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1.  Pesticide Side Effects in an Agricultural Soil Ecosystem as Measured by amoA Expression Quantification and Bacterial Diversity Changes 
PLoS ONE  2015;10(5):e0126080.
Background and Methods
Assessing the effects of pesticide hazards on microbiological processes in the soil is currently based on analyses that provide limited insight into the ongoing processes. This study proposes a more comprehensive approach. The side effects of pesticides may appear as changes in the expression of specific microbial genes or as changes in diversity. To assess the impact of pesticides on gene expression, we focused on the amoA gene, which is involved in ammonia oxidation. We prepared soil microcosms and exposed them to dazomet, mancozeb or no pesticide. We hypothesized that the amount of amoA transcript decreases upon pesticide application, and to test this hypothesis, we used reverse-transcription qPCR. We also hypothesized that bacterial diversity is affected by pesticides. This hypothesis was investigated via 454 sequencing and diversity analysis of the 16S ribosomal RNA and RNA genes, representing the active and total soil bacterial communities, respectively.
Results and Conclusion
Treatment with dazomet reduced both the bacterial and archaeal amoA transcript numbers by more than two log units and produced long-term effects for more than 28 days. Mancozeb also inhibited the numbers of amoA transcripts, but only transiently. The bacterial and archaeal amoA transcripts were both sensitive bioindicators of pesticide side effects. Additionally, the numbers of bacterial amoA transcripts correlated with nitrate production in N-amended microcosms. Dazomet reduced the total bacterial numbers by one log unit, but the population size was restored after twelve days. The diversity of the active soil bacteria also seemed to be re-established after twelve days. However, the total bacterial diversity as reflected in the 16S ribosomal RNA gene sequences was largely dominated by Firmicutes and Proteobacteria at day twelve, likely reflecting a halt in the growth of early opportunists and the re-establishment of a more diverse population. We observed no effects of mancozeb on diversity.
PMCID: PMC4418756  PMID: 25938467
2.  Evidence for the role of German final devoicing in pre-attentive speech processing: a mismatch negativity study 
Frontiers in Psychology  2014;5:1317.
Results of a mismatch negativity experiment are reported in which the pre-attentive relevance of the German phonological alternation of final devoicing (FD) is shown in two ways. The experiment employs pseudowords. (1) A deviant [vus] paired with standard /vuzə/ did not show a mismatch effect for the voicing change in /z/ versus [s] because the two can be related by FD. When standard and deviant were reversed, the two could not be related by FD and a mismatch effect for the voicing difference occurred. (2) An ill-formed deviant that violates FD, *[vuz], triggered mismatch effects that were plausibly attributed to its ill-formedness. The results show that a syllable-related process like FD is already taken into account by the processing system in early pre-attentive processing.
PMCID: PMC4243496  PMID: 25505433
mismatch negativity (MMN); event-related potentials (ERP); phonological rules; final devoicing; phonotactics; German; pre-attentive processing
3.  Combined Treatment with a BACE Inhibitor and Anti-Aβ Antibody Gantenerumab Enhances Amyloid Reduction in APPLondon Mice 
The Journal of Neuroscience  2014;34(35):11621-11630.
Therapeutic approaches for prevention or reduction of amyloidosis are currently a main objective in basic and clinical research on Alzheimer‘s disease. Among the agents explored in clinical trials are anti-Aβ peptide antibodies and secretase inhibitors. Most anti-Aβ antibodies are considered to act via inhibition of amyloidosis and enhanced clearance of existing amyloid, although secretase inhibitors reduce the de novo production of Aβ. Limited information is currently available on the efficacy and potential advantages of combinatorial antiamyloid treatment. We performed a chronic study in APPLondon transgenic mice that received treatment with anti-Aβ antibody gantenerumab and BACE inhibitor RO5508887, either as mono- or combination treatment. Treatment aimed to evaluate efficacy on amyloid progression, similar to preexisting amyloidosis as present in Alzheimer's disease patients. Mono-treatments with either compound caused a dose-dependent reduction of total brain Aβ and amyloid burden. Combination treatment with both compounds significantly enhanced the antiamyloid effect. The observed combination effect was most pronounced for lowering of amyloid plaque load and plaque number, which suggests effective inhibition of de novo plaque formation. Moreover, significantly enhanced clearance of pre-existing amyloid plaques was observed when gantenerumab was coadministered with RO5508887. BACE inhibition led to a significant time- and dose-dependent decrease in CSF Aβ, which was not observed for gantenerumab treatment. Our results demonstrate that combining these two antiamyloid agents enhances overall efficacy and suggests that combination treatments may be of clinical relevance.
