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1.
Am J Epidemiol ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38881045

ABSTRACT

Despite increasing prevalence of hypertension in youth and high adult cardiovascular mortality rates, the long-term consequences of youth-onset hypertension remain unknown. This is due to limitations of prior research such as small sample sizes, reliance on manual record review, and limited analytic methods that did not address major biases. The Study of the Epidemiology of Pediatric Hypertension (SUPERHERO) is a multisite retrospective Registry of youth evaluated by subspecialists for hypertension disorders. Sites obtain harmonized electronic health record data using standardized biomedical informatics scripts validated with randomized manual record review. Inclusion criteria are index visit for International Classification of Diseases Diagnostic Codes, 10th Revision (ICD-10 code)-defined hypertension disorder ≥January 1, 2015 and age <19 years. We exclude patients with ICD-10 code-defined pregnancy, kidney failure on dialysis, or kidney transplantation. Data include demographics, anthropomorphics, U.S. Census Bureau tract, histories, blood pressure, ICD-10 codes, medications, laboratory and imaging results, and ambulatory blood pressure. SUPERHERO leverages expertise in epidemiology, statistics, clinical care, and biomedical informatics to create the largest and most diverse registry of youth with newly diagnosed hypertension disorders. SUPERHERO's goals are to (i) reduce CVD burden across the life course and (ii) establish gold-standard biomedical informatics methods for youth with hypertension disorders.

2.
Environ Sci Technol ; 58(27): 11958-11969, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38922292

ABSTRACT

This study presents an updated analysis spanning over two decades (1999-2023) of climate, water quality, and operational data from two drinking water facilities in Atlantic Canada that previously experienced gradual increases in the natural organic matter (NOM) concentration and brownification. The goal was to assess the impact of recent extreme weather events on acute NOM concentration increases and drinking water treatment processes. In 2023, a dry spring combined with a warm and wet summer caused NOM in the water supplies to increase by >67% (as measured by color). To mitigate increased NOM concentration, the alum dose nearly doubled in 2023 compared to that in 2022. Disinfection byproducts were elevated following the event but remained within the compliance levels. From 1999 to 2023, the two plants responded to gradual climate change impacts and brownification, with alum dose increases of between 4.1 and 8.3 times. Equivalent CO2 emissions were estimated for alum usage, which increased by 3 to 7-fold in 2023 compared to when the plants were commissioned decades prior. The plants were not only adversely impacted by climate change but also contributed to the global CO2 burden. Thus, a paradigm shift toward sustainable alternatives for NOM removal is required in the water sector, and climate change adaptation and mitigation principles are urgently needed.


Subject(s)
Climate Change , Drinking Water , Water Purification , Drinking Water/chemistry , Water Supply , Water Quality , Canada
3.
Transfusion ; 63 Suppl 3: S46-S53, 2023 05.
Article in English | MEDLINE | ID: mdl-36971017

ABSTRACT

BACKGROUND: Questions persist about the safety of switching non-group O recipients of group O uncrossmatched red blood cells (RBC) or low titer group O whole blood (LTOWB) to ABO-identical RBCs during their resuscitation. METHODS: The database of an earlier nine-center study of transfusing incompatible plasma to trauma patients was reanalyzed. The patients were divided into three groups based on 24-h RBC transfusion: (1) group O patients who received group O RBC/LTOWB units (control group, n = 1203), (2) non-group O recipients who received only group O units (n = 646), (3) non-group O recipients who received at least one unit of group O and non-group O units (n = 562). Fixed marginal effect of receipt of non-O RBC units on 6- and 24-h and 30-day mortality was calculated. RESULTS: The non-O patients who received only group O RBCs received fewer RBC/LTOWB units and had slightly but significantly lower injury severity score compared to control group; non-group O patients who received both group O and non-O units received significantly more RBC/LTOWB units and had a slightly but significantly higher injury severity score compared to control group. In the multivariate analysis, the non-O patients who received only group O RBCs had significantly higher mortality at 6-h compared to the controls; the non-group O recipients of O and non-O RBCs did not demonstrate higher mortality. At 24-h and 30-days, there were no differences in survival between the groups. CONCLUSION: Providing non-group O RBCs to non-group O trauma patients who also received group O RBC units is not associated with higher mortality.


