Reductions in particulate matter concentrations resulting from air filtration: A randomized sham-controlled crossover study.

One-hundred seventy-two households were recruited from regions with high outdoor air pollution (Fresno and Riverside, CA) to participate in a randomized, sham-controlled, cross-over study to determine the effectiveness of high-efficiency air filtration to reduce indoor particle exposures. In 129 households, stand-alone HEPA air cleaners were placed in a bedroom and in the main living area. In 43 households, high-efficiency MERV 16 filters were installed in central forced-air heating and cooling systems and the participating households were asked to run the system on a clean-air cycle for 15 min per hour. Participating households that completed the study received true air filtration for a year and sham air filtration for a year. Air pollution samples were collected at approximately 6-month intervals, with two measurements in each of the sham and true filtration periods. One week indoor and outdoor time-integrated samples were collected for measurement of PM2.5 , PM10 , and ultrafine particulate matter (UFP) measured as PM0.2 . Reflectance measurements were also made on the PM2.5 filters to estimate black carbon. True filtration significantly improved indoor air quality, with a 48% reduction in the geometric mean indoor PM0.2 and PM2.5 concentrations, and a 31% reduction in PM10 . Geometric mean concentrations of indoor/outdoor reflectance values, indicating fraction of particles of outdoor origin remaining indoors, decreased by 77%. Improvements in particle concentrations were greater with continuously operating stand-alone air cleaners than with intermittent central system filtration. Keeping windows closed and increased utilization of the filtration systems further improved indoor air quality.

Comparing helpful and hindering processes in good and poor outcome cases: A qualitative metasynthesis of eight Hermeneutic Single Case Efficacy Design studies.

Objective: We tested qualitative metasynthesis of a series of Hermeneutic Single Case Efficacy Design (HSCED) studies as a method for comparing within-session processes that may explain good and poor therapeutic outcome. Method: We selected eight HSCED studies according to change in clients' scores on the Strathclyde Inventory (SI), a brief self-report instrument used to measure outcome in person-centered psychotherapy. Four of the case studies investigated the experience of clients whose pre-post change in SI scores showed improvement by the end of therapy, and the other four focused on clients whose change in SI scores indicated deterioration. We conducted a qualitative metasynthesis, adopting a generic descriptive-interpretive approach to analyze and compare the data generated by the HSCED studies. Results: In contrast to improvers, deteriorators appeared to be less ready to engage in therapeutic work at the beginning of therapy, and found the process more difficult; their therapists were less able to respond to these difficulties in a responsive, empathic manner; deteriorators were less able to cope successfully with changes of therapist and, eventually, gave up on therapy. Conclusion: We found that our qualitative metasynthesis of a series of HSCED studies produced a plausible explanation for the contrasting outcomes that occurred.

Do flame retardant concentrations change in dust after older upholstered furniture is replaced?

Upholstered furniture has been a major source of chemical flame retardant (FR) exposures in US homes since the 1970s. FRs are a large group of chemicals, many of which are associated with adverse health effects, including cancer, reproductive toxicity, and neurotoxicity. California homes have some of the highest dust concentrations of FRs, due to Technical Bulletin 117 (TB117), California's outdated flammability standard for furniture foam that was generally followed across the US and Canada. In 2014, this standard was updated to a smolder standard for furniture fabric called TB117-2013, and it is no longer reliant on FRs. This update provided an opportunity to measure differences in FR dust levels in California homes before and after residents replaced older upholstered furniture, or its foam, with products that met the new standard and were expected to be FR-free. We collected dust from homes of participants who had plans to replace older upholstered furniture, or furniture foam, with FR-free options. We returned for follow-up dust collection six, 12, and 18 months following replacement. Concentrations of three polybrominated diphenyl ethers (PBDEs) (BDE-47, BDE-99, BDE-100), three chlorinated organophosphate ester FRs (tris(2-chloroethyl) phosphate (TCEP), tris(2-chloroisopropyl) phosphate (TCIPP), and tris(1,3-dichloroisopropyl) phosphate (TDCIPP)), and one aryl organophosphate ester FR triphenyl phosphate (TPHP), were widely detected in participant homes. All measured FRs decreased in nearly all homes after the older upholstered furniture was replaced. The decreases in FRs were significant in both homes that replaced entire pieces of furniture and those that replaced only the furniture foam. This study demonstrates that replacing older upholstered furniture or foam significantly reduces concentrations of a range of FRs in the home. Foam replacement offers a potentially more economic alternative that produces a lower volume of waste.

