the congenital heart disease (CHD) population, and it significantly increases morbidity and mortality. Atrial antitachycardia devices (ATDs) capable of atrial antitachycardia pacing (ATP) therapy have been used to manage IART in the CHD population, but there are limited data on their safety and efficacy.To determine whether ATD implantation was associated with reduced direct current (DC) cardioversions and to compare ATP success between different CHD diagnoses and ATP programs.A single-center retrospective chart review was performed on CHD patients with ATDs. Demographic data were collected in addition to the number of DC cardioversions required before and after ATD implantation; data on ATP efficacy and the specific ATP program utilized; and adverse events related to ATD implantation or subsequent ATP treatments.ATD implantation in 91 CHD patients was associated with a significant reduction in DC cardioversions (P.01). Overall, 72% of IART episodes were successfully terminated by ATP. Patients with levo-transposition of the great arteries experienced lower rates of ATP success than the remainder of the cohort (P.01). There was no evidence of degeneration to ventricular arrhythmia or death directly attributed to ATP.ATD implantation was associated with reduced DC cardioversion burden. Patients with levo-transposition of the great arteries may experience lower ATP efficacy than patients with other CHDs; however, a larger patient population is required to better determine subgroup efficacy. These results support the safety and efficacy of ATP in the CHD population.

Closed-loop automation of critical care therapy has the potential to reduce the workload of clinical personnel while maintaining the quality of care. In the real-world clinical arena, critically ill patients receive multiple medical treatments. However, existing body of work has predominantly focused on closed-loop automation of isolated individual treatments. How these individual treatment loops interact with each other has not been investigated. The goal of this work is to garner insights on the safety of critical care therapy and potential deleterious conflicts therein when multiple isolated and individually closed-loop controlled medical treatments act upon a patient, using a case study of hemorrhage resuscitation and intravenous propofol sedation. For this purpose, a physiological model of a critically ill patient was developed and experimentally validated to describe the collective cardiovascular and pharmacological effects of these treatments. Then, isolated and individually closed-loop controlled hemorrhage resuscitation and intravenous propofol sedation treatments were simultaneously applied to the physiological model and their interactive behavior was investigated. The results showed that (i) the influence of one treatment on the other must be taken into account in selecting treatment set point to maintain the safety of overall therapy, and that (ii) information sharing between control loops may enhance the efficacy and robustness of individual treatment loops. In sum, it was concluded that hemorrhage resuscitation and intravenous propofol sedation treatments may benefit from coordination both at the set point and the loop levels. The conclusion may generalize to a wide spectrum of multiple closed-loop controlled medical treatments.

Among the congenital heart disease (CHD) population, intra-atrial reentrant tachycardia (IART) is a common sequela resulting from anatomical anomalies and surgical scars that significantly increases morbidity and mortality. Atrial antitachycardia pacing (ATP) delivered by atrial antitachycardia devices (ATDs) has been used to treat IART in the CHD population. However, there remains limited data on the safety and efficacy of ATP, as well as on comparisons of its effects amongst different CHD subtypes. The purpose of the current study is to describe the clinical history and ATP efficacy in three patients with unique forms of complex CHD. During this study, a single-center review of three patients with ATDs was performed. One patient with each of the following CHD anomalies was selected for inclusion: systemic left ventricle, systemic right ventricle, and single ventricle. Data collected included ATP success rates, medications in use, direct current (DC) cardioversions, and any complications related to the ATDs. Study findings revealed the patient with a systemic left ventricle had an ATD implanted for approximately 9.5 years, with 695 of 956 (73%) episodes successfully converted. Unsuccessfully treated episodes were generally asymptomatic and self-terminating in this patient. The patient with a systemic right ventricle had an ATD implanted for approximately 16 years, with 333 of 348 (96%) episodes being successfully converted. The patient with a single ventricle had an ATD implanted for approximately 12.5 years, with 404 of 416 (97%) episodes successfully converted. The patients with biventricular physiology were able to forgo DC cardioversion after receiving their ATDs. However, due to medical noncompliance as well as multiple episodes of IART, which presented with 1:1 conduction or low rates, the single-ventricle patient still required DC cardioversions post-ATD implantation. In conclusion, this study’s findings demonstrate that, while ATP can be effective in a wide variety of CHDs, experiences can vary based on individual arrhythmia substrates, cardiac anatomy, and medical compliance. Additionally, challenges remain in IART detection in patients with especially complex CHD anatomies.