PMCID: PMC4145168  PMID: 25164658
Aβ-antibody; Alzheimer's disease; amyloidosis; BACE; tg-APP mouse
4.  Clinical phenotype associations with various types of anti-dsDNA antibodies in patients with recent onset of rheumatic symptoms. Results from a multicentre observational study 
Lupus Science & Medicine  2014;1(1):e000007.
Despite anti-dsDNA antibodies constitute a wide range of specificities, they are considered as the hallmark for systemic lupus erythematosus (SLE).
To identify clinical phenotypes associated with anti-dsDNA antibodies, independently of any clinical diagnoses.
Patients with recent onset of any rheumatic symptoms were screened for antinuclear antibodies (ANA). All ANA-positive and matching ANA-negative patients were examined, and their clinical phenotypes were registered, using a systematic chart formulated after consensus between the participating centres. All patients were tested for different anti-dsDNA antibody specificities with assays habitually used in each participating laboratory. Crithidia Luciliae Immuno Fluorescence Test (CLIFT) was performed three times (with two different commercial kits); solid and solution phase ELISA were performed four times. Associations between clinical phenotypes and results of anti-dsDNA assays were evaluated by linear regression analysis (LRA) and principal component analysis (PCA).
Totally, 292 ANA-positive and 292 matching ANA-negative patients were included in the study. A full dataset for statistical analysis was obtained in 547 patients. Anti-dsDNA antibodies were most frequently detected by ELISA. LRA showed that overall positivity of anti-dsDNA antibodies was associated with proteinuria and pleuritis. Alopecia was significantly associated only with CLIFT-positivity. Besides confirming the same findings, PCA showed that combined positivity of CLIFT and ELISA was also associated with lymphopenia.
Our results show that different anti-dsDNA antibody specificities are associated with nephropathy, pleuritis, alopecia and lymphopenia, regardless of the diagnosis. It may challenge the importance of anti-dsDNA antibodies as a diagnostic hallmark for SLE.
PMCID: PMC4225731  PMID: 25396058
Autoantibodies; Autoimmunity; Systemic Lupus Erythematosus; Lupus Nephritis; Autoimmune Diseases
5.  Interobserver agreement for the spine instability neoplastic score varies according to the experience of the evaluator 
Clinics  2013;68(2):213-217.
To evaluate the interobserver agreement for the Neoplastic Spine Instability Score (SINS) among spine surgeons with or without experience in vertebral metastasis treatment and physicians in other specialties.
Case descriptions were produced based on the medical records of 40 patients with vertebral metastases. The descriptions were then published online. Physicians were invited to evaluate the descriptions by answering questions according to the Neoplastic Spine Instability Score (SINS). The agreement among physicians was calculated using the kappa coefficient.
Seventeen physicians agreed to participate: three highly experienced spine surgeons, seven less-experienced spine surgeons, three surgeons of other specialties, and four general practitioners (n = 17). The agreement for the final SINS score among all participants was fair, and it varied according to the SINS component. The agreement was substantial for the spine location only. The agreement was higher among experienced surgeons. The agreement was nearly perfect for spinal location among the spine surgeons who were highly experienced in vertebral metastases.
This study demonstrates that the experience of the evaluator has an impact on SINS scale classification. The interobserver agreement was only fair among physicians who were not spine surgeons and among spine surgeons who were not experienced in the treatment of vertebral metastases, which may limit the use of the SINS scale for the screening of unstable lesions by less-experienced evaluators.
PMCID: PMC3584270  PMID: 23525318
Spine; Health Services Research; Models, Statistical; Observer Variation
6.  Transport and Distribution of Salmonella enterica Serovar Typhimurium in Loamy and Sandy Soil Monoliths with Applied Liquid Manure ▿  
A leaching experiment, where liquid manure spiked with Salmonella enterica serovar Typhimurium (Tet+) DSM554 was applied to soil surfaces, was conducted on intact soil monoliths (60 cm in diameter and 100 cm long). A total of 6.5 × 1010 CFU was applied to each column. We found that Salmonella serovar Typhimurium could be transported to a 1-m depth in loamy soil at concentrations reaching 1.3 × 105 CFU/ml of leachate. The test strain was found in concentrations ranging from 300 to 1.35 cells/ml in loamy soil throughout the 27 days of the experiment, while concentrations below 20 cells/ml were sporadically detected in the leachates from sandy monoliths. Real-time PCR targeting invA DNA showed a clear correspondence between the total and culturable numbers of cells in the leachate, indicating that most cells leached were viable. On day 28, distribution of Salmonella serovar Typhimurium at five depths in the four monoliths was determined. The highest recovery rate, ranging from 1.5% to 3.8% of the total applied inoculum, was found in the top 0.2 m.