Health research systems in change: the case of 'Push the Pace' in the National Institute for Health Research.

BACKGROUND: Those running well-organised health research systems are likely to be alert for ways in which they might increase the quality of the services they provide and address any problems identified. This is important because the efficiency of the research system can have a major impact on how long it takes for new treatments to be developed and reach patients. This opinion piece reflects on the experience and learning of the United Kingdom-based National Institute for Health Research (NIHR) when it implemented continuous improvement activity to improve its processes. DISCUSSION: This paper describes the structure and work of the NIHR and why, despite is successes as a health research system and ongoing local continuous improvement, it believed in the value of an organisation-wide continuous improvement activity. It did this by implementing an approach called 'Push the Pace'. Initially, the organisation focused on reducing the amount of time it took for research to transition from an early concept to evidence that changes lives. This scrutiny enabled the NIHR to realise further areas of improvement it could make - additional goals were increased transparency, process simplification, and improved customer and stakeholder experience. We discuss our experience of Push the Pace with reference to literature on continuous improvement. CONCLUSION: Continuous improvement is a cycle, an activity that is done constantly and over time, rather than an act or linear activity (such as Push the Pace). We believe that the work of Push the Pace has initiated a strong commitment to a culture of continuous improvement in the NIHR. This is significant because culture change is widely recognised as immensely challenging, particularly in such a large and distributed organisation. However, our biggest challenge will be to enable all staff and stakeholders of the NIHR to participate in the continuous improvement cycle.

Evaluation of stakeholder views on peer review of NIHR applications for funding: a qualitative study.

OBJECTIVES: Innovations resulting from research have both national and global impact, so selecting the most promising research studies to fund is crucial. Peer review of research funding applications is part of the selection process, and requires considerable resources. This study aimed to elicit stakeholder opinions about which factors contribute to and influence effective peer review of funding applications to the UK National Institute for Health Research (NIHR), and to identify possible minor improvements to current processes and any major changes or potential innovations to achieve a more efficient peer review process. DESIGN: Qualitative interviews with 30 stakeholders involved in the peer review process. PARTICIPANTS: Participants were drawn from three NIHR coordinating centres and represented four types of stakeholders: board members with responsibility for making funding decisions, applicants, external peer reviewers and NIHR staff. METHODS: All interviews were conducted by telephone apart from three that were face to face with NIHR staff. Data were analysed using a thematic template method. RESULTS: The responses from NIHR staff, board members and reviewers differed from those received from applicants. The first three groups focused on how well the process of peer review did or did not function. The applicants mentioned these points but in addition often reflected on how their personal application was assessed. Process improvements suggested included: developing a more proportionate review process; providing greater guidance, feedback, training, acknowledgement or incentives for peer reviewers; reducing the time commitment and amount of paperwork; and asking reviewers to comment on the importance, strengths and weaknesses of applications and flaws which are potentially 'fixable'. CONCLUSIONS: Overall, participants were supportive of the need for peer review in evaluating applications for research funding. This study revealed which parts of the process are working well and are valued, and barriers, difficulties and potential areas for improvement and development.