Subject(s)
Blood Transfusion , Wounds and Injuries , Humans , Erythrocyte Transfusion/adverse effects , Resuscitation , Erythrocytes , ABO Blood-Group System , Wounds and Injuries/therapy
4.
Int J Behav Med ; 2023 Nov 03.
Article in English | MEDLINE | ID: mdl-37923884

ABSTRACT

BACKGROUND: Chronic vulvovaginal pain (CVVP), an umbrella term encompassing several gynecological pain conditions (e.g., vulvodynia, vaginismus), has a prevalence rate of 7-8% in the USA and is characterized by considerable diagnostic delay in patient experience research. Furthermore, current research in this area focuses largely on the experiences of white women, while the experiences of women of color are underrepresented. METHOD: In the present cross-sectional study (N = 488), we surveyed women of color (i.e., Asian, Black, and/or Hispanic/Latinx women) with CVVP about their perceptions and experiences with medical mistrust, healthcare seeking, and healthcare avoidance. RESULTS: Using the suspicion subscale of the Group-Based Medical Mistrust Scale, we found significant racial and ethnic differences in medical suspicion scores, with non-Black Hispanic/Latinx women reporting the highest suspicion scores and non-Hispanic/Latinx Black women reporting the lowest scores. Racial differences disappeared, however, after examining medical mistrust and perceived discrimination as predictors for various healthcare outcomes related to the journey to diagnosis and healthcare avoidance behaviors. We found that while suspicion was a reliable predictor of increased diagnostic delay and healthcare avoidance in many contexts, the results for perceived discrimination were more varied, suggesting considerable nuance in the relationship between medical mistrust, perceived discrimination, and healthcare seeking outcomes. CONCLUSION: These findings point to shared experiences of medical mistrust via suspicion that broadly characterize women of color's experiences in seeking CVVP-related care-future research is needed to examine nuances within racial and ethnic groups regarding their healthcare seeking experiences in the CVVP context.

5.
Sex Cult ; : 1-24, 2023 May 18.
Article in English | MEDLINE | ID: mdl-37360016

ABSTRACT

Around 142 million American adults are currently single; at least half of these singles want to pursue a romantic partner. Romantic dating can involve exposure to numerous people. Thus, dating can significantly impact pathogen exposure risk. In a demographically-representative cross-sectional survey conducted in 2021 (N = 5,000), we examined U.S. American singles' COVID-19 vaccination status, assessed their preferences around a potential partner's COVID-19 vaccination status, and identified demographic subgroups of singles particularly opposed to or indifferent to a partner being vaccinated against COVID-19. Our results showed 65% of participants were fully vaccinated, 10% were partially vaccinated, and 26% were unvaccinated against COVID-19. With regards to partner preferences, half wanted a vaccinated partner; 18.9% wanted a vaccinated partner but would make exceptions; 6.1% wanted an unvaccinated partner; and 25% reported that they did not care about their dating partner's vaccination status. Partner preferences were largely aligned with participants' own vaccination status, such that vaccinated participants preferred vaccinated partners. However, those preferring unvaccinated partners-or those willing to make exceptions for a partner-were most likely to identify as men, younger in age, a political affiliation outside of the two-party political system, a gender or sexual minority, or as a racial minority (i.e., Black/African-American or South Asian). Additionally, participants who were employed (vs. unemployed) were more likely to make exceptions for or prefer an unvaccinated partner. These results suggest that singles prefer homophily in COVID-19 vaccine status, and that minoritized subgroups of singles are more likely to maintain a social network including unvaccinated close others. Supplementary Information: The online version contains supplementary material available at 10.1007/s12119-023-10097-9.

