Machine learning seizure prediction: one problematic but accepted practice.

Objective.Epilepsy is one of the most common neurological disorders and can have a devastating effect on a person's quality of life. As such, the search for markers which indicate an upcoming seizure is a critically important area of research which would allow either on-demand treatment or early warning for people suffering with these disorders. There is a growing body of work which uses machine learning methods to detect pre-seizure biomarkers from electroencephalography (EEG), however the high prediction rates published do not translate into the clinical setting. Our objective is to investigate a potential reason for this.Approach.We conduct an empirical study of a commonly used data labelling method for EEG seizure prediction which relies on labelling small windows of EEG data in temporal groups then selecting randomly from those windows to validate results. We investigate a confound for this approach for seizure prediction and demonstrate the ease at which it can be inadvertently learned by a machine learning system.Main results.We find that non-seizure signals can create decision surfaces for machine learning approaches which can result in false high prediction accuracy on validation datasets. We prove this by training an artificial neural network to learn fake seizures (fully decoupled from biology) in real EEG.Significance.The significance of our findings is that many existing works may be reporting results based on this confound and that future work should adhere to stricter requirements in mitigating this confound. The problematic, but commonly accepted approach in the literature for seizure prediction labelling is potentially preventing real advances in developing solutions for these sufferers. By adhering to the guidelines in this paper future work in machine learning seizure prediction is more likely to be clinically relevant.

Hybrid Synthetic and Computational Study of an Optimized, Solvent-Free Approach to Curcuminoids.

A green and optimized protocol has been developed for the preparation of symmetric 1,7-bis(aryl)-1,6-heptadiene-3,5-diones and asymmetric 2-aryl-6-arylidenecyclohexanones with modified substrate scope and good functional group tolerance. Syntheses proceed smoothly under solvent-free conditions, providing moderate to excellent product yields with a minimal workup procedure. Control experiments, spectroscopic, and computational studies support a mechanism involving the boron-assisted in situ generation of imine intermediates. Crystal structures of three curcuminoids and isolated mechanistic intermediates are reported. The data provide insight for the further development of solvent-free protocols toward diverse curcumin derivatives in the fields of pharmaceutical and synthetic chemistries.

Preventive Treatment of Hereditary Angioedema: A Review of Phase III Clinical Trial Data for Subcutaneous C1 Inhibitor and Relevance for Patient Management.

PURPOSE: Hereditary angioedema (HAE), most often caused by a genetically mediated deficiency in the activity of C1 inhibitor (C1INH) protein, is characterized clinically by recurrent episodes of localized swelling without wheals. HAE attacks can be painful, debilitating, and even fatal, resulting in physical discomfort, emotional stress, and interruptions of work, school, and/or social activities, all of which can affect health-related quality of life (HRQoL). Subcutaneous C1INH (C1INH[SC]) is recommended as a first-line option for long-term prophylaxis (LTP) in HAE. This narrative review provides a concise but comprehensive overview of all published data generated from the pivotal Phase III Clinical Study for Optimal Management of Preventing Angioedema With Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT) study program, which evaluated the use of C1INH(SC) as LTP. METHODS: A PubMed search was performed using the search terms subcutaneous C1 inhibitor plus COMPACT with no filters, and another search was performed using the term subcutaneous C1 inhibitor, with output limited to clinical trial data only. All publications that reported data generated during the Phase III COMPACT study were included. Data presentation focused on the US Food and Drug Administration-approved dose of 60 IU/kg. FINDINGS: The search strategy identified a total of 11 publications that reported data and analyses from the Phase III COMPACT study. Publications reported overall findings from the double-blind, placebo-controlled, crossover COMPACT study and a subsequent long-term open-label extension (OLE) study. Other published analyses included pharmacokinetic/pharmacodynamic data, HRQoL assessments, and findings in patient subgroups including women, pediatric patients, and patients ≥65 years of age. Subgroup analyses reported good safety and efficacy profiles among age-based subgroups from the COMPACT OLE, including pediatric patients, patients ≥65 years of age with comorbidities, and among female patients, despite a tendency for HAE to be more severe in women. A number of significant HRQoL improvements were noted with C1INH(SC) use, including better overall health status, less anxiety, and less work- and activity-related impairment versus placebo (double-blind study), and compared with baseline (OLE). IMPLICATIONS: This review provides a concise overview of all published COMPACT study data with C1INH(SC). The data reviewed here portray a high level of efficacy and tolerability with C1INH(SC), even during periods of treatment that exceed 2 years, which does not appear to vary based on patient age or sex. Clinically relevant improvements in multiple facets of HRQoL were also reported, including better overall HRQoL, less anxiety and depression, and less disruptions in work attendance and productivity. These data should be useful for assessing the appropriateness of C1INH(SC) therapy for individual patients.

