A field-validated equilibrium passive sampler for the monitoring of per- and polyfluoroalkyl substances (PFAS) in sediment pore water and surface water.

A simple equilibrium passive sampler, consisting of water in an inert container capped with a rate-limiting barrier, for the monitoring of per- and polyfluoroalkyl substances (PFAS) in sediment pore water and surface water was developed and tested through a series of laboratory and field experiments. The objectives of the laboratory experiments were to determine (1) the membrane type that could serve as the sampler's rate-limiting barrier, (2) the mass transfer coefficient of environmentally relevant PFAS through the selected membrane, and (3) the performance reference compounds (PRCs) that could be used to infer the kinetics of PFAS diffusing into the sampler. Of the membranes tested, the polycarbonate (PC) membrane was deemed the most suitable rate-limiting barrier, given that it did not appreciably adsorb the studied PFAS (which have ≤8 carbons), and that the migration of these compounds through this membrane could be described by Fick's law of diffusion. When employed as the PRC, the isotopically labelled PFAS M2PFOA and M4PFOS were able to predict the mass transfer coefficients of the studied PFAS analytes. In contrast, the mass transfer coefficients were underpredicted by Br- and M3PFPeA. For validation, the PC-based passive samplers consisting of these four PRCs, as well as two other PRCs (i.e., M8PFOA and C8H17SO3-), were deployed in the sediment and water at a PFAS-impacted field site. The concentration-time profiles of the PRCs indicated that the samplers deployed in the sediment required at least 6 to 7 weeks to reach 90% equilibrium. If the deployment times are shorter (e.g., 2 to 4 weeks), PFAS concentrations at equilibrium could be estimated based on the concentrations of the PRCs remaining in the sampler at retrieval. All PFAS concentrations determined via this approach were within a factor of two compared to those measured in the mechanically extracted sediment pore water and surface water samples obtained adjacent to the sampler deployment locations. Neither biofouling of the rate-limiting barrier nor any physical change to it was observed on the sampler after retrieval. The passive sampler developed in this study could be a promising tool for the monitoring of PFAS in pore water and surface water.

Coverage and Estimated Effectiveness of mRNA COVID-19 Vaccines Among US Veterans.

Importance: Effectiveness of mRNA vaccinations in a diverse older population with high comorbidity is unknown. Objectives: To describe the scope of the COVID-19 vaccination rollout among US veterans, and to estimate mRNA COVID-19 vaccine effectiveness (VE) as measured by rates of SARS-CoV-2 infection. Design, Setting, and Participants: This matched test-negative case-control study was conducted using SARS-CoV-2 test results at Veterans Health Administration sites from December 14, 2020, to March 14, 2021. Vaccine coverage was estimated for all veterans. VE against SARS-CoV-2 infection and COVID-19-related hospitalization and death were estimated using electronic health records from veterans who routinely sought care at a VHA facility and had a test result positive for SARS-CoV-2 (cases) or negative for SARS-CoV-2 (controls). Cases and controls were matched on time of test and geographic region. Data were analyzed from May to July 2021. Exposures: Vaccination status, defined as unvaccinated, partially vaccinated (≥14 days after first dose until second dose), or fully vaccinated (≥14 days after second dose), at time of test. Main Outcomes and Measures: The main outcome of interest was a positive result for SARS-CoV-2 on a polymerase chain reaction or antigen test. Secondary outcomes included COVID-19-related hospitalization and death, defined by discharge data and proximity of event to positive test result. VE was estimated from odds ratios for SARS-CoV-2 infection with 95% CIs. Results: Among 6 647 733 veterans included (3 350 373 veterans [50%] aged ≥65 years; 6 014 798 [90%] men and 632 935 [10%] women; 461 645 Hispanic veterans of any race [7%], 1 102 471 non-Hispanic Black veterans [17%], and 4 361 621 non-Hispanic White veterans [66%]), 1 363 180 (21%) received at least 1 COVID-19 vaccination by March 7, 2021. In this period, during which the share of SARS-CoV-2 variants Alpha, Epsilon, and Iota had started to increase in the US, estimates of COVID-19 VE against infection, regardless of symptoms, was 95% (95% CI, 93%-96%) for full vaccination and 64% (95% CI, 59%-68%) for partial vaccination. Estimated VE against COVID-19-related hospitalization for full vaccination was 91% (95% CI 83%-95%); there were no deaths among veterans who were fully vaccinated. VE against infection was similar across subpopulations (non-Hispanic Black, 94% [95% CI, 88%-97%]; Hispanic [any race], 83% [95% CI, 45%-95%]; non-Hispanic White, 92% [95% CI 88%-94%]; rural, 94% [95% CI, 89%-96%]; urban, 93% 95% CI, 89%-95%]). Conclusions and Relevance: For veterans of all racial and ethnic subgroups living in urban or rural areas, mRNA vaccination was associated with substantially decreased risk of COVID-19 infection and hospitalization, with no deaths among fully vaccinated veterans.