6.
J Anat ; 241(2): 195-210, 2022 08.
Article in English | MEDLINE | ID: mdl-35527424

ABSTRACT

Frontal sinus morphology is highly variable across individuals, but little is known regarding how or at what age that variation is reached. Existing ontogenetic studies are conflicting and often cross-sectional in nature, limiting understanding of individualistic growth. Studies investigating sinus growth with longitudinal series often focus on lateral cephalograms and consequently do not capture the sinus morphological features that are most relevant to clinical and medicolegal settings (e.g., arcade/scalloping, width-to-height dimensions, asymmetry). Longitudinal analysis of sinus morphology from frontal radiographs is important to understand when sinus morphology stabilizes. The purpose of this study was to investigate at what age the frontal sinus attains its final shape, and whether sex-based differences in ontogeny are evident, using a longitudinal sample of posterior-anterior (PA) frontal radiographs from the AAOF Legacy Collection. Frontal sinus outlines were manually traced in 935 radiographs from 111 individuals (55F/56M) spanning 8-29 years of age. Outlines were subjected to elliptical Fourier analysis (EFA) and underwent principal components analysis (PCA). PC1 (51.02% of variation) appears to represent the relative height and breadth of the sinus, PC2 (11.73%) and PC3 (10.03%) captures the degree of relative complexity in the outlines. Individual PC scores were plotted against age-in-months with individual Loess growth curves. Overall, younger individuals typically display relatively shorter, flatter sinuses, increasing in vertical complexity with age. Mixed-effect models on PC1 indicate significant effects for the repeated measure of years (p < 0.001). Within individuals, Euclidean distances of PCs between each sinus outline and their oldest-age outline (i.e., final morphology) were calculated and plotted against age-in-months with Loess growth curves. The results indicate that final frontal sinus morphology is mostly attained by 20 yoa regardless of sex. There is sexual dimorphism in ontogenetic trajectories: females attain frontal sinus shape earlier than males. Specifically, Loess growth curves of the Euclidean distances to final sinus shape indicate that female shape shows decreased development at 14-16 yoa, with males approaching stabilization at 18-20 yoa. These trends were supported by paired t-tests on PC1 between each year and the oldest age, whereby significant differences end for females starting at 15 and 18 yoa for males. The timing of shape-stabilization in the current study closely aligns with previous studies on linear and size dimensions, indicating a close relationship between the ontogeny of frontal sinus shape and size. This research has several implications in diverse fields. Documenting ontogenetic patterns in modern humans could lead to more accurate interpretations of frontal sinus variation in hominin lineages. Understanding the age at which frontal sinus shape and size stabilizes in pediatric populations has important clinical implications, with future studies needed to investigate if/how sinus development directly relates to sinonasal disease susceptibility (e.g., sinusitis), surgical complications, and/or expected trauma patterns. For forensic practitioners utilizing frontal sinus comparisons for decedent identifications, it is important to know at what age these features stabilize to understand how much change may be expected between antemortem and postmortem radiographs.


Subject(s)
Frontal Sinus , Child , Cross-Sectional Studies , Female , Fourier Analysis , Frontal Sinus/anatomy & histology , Frontal Sinus/diagnostic imaging , Humans , Longitudinal Studies , Male , Radiography
7.
J Lesbian Stud ; 26(4): 354-366, 2022.
Article in English | MEDLINE | ID: mdl-36070495

ABSTRACT

The introductions of scholarly works on queer desire between eighteenth- and nineteenth-century British women typically pose some version of the question "do they count as lesbians?" Historians and literary critics have responded with a variety of answers; while some embrace the term "lesbian" despite the anachronism, others hesitate, using words like "Sapphic" or longer phrases like "women who loved women" to characterize the object of study. Indeed, in the absence of a noun or a recognized social role for women who loved other women before the twentieth century, the ways such women conceptualized themselves necessarily diverge from modern lesbian identity. But although the hesitation to use modern terminology makes sense in the case of many women, I argue in this paper that Anne Lister (1791-1840) is an exception. From her own descriptions in her extensive diaries, it is clear that Lister's thoughts, feelings, and actions are largely consistent with modern lesbian identity-particularly given that "modern lesbian identity" is not a monolith. I support this contention by examining evidence from the journals themselves as well as by considering recent arguments that focus on the fluidity and capaciousness of terminology itself. Finally, I suggest that applying the word "lesbian" to Lister is a strategic way to communicate the extent of her relationships with women to a public that still sometimes refuses to admit that such relationships existed in the past.


Subject(s)
Homosexuality, Female , Sexual and Gender Minorities , Female , Humans , Emotions
8.
Eur Arch Otorhinolaryngol ; 278(5): 1471-1476, 2021 May.
Article in English | MEDLINE | ID: mdl-33141253

ABSTRACT

PURPOSE: Chronic rhinosinusitis (CRS) is increasingly common in the elderly population (≥ 65 years old). Compared to their younger counterparts, differences exist in the etiology of CRS and outcomes of Endoscopic Sinus Surgery (ESS) for elderly patients. The aim of this study is to determine if differences in surgical outcomes are present between these two patient populations to facilitate patient pre-operative counseling by their healthcare providers. METHODS: Retrospective chart review conducted at a single tertiary care center for patients undergoing ESS between June 2014 and June 2019. Patients were classified into two cohorts (adult and elderly) based on age (< 65 and ≥ 65 years old). Demographics, surgical, and postoperative variables were extracted from our institution's electronic medical records. ANOVA and t-test analysis were performed to determine the presence of significant differences between the two cohorts. SNOT-22 scores were used to determine QOL improvements. RESULTS: Compared to the adult cohort, elderly patients had significant QOL improvement after surgical treatment (p = 0.001), but had a similar successful response to treatment (p = 0.74). Elderly patients had no difference in the incidence of operative/perioperative complications (p = 0.89) or intraoperative or postoperative bleeding (p = 0.301, p = 0.62), but had an increased incidence of postoperative infection (p = 0.000). CONCLUSION: ESS remains an effective treatment modality for the management of CRS, and a safe practice for elderly patients despite the increase in complexity of their medical comorbidities and polypharmacy. QOL improvements are significant, though patient counseling should take into account that improvements may not be as pronounced as in younger patients.