PMCID: PMC2813018  PMID: 20023094
7.  Elucidating the Key Member of a Linuron-Mineralizing Bacterial Community by PCR and Reverse Transcription-PCR Denaturing Gradient Gel Electrophoresis 16S rRNA Gene Fingerprinting and Cultivation 
A bacterial community from Danish agricultural soil was enriched with linuron [N-(3,4-dichlorophenyl)-N′-methoxy-N′-methylurea] as the sole carbon and nitrogen source. The community mineralized [ring-U-14C]linuron completely to 14CO2 and 14C-biomass. Denaturing gradient gel electrophoresis analysis and cultivation revealed that a Variovorax sp. was responsible for the mineralization activity.
PMCID: PMC1169018  PMID: 16000836
8.  Tumor necrosis factor-alpha inhibits stem cell factor-induced proliferation of human bone marrow progenitor cells in vitro. Role of p55 and p75 tumor necrosis factor receptors. 
Journal of Clinical Investigation  1994;94(1):165-172.
Stem cell factor (SCF), a key regulator of hematopoiesis, potently synergizes with a number of hematopoietic growth factors. However, little is known about growth factors capable of inhibiting the actions of SCF. TNF-alpha has been shown to act as a bidirectional regulator of myeloid cell proliferation and differentiation. This study was designed to examine interactions between TNF-alpha and SCF. Here, we demonstrate that TNF-alpha potently and directly inhibits SCF-stimulated proliferation of CD34+ hematopoietic progenitor cells. Furthermore, TNF-alpha blocked all colony formation stimulated by SCF in combination with granulocyte colony-stimulating factor (CSF) or CSF-1. The synergistic effect of SCF observed in combination with GM-CSF or IL-3 was also inhibited by TNF-alpha, resulting in colony numbers similar to those obtained in the absence of SCF. These effects of TNF-alpha were mediated through the p55 TNF receptor, whereas little or no inhibition was signaled through the p75 TNF receptor. Finally, TNF-alpha downregulated c-kit cell-surface expression on CD34+ bone marrow cells, and this was predominantly a p55 TNF receptor-mediated event as well.
PMCID: PMC296294  PMID: 7518828
9.  Ethanol Reassimilation and Ethanol Tolerance in Pichia stipitis CBS 6054 as Studied by 13C Nuclear Magnetic Resonance Spectroscopy 
Ethanol reassimilation in Pichia stipitis CBS 6054 was studied by using continuous cultures, and the oxidation of [1-13C]ethanol was monitored by in vivo and in vitro 13C nuclear magnetic resonance spectroscopy. Acetate was formed when ethanol was reassimilated. The ATP/ADP ratio and the carbon dioxide production decreased, whereas the malate dehydrogenase activity increased, in ethanol-reassimilating cells. The results are discussed in terms of the low ethanol tolerance in P. stipitis compared with that in Saccharomyces cerevisiae (S. W. Brown, S. G. Oliver, D. E. F. Harrison, and R. C. Righelato, Eur. J. Appl. Microbiol. Biotechnol. 11:151-155, 1981).
PMCID: PMC195820  PMID: 16348754
10.  Perceptions of Prostate Cancer Screening Controversy and Informed Decision Making: Implications for Development of a Targeted Decision Aid for Unaffected Male First-Degree Relatives 
First-degree relatives (FDRs) of prostate cancer (PC) patients should consider multiple concurrent personal risk factors when engaging in informed decision making (IDM) about PC screening. This study assessed perceptions of IDM recommendations and risk-appropriate strategies for IDM among FDRs of varied race/ethnicity.
A cross-sectional, qualitative
Study setting was a cancer center in southwest Florida.
The study comprised 44 participants (24 PC patients and 20 unaffected FDRs).
Focus groups and individual interviews were conducted and analyzed using content analysis and constant comparison methods.
Patients and FDRs found the PC screening debate and IDM recommendations to be complex and counterintuitive. They overwhelmingly believed screening saves lives and does not have associated harms. There was a strongly expressed need to improve communication between patients and FDRs. A single decision aid that addresses the needs of all FDRs, rather than separating by race/ethnicity, was recommended as sufficient by study participants. These perspectives guided the development of an innovative decision aid that deconstructs the screening controversy and IDM processes into simpler concepts and provides step-by-step strategies for FDRs to engage in IDM.
Implementing IDM among FDRs is challenging because the IDM paradigm departs from historical messages promoting routine screening. These contradictions should be recognized and addressed for men to participate effectively in IDM. A randomized pilot study evaluating outcomes of the resulting decision aid is underway.
