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1.
J Vis ; 24(3): 4, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38488409

ABSTRACT

Accommodation is the process of adjusting the eye's optical power so as to focus at different distances. Uncorrected refractive error and/or functional presbyopia mean that sharp focus may not be achievable for some distances, so observers experience sustained defocus. Here, we identify a problem with current models of accommodative control: They predict excessive internal responses to stimuli outside accommodative range, leading to unrealistic adaptation effects. Specifically, after prolonged exposure to stimuli outside range, current models predict long latencies in the accommodative response to stimuli within range, as well as unrealistic dynamics and amplitudes of accommodative vergence innervation driven by the accommodative neural controller. These behaviors are not observed empirically. To solve this issue, we propose that the input to blur-driven accommodation is not retinal defocus, but correctable defocus. Predictive models of accommodative control already estimate demand from sensed defocus, using a realistic "virtual plant" to estimate accommodation. Correctable defocus can be obtained by restricting this demand to values physically attainable by the eye. If we further postulate that correctable defocus is computed using an idealized virtual plant that retains a young accommodative range, we can explain why accommodative-convergence responses are observed for stimuli that are too near-but not too far-to focus on. We model cycloplegia as a change in gain, and postulate a form of neural myopia to explain the additional relaxation of accommodation often seen with cycloplegia. This model produces plausible predictions for the accommodative response and accommodative convergence signal in a wide range of clinically relevant situations.


Subject(s)
Myopia , Presbyopia , Refractive Errors , Humans , Accommodation, Ocular , Retina
2.
Psychiatry Res ; 334: 115785, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38377800

ABSTRACT

Tobacco use has been established as a possible risk factor for psychosis, but the effect of electronic nicotine delivery systems (ex. nicotine vapes) has not been independently established. Using the Population Assessment of Tobacco and Health study, we found that use of electronic nicotine products was significantly associated with later first episode psychosis after controlling for substance use and other confounders, and that this relationship was only significant among the heaviest users (>20 puffs/day). Given the rapid rise in electronic nicotine products use, clinicians and public health professionals should consider potential impacts and closely monitor trends in the coming years.


Subject(s)
Electronic Nicotine Delivery Systems , Psychotic Disorders , Vaping , Humans , Nicotine/adverse effects , Vaping/epidemiology , Risk Factors , Tobacco Use , Psychotic Disorders/epidemiology
3.
PLoS One ; 19(2): e0290105, 2024.
Article in English | MEDLINE | ID: mdl-38416784

ABSTRACT

BACKGROUND: Pervasive differences in cancer screening among race/ethnicity and insurance groups presents a challenge to achieving equitable healthcare access and health outcomes. However, the change in the magnitude of cancer screening disparities over time has not been thoroughly examined using recent public health survey data. METHODS: A retrospective cross-sectional analysis of the 2008 and 2018 National Health Interview Survey (NHIS) database focused on breast, cervical, and colorectal cancer screening rates among race/ethnicity and insurance groups. Multivariable logistic regression models were used to assess the relationship between cancer screening rates, race/ethnicity, and insurance coverage, and to quantify the changes in disparities in 2008 and 2018, adjusting for potential confounders. RESULTS: Colorectal cancer screening rates increased for all groups, but cervical and mammogram rates remained stagnant for specific groups. Non-Hispanic Asians continued to report consistently lower odds of receiving cervical tests (OR: 0.42, 95% CI: 0.32-0.55, p<0.001) and colorectal cancer screening (OR: 0.55, 95% CI: 0.42-0.72, p<0.001) compared to non-Hispanic Whites in 2018, despite significant improvements since 2008. Non-Hispanic Blacks continued to report higher odds of recent cervical cancer screening (OR: 1.98, 95% CI: 1.47-2.68, p<0.001) and mammograms (OR: 1.32, 95% CI: 1.02-1.71, p<0.05) than non-Hispanic Whites in 2018, consistent with higher odds observed in 2008. Hispanic individuals reported improved colorectal cancer screening over time, with no significant difference compared to non-Hispanics Whites in 2018, despite reporting lower odds in 2008. The uninsured status was associated with significantly lower odds of cancer screening than private insurance for all three cancers in 2008 and 2018. CONCLUSION: Despite an overall increase in breast and colorectal cancer screening rates between 2008 and 2018, persistent racial/ethnic and insurance disparities exist among race/ethnicity and insurance groups. These findings highlight the importance of addressing underlying factors contributing to disparities among underserved populations and developing corresponding interventions.