Subject(s)
Paranasal Sinuses , Rhinitis , Sinusitis , Adult , Aged , Chronic Disease , Endoscopy , Humans , Paranasal Sinuses/surgery , Quality of Life , Retrospective Studies , Rhinitis/epidemiology , Rhinitis/surgery , Sinusitis/epidemiology , Sinusitis/surgery , Treatment Outcome
9.
J Hand Ther ; 34(1): 121-126, 2021.
Article in English | MEDLINE | ID: mdl-31956019

ABSTRACT

STUDY DESIGN: Survey research. METHODS: A pilot tested survey was administered through an electronic mailing system to 5777 CHTs with email addresses on file at Hand Therapy Certification Commission. The survey was electronically distributed on two separate occasions to maximize the response rate. RESULTS: The response rate was 53% (n = 1271). The majority of the respondents who were not members of ASHT, 49% (441), indicated that member fees are too expensive, and 35% (311) respondents selected other as the reason. They specified that they were members in another country, the expenses were too high, or that they were retired. Ten percent (93) of respondents answered that they did not know what member benefits were offered, and 4% (40) responded that they do not value the member benefits offered. Finally, 2% (14) of participants answered that they do not value membership in any other professional organization. DISCUSSION: While ASHT membership cost is lower than the benefits the member receives, some do not believe that the costs outweighs the benefits. The combination of these factors accounts for approximately half of all CHTs choosing not to join ASHT. CONCLUSION: Many established members value their membership and find it beneficial not only for themselves but also for furthering the profession as well. Many CHTs identified cost as the most apparent factor for not joining ASHT.


Subject(s)
Certification , Societies , Humans , Surveys and Questionnaires , United States
10.
Transfusion ; 60(11): 2517-2528, 2020 11.
Article in English | MEDLINE | ID: mdl-32901965

ABSTRACT

BACKGROUND: This study investigated the effect on mortality of transfusing ABO-incompatible plasma from all sources during trauma resuscitation. METHODS: Demographic, transfusion, and survival data were retrospectively extracted on civilian trauma patients. Patients were divided by receipt of any quantity of ABO-incompatible plasma from any blood product (incompatible group) or receipt of solely ABO-compatible plasma (compatible group). The primary outcome was 30-day mortality, while other outcomes included 6- and 24-hour mortality. Mixed-effects logistic regression was used to model the effect of various predictor variables, including receipt of incompatible plasma, on mortality outcomes. RESULTS: Nine hospitals contributed data on a total of 2618 trauma patients. There were 1282 patients in the incompatible group and 1336 patients in the compatible group. In both the unadjusted and adjusted models, the 6-hour, 24-hour, and 30-day mortality rates were not significantly different between these groups. The patients in the incompatible group were then divided into high volume (>342 mL) and low volume (≤342 mL) incompatible plasma recipients. In the adjusted model, the high-volume group had higher 24-hour mortality when the Trauma Injury Severity Score survival prediction was >50%. Mortality at 6 hours and 30 days was not higher in this model. The low-volume group did not have increased mortality at any of the time points in this adjusted model. CONCLUSION: The transfusion of incompatible plasma in civilian trauma resuscitation does not lead to higher 30-day mortality. The finding of higher mortality in a select group of recipients in the secondary analysis warrants further study.


Subject(s)
ABO Blood-Group System/blood , Blood Component Transfusion , Blood Group Incompatibility , Models, Biological , Resuscitation , Wounds and Injuries , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Humans , Male , Middle Aged , Retrospective Studies , Survival Rate , Trauma Severity Indices , Wounds and Injuries/blood , Wounds and Injuries/mortality , Wounds and Injuries/therapy
11.
Environ Sci Technol ; 54(4): 2192-2201, 2020 02 18.
Article in English | MEDLINE | ID: mdl-31961665