Polybrominated diphenyl ether serum concentrations in a Californian population of children, their parents, and older adults: an exposure assessment study.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in many household items. Given concerns over their potential adverse health effects, we identified predictors and evaluated temporal changes of PBDE serum concentrations. METHODS: PBDE serum concentrations were measured in young children (2-8 years old; N = 67), parents of young children (<55 years old; N = 90), and older adults (≥55 years old; N = 59) in California, with concurrent floor wipe samples collected in participants' homes in 2008-2009. We also measured serum concentrations one year later in a subset of children (N = 19) and parents (N = 42). RESULTS: PBDE serum concentrations in children were significantly higher than in adults. Floor wipe concentration is a significant predictor of serum BDE-47, 99, 100 and 154. Positive associations were observed between the intake frequency of canned meat and serum concentrations of BDE-47, 99 and 154, between canned meat entrees and BDE-154 and 209, as well as between tuna and white fish and BDE-153. The model with the floor wipe concentration and food intake frequencies explained up to 40% of the mean square prediction error of some congeners. Lower home values and renting (vs. owning) a home were associated with higher serum concentrations of BDE-47, 99 and 100. Serum concentrations measured one year apart were strongly correlated as expected (r = 0.70-0.97) with a slight decreasing trend. CONCLUSIONS: Floor wipe concentration, food intake frequency, and housing characteristics can explain 12-40% of the prediction error of PBDE serum concentrations. Decreasing temporal trends should be considered when characterizing long-term exposure.

Serum concentrations of perfluorinated compounds (PFC) among selected populations of children and adults in California.

Perfluorinated compounds (PFCs) have been widely used in industrial applications and consumer products. Their persistent nature and potential health impacts are of concern. Given the high cost of collecting serum samples, this study is to understand whether we can quantify PFC serum concentrations using factors extracted from questionnaire responses and indirect measurements, and whether a single serum measurement can be used to classify an individual's exposure over a one-year period. The study population included three demographic groups: young children (2-8 years old) (N=67), parents of young children (<55 years old) (N=90), and older adults (>55 years old) (N=59). PFC serum concentrations, house dust concentrations, and questionnaires were collected. The geometric mean of perfluorooctane sulfonic acid (PFOS) was highest for the older adults. In contrast, the geometric mean of perfluorooctanoic acid (PFOA) was highest for children. Serum concentrations of the parent and the child from the same family were moderately correlated (Spearman correlation (r)=0.26-0.79, p<0.05), indicating common sources within a family. For adults, age, having occupational exposure or having used fire extinguisher, frequencies of consuming butter/margarine, pork, canned meat entrées, tuna and white fish, freshwater fish, and whether they ate microwave popcorn were significantly positively associated with serum concentrations of individual PFCs. For children, residential dust concentrations, frequency of wearing waterproof clothes, frequency of having canned fish, hotdogs, chicken nuggets, French fries, and chips, and whether they ate microwave popcorn were significant positive predictors of individual PFC serum concentrations. In addition, the serum concentrations collected in a subset of young children (N=20) and the parents (N=42) one year later were strongly correlated (r=0.68-0.98, p<0.001) with the levels measured at the first visits, but showed a decreasing trend. Children had moderate correlation (r=0.43) between serum and dust concentrations of PFOS, indicating indoor sources contribute to exposure. In conclusion, besides food intake, occupational exposure, consumer product use, and exposure to residential dust contribute to PFC exposure. The downward temporal trend of serum concentrations reflects the reduction of PFCs use in recent years while the year-to-year correlation indicates that a single serum measurement could be an estimate of exposure relative to the population for a one-year period in epidemiology studies.

Urinary pyrethroid and chlorpyrifos metabolite concentrations in Northern California families and their relationship to indoor residential insecticide levels, part of the Study of Use of Products and Exposure Related Behavior (SUPERB).