Our reaction on the letter of Yosiko Myoken et al.(2020): Yosiko Myoken et al. commented on our article about the effect of using a mobile application ("WhiteTeeth") on improving oral hygiene 2 . Although they commended our article, they raised some questions that we would like to respond to. First, Myoken et al. believed that we should have evaluated the effectiveness of our intervention over a longer study period of at least six months to obtain accurate results.

To determine the effectiveness of colonic fluid absorption as a route for fluid resuscitation of a major burn. In order to assess the feasibility and performance of colonic resuscitation, the authors compared plasma volume expansion and hemodynamic parameters of animals submitted to colonic or intravenous fluid resuscitation. Twelve anesthetized swine were submitted to a 40% full thickness flame burn. Thirty minutes later fluid resuscitation was initiated with either intravenous or colonic infusion of crystalloid based on the Parkland formula. This treatment lasted 4.5 hours. The volume of fluid infused was 86 ± 18 ml/kg for the intravenous treatment and 89 ± 14 ml/kg for the colonic treatment. The percentage of fluid absorbed by the colon at the end of the protocol was 30 ± 13% of the infused fluid. Enteral resuscitation was equally effective in expanding plasma volume at the end of the protocol. Laboratorial and hemodynamic parameters were similar between the two resuscitation strategies throughout the study. Urine output was significantly higher in the intravenous group (7.9 ± 4.2 ml/kg/hr vs 0.9 ± 0.3 ml/kg/hr, P = .03). This study demonstrates that colonic infusion of normal saline in a severe burn injury model can restore hemodynamic stability and expand plasma volume to a degree that rivals the effect of direct intravenous infusion for early burn resuscitation in a swine model.

Vasopressors provide a rapid and effective approach to correct hypotension in the perioperative setting. Our group developed a closed-loop control (CLC) system that titrates phenylephrine (PHP) based on the mean arterial pressure (MAP) during general anesthesia. As a means of evaluating system competence, we compared the performance of the automated CLC with physicians. We hypothesized that our CLC algorithm more effectively maintains blood pressure at a specified target with less blood pressure variability and reduces the dose of PHP required. In a crossover study design, 6 swine under general anesthesia were subjected to a normovolemic hypotensive challenge induced by sodium nitroprusside. The physicians (MD) manually changed the PHP infusion rate, and the CLC system performed this task autonomously, adjusted every 3 seconds to achieve a predetermined MAP. The CLC maintained MAP within 5 mm Hg of the target for (mean ± standard deviation) 93.5% ± 3.9% of the time versus 72.4% ± 26.8% for the MD treatment (P = .054). The mean (standard deviation) percentage of time that the CLC and MD interventions were above target range was 2.1% ± 3.3% and 25.8% ± 27.4% (P = .06), respectively. Control statistics, performance error, median performance error, and median absolute performance error were not different between CLC and MD interventions. PHP infusion rate adjustments by the physician were performed 12 to 80 times in individual studies over a 60-minute period. The total dose of PHP used was not different between the 2 interventions. The CLC system performed as well as an anesthesiologist totally focused on MAP control by infusing PHP. Computerized CLC infusion of PHP provided tight blood pressure control under conditions of experimental vasodilation.

Introduction This review was designed to make recommendations on future educational needs, principles of curricular development, and how the International Society for Sexual Medicine (ISSM) should address the need to enhance and promote human sexuality education around the world. Aim To explore the ways in which graduate and postgraduate medical education in human sexuality has evolved and is currently delivered. Methods We reviewed existing literature concerning sexuality education, curriculum development, learning strategies, educational formats, evaluation of programs, evaluation of students, and faculty development. We reviewed literature relating to four main areas: (i) the current status of the international regulation of training in sexual medicine; (ii) the current delivery of education and training in sexual medicine; (iii) resident and postgraduate education in sexual medicine surgery; and (iv) education and training for allied health professionals. Results The main findings in these four areas are as follows. Sexual medicine has grown considerably as a specialty during the past 20 years, with many drivers being identified. However, the regulatory aspects of training, assessment, and certification are currently in the early stages of development and are in many ways lagging behind the scientific and clinical knowledge in the field. However, there are examples of the development of curricula with accompanying assessments that have attempted to set standards of education and training that might underlie the delivery of high-quality care to patients in sexual medicine. The development of competence assessment has been applied to surgical training in sexual medicine, and there is increasing interest in simulation as a means of enhancing technical skills training. Although the focus of curriculum development has largely been the medical profession, there is early interest in the development of standards for training and education of allied health professionals. Conclusion Organizations of professionals in sexual health, such as the ISSM, have an opportunity, and indeed a responsibility, to provide and disseminate learning opportunities, curricula, and standards of training for doctors and allied health professionals in sexual medicine.