Scientific and Regulatory Considerations for Efficacy Studies of Cytomegalovirus Vaccines.

The considerable public health burden due to cytomegalovirus (CMV) supports current interest in vaccine development. Clinical studies intended to support regulatory action should be designed to demonstrate substantial evidence of effectiveness. However, design and conduct of clinical endpoint studies may be hampered by low incidence of disease, especially for congenital CMV. Discussion and experience from other vaccines directed against congenital disease (including rubella and Zika) may be instructive. This article summarizes current scientific and US regulatory considerations related to design of studies of vaccines intended to prevent congenital CMV and complications of CMV in transplantation, as discussed at the 2018 workshop entitled "Cytomegalovirus Infection: Advancing Strategies for Prevention and Treatment."

Use of controlled human infection models (CHIMs) to support vaccine development: US regulatory considerations.

In 2016, the United States (U.S.) Food and Drug Administration (FDA) licensed Vaxchora® for active immunization against disease caused by Vibrio cholerae serogroup 01 in adults. Vaxchora was the first US-licensed vaccine for which the primary evidence supporting effectiveness was derived from human challenge studies. Following this precedent, FDA has received numerous inquiries from manufacturers, academic researchers, funders and other stakeholders regarding how controlled human infection models (CHIMs) can be used to support the development of safe and effective vaccines to address public health needs. The aims of this article are to discuss: (1) Chemistry, Manufacturing and Controls (CMC) for challenge inocula, (2) conduct of controlled human infection studies under US IND and (3) use of CHIMs to support vaccine development. General concepts and regulatory considerations for the safe conduct of CHIMs and use of CHIMs to evaluate vaccine effectiveness are discussed.

Comparative meta-analysis and experimental kinetic investigation of column and batch bottle microcosm treatability studies informing in situ groundwater remedial design.

A systematic comparison was performed between batch bottle and continuous-flow column microcosms (BMs and CMs, respectively) commonly used for in situ groundwater remedial design. Review of recent literature (2000-2014) showed a preference for reporting batch kinetics, even when corresponding column data were available. Additionally, CMs produced higher observed rate constants, exceeding those of BMs by a factor of 6.1±1.1 standard error. In a subsequent laboratory investigation, 12 equivalent microcosm pairs were constructed from fractured bedrock and perchloroethylene (PCE) impacted groundwater. First-order PCE transformation kinetics of CMs were 8.0±4.8 times faster than BMs (rates: 1.23±0.87 vs. 0.16±0.05d-1, respectively). Additionally, CMs transformed 16.1±8.0-times more mass than BMs owing to continuous-feed operation. CMs are concluded to yield more reliable kinetic estimates because of much higher data density stemming from long-term, steady-state conditions. Since information from BMs and CMs is valuable and complementary, treatability studies should report kinetic data from both when available. This first systematic investigation of BMs and CMs highlights the need for a more unified framework for data use and reporting in treatability studies informing decision-making for field-scale groundwater remediation.

Maternal immunization: opportunities for scientific advancement.