PMCID: PMC4277494  PMID: 24968183
Prostate Cancer; Informed Decision Making; Decision Aid; First-Degree Relatives; Family History; Health Promotion; Prevention Research. Manuscript format: research; Research purpose: descriptive; Study design: qualitative; Outcome measure: behavioral; Setting: clinical/healthcare; Health focus: social health; Strategy: education, skill building/behavior change, and culture change; Target population age: adults; Target population circumstances: race/ethnicity and male first-degree relatives
11.  Cognitive Functioning in Men Receiving Androgen Deprivation Therapy for Prostate Cancer: A Systematic Review and Meta-Analysis 
Prior research examining the impact of androgen deprivation therapy (ADT) for prostate cancer on cognitive performance has found inconsistent relationships. The purpose of this study was to systematically review the existing literature and determine the effect of ADT on performance across seven cognitive domains using meta-analysis.
A search of PubMed Medline, PsycINFO, Cochrane Library, and Web of Knowledge/Science databases yielded 157 unique abstracts reviewed by independent pairs of raters. Fourteen studies with a total of 417 patients treated with ADT were included in the meta-analysis. Objective neuropsychological tests were categorized into seven cognitive domains: attention/working memory, executive functioning, language, verbal memory, visual memory, visuomotor ability, and visuospatial ability.
Separate effect sizes were calculated for each cognitive domain using pairwise comparisons of patients who received ADT with 1) prostate cancer patient controls, 2) non-cancer controls, or 3) ADT patients’ own pre-ADT baselines. Patients treated with ADT performed worse than controls or their own baseline on visuomotor tasks (g=−0.67, p=.008; n=193). The magnitude of the deficits was larger in studies with a shorter time to follow-up (p=.04). No significant effect sizes were observed for the other six cognitive domains (p=.08=–.98).
Prostate cancer patients who received ADT performed significantly worse on visuomotor tasks compared to non-cancer control groups. These findings are consistent with the known effects of testosterone on cognitive functioning in healthy men. Knowledge of the cognitive effects of ADT may help patients and providers better understand the impact of ADT on quality of life.
PMCID: PMC4090762  PMID: 24859915
cognition; neuropsychological tests; androgen deprivation therapy; prostatic neoplasms; meta-analysis; systematic review
12.  Characteristics associated with post-discharge medication errors 
Mayo Clinic proceedings  2014;89(8):1042-1051.
To examine the association of patient- and medication-related factors with post-discharge medication errors.
Patients and Methods
The Vanderbilt Inpatient Cohort Study (VICS) includes adults hospitalized with acute coronary syndromes (ACS) and/or acute decompensated heart failure (ADHF). We measured health literacy, subjective numeracy, marital status, cognition, social support, education, income, depression, global health status, and medication adherence in patients enrolled between October 2011 and August 2012. We used binomial logistic regression to determine predictors of discordance between the discharge medication list and patient-reported list during post-discharge medication review.
Among 471 patients, mean age was 59 years; mean total number of medications reported was 12; and 17% had inadequate or marginal health literacy. Half (51%) of patients had ≥1 one discordant medication (i.e., appeared either on the discharge or patient-reported list but not both); 27% failed to report a medication on their discharge list; and 36% reported a medication not on their discharge list. Additionally, 59% had a misunderstanding in indication, dose, or frequency in a cardiac medication. In multivariable analyses, higher subjective numeracy (Odds Ratio (OR)=0.81, 95% Confidence Interval (CI) 0.67-0.98) was associated with lower odds of having discordant medications. For cardiac medications, participants with higher health literacy (OR=0.84, CI 0.74-0.95), higher subjective numeracy (OR=0.77, CI 0.63-0.95), and who were female (OR=0.60, CI 0.46-0.78) had lower odds of misunderstandings in indication, dose, or frequency.
Medication errors are present in approximately half of patients following hospital discharge and are more common among patients with lower numeracy or health literacy.
PMCID: PMC4126191  PMID: 24998906
medication errors; health literacy; hospital discharge; patient safety
13.  Work stress, sleep deficiency and predicted 10-year cardiometabolic risk in a female patient care worker population 
The aim of this study was to investigate the longitudinal effect of work-related stress, sleep deficiency and physical activity on 10-year cardiometabolic risk among an all-female worker population.
Data on patient care workers (n=99) was collected two years apart. Baseline measures included: job stress, physical activity, night work and sleep deficiency. Biomarkers and objective measurements were used to estimate 10-year cardiometabolic risk at follow-up. Significant associations (P<0.05) from baseline analyses were used to build a multivariable linear regression model.