Since the 2001 U.S. federally mandated phase-out of residential uses of organophosphates (OPs), use of and potential for human exposure to pyrethroids in the indoor residential environment has increased. We report concentrations of common pyrethroids, pyrethroid metabolites, and chlorpyrifos in floor wipes, and urinary concentrations of pyrethroid metabolites and 3,5,6-trichloro-2-pyridinol (TCPy) in samples collected in 2007-2009 from 90 northern California families as part of the Study of Use of Products and Exposure Related Behavior (SUPERB). Correlation and regression analyses examined associations between floor wipe and urine sample concentrations. The most frequently detected urinary metabolites were TCPy (64.7%, median concentration of 1.47 ng/mL) and 3-phenoxybenzoic acid (3PBA) (62.4%, 0.79 ng/mL). Compared to the National Health and Nutrition Examination Survey (NHANES) 2001-2002 general U.S. population, this population had substantially higher pyrethroid metabolite and lower TCPy urinary concentrations. This may be related to the increased residential use of pyrethroids after the phase-out of OPs. Chlorpyrifos (98.7%), cis- and trans-permethrin (97.5%), bifenthrin (59.3%), and 3PBA (98.7%) were frequently detected in the floor wipes. Floor wipe concentrations for pyrethroid insecticides were found to be significant predictors of child creatinine-adjusted urinary metabolite concentrations (log-log regression coefficients ranging from 0.26 to 0.29; p < 0.05) suggesting that indoor residential exposure to pyrethroid insecticides is an important exposure route for children.

Occupational exposure to particulate matter from three agricultural crops in California.

Agricultural work is a major contributor to California's and the nation's economy and employs a large number of workers. However, agricultural work can have numerous risks, such as exposure to elevated levels of particulate matter (PM) and other airborne pollutants with potential adverse health effects. To determine the magnitude of occupational exposures, PM levels were assessed for 89 workers from three major crops in California; almonds, melons and tomatoes. Personal samples were collected for PM2.5 and inhalable PM using personal sampling equipment. Geometric mean concentrations from personal exposure for workers in almonds (inhalable PM=4368 µg/m(3), PM2.5=122 µg/m(3), N=5), tomatoes (inhalable PM=1410 µg/m(3), PM2.5=12 µg/m(3), N=33), and melons (inhalable PM=1118 µg/m(3), PM2.5=19 µg/m(3), N=51) showed high PM exposure when working with these three crops. Large exposure differences by crop were more common than by task (i.e. harvesting, packing and weeding) among the three crops studied. This is the largest study of agricultural workers engaged in hand harvesting, a significant employer of farm labor, and relatively high levels of exposure to PM were measured.

"Blueberry muffin" rash and large right thigh mass: a unique presentation of Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a clonal proliferation of bone marrow derived antigen-presenting cells that can involve a spectrum of cutaneous findings, with or without internal organ involvement. Neonatal LCH almost always presents with skin findings, usually petechial papules and/or erosions in a seborrheic distribution, with or without extracutaneous involvement. Previously described as varying entities, LCH is now considered a single disease process demonstrating a spectrum of clinical findings. We report a unique case of neonatal LCH presenting with a "blueberry muffin" rash in conjunction with a large soft tissue tumor.

Prioritizing environmental risk of prescription pharmaceuticals.

Low levels of pharmaceutical compounds have been detected in aquatic environments worldwide, but their human and ecological health risks associated with low dose environmental exposure is largely unknown due to the large number of these compounds and a lack of information. Therefore prioritization and ranking methods are needed for screening target compounds for research and risk assessment. Previous efforts to rank pharmaceutical compounds have often focused on occurrence data and have paid less attention to removal mechanisms such as human metabolism. This study proposes a simple prioritization approach based on number of prescriptions and toxicity information, accounting for metabolism and wastewater treatment removal, and can be applied to unmeasured compounds. The approach was performed on the 200 most-prescribed drugs in the US in 2009. Our results showed that under-studied compounds such as levothyroxine and montelukast sodium received the highest scores, suggesting the importance of removal mechanisms in influencing the ranking, and the need for future environmental research to include other less-studied but potentially harmful pharmaceutical compounds.

An uneven spread: a review of public involvement in the National Institute of Health Research's Health Technology Assessment program.