Subject(s)
Colorectal Neoplasms , Uterine Cervical Neoplasms , Female , Humans , United States/epidemiology , Ethnicity , Early Detection of Cancer , Cross-Sectional Studies , Retrospective Studies , Uterine Cervical Neoplasms/diagnosis , Insurance Coverage , Colorectal Neoplasms/diagnosis , Healthcare Disparities , Insurance, Health
4.
Ann Pharmacother ; 58(5): 480-493, 2024 May.
Article in English | MEDLINE | ID: mdl-37589369

ABSTRACT

BACKGROUND: Bacterial vaginosis (BV) is a highly prevalent vaginal infection. OBJECTIVES: Primary objectives of this study were to examine treatment patterns among female patients with Medicaid coverage who were diagnosed with incident BV, the frequency of BV-associated complications, and health care resource utilization (HCRU) and associated costs of incident BV and its recurrence. Secondary objectives were to identify predictors of total all-cause health care costs and number of treatment courses. METHODS: Female patients aged 12-49 years with an incident vaginitis diagnosis and ≥1 pharmacy claim for a BV medication were selected from the Merative MarketScan Medicaid database (2017-2020). Additional treatment courses were evaluated during a ≥12-month follow-up period, in which new cases of BV-associated complications and HCRU and the associated costs were also measured. Generalized linear models were used to identify baseline predictors of total all-cause health care costs and number of treatment courses. RESULTS: An incident vaginitis diagnosis and ≥1 BV medication claim were present in 114 313 patients (mean age: 28.4 years; 48.6% black). During the follow-up, 56.6% had 1 treatment course, 24.9% had 2, 10.2% had 3, and 8.3% had ≥4; 43.4% had BV recurrence. Oral metronidazole (88.5%) was the most frequently prescribed medication. Nearly 1 in 5 had a new occurrence of a BV-associated complication; most (76.6%) were sexually transmitted infections (STIs). Total all-cause and BV-related costs averaged $5794 and $300, respectively, per patient; both increased among those with more treatment courses. Older age, pregnancy, comorbidity, any STIs, postprocedural gynecological infection (PGI), and infertility were predictive of higher total all-cause health care costs, while race/ethnicity other than white was predictive of lower costs. Older age, black race, any STIs, pelvic inflammatory disease, and PGI were predictive of >1 treatment courses. CONCLUSION AND RELEVANCE: The high recurrence of BV represents an unmet need in women's health care and better treatments are necessary.


Subject(s)
Sexually Transmitted Diseases , Vaginitis , Vaginosis, Bacterial , Pregnancy , Female , Humans , United States/epidemiology , Adult , Vaginosis, Bacterial/drug therapy , Vaginosis, Bacterial/epidemiology , Vaginosis, Bacterial/microbiology , Medicaid , Financial Stress , Health Care Costs
5.
Vision Res ; 214: 108329, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37951053

ABSTRACT

Free-fusion stereograms are routinely used for demonstrating various stereoscopic effects. Yet, untrained observers find it challenging to perform this task. This study showed that only less than 1/3rd of sixty-one pre-presbyopic adults with normal binocular vision could successfully free-fuse random-dot image pairs and identify the stereoscopic shapes embedded in these patterns. Another one-third of participants performed the task with poor success rates, while the remaining could not perform the task. There was a clear dissociation of vergence and accommodative responses in participants who were successful with free-fusion, as recorded using a dynamic infrared eye tracker and photorefractor. Those in the unsuccessful cluster either showed strong vergence and accommodation or weak vergence and strong accommodation during the task. These response patterns, however, were specific to the free-fusion task because all these participants generated good convergence/accommodation to real-world targets and to conflicting vergence and accommodative demands stimulated with prisms or lenses. Task performance of the unsuccessful cluster also improved significantly following pharmacological paralysis of accommodation and reached the performance levels of the successful cluster. A minority of participants also appeared to progressively learn to dissociate one of the two directions of their vergence and accommodation crosslinks with repeated free-fusion trials. These results suggest that successful free-fusion might depend upon how well participants generate a combination of volitional and reflex vergence responses to large differences in disparity with conflicting static accommodative demands. Such responses would require that only one direction of the vergence-accommodation crosslinks be active at any given time. The sequence of near-responses could also be learnt through repeated trials to optimize task performance.