The participants were mostly white nurses with a mean age of 41 years. Adjusted linear regression showed that having sleep maintenance problems, a different occupation than nurse, and/or not exercising at recommended levels at baseline increased the 10-year cardiometabolic risk at follow-up.
In female workers prone to work-related stress and sleep deficiency, maintaining sleep and exercise patterns had a strong impact on modifiable 10-year cardiometabolic risk.
PMCID: PMC4111954  PMID: 24809311
Cardiometabolic risk; Nurses; Sleep maintenance; Physical activity; Follow-up; work-family conflict; sleep
14.  Gender and Obesity Specific MicroRNA Expression in Adipose Tissue from Lean and Obese Pigs 
PLoS ONE  2015;10(7):e0131650.
Obesity is a complex condition that increases the risk of life threatening diseases such as cardiovascular disease and diabetes. Studying the gene regulation of obesity is important for understanding the molecular mechanisms behind the obesity derived diseases and may lead to better intervention and treatment plans. MicroRNAs (miRNAs) are short non-coding RNAs regulating target mRNA by binding to their 3’UTR. They are involved in numerous biological processes and diseases, including obesity. In this study we use a mixed breed pig model designed for obesity studies to investigate differentially expressed miRNAs in subcutaneous adipose tissue by RNA sequencing (RNAseq). Both male and female pigs are included to explore gender differences. The RNAseq study shows that the most highly expressed miRNAs are in accordance with comparable studies in pigs and humans. A total of six miRNAs are differentially expressed in subcutaneous adipose tissue between the lean and obese group of pigs, and in addition gender specific significant differential expression is observed for a number of miRNAs. The differentially expressed miRNAs have been verified using qPCR. The results of these studies in general confirm the trends found by RNAseq. Mir-9 and mir-124a are significantly differentially expressed with large fold changes in subcutaneous adipose tissue between lean and obese pigs. Mir-9 is more highly expressed in the obese pigs with a fold change of 10 and a p-value < 0.001. Mir-124a is more highly expressed in the obese pigs with a fold change of 114 and a p-value < 0.001. In addition, mir-124a is significantly higher expressed in abdominal adipose tissue in male pigs with a fold change of 119 and a p-value < 0.05. Both miRNAs are also significantly higher expressed in the liver of obese male pigs where mir-124a has a fold change of 12 and mir-9 has a fold change of 1.6, both with p-values < 0.05.
PMCID: PMC4519260  PMID: 26222688
15.  Feasibility of a Spanish-language multimedia clinical trial educational intervention 
Clinical trials (London, England)  2013;10(5):767-774.
Hispanic cancer patients are underrepresented in clinical trials (CTs). Research suggests lack of knowledge and language barriers contribute to low accrual. Audiovisual materials offer advantages to Hispanic populations because they have high acceptability; are easy to disseminate; and can be viewed with family.
Hispanic cancer patients and caregivers participated in focus groups to aid in developing a Spanish language audiovisual intervention. This project explored the feasibility of delivering the intervention in medical oncology clinics.
35 patients were randomized to either the intervention condition where they were given the audiovisual intervention (n=18); or a control condition where they were asked to read the National Cancer Institute's Spanish language brochure (n=17). Self-report data on knowledge, attitudes, and self efficacy for participating in a CT, intention to participate in a CT, and receptivity to CT information, were collected at two time points
Knowledge in the intervention condition improved (p=0.06). Intention to participate in a CT remained positive in the intervention condition (p=0.484), but declined over time in the control condition (p=0.031). There were no statistical differences in attitudes or self-efficacy for making a decision to participate in a CT.
Preliminary pilot data should be confirmed in a larger randomized control trial as the sample size was small. Although the patients randomized to the intervention group believed themselves to be willing to participate in a CT, this decision was hypothetical. Not all patients were being considered for enrollment in a CT which may have removed any fear or uncertainty from the situation. In addition, the study was conducted with a small sample of Spanish-speaking Hispanic cancer patients at a comprehensive cancer center in Florida. Thus, the results may not generalize to other populations.
The pilot showed feasibility to deliver an audiovisual intervention in medical oncology clinics. The audiovisual intervention increased Hispanic patients’ knowledge of CTs and positive intention to participate in a CT. An audiovisual may improve quality of care for Hispanic cancer patients who are eligible for CTs.
PMCID: PMC4510979  PMID: 23935161
cancer clinical trials; Hispanic cancer patients; audiovisual intervention
16.  Stable Gold(III) Catalysts by Oxidative Addition of a Carbon-Carbon Bond 
Nature  2015;517(7535):449-454.