Single-basin tidal range power plants have the advantage of predictable energy outputs, but feature non-generation periods in every tidal cycle. Linked-basin tidal power systems can reduce this variability and consistently generate power. However, as a concept the latter are under-studied with limited information on their performance relative to single-basin designs. In addressing this, we outline the basic principles of linked-basin power plant operation and report results from their numerical simulation. Tidal range energy operational models are applied to gauge their capabilities relative to conventional, single-basin tidal power plants. A coastal ocean model (Thetis) is then refined with linked-basin modelling capabilities. Simulations demonstrate that linked-basin systems can reduce non-generation periods at the expense of the extractable energy output relative to conventional tidal lagoons and barrages. As an example, a hypothetical case is considered for a site in the Severn Estuary, UK. The linked-basin system is seen to generate energy 80–100% of the time over a spring-neap cycle, but harnesses at best ≈ 30% of the energy of an equivalent-area single-basin design.

Purpose of Review Probiotics are promising remedial treatments for symptoms of small intestine (SI) diseases and promoters of overall good health. Probiotics play an important role in supporting a healthy SI microbiome (eubiosis), and in preventing establishment of unhealthy microbiota. SI eubiosis promotes optimal nutrient uptake, and optimal nutritional status maintains a healthy SI, reducing the likelihood of SI diseases. It is important to understand the advantages and limitations of probiotic therapies. Recent Findings Microbial dysbiosis decreases the capacity of the small bowel to utilize and absorb dietary compounds. In some studies, probiotic supplements containing lactic acid bacteria and Bifidobacterium have been demonstrated effective in supporting beneficial microbes in the SI while improving barrier integrity and reducing nutrient malabsorption and SI disease-related pathology. Summary Strain-specific probiotic therapy may be a natural and effective approach to restoring SI barrier integrity and eubiosis, resulting in improved nutrient absorption and better health, including reducing the incidence of and severity of SI diseases.

Dissatisfaction with current methods of burn resuscitation exclusively using Lactated Ringer’s and physician-directed adjustments in hourly fluid infusions are based on a record of excessive total fluid volume infused and complications of fluid overload. Alternative approaches to current standard of care include early use of albumin, supplements of high dose vitamin C and nurse-driven, protocolized care. However, electronic urinary output monitors and computerized decision support technologies are emerging. The efficacy of these approaches of different fluids and computerized solutions remains to be proven with current multicenter trials.

There is a scarcity of literature exploring the consequences of Failure To Extubate (FTE) and Delayed Reintubation (DRI) in spine surgery. While it is reasonable to believe that patients who FTE or undergo DRI after Posterior Lumbar Fusion (PLF) and Transforaminal Lumbar Interbody Fusion (TLIF) are at risk for graver outcomes, there is minimal data to explicitly support that. The goal of this study was to investigate the morbidity and mortality associated with FTE and DRI after lumbar spine surgery in a large pool of patients.We conducted a retrospective multicenter study of patients that underwent elective posterior lumbar fusion (PLF) and transforaminal lumbar interbody fusion (TLIF) using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2006 to 2016. We excluded patients with disseminated cancer, metastatic disease to the neural axis, patient with spinal epidural abscess, and patients with ventilator dependency prior to the operation.57,677 patients from 2006 to 2016 were identified; 55 patients (0.1 %) had FTE and 262 patients (0.46 %) had DRI. The incidence of pneumonia was 27.2-fold greater in the FTE group and septic shock was 63.5-fold greater. All complications listed below are significance to p 0.001. Deep vein thrombosis, pulmonary embolism, myocardial infarction and cardiac arrest were respectively, 10.4-, 12.2-, 22.8-, and 45.5- fold greater in the FTE group. Overall complication rate differed significantly between the two groups and were 9.8-fold greater in the FTE group. FTE was associated with increased, length of stay and all complications except DVT and pulmonary embolism. FTE was profoundly associated with severe complications (OR 13.0, 95 % CI 7.2-23.5) and mortality (OR = 21.5, CI = 7.5-61.0). The DRI group had a significantly higher morbidity (OR = 71.0, CI = 44.1-114.4), including overall complication (OR = 21.2, CI = 16.0-28.0) and severe complications (OR = 34.4, CI = 26.1-45.3). The DRI group had significantly higher rates of pneumonia (OR = 37.0), DVT (OR = 9.6) and pulmonary embolism (OR = 7.0), septic shock (OR = 60.5), myocardial infarction (OR = 32.1,) and cardiac arrest (OR = 236.4).FTE and DRI were highly predictive of morbidity and mortality. Overall, investigations of the effects of FTE and DRI following spine procedures are lacking. This large multi-center national database review is one of the first to provide insight into the consequences of FTE and DRI in lumbar fusion cases. Future investigation into the consequences and predictors of FTE and DRI in spine surgery are required.