Subject(s)
Accommodation, Ocular , Convergence, Ocular , Adult , Humans , Learning , Vision, Binocular/physiology
6.
J Comp Eff Res ; 13(1): e230079, 2024 01.
Article in English | MEDLINE | ID: mdl-38099520

ABSTRACT

Aim: Bacterial vaginosis (BV) is a common vaginal dysbiosis associated with adverse clinical sequelae, most notably, increased risk of sexually transmitted infections (STIs). The aims of this study were to estimate the frequency of BV recurrence, treatment patterns, other gynecological (GYN) conditions, and the associated healthcare resource utilization (HCRU) and costs among commercially insured patients in the USA. Patients & methods: Female patients aged 12-49 years with an incident vaginitis diagnosis and ≥1 pharmacy claim for a BV medication (fungal treatment only excluded) were selected from the Merative™ MarketScan commercial database (2017-2020). During a minimum 12-month follow-up, additional treatment courses, treatment patterns, frequency of other GYN conditions, and HCRU and costs were assessed. Generalized linear models were used to identify baseline predictors of total all-cause healthcare costs and number of treatment courses. Results: The study population included 140,826 patients (mean age: 31.5 years) with an incident vaginitis diagnosis and ≥1 BV medication claim. During the follow-up, 64.2% had 1 treatment course, 22.0% had 2, 8.1% had 3, and 5.8% had ≥4; 35.8% had a BV recurrence (≥2 BV medication claims). The most commonly prescribed BV medication was oral metronidazole (73.6%). Approximately 12% (n = 16,619) of patients had a new diagnosis of another GYN condition in the follow-up; 8.2% had a new STI, which were more common among patients with ≥4 treatment courses (12.9%). During follow-up, total all-cause healthcare costs averaged $8987 per patient per year (PPPY) of which $470 was BV-related. BV-related healthcare costs increased from $403 PPPY among those with 1 treatment course to $806 PPPY among those with ≥4 with nearly half the costs attributed to outpatient office visits. Conclusion: BV recurrence among this population represented a substantial clinical and healthcare economic burden warranting improvements in women's healthcare.


Subject(s)
Vaginosis, Bacterial , Humans , Female , United States/epidemiology , Adult , Vaginosis, Bacterial/drug therapy , Vaginosis, Bacterial/epidemiology , Vaginosis, Bacterial/chemically induced , Financial Stress , Metronidazole/adverse effects , Health Care Costs , Delivery of Health Care , Retrospective Studies
7.
Dent J (Basel) ; 11(8)2023 Jul 28.
Article in English | MEDLINE | ID: mdl-37623278

ABSTRACT

OBJECTIVES: This study sought to evaluate the remineralization of ex vivo human teeth using commercially available artificial saliva, SalivaMAX®, a supersaturated calcium phosphate rinse (SSCPR). METHODS: early enamel lesions were artificially induced on ex vivo human teeth by chemical means. The teeth were exposed to the SSCPR for two minutes (experimental) or dH2O (control) four times per day for a total of 35 days. At time points of 0, 2.5, 21, and 35 days, micro-CT was utilized to determine the mineral density profile across the lesion and evaluate lesion depth. The relative percent remineralization was calculated from the initial lesion depth (Time 0) at each evaluation time. Student's t-test was used to compare the extent of remineralization between the SSCPR and control groups for statistical significance at each time. To evaluate the changes in percent remineralization over time, a two-way ANOVA was used. RESULTS: At Time 0 and 2.5 days, there was no difference in the percent remineralization between the SSCPR and control groups (p > 0.05). After 21 days, the teeth exposed to the SSCPR remineralized 56.7 ± 3.7%, while the control only remineralized 10.7 ± 11.0% (p < 0.0001). At day 35, the remineralization was 73.7 ± 5.4% and 18.2 ± 10.8% (p < 0.0001) for the SSCPR and control groups, respectively. CONCLUSIONS: A marked increase in remineralization occurred with the use of the SSCPR. Notably, the remineralization of the SSCPR occurred deep within the tooth and progressed toward the surface over time.