Assessment of Disparities Associated With a Crisis Standards of Care Resource Allocation Algorithm for Patients in 2 US Hospitals During the COVID-19 Pandemic.

Importance: Significant concern has been raised that crisis standards of care policies aimed at guiding resource allocation may be biased against people based on race/ethnicity. Objective: To evaluate whether unanticipated disparities by race or ethnicity arise from a single institution's resource allocation policy. Design, Setting, and Participants: This cohort study included adults (aged ≥18 years) who were cared for on a coronavirus disease 2019 (COVID-19) ward or in a monitored unit requiring invasive or noninvasive ventilation or high-flow nasal cannula between May 26 and July 14, 2020, at 2 academic hospitals in Miami, Florida. Exposures: Race (ie, White, Black, Asian, multiracial) and ethnicity (ie, non-Hispanic, Hispanic). Main Outcomes and Measures: The primary outcome was based on a resource allocation priority score (range, 1-8, with 1 indicating highest and 8 indicating lowest priority) that was assigned daily based on both estimated short-term (using Sequential Organ Failure Assessment score) and longer-term (using comorbidities) mortality. There were 2 coprimary outcomes: maximum and minimum score for each patient over all eligible patient-days. Standard summary statistics were used to describe the cohort, and multivariable Poisson regression was used to identify associations of race and ethnicity with each outcome. Results: The cohort consisted of 5613 patient-days of data from 1127 patients (median [interquartile range {IQR}] age, 62.7 [51.7-73.7]; 607 [53.9%] men). Of these, 711 (63.1%) were White patients, 323 (28.7%) were Black patients, 8 (0.7%) were Asian patients, and 31 (2.8%) were multiracial patients; 480 (42.6%) were non-Hispanic patients, and 611 (54.2%) were Hispanic patients. The median (IQR) maximum priority score for the cohort was 3 (1-4); the median (IQR) minimum score was 2 (1-3). After adjustment, there was no association of race with maximum priority score using White patients as the reference group (Black patients: incidence rate ratio [IRR], 1.00; 95% CI, 0.89-1.12; Asian patients: IRR, 0.95; 95% CI. 0.62-1.45; multiracial patients: IRR, 0.93; 95% CI, 0.72-1.19) or of ethnicity using non-Hispanic patients as the reference group (Hispanic patients: IRR, 0.98; 95% CI, 0.88-1.10); similarly, no association was found with minimum score for race, again with White patients as the reference group (Black patients: IRR, 1.01; 95% CI, 0.90-1.14; Asian patients: IRR, 0.96; 95% CI, 0.62-1.49; multiracial patients: IRR, 0.81; 95% CI, 0.61-1.07) or ethnicity, again with non-Hispanic patients as the reference group (Hispanic patients: IRR, 1.00; 95% CI, 0.89-1.13). Conclusions and Relevance: In this cohort study of adult patients admitted to a COVID-19 unit at 2 US hospitals, there was no association of race or ethnicity with the priority score underpinning the resource allocation policy. Despite this finding, any policy to guide altered standards of care during a crisis should be monitored to ensure equitable distribution of resources.

Dental visits in Medicaid-enrolled youth with mental illness: an analysis of administrative claims data.