In the drive towards a carbon-free society, tidal energy has the potential to become a valuable part of the UK energy supply. Developments are subject to intense scrutiny, and potential environmental impacts must be assessed. Unfortunately many of these impacts are still poorly understood, including the implications that come with altering the hydrodynamics. Here, methods are proposed to quantify ecological impact and to incorporate its minimisation into the array design process. Four tidal developments in the Pentland Firth are modelled with the array optimisation tool OpenTidalFarm, that designs arrays to generate the maximum possible profit. Maximum entropy modelling is used to create habitat suitability maps for species that respond to changes in bed-shear stress. Changes in habitat suitability caused by an altered tidal regime are assessed. OpenTidalFarm is adapted to simultaneously optimise array design to maximise both this habitat suitability and to maximise the profit of the array. The problem is thus posed as a multi-objective optimisation problem, and a set of Pareto solutions found, allowing trade-offs between these two objectives to be identified. The methods proposed generate array designs that have reduced negative impact, or even positive impact, on the habitat suitability of specific species or habitats of interest.

An 11-year-old girl presented at an orthodontist asking for the correction of the crooked position of her upper and lower front teeth. In addition, the patient was concerned about the abnormal shape and size of tooth 21. There was a disto-occlusion, crowding and tooth gemination of tooth 21 with the shape of a dens invaginatus. The tooth, moreover, was infected. Teeth 21 and 14 were extracted as part of the treatment. By means of a guided transposition, tooth 23 was brought to the extraction site of tooth 21. Treatment was performed with hybrid fixed appliance techniques.Een 11-jarig meisje meldde zich bij een orthodontist met het verzoek de scheefstand van haar boven- en onderfront te corrigeren. Daarnaast stoorde de patiënt zich aan de afwijkende vorm en grootte van gebitselement 21. Er was sprake van een disto-occlusie, ruimtegebrek, geminatio dentis van gebitselement 21 met de vorm van een dens invaginatus. Het gebitselement was bovendien ontstoken. Gebitselementen 21 en 14 werden in het kader van de behandeling geëxtraheerd. Op plek van het verwijderde gebitselement 21 werd gebitselement 23 gebracht door middel van geforceerde transpositie. Er is gebruikgemaakt van hybride orthodontische technieken.

As the tidal energy industry moves from demonstrator arrays comprising just a few turbines to large-scale arrays made up of potentially hundreds of turbines, there is a need to optimise both the number of turbines and their spatial distribution in order to minimise cost of energy. Optimising array design manually may be feasible for small arrays, but becomes an impractically large approach when the number of devices is high, especially if taking into account both the cost effectiveness of each turbine and also the coupled nature of the turbine locations and the local as well as far-field hydrodynamics. Previous work has largely focused on producing computational tools to automatically design the size and layout of large-scale tidal turbine arrays to optimise power. There has been some limited preliminary work to incorporate costs into these models, in order to improve the economic viability of tidal arrays. This paper provides the first in depth implementation and analysis of economic functionals, based upon metrics such as break even power and levelised cost of energy, used for design of explicit array sizing and spatial variation. The addition of these new economic functionals introduces complexity by increasing the number of inputs to the model, each of which are subject to their own uncertainty in value. For this reason, sensitivity analysis becomes both more important as well as more difficult to undertake. This paper presents a novel rapid methodology for deriving the optimal array design (number of turbines and their spatial distribution throughout the farm area) to minimise cost functionals, and its sensitivity to variations in the economic inputs. Importantly, the new aspects of this method introduced here do not rely on repeated model runs and iterative optimisation, two aspects that typically prove to be impractically expensive computationally. This more readily allows for the impact of changes in investor priorities to be investigated. It is also shown that, while the optimal solution varies greatly with uncertainty in the input parameters, this uncertainty is reduced significantly through Monte Carlo analysis.