8.
Psychiatry Res ; 323: 115166, 2023 05.
Article in English | MEDLINE | ID: mdl-36989909

ABSTRACT

The Long COVID syndrome has now been documented clearly in the literature, but whether or not psychiatric symptoms are prominent is unclear. We performed a retrospective chart review of all patients receiving medical care during the pandemic in an outpatient Long-COVID specialty clinic that serves a large racial and ethnic minority population. As many as 44% of patients had symptoms that necessitated referrals to psychiatrists, predominantly depression or anxiety. Spanish speaking patients had greater COVID severity (48%) than did predominantly English speakers (15%). We conclude that the long COVID syndrome is predominantly a cluster of physical symptoms that are sequelae of the viral infection.


Subject(s)
COVID-19 , Post-Acute COVID-19 Syndrome , Humans , Depression/epidemiology , Depression/psychology , Retrospective Studies , Prevalence , Ethnicity , SARS-CoV-2 , Minority Groups
9.
Toxicol Appl Pharmacol ; 459: 116355, 2023 01 15.
Article in English | MEDLINE | ID: mdl-36535553

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) represent a large chemical class lacking hazard, toxicokinetic, and exposure information. To accelerate PFAS hazard evaluation, new approach methodologies (NAMs) comprised of in vitro high-throughput toxicity screening, toxicokinetic data, and computational modeling are being employed in read across strategies to evaluate the larger PFAS landscape. A critical consideration to ensure robust evaluations is a parallel assessment of the quality of the screening stock solutions, where dimethyl sulfoxide (DMSO) is often the diluent of choice. Challenged by the lack of commercially available reference standards for many of the selected PFAS and reliance on mass spectrometry approaches for such an evaluation, we developed a high-throughput framework to evaluate the quality of screening stocks for 205 PFAS selected for these NAM efforts. Using mass spectrometry coupled with either liquid or gas chromatography, a quality scoring system was developed that incorporated observations during mass spectral examination to provide a simple pass or fail notation. Informational flags were used to further describe findings regarding parent analyte presence through accurate mass identification, evidence of contaminants and/or degradation, or further describe characteristics such as isomer presence. Across the PFAS-DMSO stocks tested, 148 unique PFAS received passing quality scores to allow for further in vitro testing whereas 57 received a failing score primarily due to detection issues or confounding effects of DMSO. Principle component analysis indicated vapor pressure and Henry's Law Constant as top indicators for a failed quality score for those analyzed by gas chromatography. Three PFAS in the hexafluoropropylene oxide family failed due to degradation in DMSO. As the PFAS evaluated spanned over 20 different structural categories, additional commentary describes analytical observations across specific groups related to PFAS stock composition, detection, stability, and methodologic considerations that will be useful for informing future analytical assessment and downstream HTS efforts. The high-throughput stock quality scoring workflow presented holds value as a tool to evaluate chemical presence and quality efficiently and for informing data inclusion in PFAS or other NAM screening efforts.


Subject(s)
Dimethyl Sulfoxide , Fluorocarbons , High-Throughput Screening Assays , Computer Simulation , Excipients , Fluorocarbons/toxicity
10.
ALTEX ; 40(2): 248­270, 2023.
Article in English | MEDLINE | ID: mdl-36129398