ABSTRACT

Access to clean and safe drinking water is a perpetual concern in Arctic communities because of challenging climatic conditions, limited options for the transportation of equipment and process chemicals, and the ongoing effects of colonialism. Water samples were gathered from multiple locations in a decentralized trucked drinking water system in Nunavut, Canada, over the course of one year. The results indicate that point of use drinking water quality was impacted by conditions in the source water and in individual buildings and strongly suggest that lead and copper measured at the tap were related to corrosion of onsite premise plumbing components. Humic-like substances were the dominant organic fraction in all samples, as determined by regional integration of fluorescence data. Iron and manganese levels in the source water and throughout the water system were higher in the winter and lower in the summer months. Elevated concentrations of copper (>2000 µg L-1) and lead (>5 µg L-1) were detected in tap water from some buildings. Field flow fractionation coupled with inductively coupled plasma mass spectrometry and ultraviolet-visible spectrometry was used to demonstrate the link between source water characteristics (high organics, iron and manganese) and lead and copper in point of use drinking water.


Subject(s)
Drinking Water , Water Pollutants, Chemical , Canada , Corrosion , Nunavut , Water Quality , Water Supply
12.
Pediatr Nephrol ; 34(7): 1261-1268, 2019 07.
Article in English | MEDLINE | ID: mdl-30778828

ABSTRACT

BACKGROUND: Left ventricular hypertrophy (LVH) and arterial stiffness measured by pulse wave velocity (PWV) are independent predictors of cardiovascular (CV) mortality in adults receiving chronic dialysis. Hypertension strongly associates with elevated left ventricular mass index (LVMI) and PWV, with ambulatory blood pressure monitoring (ABPM), and central blood pressure (CBP) superior to office blood pressures (BP) in predicting CV morbidity. Few studies have described associations of office BP, ABPM, and CBP with LVMI and PWV in adolescent and young adult patients receiving hemodialysis (HD). METHODS: Cross-sectional study of 22 adolescents and young adults receiving chronic HD. Pre- and post-dialysis office BP and CBP using applanation tonometry were obtained. Twenty-four-hour ABPM was obtained midweek post-dialysis. Pre- and post-dialysis carotid-brachial PWV were obtained same day as BP measurements. Annual echocardiograms for standard care were reviewed for LVH. RESULTS: Pre-dialysis CBP index correlated with LVMI (r = 0.3, p = 0.04) and PWV (r = 0.48, p = 0.02). Hypertensive patients identified by ABPM had worse LVMI; daytime ABPM systolic BP index correlated with LVMI (r = 0.5, p = 0.02). Office BP was not associated with LVMI; only office diastolic BP was associated with PWV (r = 0.46, p = 0.02). There was no correlation of LVMI or PWV with bone health parameters, anemia, interdialytic weight gain, or residual renal function. CONCLUSIONS: Ambulatory blood pressure monitoring is superior to casual office BP obtained at time of dialysis in delineating cardiovascular morbidity in adolescent and young adult HD patients. CBP is easily performed and correlates with LVMI and PWV in adolescent and young adult HD patients; however, large-scale normative data is needed.


Subject(s)
Arterial Pressure , Blood Pressure Monitoring, Ambulatory , Hypertension/diagnosis , Hypertrophy, Left Ventricular/etiology , Kidney Failure, Chronic/complications , Vascular Stiffness , Adolescent , Adult , Arteries/physiopathology , Child , Cross-Sectional Studies , Female , Humans , Hypertension/etiology , Kidney Failure, Chronic/therapy , Male , Pulse Wave Analysis , Renal Dialysis , Young Adult
13.
Aust J Rural Health ; 27(5): 419-426, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31571313

ABSTRACT

OBJECTIVE: To examine allied health client, provider and community referrer perceptions of telehealth for the delivery of rural paediatric allied health services to facilitate adoption. DESIGN: A qualitative design employed semistructured interviews with the three key stakeholder groups. SETTING: Stakeholders were associated with BUSHkids (The Royal Queensland Bush Children's Health Scheme), a not-for-profit organisation serving children and families in Queensland, Australia. PARTICIPANTS: Thirty-nine stakeholders (12 clients, 16 providers and 11 community referrers). MAIN OUTCOME MEASURES: Participants were asked about familiarity with telehealth, willingness to use telehealth and perceived barriers and facilitators to telehealth acceptability. RESULT: Fifty-nine percent of participants had experienced telehealth and 77 percent were willing to use it. Participants perceived that technology problems were a barrier to telehealth, that children would not be able to concentrate on or enjoy telehealth sessions, that relationships and communication would be inferior to in-person sessions, and that telehealth was inappropriate for disciplines employing physical touch. Participants identified access to health services as a key benefit of telehealth, said that technology problems could be worked around, and said that telehealth services could be supported with internal partners (eg, assistants) and external partners (eg, local medical centres). They also identified a variety of telehealth benefits to families (eg, convenience, privacy). CONCLUSION: Overall, telehealth was acceptable to stakeholders. Providers need training to facilitate child participation online and identify alternatives to physical touch. Co-learning opportunities should be used to address low provider and referrer self-efficacy.