BACKGROUND: State Medicaid plans across the United States provide dental insurance coverage to millions of young persons with mental illness (MI), including those with attention deficit hyperactivity disorder (ADHD), depression, anxiety, bipolar disorder, and schizophrenia. There are significant oral health challenges associated with MI, and providing dental care to persons with MI while they are young provides a foundation for future oral health. However, little is known about the factors associated with the receipt of dental care in young Medicaid enrollees with MI. We aimed to identify mental and physical health and sociodemographic characteristics associated with dental visits among this population. METHODS: We retrospectively analyzed administrative claims data from a Medicaid specialty health plan (September 2014 to December 2015). All enrollees in the plan had MI and were ≥ 7 years of age; data for enrollees aged 7 to 20 years were analyzed. We used two-level, mixed effects regression models to explore the relationships between enrollee characteristics and dental visits during 2015. RESULTS: Of 6564 Medicaid-enrolled youth with MI, 29.0% (95% CI, 27.9, 30.1%) had one or more visits with a dentist or dental hygienist. Within youth with MI, neither anxiety (Adjusted odds ratio [AOR] = 1.15, p = 0.111), post-traumatic stress disorder (AOR = 1.31, p = 0.075), depression (AOR = 1.02, p = 0.831), bipolar disorder (AOR = 0.97, p = 0.759), nor schizophrenia (AOR = 0.83, p = 0.199) was associated with dental visits in adjusted analyses, although having ADHD was significantly associated with higher odds of dental visits relative to not having this condition (AOR = 1.34, p < 0.001). Age, sex, race/ethnicity, language, and education were also significantly associated with visits (p < 0.05 for all). CONCLUSIONS: Dental utilization as measured by annual dental visits was lower in Medicaid-enrolled youth with MI relative to the general population of Medicaid-enrolled youth. However, utilization varied within the population of Medicaid-enrolled youth with MI, and we identified a number of characteristics significantly associated with the receipt of dental services. By identifying these variations in dental service use this study facilitates the development of targeted strategies to increase the use of dental care in - and consequently improve the current and long-term wellbeing of - the vulnerable population of Medicaid-enrolled youth with MI.

Evaluation of electrical properties of ex vivo human hepatic tissue with metastatic colorectal cancer.

OBJECTIVE: To probe the distribution of electrical properties in tumor-bearing human hepatic tissues with metastatic colorectal cancer. APPROACH: Electrochemical impedance spectroscopy (EIS) and a non-contact electromagnetic probe were used for distinguishing spatial heterogeneities in fresh, unfixed human hepatic tissues ex vivo from patients with metastatic colorectal cancer (CRC). MAIN RESULTS: Point-wise EIS measurements reported over a frequency range of 100 Hz-1 MHz showed that the interface tissue between visible tumor and normal tissue exhibits an electrically different domain (p < 0.05) from both normal tissue (over 100 Hz-100 kHz) and tumor tissue (over 100 Hz-1 MHz). Observations of the microstructure on tumor-bearing hepatic tissue from hematoxylin and eosin stained images and the equivalent circuit modelling were used to validate the impedance measurements and characterize previously unidentified interfacial domain between normal and tumor tissue. Lastly, in a proof of concept study, a new in-house designed non-contact electromagnetic probe, as opposed to the invasive EIS measurements, was demonstrated for distinguishing tumor tissue from the normal tissue in a hepatic tissue specimen from a patient with metastatic CRC. SIGNIFICANCE: EIS measurements, correlated with histological observations, show potential for mapping electrical properties in tumor-bearing human hepatic tissue.

Academic and Community Partnerships: Increasing Access Through Collaborative Care.

Access to quality dental care for many adults and children remains a serious concern. Many communities throughout the U.S. are at great disadvantage for preventive care and treatment due to payment concerns, location and types of providers, and poor communication between dental providers and primary care professionals. Voids in shared technology and information also persist. Integrating primary care with oral health can boost both preventive care and interventions focused on increasing efficacy and efficiency between dental and primary care professionals in addressing the onset and duration of disease. Academic and community partnerships can help increase access to care and bring together the dental and medical communities for better integration and care coordination. Academic and community partnerships promote the sharing of information, facilitate provision of basic diagnostic services, and bring the bidirectional flow of knowledge, training, and skills to one another in a systematic and sustained manner.

Reactions of Germylenes and Stannylenes with Halo(hydrocarbyl)- and Chloro(amino)phosphines: Oxidative Addition versus Ligand Transfer.