Maternal immunization is an effective strategy to prevent and/or minimize the severity of infectious diseases in pregnant women and their infants. Based on the success of vaccination programs to prevent maternal and neonatal tetanus, maternal immunization has been well received in the United States and globally as a promising strategy for the prevention of other vaccine-preventable diseases that threaten pregnant women and infants, such as influenza and pertussis. Given the promise for reducing the burden of infectious conditions of perinatal significance through the development of vaccines against relevant pathogens, the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) sponsored a series of meetings to foster progress toward clinical development of vaccines for use in pregnancy. A multidisciplinary group of stakeholders convened at the NIH in December 2013 to identify potential barriers and opportunities for scientific advancement in maternal immunization.

Quantitation of physiological and biochemical barriers to siRNA liver delivery via lipid nanoparticle platform.

Effective delivery of small interfering RNA (siRNA) requires efficient cellular uptake and release into cytosol where it forms an active complex with RNAi induced silencing complex (RISC). Despite rapid developments in RNAi therapeutics, improvements in delivery efficiency of siRNA are needed to realize the full potential of this modality in broad therapeutic applications. We evaluated potential physiological and biochemical barrier(s) to the effective liver delivery of siRNA formulated in lipid nanoparticle (LNP) delivery vehicles. The comparative siRNA delivery performance of three LNPs was investigated in rats. They were assembled with either C14- or C18-anchored PEG-lipid(s), cationic lipid(s), and various helper lipid(s) and contained the same siRNA duplex. These LNPs demonstrated differentiated potency with ED50's ranging from 0.02 to 0.25 mg/kg. The two C14-PEG-LNPs had comparable siRNA exposure in plasma and liver, while the C18-PEG-LNP demonstrated a higher plasma siRNA exposure and a slower but sustained liver uptake. RISC bound siRNA within the liver, a more proximal measure of the pharmacologically active siRNA species, displayed loading kinetics that paralleled the target mRNA knockdown profile, with greater RISC loading associated with more potent LNPs. Liver perfusion and hepatocyte isolation experiments were performed following treatment of rats with LNPs containing VivoTag-fluorescently labeled siRNA. One hour after dosing a majority of the siRNA within the liver was associated with hepatocytes and was internalized (within small subcellular vesicles) with no significant cell surface association, indicating good liver tissue penetration, hepatocellular distribution, and internalization. Comparison of siRNA amounts in hepatocytes and subcellular fractions of the three LNPs suggests that endosomal escape is a significant barrier to siRNA delivery where cationic lipid seems to have a great impact. Quantitation of Ago-2 associated siRNA revealed that after endosomal escape further loss of siRNA occurs prior to RISC loading. This quantitative assessment of LNP-mediated siRNA delivery has highlighted potential barriers with respect to endosomal escape and incomplete RISC loading for delivery optimization efforts.

The diagnosis and management of ovarian hyperstimulation syndrome: No. 268, November 2011.

OBJECTIVE: To review the clinical aspects of ovarian hyperstimulation syndrome and provide recommendations on its diagnosis and clinical management. OUTCOMES: These guidelines will assist in the early recognition and management of ovarian hyperstimulation. Early recognition and prompt systematic supportive care will help avert poor outcomes. EVIDENCE: Medline, Embase, and the Cochrane database were searched for relevant articles, using the key words "ovarian hyperstimulation syndrome" and "gonadotropins," and guidelines created by other professional societies were reviewed. VALUES: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table 1).

Use of statistical tools to evaluate the reductive dechlorination of high levels of TCE in microcosm studies.