Subject(s)
Adoption , Attitude of Health Personnel , Child Health Services/organization & administration , Delivery of Health Care/organization & administration , Rural Health Services/organization & administration , Telemedicine , Adult , Aged , Child , Female , Humans , Interviews as Topic , Male , Middle Aged , Qualitative Research , Queensland
14.
Radiology ; 287(3): 778-786, 2018 06.
Article in English | MEDLINE | ID: mdl-29431574

ABSTRACT

Purpose To identify dynamic optical imaging features that associate with the degree of pathologic response in patients with breast cancer during neoadjuvant chemotherapy (NAC). Materials and Methods Of 40 patients with breast cancer who participated in a longitudinal study between June 2011 and March 2016, 34 completed the study. There were 13 patients who obtained a pathologic complete response (pCR) and 21 patients who did not obtain a pCR. Imaging data from six subjects were excluded from the study because either the patients dropped out of the study before it was finished or there was an instrumentation malfunction. Two weeks into the treatment regimen, three-dimensional images of both breasts during a breath hold were acquired by using dynamic diffuse optical tomography. Features from the breath-hold traces were used to distinguish between response groups. Receiver operating characteristic (ROC) curves and sensitivity analysis were used to determine the degree of association with 5-month treatment outcome. Results An ROC curve analysis showed that this method could identify patients with a pCR with a positive predictive value of 70.6% (12 of 17), a negative predictive value of 94.1% (16 of 17), a sensitivity of 92.3% (12 of 13), a specificity of 76.2% (16 of 21), and an area under the ROC curve of 0.85. Conclusion Several dynamic optical imaging features obtained within 2 weeks of NAC initiation were identified that showed statistically significant differences between patients with pCR and patients without pCR as determined 5 months after treatment initiation. If confirmed in a larger cohort prospective study, these dynamic imaging features may be used to predict treatment outcome as early as 2 weeks after treatment initiation. © RSNA, 2018 Online supplemental material is available for this article.


Subject(s)
Breast Neoplasms/diagnostic imaging , Breast Neoplasms/drug therapy , Neoadjuvant Therapy/methods , Tomography, Optical/methods , Adult , Breast/diagnostic imaging , Chemotherapy, Adjuvant , Female , Humans , Longitudinal Studies , Middle Aged , Sensitivity and Specificity , Treatment Outcome
15.
Biotechnol Bioeng ; 115(2): 413-422, 2018 02.
Article in English | MEDLINE | ID: mdl-29064563

ABSTRACT

Host cell proteins (HCPs) are a heterogeneous mixture of impurities that should be minimized in bulk preparations of biotechnologically produced medicines. Immunoassays are commonly used to detect and measure HCPs in therapeutic products, and a successful assay is directly dependent on the quality of the polyclonal antibodies (pAbs) used. These pAbs are enriched from antisera of animals immunized with a broad mixture of HCPs, but there is limited information regarding the best strategy for purification of these critical reagents. The use of protein A or protein G affinity chromatography results in purified pAbs that are not entirely HCP-specific, while the use of HCP affinity chromatography results in a more specific pAb population but may be harder to recover fully. In theory, both approaches have advantages and disadvantages for generating optimal reagents. In this study, we compared reagents from these two purification procedures using the same starting material, as well as those from a step-wise combination of the two by evaluating purity, concentration, reagent coverage by Western blotting, and performance in an enzyme-linked immunosorbent assay (ELISA). This study demonstrates that pAbs purified by each of the methods are very similar in terms of sensitivity, the ability to recognize a broad range of HCPs, and overall performance in an ELISA measuring a range of HCPs in upstream process and final drug substance (DS) samples.