Oxidative addition (OA) is an important elementary step in chemistry, but it has been studied mainly in the context of transition-metal-catalyzed reactions and mainly with carbon-X substrates (X = halogen, H). Reports of main-group metal compounds undergoing OA are rare by comparison, and those involving phosphorus-halogen substrates are rarer still. Acyclic and cyclic diazagermylenes and -stannylenes react with chloro(hydrocarbyl)phosphines with the intermediacy of oxidative addition products. Stannylenes react faster than germylenes, and these reactions are first-order in both reactants and slowed by steric bulk. Kinetic data and the structures of intermediates and products had suggested an adduct/insertion mechanism for these reactions. To gain further insight into these transformations, the work presented herein was extended to chloro(hydrocarbyl)phosphines with varying organic substituents. These studies confirmed prior conclusions concerning the rate-diminishing effect of steric bulk, and the rate dependence on leaving groups also seems to suggest adduct/insertion or SN2 mechanisms. Importantly, these new data now also point to associative decomposition pathways. In the course of the investigation, it was discovered that aliphatic chloro(amino)phosphines react differently with the carbene analogues, giving oxidative addition products for germylenes but metathesis reactions for stannylenes.

Effects of Omalizumab on Rhinovirus Infections, Illnesses, and Exacerbations of Asthma.

RATIONALE: Allergic inflammation has been linked to increased susceptibility to viral illnesses, but it is unclear whether this association is causal. OBJECTIVES: To test whether omalizumab treatment to reduce IgE would shorten the frequency and duration of rhinovirus (RV) illnesses in children with allergic asthma. METHODS: In the PROSE (Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations) study, we examined children with allergic asthma (aged 6-17 yr; n = 478) from low-income census tracts in eight U.S. cities, and we analyzed virology for the groups randomized to treatment with guidelines-based asthma care (n = 89) or add-on omalizumab (n = 259). Weekly nasal mucus samples were analyzed for RVs, and respiratory symptoms and asthma exacerbations were recorded over a 90-day period during the fall seasons of 2012 or 2013. Adjusted illness rates (illnesses per sample) by treatment arm were calculated using Poisson regression. MEASUREMENTS AND MAIN RESULTS: RVs were detected in 97 (57%) of 171 exacerbation samples and 2,150 (36%) of 5,959 nonexacerbation samples (OR, 2.32; P < 0.001). Exacerbations were significantly associated with detection of rhinovirus C (OR, 2.85; P < 0.001) and rhinovirus A (OR, 2.92; P < 0.001), as well as, to a lesser extent, rhinovirus B (OR, 1.98; P = 0.019). Omalizumab decreased the duration of RV infection (11.2 d vs. 12.4 d; P = 0.03) and reduced peak RV shedding by 0.4 log units (95% confidence interval, -0.77 to -0.02; P = 0.04). Finally, omalizumab decreased the frequency of RV illnesses (risk ratio, 0.64; 95% confidence interval, 0.49-0.84). CONCLUSIONS: In children with allergic asthma, treatment with omalizumab decreased the duration of RV infections, viral shedding, and the risk of RV illnesses. These findings provide direct evidence that blocking IgE decreases susceptibility to RV infections and illness. Clinical trial registered with www.clinicaltrials.gov (NCT01430403).

Can we predict fall asthma exacerbations? Validation of the seasonal asthma exacerbation index.

BACKGROUND: A Seasonal Asthma Exacerbation Predictive Index (saEPI) was previously reported based on 2 prior National Institute of Allergy and Infectious Diseases Inner City Asthma Consortium trials. OBJECTIVE: This study sought to validate the saEPI in a separate trial designed to prevent fall exacerbations with omalizumab therapy. METHODS: The saEPI and its components were analyzed to characterize those who had an asthma exacerbation during the Preventative Omalizumab or Step-Up Therapy for Fall Exacerbations (PROSE) study. We characterized those inner-city children with and without asthma exacerbations in the fall period treated with guidelines-based therapy (GBT) in the absence and presence of omalizumab. RESULTS: A higher saEPI was associated with an exacerbation in both the GBT alone (P < .001; area under the curve, 0.76) and the GBT + omalizumab group (P < .01; area under the curve, 0.65). In the GBT group, younger age at recruitment, higher total IgE, higher blood eosinophil percentage and number, and higher treatment step were associated with those who had an exacerbation compared with those who did not. In the GBT + omalizumab group, younger age at recruitment, increased eosinophil number, recent exacerbation, and higher treatment step were also associated with those who had an exacerbation. The saEPI was associated with a high negative predictive value in both groups. CONCLUSIONS: An exacerbation in children treated with GBT with or without omalizumab was associated with a higher saEPI along with higher markers of allergic inflammation, treatment step, and a recent exacerbation. Those that exacerbated on omalizumab had similar features with the exception of some markers of allergic sensitization, indicating a need to develop better markers to predict poor response to omalizumab therapy and alternative treatment strategies for children with these risk factors. The saEPI was able to reliably predict those children unlikely to have an asthma exacerbation in both groups.