A large, multi-laboratory microcosm study was performed to select amendments for supporting reductive dechlorination of high levels of trichloroethylene (TCE) found at an industrial site in the United Kingdom (UK) containing dense non-aqueous phase liquid (DNAPL) TCE. The study was designed as a fractional factorial experiment involving 177 bottles distributed between four industrial laboratories and was used to assess the impact of six electron donors, bioaugmentation, addition of supplemental nutrients, and two TCE levels (0.57 and 1.90 mM or 75 and 250 mg/L in the aqueous phase) on TCE dechlorination. Performance was assessed based on the concentration changes of TCE and reductive dechlorination degradation products. The chemical data was evaluated using analysis of variance (ANOVA) and survival analysis techniques to determine both main effects and important interactions for all the experimental variables during the 203-day study. The statistically based design and analysis provided powerful tools that aided decision-making for field application of this technology. The analysis showed that emulsified vegetable oil (EVO), lactate, and methanol were the most effective electron donors, promoting rapid and complete dechlorination of TCE to ethene. Bioaugmentation and nutrient addition also had a statistically significant positive impact on TCE dechlorination. In addition, the microbial community was measured using phospholipid fatty acid analysis (PLFA) for quantification of total biomass and characterization of the community structure and quantitative polymerase chain reaction (qPCR) for enumeration of Dehalococcoides organisms (Dhc) and the vinyl chloride reductase (vcrA) gene. The highest increase in levels of total biomass and Dhc was observed in the EVO microcosms, which correlated well with the dechlorination results.

Perspectives on parenthood and working of female athletic trainers in the secondary school and collegiate settings.

CONTEXT: Female athletic trainers (ATs) are currently underrepresented in the collegiate setting. Parenting and family obligations may play a role in this underrepresentation. OBJECTIVE: To examine female ATs' perspectives on parenting and working in the secondary school and collegiate employment settings. DESIGN: Cross-sectional study. SETTING: Online survey. PATIENTS OR OTHER PARTICIPANTS: A total of 1000 nonstudent, female certified ATs who were currently members of the National Athletic Trainers' Association. MAIN OUTCOME MEASURE(S): An original survey was developed to assess perceptions related to motherhood and work responsibilities. Descriptive statistics were used to assess age, years of experience as a certified AT, employment position, and parent or nonparent status. A correlation matrix was conducted to determine factors among parent and nonparent status, perceptions of motherhood, and employment-setting decisions. RESULTS: Of the 1000 surveys sent via e-mail, 411 (41.1%) female ATs responded. Responses indicated that a majority of the female ATs worked in the secondary school setting. Sixty-one percent of the respondents did not have children. Past female ATs' experiences indicated a perception that motherhood created more challenges or struggles (or both) in the work and family settings. Whether parents considered children a factor in employment-setting changes produced conflicting results: no significant correlations or differences were found among responses. CONCLUSIONS: Parenting considerations had influences on both the home and employment settings. Although parents and nonparents had different views on the implications of parenting in the workplace, both groups agreed that parenting could affect the work environment and the choice to change employment settings and careers. Administrative decisions need to be considered in relation to parenting concerns. Mentoring that includes employment-setting choices relative to life goals should be provided to ATs, regardless of sex.

Adherence to drug-dispensation and drug-administration laws and guidelines in collegiate athletic training rooms: a 5-year review.

CONTEXT: To both ensure athletes' safety and avoid legal penalties, athletic trainers' (ATs') handling of medications in the athletic training room should conform with federal and state statutes. OBJECTIVE: To revisit drug dispensation and administration in collegiate athletic training rooms 5 years after the initial study. DESIGN: Survey study. SETTING: College and university athletic training rooms. PATIENTS OR OTHER PARTICIPANTS: All 4627 certified ATs employed in National Collegiate Athletic Association Divisions I, II, and III and National Association of Intercollegiate Athletics institutions, as listed by the National Athletic Trainers' Association, were surveyed. DATA COLLECTION AND ANALYSIS: The survey was created for the 2001 study based on federal laws. We used analyses of variance to study compliance by division (I, II, or III) and sex and by sex and employment status (head or assistant AT). RESULTS: A total of 2330 ATs (N = 4627, 50%) provided 1535 usable responses. For comparison with the 2001 data, only head ATs' responses were included (n = 670). In general, drug distribution compliance scores among head ATs were low (mean = 6.37 +/- 0.15, range = 0-25 points). The ATs were less compliant when handling over-the-counter (OTC) medications. Only 55.5% of ATs stored medications in a locked cabinet, compared with 67.1% in 2001. A large number of ATs administered OTC drugs in any amount necessary (n = 689, 44%), and 3.6% (n = 55) allowed athletes access without any consultation, compared with 53.8% and 4.9%, respectively, in 2001. However, prescription medication practices improved since the first study. Also, we noted a main effect of employment status (F(1,934) = 5.57, P < .05): head ATs were less compliant than assistant ATs. CONCLUSIONS: Compared with 5 years ago, ATs appear to be more compliant with federal statutes regarding prescription drug regulation. A thorough understanding of appropriate OTC medication administration practices still appears to be lacking.