ABSTRACT

A structurally diverse set of 147 per- and polyfluoroalkyl substances (PFAS) was screened in a panel of 12 human primary cell systems by measuring 148 biomarkers relevant to (patho)physiological pathways to inform hypotheses about potential mechanistic effects of data-poor PFAS in human model systems. This analysis focused on immunosuppressive activity, which was previously reported as an in vivo effect of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), by comparing PFAS responses to four pharmacological immunosuppressants. The PFOS response profile had little correlation with reference immunosuppressants, suggesting in vivo activity does not occur by similar mechanisms. The PFOA response profile did share features with the profile of dexamethasone, although some distinct features were lacking. Other PFAS, including 2,2,3,3-tetrafluoropropyl acrylate, demonstrated more similarity to the reference immunosuppressants but with additional activities not found in the reference immunosuppressive drugs. Correlation of PFAS profiles with a database of environmental chemical responses and pharmacological probes identified potential mechanisms of bioactivity for some PFAS, including responses similar to ubiquitin ligase inhibitors, deubiquitylating enzyme (DUB) inhibitors, and thioredoxin reductase inhibitors. Approximately 21% of the 147 PFAS with confirmed sample quality were bioactive at nominal testing concentrations in the 1-60 micromolar range in these human primary cell systems. These data provide new hypotheses for mechanisms of action for a subset of PFAS and may further aid in development of a PFAS categorization strategy useful in safety assessment.


Subject(s)
Alkanesulfonic Acids , Environmental Pollutants , Fluorocarbons , Humans , Alkanesulfonic Acids/toxicity , Caprylates , Fluorocarbons/toxicity , Fluorocarbons/analysis
11.
J Vis ; 22(9): 4, 2022 08 01.
Article in English | MEDLINE | ID: mdl-35925580

ABSTRACT

Ocular accommodation is the process of adjusting the eye's crystalline lens so as to bring the retinal image into sharp focus. The major stimulus to accommodation is therefore retinal defocus, and in essence, the job of accommodative control is to send a signal to the ciliary muscle which will minimize the magnitude of defocus. In this article, we first provide a tutorial introduction to control theory to aid vision scientists without this background. We then present a unified model of accommodative control that explains properties of the accommodative response for a wide range of accommodative stimuli. Following previous work, we conclude that most aspects of accommodation are well explained by dual integral control, with a "fast" or "phasic" integrator enabling response to rapid changes in demand, which hands over control to a "slow" or "tonic" integrator which maintains the response to steady demand. Control is complicated by the sensorimotor latencies within the system, which delay both information about defocus and the accommodation changes made in response, and by the sluggish response of the motor plant. These can be overcome by incorporating a Smith predictor, whereby the system predicts the delayed sensory consequences of its own motor actions. For the first time, we show that critically-damped dual integral control with a Smith predictor accounts for adaptation effects as well as for the gain and phase for sinusoidal oscillations in demand. In addition, we propose a novel proportional-control signal to account for the power spectrum of accommodative microfluctuations during steady fixation, which may be important in hunting for optimal focus, and for the nonlinear resonance observed for low-amplitude, high-frequency input. Complete Matlab/Simulink code implementing the model is provided at https://doi.org/10.25405/data.ncl.14945550.


Subject(s)
Accommodation, Ocular , Lens, Crystalline , Humans
13.
Ann Surg Oncol ; 29(9): 5462-5473, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35657463