Introduction Patients supported with left ventricular assist devices (LVADs) are burdened by frequent hemocompatibility-related adverse events related to patient-pump interactions. These predominantly vascular events include stroke, gastrointestinal bleeding, and pump thrombosis. Our center performs routine, invasive hemodynamic ramp speed titrations in LVAD patients to determine the optimal rotational speed after implantation. We sought to interrogate changes in vascular hemodynamics during an exercise ramp study to understand the influence of pump speed and exercise on outflow graft and cerebrovascular flow. Case Report A 71-year-old male patient supported by Heartware HVAD operating at a baseline speed of 2700 RPM presented for LVAD ramp and exercise study with vascular imaging. A right heart catheterization, echocardiography with Doppler imaging of the patient's LVAD outflow graft, and vascular Doppler of the left common carotid artery and middle cerebral artery were performed. The patient's LVAD operating speed was reduced to 2400 RPM and then increased stepwise to a maximum speed of 3000 RPM. At each increment of operating speed, Doppler imaging was attempted and right heart catheterization was repeated. After reviewing data from the ramp study, the patient's operating speed was set to 2900 RPM and then a staged exercise protocol with bicycle ergometer was performed. Pertinent findings of vascular imaging include a blunting of peak systolic to end-diastolic velocity ratio in vascular beds with incremental speed increase and partial recovery of pulsatility with exercise (Figure). Summary This case demonstrates the influence LVAD speed adjustment and exercise have on carotid artery and outflow graft pulsatility. With exercise the outflow graft and carotid artery peak systolic and end-diastolic velocities were similar to those at the lowest LVAD pump speed, suggesting that intrinsic contractility and native LV unloading was restored with exercise despite a higher pump speed.

The Special Interest Groups of the American Burn Association provide a forum for interested members of the multidisciplinary burn team to congregate and discuss matters of mutual interest. At the 47th Annual Meeting of the American Burn Association in Chicago, IL, the Fluid Resuscitation Special Interest Group sponsored a special symposium on burn resuscitation. The purpose of the symposium was to review the history, current status, and future direction of fluid resuscitation of patients with burn shock. The reader will note several themes running through the following presentations. One is the perennial question of the proper role for albumin or other fluid-sparing strategies. Another is the unique characteristics of the pediatric burn patient. A third is the need for multicenter trials of burn resuscitation, while recognizing the obstacles to conducting randomized controlled trials in this setting.

Electronic urinary output monitors, intended to provide urine output information to guide fluid therapy during burn resuscitation, can be inaccurate because of airlocks causing urine retention in the drainage tube and bladder. In this study, the authors explore the effects of airlock formation on urine output measured using an electronic urinary output monitor connected to either a standard commercial drainage tubing system or a drainage tubing system with an automated airlock clearing mechanism. In a multicenter study in the burn intensive care unit, urine output was compared between 10 control patients with a standard commercial drainage tubing system and 10 test patients with a novel automated airlock clearing drainage tubing system. The comparison was focused on identifying the number and magnitude of surges in urinary output because of airlocks and associated periods of false oliguria. In the control group, 5 of 10 (50%) patients had drainage line flow impediments from 8 airlocks. In addition, control patients experienced six associated periods of false oliguria. Airlock surge volumes ranged from 50 to 329 ml, and false oliguria duration ranged from 39.4 to 185.2 minutes. In the test group, 0 of 10 (0%) patients had drainage line impediments from airlocks (P < .01), and hence, there were no periods of false oliguria. Airlocks and associated periods of false oliguria occur with standard commercial drainage tubing and are eliminated using an automated airlock clearing drainage tube. Electronic urinary output monitoring with self-clearing drainage has the potential to improve tracking of real-time urine output and decrease caregiver workload.

This paper presents a new approach for optimising the design of tidal stream turbine farms. In this approach, the turbine farm is represented by a turbine density function that specifies the number of turbines per unit area and an associated continuous locally-enhanced bottom friction field. The farm design question is formulated as a mathematical optimisation problem constrained by the shallow water equations and solved with efficient, gradient-based optimisation methods. The resulting method is accurate, computationally efficient, allows complex installation constraints, and supports different goal quantities such as to maximise power or profit. The outputs of the optimisation are the optimal number of turbines, their location within the farm, the overall farm profit, the farm's power extraction, and the installation cost. We demonstrate the capabilities of the method on a validated numerical model of the Pentland Firth, Scotland. We optimise the design of four tidal farms simultaneously, as well as individually, and study how farms in close proximity may impact upon one another.