Subject(s)
Antibodies/isolation & purification , Blotting, Western/methods , Chromatography, Affinity/methods , Enzyme-Linked Immunosorbent Assay/methods , Animals , Antibodies/analysis , Antibodies/chemistry , Biotechnology , CHO Cells , Cricetinae , Cricetulus , Proteins/chemistry
16.
Breast Cancer Res Treat ; 162(3): 533-540, 2017 04.
Article in English | MEDLINE | ID: mdl-28190249

ABSTRACT

PURPOSE: Breast cancer (BC) patients who achieve a favorable residual cancer burden (RCB) after neoadjuvant chemotherapy (NACT) have an improved recurrence-free survival. Those who have an unfavorable RCB will have gone through months of ineffective chemotherapy. No ideal method exists to predict a favorable RCB early during NACT. Diffuse optical tomography (DOT) is a novel imaging modality that uses near-infrared light to assess hemoglobin concentrations within breast tumors. We hypothesized that the 2-week percent change in DOT-measured hemoglobin concentrations would associate with RCB. METHODS: We conducted an observational study of 40 women with stage II-IIIC BC who received standard NACT. DOT imaging was performed at baseline and 2 weeks after treatment initiation. We evaluated the associations between the RCB index (continuous measure), class (categorical 0, I, II, III), and response (RCB class 0/I = favorable, RCB class II/III = unfavorable) with changes in DOT-measured hemoglobin concentrations. RESULTS: The RCB index correlated significantly with the 2-week percent change in oxyhemoglobin [HbO2] (r = 0.5, p = 0.003), deoxyhemoglobin [Hb] (r = 0.37, p = 0.03), and total hemoglobin concentrations [HbT] (r = 0.5, p = 0.003). The RCB class and response significantly associated with the 2-week percent change in [HbO2] (p ≤ 0.01) and [HbT] (p ≤ 0.02). [HbT] 2-week percent change had sensitivity, specificity, positive, and negative predictive values for a favorable RCB response of 86.7, 68.4, 68.4, and 86.7%, respectively. CONCLUSION: The 2-week percent change in DOT-measured hemoglobin concentrations was associated with the RCB index, class, and response. DOT may help guide NACT for women with BC.


Subject(s)
Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Neoplasm, Residual/pathology , Tomography, Optical , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor , Breast Neoplasms/drug therapy , Female , Humans , Magnetic Resonance Imaging , Mammography , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Sensitivity and Specificity , Tomography, Optical/methods , Tumor Burden
17.
PLoS Pathog ; 10(8): e1004350, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25166009

ABSTRACT

In this study, we have identified a unique mechanism in which human cytomegalovirus (HCMV) protein pUL79 acts as an elongation factor to direct cellular RNA polymerase II for viral transcription during late times of infection. We and others previously reported that pUL79 and its homologues are required for viral transcript accumulation after viral DNA synthesis. We hypothesized that pUL79 represented a unique mechanism to regulate viral transcription at late times during HCMV infection. To test this hypothesis, we analyzed the proteome associated with pUL79 during virus infection by mass spectrometry. We identified both cellular transcriptional factors, including multiple RNA polymerase II (RNAP II) subunits, and novel viral transactivators, including pUL87 and pUL95, as protein binding partners of pUL79. Co-immunoprecipitation (co-IP) followed by immunoblot analysis confirmed the pUL79-RNAP II interaction, and this interaction was independent of any other viral proteins. Using a recombinant HCMV virus where pUL79 protein is conditionally regulated by a protein destabilization domain ddFKBP, we showed that this interaction did not alter the total levels of RNAP II or its recruitment to viral late promoters. Furthermore, pUL79 did not alter the phosphorylation profiles of the RNAP II C-terminal domain, which was critical for transcriptional regulation. Rather, a nuclear run-on assay indicated that, in the absence of pUL79, RNAP II failed to elongate and stalled on the viral DNA. pUL79-dependent RNAP II elongation was required for transcription from all three kinetic classes of viral genes (i.e. immediate-early, early, and late) at late times during virus infection. In contrast, host gene transcription during HCMV infection was independent of pUL79. In summary, we have identified a novel viral mechanism by which pUL79, and potentially other viral factors, regulates the rate of RNAP II transcription machinery on viral transcription during late stages of HCMV infection.


Subject(s)
Cytomegalovirus Infections/genetics , Gene Expression Regulation, Viral/genetics , Peptide Elongation Factors/genetics , RNA Polymerase II/genetics , Viral Proteins/genetics , Chromatin Immunoprecipitation , Cytomegalovirus/genetics , Fibroblasts/virology , Genes, Viral , HEK293 Cells , Humans , Immunoblotting , Immunoprecipitation , Mass Spectrometry , Transcription, Genetic , Transfection
18.
Nutrients ; 16(4)2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38398860