OBJECTIVES: This study comprises a review of public involvement strategies across the five stages of research management in the UK's HTA program at the end of a 10-year period. These five stages are: identification of topics; prioritization of these topics as researchable questions; commissioning of research; monitoring of projects throughout their implementation; and publication and dissemination of findings. METHODS: Internal HTA documentation was analyzed alongside narrative analysis of semi-structured interviews of program staff, and a rapid review of published literature. RESULTS: Public involvement strategies have developed with the growth of the HTA program but were spread unevenly across the five stages of research management. Public involvement was present in identification, strongest in prioritization, present in commissioning but minimal in monitoring and absent in publication and dissemination. CONCLUSIONS: The HTA program has developed public involvement strategies but mainly in prioritization. Further research is required to ascertain where public involvement can be most appropriately used and to evaluate its impact.

Developing a matrix to identify and prioritise research recommendations in HIV prevention.

BACKGROUND: HIV prevention continues to be problematic in the UK, as it does globally. The UK Department of Health has a strategic direction with greater focus on prevention as part of its World Class Commissioning Programme. There is a need for targeted evidence-based prevention initiatives. This is an exploratory study to develop an evidence mapping tool in the form of a matrix: this will be used to identify important gaps in contemporary HIV prevention evidence relevant to the UK. It has the potential to aid prioritisation in future research. METHODS: Categories for prevention and risk groups were developed for HIV prevention in consultation with external experts. These were used as axes on a matrix tool to map evidence. Systematic searches for publications on HIV prevention were undertaken using electronic databases for primary and secondary research undertaken mainly in UK, USA, Canada, Australia and New Zealand, 2006-9. Each publication was screened for inclusion then coded. The risk groups and prevention areas in each paper were counted: several publications addressed multiple risk groups. The counts were exported to the matrix and clearly illustrate the concentrations and gaps of literature in HIV prevention. RESULTS: 716 systematic reviews, randomised control trials and other primary research met the inclusion criteria for HIV prevention. The matrix identified several under researched areas in HIV prevention. CONCLUSIONS: This is the first categorisation system for HIV prevention and the matrix is a novel tool for evidence mapping. Some important yet under-researched areas have been identified in HIV prevention evidence: identifying the undiagnosed population; international adaptation; education; intervention combinations; transgender; sex-workers; heterosexuals and older age groups.

Multiparameter metabolic analysis reveals a close link between attenuated mitochondrial bioenergetic function and enhanced glycolysis dependency in human tumor cells.

Increased conversion of glucose to lactic acid associated with decreased mitochondrial respiration is a unique feature of tumors first described by Otto Warburg in the 1920s. Recent evidence suggests that the Warburg effect is caused by oncogenes and is an underlying mechanism of malignant transformation. Using a novel approach to measure cellular metabolic rates in vitro, the bioenergetic basis of this increased glycolysis and reduced mitochondrial respiration was investigated in two human cancer cell lines, H460 and A549. The bioenergetic phenotype was analyzed by measuring cellular respiration, glycolysis rate, and ATP turnover of the cells in response to various pharmacological modulators. H460 and A549 cells displayed a dependency on glycolysis and an ability to significantly upregulate this pathway when their respiration was inhibited. The converse, however, was not true. The cell lines were attenuated in oxidative phosphorylation (OXPHOS) capacity and were unable to sufficiently upregulate mitochondrial OXPHOS when glycolysis was disabled. This observed mitochondrial impairment was intimately linked to the increased dependency on glycolysis. Furthermore, it was demonstrated that H460 cells were more glycolytic, having a greater impairment of mitochondrial respiration, compared with A549 cells. Finally, the upregulation of glycolysis in response to mitochondrial ATP synthesis inhibition was dependent on AMP-activated protein kinase activity. In summary, our results demonstrate a bioenergetic phenotype of these two cancer cell lines characterized by increased rate of glycolysis and a linked attenuation in their OXPHOS capacity. These metabolic alterations provide a mechanistic explanation for the growth advantage and apoptotic resistance of tumor cells.