Whereas low-valent late transition metal catalysis has become indispensible for chemical synthesis, homogeneous high-valent transition metal catalysis is underdeveloped, mainly due to the reactivity of high-valent transition metal complexes and the challenges associated with synthesizing them. In this manuscript, we report a mild carbon-carbon bond cleavage reaction by a Au(I) complex that generates a stable Au(III) cationic complex. Complementary to the well-established soft and carbophilic Au(I) catalyst, this Au(III) complex exhibits hard, oxophilic Lewis acidity. This is exemplified by catalytic activation of α,β-unsaturated aldehydes towards selective conjugate additions as well as activation of an unsaturated aldehyde-allene for a [2 + 2] cycloaddition reaction. The origin of the regioselectivity and catalytic activity was elucidated by X-ray crystallographic analysis of an isolated Au(III)-activated cinnamaldehyde intermediate. The concepts revealed in this study provide a strategy for accessing high-valent transition metal catalysis from readily available precursors.
PMCID: PMC4304402  PMID: 25612049
17.  Florida Initiative for Quality Cancer Care: Improvements in Breast Cancer Quality Indicators During a 3-Year Interval 
The Florida Initiative for Quality Cancer Care (FIQCC), composed of 11 practice sites across Florida, conducted its initial evaluation of adherence to breast cancer quality of care indicators (QCI) in 2006, with feedback provided to encourage quality improvement efforts at participating sites. In this study, our objective was to reassess changes over time resulting from these efforts.
Quality care indicators were derived from the Quality Oncology Practice Initiative, the National Comprehensive Cancer Network, the American College of Surgeons, and expert panel consensus. Medical records were reviewed for breast cancer patients first seen by medical oncologists in 2009 at the FIQCC sites, using the same performance indicators as in 2006. Statistical comparisons of 2006 vs 2009 data across sites were made by Pearson chi-square exact test using Monte Carlo estimation.
Charts of 602 patients in 2006 and 636 patients in 2009 were compared. Performance on medical oncology QCI improved over time for documentation of clinical trial participation discussion (p = 0.001), documentation of consent for chemotherapy (p = 0.047), definitive surgery done after neoadjuvant chemotherapy (p = 0.017), and planned dose of chemotherapy consistent with published regimens (p = 0.02). Improvements in surgical QCI were seen for documentation of specimen orientation (p < 0.001), inking of margins (p < 0.0001), and performance of sentinel lymph node biopsy (p = 0.035).
The 2006 FIQCC study identified several medical and surgical oncology QCI improvement needs. Quality improvement efforts resulted in better performance for numerous metrics, therefore speaking to the benefits of reassessment of adherence to performance indicators to guide QCI efforts.
PMCID: PMC4505727  PMID: 25086813
18.  A patterned microtexture to reduce friction and increase longevity of prosthetic hip joints 
More than 285,000 total hip replacement surgeries are performed in the US each year. Most prosthetic hip joints consist of a cobalt-chromium (CoCr) femoral head that articulates with a polyethylene acetabular component, lubricated with synovial fluid. The statistical survivorship of these metal-on-polyethylene prosthetic hip joints declines significantly after 10 to 15 years of use, primarily as a result of polyethylene wear and wear debris incited disease. The current engineering paradigm to increase the longevity of prosthetic hip joints is to improve the mechanical properties of the polyethylene component, and to manufacture ultra-smooth articulating surfaces. In contrast, we show that adding a patterned microtexture to the ultra-smooth CoCr femoral head reduces friction when articulating with the polyethylene acetabular liner. The microtexture increases the load-carrying capacity and the thickness of the joint lubricant film, which reduces contact between the articulating surfaces. As a result, friction and wear is reduced. We have used a lubrication model to design the geometry of the patterned microtexture, and experimentally demonstrate reduced friction for the microtextured compared to conventional smooth surrogate prosthetic hip joints.
PMCID: PMC4084735  PMID: 25013240
Prosthetic hip joint; Friction; Polyethylene; Microtexture; Laser surface texturing
19.  Stratified Sampling of Neighborhood Sections for Population Estimation: A Case Study of Bo City, Sierra Leone 
PLoS ONE  2015;10(7):e0132850.
There is a need for better estimators of population size in places that have undergone rapid growth and where collection of census data is difficult. We explored simulated estimates of urban population based on survey data from Bo, Sierra Leone, using two approaches: (1) stratified sampling from across 20 neighborhoods and (2) stratified single-stage cluster sampling of only four randomly-sampled neighborhoods. The stratification variables evaluated were (a) occupants per individual residence, (b) occupants per neighborhood, and (c) residential structures per neighborhood. For method (1), stratification variable (a) yielded the most accurate re-estimate of the current total population. Stratification variable (c), which can be estimated from aerial photography and zoning type verification, and variable (b), which could be ascertained by surveying a limited number of households, increased the accuracy of method (2). Small household-level surveys with appropriate sampling methods can yield reasonably accurate estimations of urban populations.