Discrepancies between direct catheter and echocardiography-based values in aortic stenosis.

OBJECTIVES: The goal of this article is to examine the correlation of catheter (cath) based and echocardiographic assessment of aortic stenosis (AS) in a community-based academic hospital setting, particularly in the degree that decision to refer for surgery is altered. BACKGROUND: Current guidelines discourage AS evaluation by invasive pressure measurement if echocardiography (echo) is adequate, but several studies show sizable differences between echo and cardiac catheterization lab (CCL) measurements. We examine this correlation using high quality CCL techniques. METHODS: Sequential patients with suspected AS by echo (n = 40) aged 61-94 underwent catheterization with pressure gradients via left ventricular pressure wire and ascending aorta catheter. The echos leading to the catheterization were independently reviewed by an expert panel to assess the quality of community-based readings. RESULTS: CCL changed assessment of severity of aortic valve area (AVA) by more than 0.3 cm(2) in 25% and 0.5 cm(2) in 8%. Values changed to over or under the surgical threshold of AVA < 1 cm(2) in 30% of the patients. Pearson correlation of 0.35 between measurements of AVA by echo and CCL is lower than earlier studies, which often reported correlation values of 0.90 or greater. Echo expert reviews provided minimal improvement in discrepancies (Pearson correlation of 0.46), suggesting quality of initial interpretation was not the issue. CONCLUSIONS: Cath-echo correlation of AS severity is lower in contemporaneous practice than previously assumed. This can alter the decision for aortic valve replacement. Sole reliance on echo-derived assessment of AS may at times be problematic.

Non-contact method for directing electrotaxis.

We present a method to induce electric fields and drive electrotaxis (galvanotaxis) without the need for electrodes to be in contact with the media containing the cell cultures. We report experimental results using a modification of the transmembrane assay, demonstrating the hindrance of migration of breast cancer cells (SCP2) when an induced a.c. electric field is present in the appropriate direction (i.e. in the direction of migration). Of significance is that migration of these cells is hindered at electric field strengths many orders of magnitude (5 to 6) below those previously reported for d.c. electrotaxis, and even in the presence of a chemokine (SDF-1α) or a growth factor (EGF). Induced a.c. electric fields applied in the direction of migration are also shown to hinder motility of non-transformed human mammary epithelial cells (MCF10A) in the presence of the growth factor EGF. In addition, we also show how our method can be applied to other cell migration assays (scratch assay), and by changing the coil design and holder, that it is also compatible with commercially available multi-well culture plates.

Racial disparities in diabetes mortality in the 50 most populous US cities.

While studies have consistently shown that in the USA, non-Hispanic Blacks (Blacks) have higher diabetes prevalence, complication and death rates than non-Hispanic Whites (Whites), there are no studies that compare disparities in diabetes mortality across the largest US cities. This study presents and compares Black/White age-adjusted diabetes mortality rate ratios (RRs), calculated using national death files and census data, for the 50 most populous US cities. Relationships between city-level diabetes mortality RRs and 12 ecological variables were explored using bivariate correlation analyses. Multivariate analyses were conducted using negative binomial regression to examine how much of the disparity could be explained by these variables. Blacks had statistically significantly higher mortality rates compared to Whites in 39 of the 41 cities included in analyses, with statistically significant rate ratios ranging from 1.57 (95 % CI: 1.33-1.86) in Baltimore to 3.78 (95 % CI: 2.84-5.02) in Washington, DC. Analyses showed that economic inequality was strongly correlated with the diabetes mortality disparity, driven by differences in White poverty levels. This was followed by segregation. Multivariate analyses showed that adjusting for Black/White poverty alone explained 58.5 % of the disparity. Adjusting for Black/White poverty and segregation explained 72.6 % of the disparity. This study emphasizes the role that inequalities in social and economic determinants, rather than for example poverty on its own, play in Black/White diabetes mortality disparities. It also highlights how the magnitude of the disparity and the factors that influence it can vary greatly across cities, underscoring the importance of using local data to identify context specific barriers and develop effective interventions to eliminate health disparities.