Purpose: This study aimed to investigate the influence of display window setting on technologist performance detecting subtle but clinically relevant artifacts in daily computed tomography (CT) quality control (dQC) images. Methods: Fifty three sets of dQC images were retrospectively selected, including 30 sets without artifacts, and 23 with subtle but clinically relevant artifacts. They were randomized and shown to six CT technologists (two new and four experienced). Each technologist reviewed all images in each of two sessions, one with a display window width (WW) of 100 HU, which is currently recommended by the American College of Radiology, and the other with a narrow WW of 40 HU, both at a window level of 0 HU. For each case, technologists rated the presence of image artifacts based on a five point scale. The area under the receiver operating characteristic curve (AUC) was used to evaluate the artifact detection performance. Results: At a WW of 100 HU, the AUC (95% confidence interval) was 0.658 (0.576, 0.740), 0.532 (0.429, 0.635), and 0.616 (0.543, 0.619) for the experienced, new, and all technologists, respectively. At a WW of 40 HU, the AUC was 0.768 (0.687, 0.850), 0.546 (0.433, 0.658), and 0.694 (0.619, 0.769), respectively. The performance significantly improved at WW of 40 HU for experienced technologists (p = 0.009) and for all technologists (p = 0.040). Conclusions: Use of a narrow display WW significantly improved technologists’ performance in dQC for detecting subtle but clinically relevant artifacts as compared to that using a 100 HU display WW.

Biologics have increased in popularity lately as a novel and exciting new therapy for men with a spectrum of sexual dysfunction ailments-ranging from erectile dysfunction, Peyronie's disease, and ejaculatory disorders. In this series, sequential patients were analyzed who received biologic materials at the time of their penile implant surgery, with various metrics assessed. The information gathered includes recovery time, need for postoperative analgesics, and satisfaction with the final outcome. In this study, early metrics appear to point to improved outcomes in select criteria. Further study will need to address whether treatment with biologics has broader appeal, but in the penile implant patient, the surgery seems to be augmented with the placement of biologic material into the surgical wound.

A 1st-principles-inspired physiological model was developed that can predict the redistribution of fluid and albumin in the patient after thermal injury. The key components of the model include volume kinetics, renal function, and burn-induced perturbations in circulatory physiology. The model was developed in such a way that it can be fully characterized by the patient weight, height, and total burn surface area (TBSA) as well as a small set of model parameters to be individualized to predict the patient's response to thermal injury and resuscitation. Based on the underlying physics and constraints of organs, new mathematical functions were developed to describe the renal function and lymph return. A novel approach was employed to implement the effect of burn on the pertinent physiology of patients' body. The model was identified and tested using two groups of sheep undergoing burn injury and resuscitation. The results suggested that the model can boast acceptable accuracy in reproducing experimentally observed plasma volume and urinary output despite its simplicity. Such a model, after meeting the requirements on accuracy and physiological credibility, may facilitate the validation and testing of burn resuscitation protocols and closed-loop decision support systems.

Although forecasts and other mathematical models have the potential to play an important role in mitigating the impact of infectious disease outbreaks, the extent to which these tools are used in public health decision making in the United States is unclear. Throughout 2015, we invited public health practitioners belonging to three national public health organizations to complete a cross-sectional survey containing questions on model awareness, model use, and communication with modelers. Of 39 respondents, 46.15% used models in their work, and 20.51% reported direct communication with those who create models. Over half (64.10%) were aware that influenza forecasts exist. The need for improved communication between practitioners and modelers was overwhelmingly endorsed, with over 50% of participants indicating the need for models more relevant to public health questions, increased frequency of telecommunication, and more plain language in discussing models. Model use for public health decision making must be improved if models are to reach their full potential as public health tools. Increased quality and frequency of communication between practitioners and modelers could be particularly useful in achieving this goal. It is important that improvements be made now, rather than waiting for the next public health crisis to occur.