ABSTRACT

BACKGROUND: Unresectable intrahepatic cholangiocarcinoma (ICC) carries a poor prognosis, and currently there are moderately established chemotherapeutic [gemcitabine/cisplatin (Gem/Cis)] treatments to prolong survival. The purpose of this study was to assess the efficacy of irinotecan drug-eluting beads (DEBIRI) therapy by transarterial infusion in combination with systemic therapy in unresectable ICC. PATIENTS AND METHODS: This is a prospective, multicenter, open-label, randomized phase II study (Clin Trials: NCT01648023-DELTIC trial) of patients with ICC randomly assigned to Gem/Cis with DEBIRI or Gem/Cis alone. The primary endpoint was response rate. RESULTS: The intention-to-treat population comprised 48 patients: 24 treated with Gem/Cis and DEBIRI and 22 with Gem/Cis alone (2 screen failures). The two groups were similar with respect to the extent of liver involvement (35% versus 38%) and presence of extrahepatic disease (29% versus 14%, p = 0.12). Median numbers of chemotherapy cycles were similar (6 versus 6), as were rates of grade 3/4 adverse events (34% for the Gem/Cis-DEBIRI group versus 36% for the Gem/Cis group). The overall response rate was significantly greater in the Gem/Cis-DEBIRI arm versus the Gem/Cis arm at 2 (p < 0.04), 4 (p < 0.03), and 6 months (p < 0.05). There was significantly more downsizing to resection/ablation in the Gem/Cis-DEBIRI arm versus the Gem/Cis arm (25% versus 8%, p < 005), and there was improved median progression-free survival [31.9 (95% CI 8.5-75.3) months versus 10.1 (95% CI 5.3-13.5) months, p = 0.028] and improved overall survival [33.7 (95% CI 13.5-54.5) months versus 12.6 (95% CI 8.7-33.4) months, p = 0.048]. CONCLUSION: Combination Gem/Cis with DEBIRI is safe, and leads to significant improvement in downsizing to resection, improved progression-free survival, and overall survival.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Liver Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bile Duct Neoplasms/drug therapy , Bile Duct Neoplasms/etiology , Bile Ducts, Intrahepatic , Camptothecin , Cholangiocarcinoma/drug therapy , Cisplatin/therapeutic use , Deoxycytidine/analogs & derivatives , Humans , Irinotecan/therapeutic use , Prospective Studies , Treatment Outcome , Gemcitabine
14.
Suicide Life Threat Behav ; 52(4): 782-791, 2022 08.
Article in English | MEDLINE | ID: mdl-35384040

ABSTRACT

OBJECTIVES: To improve the accuracy of classification of deaths of undetermined intent and to examine racial differences in misclassification. METHODS: We used natural language processing and statistical text analysis on restricted-access case narratives of suicides, homicides, and undetermined deaths in 37 states collected from the National Violent Death Reporting System (NVDRS) (2017). We fit separate race-specific classification models to predict suicide among undetermined cases using data from known homicide cases (true negatives) and known suicide cases (true positives). RESULTS: A classifier trained on an all-race dataset predicts less than half of these cases as suicide. Importantly, our analysis yields an estimated suicide rate for the Black population comparable with the typical detection rate for the White population, indicating that misclassification excess is endemic for Black suicide. This problem may be mitigated by using race-specific data. Our findings, based on the statistical text analysis, also reveal systematic differences in the phrases identified as most predictive of suicide. CONCLUSIONS: This study highlights the need to understand the reasons underlying suicide rate differences and for further testing of strategies to reduce misclassification, particularly among people of color.


Subject(s)
Suicide , Cause of Death , Homicide , Humans , Natural Language Processing , Population Surveillance , United States , Violence
15.
Psychiatr Serv ; 73(2): 180-187, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-34253036

ABSTRACT

OBJECTIVE: Persons with serious mental illness face adverse psychiatric and medical outcomes, and their care is associated with a large burden of health care costs. Care management, in which assessment, care planning, and care coordination are provided, is a common model of support, yet the evidence supporting its use among psychiatric populations is mixed. A systematic review and a meta-analysis were undertaken to determine the impact of care management on clinical outcomes, acute care utilization, cost, and satisfaction among adults with serious mental illness. METHODS: A multidatabase literature search was performed. Articles were included if they compared standard outpatient care plus care management with standard outpatient care alone for adults with serious mental illness and reported on one or more predefined outcomes. Randomized controlled trials (RCTs) and other study designs were permitted for inclusion in the systematic review. The meta-analysis included only RCTs. RESULTS: For the systematic review, 34 articles representing 28 unique studies were included. Fifteen of these articles, representing 12 unique studies, were included in the meta-analysis, which indicated that care management was associated with small, statistically significant improvements in psychiatric symptoms, overall quality of life (QOL), and mental QOL (Hedges' g range 0.13-0.26). In addition, care management was associated with a small, statistically significant reduction in inpatient psychiatric hospital days (Hedges' g=0.16, p=0.02). CONCLUSIONS: Care management is associated with fewer psychiatric symptoms and greater QOL for persons with serious mental illness. Further work is needed to determine which components of the intervention are associated with effectiveness.