Public health program planning logic model for community engaged type 2 diabetes management and prevention.

Diabetes remains a growing epidemic with widening health inequity gaps in disease management, self-management knowledge, access to care and outcomes. Yet there is a paucity of evaluation tools for community engaged interventions aimed at closing the gaps and improving health. The Guide to Community Preventive Services (the Community Guide) developed by the Task Force on Community Preventive Services (the Task Force) at the Centers for Disease Control and Prevention (CDC) recommends two healthcare system level interventions, case management interventions and disease management programs, to improve glycemic control. However, as a public health resource guide for diabetes interventions a model for community engagement is a glaringly absent component of the Community Guide recommendations. In large part there are few evidence-based interventions featuring community engagement as a practice and system-level focus of chronic disease and Type 2 diabetes management. The central argument presented in this paper is that the absence of these types of interventions is due to the lack of tools for modeling and evaluating such interventions, especially among disparate and poor populations. A conceptual model emphasizing action-oriented micro-level community engagement is needed to complement the Community Guide and serve as the basis for testing and evaluation of these kinds of interventions. A unique logic model advancing the Community Guide diabetes recommendations toward measureable and sustainable community engagement for improved Type 2 diabetes outcomes is presented.

To fight bad suga', or diabetes, my neighborhood needs more health educators.

A health researcher who's seen the devastation in his poor Chicago community calls for national prevention programs that place these workers at the core.

Heavier carbene analogues and their derivatives as κ-El, κ2-El,N, and κ2-N,N' ligands: different reactivity patterns for acyclic and cyclic diamidogermylenes and -stannylenes.

Because of the increasing importance of N-heterocyclic carbenes in organometallic chemistry we investigated the ligand properties of structurally-related acyclic and cyclic heavier carbene analogues with transition metal chlorides. Acyclic {(Me(3)Si)(2)N}(2)El, El = Ge and Sn, react with CuCl with transfer of one (Me(3)Si)(2)N ligand to yield the known copper tetramer {(Me(3)Si)(2)NCu}(4). The cyclic Me(2)Si(µ-N(t)Bu)(2)Ge, by contrast, binds copper through germanium only, furnishing a tetranuclear ladder structure with both terminal and bridging germylenes. The tin homologue, however, inserts into the CuCl bond, and the ensuing {Me(2)Si(µ-N(t)Bu)(2)SnCl}(-) ions then coordinate one copper ion via their tin atoms while sandwiching the remaining three copper ions in an unprecedented κ(2)-N,N' fashion. Chemically-harder Cr(II)--created in a redox reaction of Me(2)Si(µ-N(t)Bu)(2)Sn with CrCl(3)(THF)(3)--is not coordinated by tin, but chelated by both nitrogen atoms of one {Me(2)Si(µ-N(t)Bu)(2)SnCl}(-) ion and more weakly through the tin-bound chloride.

Minority dental faculty development: responsibility and challenge.

Over at least the last twenty years, the American Dental Education Association (ADEA) has given attention and priority to increasing the number of underrepresented minority (URM) dental school applicants, enrollees, and faculty members and to meeting the challenges of achieving diversity in the oral health workforce of the future as racial and ethnic minorities continue to grow and are expected to comprise more than 50 percent of the U.S. population by the middle of the twenty-first century. Dental schools have the responsibility of preparing dentists to provide oral health care for the nation's population. This includes creating a workforce of adequate size and racial/ethnic composition. As part of ADEA's priorities to improve the recruitment, retention, and development of URMs in the dental profession, with funding from the W.K. Kellogg Foundation, ADEA launched the Minority Dental Faculty Development Program in 2004. The intent of the program is to foster academic partnerships, mentoring, and institutional commitment and leadership designed to increase the number of URM individuals interested in and prepared for careers in academic dentistry.