Stroke results in enduring damage to the brain which is accompanied by innate neurorestorative processes, such as reorganization of surviving circuits. Nevertheless, patients are often left with permanent residual impairments. Cell based therapy is an emerging therapeutic that may function to enhance the innate neurorestorative capacity of the brain. We previously evaluated human umbilical tissue-derived cells (hUTC) in our non-human primate model of cortical injury limited to the hand area of primary motor cortex. Injection of hUTC 24 h after injury resulted in significantly enhanced recovery of fine motor function compared to vehicle treated controls (Moore et al., 2013). These monkeys also received an injection of Bromodeoxyuridine (BrdU) 8 days after cortical injury to label cells undergoing replication. This was followed by 12 weeks of behavioral testing, which culminated 3 h prior to perfusion in a final behavioral testing session using only the impaired hand. In this session, the neuronal activity initiating hand movements leads to the upregulation of the immediate early gene c-Fos in activated cells. Following perfusion-fixation of the brain, sections were processed using immunohistochemistry to label c-Fos activated cells, pre-synaptic vesicle protein synaptophysin, and BrdU labeled neuroprogenitor cells to investigate the hypothesis that hUTC treatment enhanced behavioral recovery by facilitating reorganization of surviving cortical tissues. Quantitative analysis revealed that c-Fos activated cells were significantly increased in the ipsi- and contra-lesional ventral premotor but not the dorsal premotor cortices in the hUTC treated monkeys compared to placebo controls. Furthermore, the increase in c-Fos activated cells in the ipsi- and contra-lesional ventral premotor cortex correlated with a decrease in recovery time and improved grasp topography. Interestingly, there was no difference between treatment groups in the number of synaptophysin positive puncta in either ipsi- or contra-lesional ventral or dorsal premotor cortices. Nor was there a significant difference in the density of BrdU labeled cells in the subgranular zone of the hippocampus or the subventricular zone of the lateral ventricle. These findings support the hypothesis that hUTC treatment enhances the capacity of the brain to reorganize after cortical injury and that bilateral plasticity in ventral premotor cortex is a critical locus for this recovery of function. This reorganization may be accomplished through enhanced activation of pre-existing circuits within ventral premotor, but it could also reflect ventral premotor projections to the brainstem or spinal cord.

Timing of bilateral nephrectomy (BN) is controversial in patients with refractory symptoms of autosomal dominant polycystic kidney disease (APKD) in need of a renal transplant.Adults who underwent live donor renal transplant (LRT) + simultaneous BN (SBN) from August 2003 to 2013 at a single transplant center (n = 66) were retrospectively compared to a matched group of APKD patients who underwent LRT alone (n = 52). All patients received general health and polycystic kidney symptom surveys.Simultaneous BN increased operative duration, estimated blood loss, transfusions, intravenous fluid, and hospital length of stay. Most common indications for BN were pain, loss of abdominal domain, and early satiety. There were more intraoperative complications for LRT + SBN (6 vs 0, P = 0.03; 2 vascular, 2 splenic, and 1 liver injury; 1 reexploration to adjust graft positioning). There were no differences in Clavien-Dindo grade I or II (39% vs 25%, P = 0.12) or grade III or IV (7.5% vs 5.7%, P = 1.0) complications during the hospital course. There were no surgery-related mortalities. There were no differences in readmission rates (68% vs 48%, P = 0.19) or readmissions requiring procedures (25% vs. 20%, P = 0.51) over 12 months. One hundred percent of LRT + SBN allografts functioned at longer than 1 year for those available for follow-up. Survey response rate was 40% for LRT-alone and 56% for LRT + SBN. One hundred percent of LRT + SBN survey responders were satisfied with their choice of having BN done simultaneously.Excellent outcomes for graft survival, satisfaction, and morbidity suggest that the combined operative approach be preferred for patients with symptomatic APKD to avoid multiple procedures, dialysis, and costs of staged operations.

The location of individual turbines within a tidal current turbine array – micro-siting – can have a significant impact on the power that the array may extract from the flow. Due to the infancy of the industry and the challenges of exploiting the resource, the economic costs of realising industrial scale tidal current energy projects are significant and should be considered as one of the key drivers of array design. This paper proposes a framework for the automated design of tidal current turbine arrays in which costs over the lifespan of the array may be modelled and considered as part of the design optimisation process. To demonstrate this approach, the cost of sub-sea cabling is incorporated by implementing a cable-routing algorithm alongside an existing gradient-based array optimisation algorithm. Three idealised test scenarios are used to demonstrate the effects of a financial-return optimising design approach as contrasted with a power maximisation approach.