Subject(s)
Mental Disorders , Adult , Ambulatory Care , Humans , Mental Disorders/therapy
16.
PLoS One ; 16(8): e0239352, 2021.
Article in English | MEDLINE | ID: mdl-34370739

ABSTRACT

The U.S. with only 4% of the world's population, bears a disproportionate share of infections in the COVID-19 pandemic. To understand this puzzle, we investigate how mitigation strategies and compliance can work together (or in opposition) to reduce (or increase) the spread of COVID-19 infection. Building on the Oxford index, we create state-specific stringency indices tailored to U.S. conditions, to measure the degree of strictness of public mitigation measures. A modified time-varying SEIRD model, incorporating this Stringency Index as well as a Compliance Indicator is then estimated with daily data for a sample of 6 U.S. states: New York, New Hampshire, New Mexico, Colorado, Texas, and Arizona. We provide a simple visual policy tool to evaluate the various combinations of mitigation policies and compliance that can reduce the basic reproduction number to less than one, the acknowledged threshold in the epidemiological literature to control the pandemic. Understanding of this relationship by both the public and policy makers is key to controlling the pandemic. This tool has the potential to be used in a real-time, dynamic fashion for flexible policy options. Our methodology can be applied to other countries and has the potential to be extended to other epidemiological models as well. With this first step in attempting to quantify the factors that go into the "black box" of the transmission factor ß, we hope that our work will stimulate further research in the dual role of mitigation policies and compliance.


Subject(s)
COVID-19/epidemiology , Administrative Personnel , Basic Reproduction Number/legislation & jurisprudence , Basic Reproduction Number/prevention & control , COVID-19/prevention & control , Communicable Disease Control/legislation & jurisprudence , Communicable Disease Control/methods , Humans , Pandemics/legislation & jurisprudence , Pandemics/prevention & control , SARS-CoV-2/isolation & purification , United States/epidemiology
17.
Toxicology ; 457: 152789, 2021 06 15.
Article in English | MEDLINE | ID: mdl-33887376

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) are a broad class of hundreds of fluorinated chemicals with environmental health concerns due to their widespread presence and persistence in the environment. Several of these chemicals have been comprehensively studied for experimental toxicity, environmental fate and exposure, and human epidemiology; however, most chemicals have limited or no data available. To inform methods for prioritizing these data-poor chemicals for detailed toxicity studies, we evaluated 142 PFAS using an in vitro screening platform consisting of two multiplexed transactivation assays encompassing 81 diverse transcription factor activities and tested in concentration-response format ranging from 137 nM to 300 µM. Results showed activity for various nuclear receptors, including three known PFAS targets--specifically estrogen receptor alpha and peroxisome proliferator receptors alpha and gamma. We also report activity against the retinoid X receptor beta, the key heterodimeric partner of type II, non-steroidal nuclear receptors. Additional activities were found against the pregnane X receptor, nuclear receptor related-1 protein, and nuclear factor erythroid 2-related factor 2, a sensor of oxidative stress. Using orthogonal assay approaches, we confirmed activity of representative PFAS against several of these targets. Finally, we identified key PFAS structural features associated with nuclear receptor activity that can inform future predictive models for use in prioritizing chemicals for risk assessment and in the design of new structures devoid of biological activity.


Subject(s)
Cell Proliferation/drug effects , Fluorocarbons/chemistry , Fluorocarbons/toxicity , Signal Transduction/drug effects , Cell Proliferation/physiology , Fluorocarbons/metabolism , Hep G2 Cells , Humans , Molecular Structure , Receptors, Cytoplasmic and Nuclear/metabolism , Signal Transduction/physiology
18.
Sci Rep ; 10(1): 20880, 2020 11 30.
Article in English | MEDLINE | ID: mdl-33257761