PMCID: PMC4503693  PMID: 26177479
20.  Respiratory Health in Cleaners in Northern Europe: Is Susceptibility Established in Early Life? 
PLoS ONE  2015;10(7):e0131959.
There is some evidence that maternal smoking increases susceptibility to personal smoking’s detrimental effects. One might question whether early life disadvantage might influence susceptibility to occupational exposure.
In this cross-sectional study we investigated respiratory symptoms, asthma and self-reported chronic obstructive pulmonary disease (COPD) as related to working as a cleaner in Northern European populations, and whether early life factors influenced susceptibility to occupational cleaning’s unhealthy effects.
The RHINE III questionnaire study assessed occupational cleaning in 13,499 participants. Associations with respiratory symptoms, asthma and self-reported COPD were analysed with multiple logistic regressions, adjusting for sex, age, smoking, educational level, parent´s educational level, BMI and participating centre. Interaction of occupational cleaning with early life disadvantage (maternal smoking, severe respiratory infection <5 years, born during winter months, maternal age at birth >35 years) was investigated.
Main Results
Among 2138 ever-cleaners the risks of wheeze (OR 1.4, 95% CI 1.3–1.6), adult-onset asthma (1.5 [1.2–1.8]) and self-reported COPD (1.7 [1.3–2.2]) were increased. The risk increased with years in occupational cleaning (adult-onset asthma: ≤1 year 0.9 [0.7–1.3]; 1–4 years 1.5 [1.1–2.0]; ≥4 years 1.6 [1.2–2.1]). The association of wheeze with cleaning activity ≥4 years was significantly stronger for those with early life disadvantage than in those without (1.8 [1.5–2.3] vs. 1.3 [0.96–1.8]; pinteraction 0.035).
Occupational cleaners had increased risk of asthma and self-reported COPD. Respiratory symptom risk was particularly increased in persons with factors suggestive of early life disadvantage. We hypothesize that early life disadvantage may increase airway vulnerability to harmful exposure from cleaning agents later in life.
PMCID: PMC4500550  PMID: 26168149
21.  Risk Factors for HPV Infection among American Indian and White Women in the Northern Plains 
Gynecologic oncology  2011;121(3):532-536.
American Indian (AI) women living in the Northern Plains have high incidence and mortality rates for cervical cancer. We assessed risk factors for human papillomavirus (HPV) infection among AI and White women.
We tested cervical samples for HPV infection obtained from women ages 18-65 years attending 2 rural AI reservation clinics in South Dakota (n = 235) and an urban clinic serving predominantly White women (n = 246). Patients self-reported information on HPV risk factors. We used percentages and chi-square tests to compare risk factors, and logistic regression with HPV status as the outcome to quantify the association between HPV and risk factors.
AI women had more risk factors than White women, including younger age, less education, less vegetable consumption, more sexual partners, younger age at first sexual experience and first pregnancy, and more pregnancies (p values ≤ 0.003). AI women more often endorsed recreational drug use, history of sexually transmitted diseases, and current smoking; White women reported more alcohol consumption (p values < 0.001). In multivariate analysis, younger age and current smoking were associated with higher odds of HPV infection in AI women, whereas a higher number of sexual partners was associated with higher odds of HPV infection in White women.
AI women have a high burden of risk factors for HPV disease, and associations with HPV infection appear to differ by community. Knowledge of specific risk factors in AI populations may provide targets for public health officials to decrease HPV infection and disease.
PMCID: PMC4498572  PMID: 21414655
cervical cancer; American Indian; risk factors; screening; health disparities; human papillomavirus
22.  Fibulin-1C, C1 Esterase Inhibitor and Glucose Regulated Protein 75 Interact with the CREC Proteins, Calumenin and Reticulocalbin 
PLoS ONE  2015;10(7):e0132283.