ABSTRACT

The Human Interference Scoring System (HISS) is a novel food-based diet-quality-classification system based on the existing NOVA method. HISS involves food and fluid allocation into categories from digital imagery based on food processing levels, followed by meal plan analysis using food-servings quantification. The primary purpose of this work was to evaluate the reliability of HISS. Trained nutrition professionals analyzed digital photographs from five hypothetical 24 h food recalls and categorized foods into one of four HISS categories. A secondary purpose was to assess the nutrient composition of the food recalls and other selected foods from the HISS categories. Participants effectively categorized foods into HISS categories, with only minor discrepancies noted. High inter-rater reliability was observed in the outer HISS categories: unprocessed and ultra-processed foods. Ultra-processed items consistently displayed elevated energy, carbohydrates, and sugar compared to unprocessed foods, while unprocessed foods exhibited notably higher dietary fiber. This study introduces the HISS as a potentially useful tool for quantifying a food-quality-based system using digital-photography-based assessments. Its high inter-rater reliability and ability to capture relationships between food processing levels and nutrient composition make it a promising method for assessing dietary habits and food quality.


Subject(s)
Fast Foods , Food Quality , Humans , Reproducibility of Results , Nutritive Value , Diet , Food Handling , Energy Intake
19.
Disabil Rehabil ; 46(2): 344-353, 2024 Jan.
Article in English | MEDLINE | ID: mdl-36593725

ABSTRACT

PURPOSE: Language and communication disorders can inhibit participation in activities that have potential therapeutic benefits for recovery. This exploratory research examined the usability and feasibility of a purpose-built music listening mobile application for people living in the community with post-stroke aphasia, and examined relationships between useability and participant age, aphasia severity and time post-stroke. METHODS: Nineteen participants with chronic aphasia tested the application for two weeks. Prior to use, music preferences, technology use and confidence, self-efficacy and music engagement questionnaires were completed. System usability scale, music listening data and a satisfaction rating were completed following use. RESULTS: Overall, the application was perceived as being usable and feasible with a high system usability rating and moderate effectiveness, efficiency and satisfaction. The system usability scores were not associated with aphasia severity, age, years post-stroke, self-efficacy or music engagement. Technology confidence was positively associated with system usability. CONCLUSION: The music listening application is a feasible and usable option for listening to music in people with chronic post-stroke aphasia. This study provides a foundation for the rigorous examination of the usability of music listening technology for people with post-stroke aphasia and the potential investigation of use in acute care facilities and other clinical populations.IMPLICATIONS FOR REHABILITATIONMusic listening has potential therapeutic benefits for people with post-stroke aphasia.Applications for music listening require customisation to enable people with post-stroke aphasia opportunity to listen to their preferred music.Music listening applications that are perceived as usable and feasible by people with post-stroke aphasia may have potential application within rehabilitation and community settings.


Subject(s)
Aphasia , Mobile Applications , Music , Stroke , Humans , Feasibility Studies , Aphasia/etiology , Aphasia/therapy , Stroke/complications
20.
J Forensic Sci ; 69(4): 1155-1170, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38682435

ABSTRACT

Several code-based methods have been created for comparing the frontal sinus in skeletal identification scenarios. However, little is known regarding matched-pair accuracy rates of these methods or how varying image modalities may affect these rates. The goals of this study were to validate the exclusion rates and to establish matched-pair accuracy rates of two well-cited coding methods, Cameriere et al. [23] and Tatlisumak et al. [24]. Additionally, individual variables were assessed for consistency in scoring between image modalities. Using a sample of U.S. African American, Native American, and European American females and males (n = 225), we examined individual variable scoring and string codes between two different image modalities (radiographs and CT-based 3D models). Arcades showed poor scoring consistency between modalities (p < 0.001). Although exclusion rates were similar to those reported in the original studies (93%-96%), matched-pair accuracy rates were low (13%-18%). None of the demographics (collection, sex, age, ancestry, and orientation) had an effect on the odds of a match. Interobserver and intraobserver analyses showed moderate to near-perfect agreement for all variables except supraorbital cells, which had minimal to no agreement. Currently, we do not recommend the application of these frontal sinus coding methods independent of other supporting identification methods given low variable consistency and accuracy rates. Visual identification should still be used to include or exclude an identification when using the frontal sinus.


Subject(s)
Forensic Anthropology , Frontal Sinus , Imaging, Three-Dimensional , Tomography, X-Ray Computed , Humans , Frontal Sinus/diagnostic imaging , Frontal Sinus/anatomy & histology , Male , Forensic Anthropology/methods , Female , Adult , Young Adult , Racial Groups , Middle Aged , Adolescent , Observer Variation , Aged
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