Self-reported headgear use and concussions among collegiate men's rugby union players.

The perceived effectiveness of rugby union headgear in reducing concussions in American male collegiate rugby union athletes was assessed. Data collection was conducted by survey method distributed using electronic mail. One hundred and thirty-one men's club rugby union participants from eight university teams in the United States were surveyed. Demographic data were assessed using frequencies, means, and standard deviations. An ANOVA was used to assess differences in the frequencies of responses between players with concussions and their perception of headgear, with an increase in positive perception of headgear with increased concussions. Player position and years of experience played a role in the number of concussions and use of protective headgear. Seventy-six different athletes reported a concussion while playing, with the majority (51%) not wearing headgear. Athletes who wore headgear experienced 24% of the concussions, compared to 76% of those who did not wear headgear. The incidence of concussions and severity of concussions were perceived as less severe among the group wearing headgear. The general perception of those individuals polled as to the effectiveness of headgear in reducing head injuries was positive.

Adherence to Drug-Dispensation and Drug-Administration Laws and Guidelines in Collegiate Athletic Training Rooms.

OBJECTIVE: To assess adherence in collegiate athletic training rooms to federal drug laws and to describe current practices. DESIGN AND SETTING: We created a survey of drug-law adherence using federal drug laws and administration guidelines and mailed it to randomly selected certified athletic trainers (ATCs) in United States college and university athletic training rooms. Means, standard deviations, and cross-tabulations were calculated to assess demographic information. A nonparametric test (Kruskal-Wallis) was calculated to compare adherence-score means. RESULTS: Adherence scores were collected from 168 college and university ATCs. The data suggest that ATCs in most athletic training rooms are still not complying with federal drug laws. Drug-dispensation and -administration adherence scores ranged from 5 to 20 (20% to 80% adherence) of 25 points. On average, 49.3% of ATCs in athletic training rooms had marginal adherence to federal regulations (12.34 adherence score). The difference between adherence scores and National Collegiate Athletic Association athletic divisions (Division I, II, III, and III/National Association of Intercollegiate Athletics; P <.002) was significant. In most athletic training rooms, ATCs (55.9%) and students (13.3%) dispensed prescription drugs. In addition, ATCs in most athletic training rooms (53.8%) administered any amount of over-the-counter medication as necessary, and many did not record the transaction (46.2%). DISCUSSION: Nine years after the National Collegiate Athletic Association drug-distribution study in university athletic programs, similar problem areas persist, including unqualified personnel dispensing medications, inappropriately packaged and labeled medications, and a lack of record keeping. CONCLUSIONS: Athletic trainers should work in conjunction with members of the sports medicine team to review federal and state laws and revise institutional drug policies and procedures to comply with regulations in order to provide the best health care to student athletes in a legal and safe manner.

The genetic epidemiology of spontaneous endometriosis in the rhesus monkey.

The etiology of endometriosis is uncertain, but there is increasing evidence that it is inherited as a complex genetic trait like diabetes or asthma. In such complex traits, multiple gene loci conferring susceptibility to the disease interact with each other and the environment to produce the phenotype. The study of such interactions in humans can be problematic. Thus, the availability of an animal model, which shares many aspects of anatomy and physiology with humans, is potentially a valuable tool for investigating the genetic epidemiology of the disease. Since endometriosis develops spontaneously in the rhesus monkey (Macaca mulatta) and the tissue is morphologically identical to its human counterpart, this population provides a unique opportunity to conduct such studies in this condition.