Affinity purification, immunoprecipitation, gel electrophoresis and mass spectrometry were used to identify fibulin-1C, C1 esterase inhibitor and glucose regulated protein 75, grp75, as binding partners of the CREC proteins, calumenin and reticulocalbin. Surface plasmon resonance was used to verify the interaction of all three proteins with each of the CREC proteins. Fibulin-1C interacts with calumenin and reticulocalbin with an estimated dissociation constant around 50-60 nM. The interaction, at least for reticulocalbin, was not dependent upon the presence of Ca2+. C1 esterase inhibitor interacted with both proteins with an estimated dissociation constant at 1 μM for reticulocalbin and 150 nM for calumenin. The interaction, at least for calumenin, was dependent upon the presence of Ca2+ with strong interaction at 3.5 mM while no detectable interaction could be found at 0.1 mM. Grp75 binds with an affinity of approximately 3-7 nM with reticulocalbin as well as with calumenin. These interactions suggest functional participation of the CREC proteins in chaperone activity, cell proliferation and transformation, cellular aging, haemostasis and thrombosis as well as modulation of the complement system in fighting bacterial infection.
PMCID: PMC4498735  PMID: 26161649
23.  HIF-1α is required for hematopoietic stem cell mobilization and 4-prolyl hydroxylase inhibitors enhance mobilization by stabilizing HIF-1α 
Leukemia  2015;29(6):1366-1378.
Many patients with hematological neoplasms fail to mobilize sufficient numbers of hematopoietic stem cells (HSCs) in response to granulocyte colony-stimulating factor (G-CSF) precluding subsequent autologous HSC transplantation. Plerixafor, a specific antagonist of the chemokine receptor CXCR4, can rescue some but not all patients who failed to mobilize with G-CSF alone. These refractory poor mobilizers cannot currently benefit from autologous transplantation. To discover alternative targetable pathways to enhance HSC mobilization, we studied the role of hypoxia-inducible factor-1α (HIF-1α) and the effect of HIF-1α pharmacological stabilization on HSC mobilization in mice. We demonstrate in mice with HSC-specific conditional deletion of the Hif1a gene that the oxygen-labile transcription factor HIF-1α is essential for HSC mobilization in response to G-CSF and Plerixafor. Conversely, pharmacological stabilization of HIF-1α with the 4-prolyl hydroxylase inhibitor FG-4497 synergizes with G-CSF and Plerixafor increasing mobilization of reconstituting HSCs 20-fold compared with G-CSF plus Plerixafor, currently the most potent mobilizing combination used in the clinic.
PMCID: PMC4498452  PMID: 25578474
24.  Evaluating the quality of psychosocial care in outpatient medical oncology settings using performance indicators 
Psycho-oncology  2010;20(11):1221-1227.
An American Psychosocial Oncology Society workgroup has developed indicators of the quality of psychosocial care that can be measured through review of medical records. The present report describes the first large-scale use of these indicators to evaluate psychosocial care in outpatient medical oncology settings.
Medical records of 1660 colorectal, breast and non-small cell cancer patients first seen by a medical oncologist in 2006 at 11 practice sites in Florida were reviewed for performance on indicators of the quality of psychosocial care.
Assessment of emotional well-being was significantly less likely to be documented than assessment of pain (52 vs 87%, p<0.001). A problem with emotional well-being was documented in 13% of records and evidence of action taken was documented in 58% of these records. Ten of eleven practice sites performed below an 85% threshold on each indicator of psychosocial care. Variability in assessment of emotional-well being was associated (p<0.02) with practice site and patient gender and age while variability in assessment of pain was associated (p<0.001) with practice site and cancer type.
Findings illustrate how use of the psychosocial care indicators permits identification of specific practice sites and processes of care that should be targeted for quality improvement efforts. Additionally, findings demonstrate the extent to which routine assessment of emotional well-being lags behind routine assessment of pain in cancer patients.
PMCID: PMC4497369  PMID: 20878724
quality of care; psychosocial oncology
25.  Understanding the Psychosocial Issues of African American Couples Surviving Prostate Cancer 
African Americans are disproportionately affected by prostate cancer, yet less is known about the most salient psychosocial dimensions of quality of life. The purpose of this study was to explore the perceptions of African American prostate cancer survivors and their spouses of psychosocial issues related to quality of life. Twelve African American couples were recruited from a National Cancer Institute Comprehensive Cancer Center registry and a state-based non-profit organization to participate in individual interviews. The study was theoretically based on Ferrell's Quality of Life Conceptual Model. Common themes emerged regarding the psychosocial needs of African American couples. These themes were categorized into behavioral, social, psychological, and spiritual domains. Divergent perspectives were identified between male prostate cancer survivors and their female spouses. This study delineated unmet needs and areas for future in-depth investigations into psychosocial issues. The differing perspectives between patients and their spouses highlight the need for couple-centered interventions.
PMCID: PMC4497555  PMID: 22544536
Prostate cancer; Survivorship; Psychosocial factors; African Americans; Quality of life; Qualitative methods

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