ABSTRACT

The study aimed to compare three methods for determining total (TF) and total soluble fluorides (TSF) in 5 child formula dentifrices (CFD) using Inter-method reliability (IMR) statistical approach. The methods were direct acid-hydrolysis (DM), the least-time-consuming method; Modified direct acid-hydrolysis with standard-addition method (MDM), ISO 19448:2018 method; and modified Taves acid-HMDS diffusion analysis (TAD), the claimed gold standard method. A significant difference in the mean difference was observed for all methods at all levels (p < 0.001), except DM and TAD for TF (p = 0.622). A proportional bias was discerned in the agreement distribution between DM and TAD for TF (p < 0.001). The ICC analysis identified significant reliability between all measurements, irrespective of the model, measure, and fluoride type (p < 0.001). For TF and TSF, the IMR between DM and TAD was lower than MDM and TAD for consistency/absolute agreement reliability at single/average measures. The reliability measure for DM and MDM was higher than MDM and TAD for TSF, but was lower than MDM and TAD for TF. The ICC measure for DM-TAD was significantly lower than DM-MDM and MDM-TAD (p < 0.05). The ISO 19448:2018 MDM is a reliable test that can be used as an alternative to TAD/DM for determining TF/TSF in CFD.

19.
J Clin Pediatr Dent ; 44(5): 332-341, 2020 Sep 01.
Article in English | MEDLINE | ID: mdl-33181840

ABSTRACT

OBJECTIVE(S): To: 1) examine the fluoride concentrations in commercial child formula dentifrices (CFD)s; and 2) investigate the effect of arginine incorporation in CFDs on fluoride bioavailability. STUDY DESIGN: Five commercial CFDs were examined for fluoride concentrations. Total, total soluble, and insoluble fluorides in CFDs were determined by the modified Taves acid-diffusion method (TAD). Ionic F and MFP were estimated by modified direct method with standard addition technique. L-arginine (L-Arg)/L-arginine monohydrochloride (L-Arg.HCl) were incorporated at 2% w/w in the commercial CFDs. The pH of the toothpaste slurries, buffer capacity of the added Arg, potentially available fluorides (PAF) and 1-min PAF by TAD were determined. RESULTS: The CFDs had 4 to 32% of insoluble fluorides. Addition of L-Arg/L-Arg.HCl significantly improved the fluoride bioavailability in CFDs (p<0.05). Incorporation of L-Arg significantly increased the pH of toothpaste slurries (p<0.05); while L-Arg.HCl decreased the pH. Principal component analysis showed that L-Arg.HCl decreased the pH of toothpaste slurries due to the presence of Cl in the form of HCl; whereas the inherent elements/molecules (Na/P/Pi/F) remain distinct with unidentified influence on the variables. CONCLUSION(S): The CFDs containing NaF only have higher concentrations of bioavailable fluoride. Incorporating arginine (L-arginine or L-arginine monohydrochloride) at 2% w/w improves fluoride bioavailability of the child formula dentifrices.


Subject(s)
Dentifrices , Fluorides , Arginine , Biological Availability , Cariostatic Agents , Child , Humans , Phosphates , Sodium Fluoride , Toothpastes
20.
Biotechnol Prog ; 36(6): e3056, 2020 11.
Article in English | MEDLINE | ID: mdl-32715664

ABSTRACT

Bacteria must be separated from septic whole blood in preparation for rapid antibiotic susceptibility tests. This work improves upon past work isolating bacteria from whole blood by exploring an important experimental factor: Whole blood dilution. Herein, we use the continuity equation to model red blood cell sedimentation and show that overall spinning time decreases as the blood is diluted. We found that the bacteria can also be captured more efficiently from diluted blood, up to approximately 68 ± 8% recovery (95% confidence interval). However, diluting blood both requires and creates extra fluid that end users must handle; an optimal dilution, which maximizes bacteria recovery and minimizes waste, was found to scale with the square root of the whole blood hematocrit. This work also explores a hypothesis that plasma backflow, which occurs as red cells move radially outward, causes bacterial enrichment in the supernatant plasma with an impact proportional to the plasma backflow velocity. Bacteria experiments carried out with diluted blood demonstrate such bacterial enrichment, but not in the hypothesized manner as enrichment occurred only in undiluted blood samples at physiological hematocrit.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteria/isolation & purification , Blood Sedimentation , Microbial Sensitivity Tests/methods , Bacteria/chemistry , Erythrocytes/microbiology , Humans
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