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2.  On Averages and Peaks: How Do People Integrate Attitudes about Multiple Diseases to Reach a Decision about Multiplex Genetic Testing? 
Background
The aim of the current study was to learn how people integrate attitudes about multiple health conditions to make a decision about genetic testing uptake.
Methods
This study recruited 294 healthy young adults from a parent research project, the Multiplex Initiative, conducted in a large health care system in Detroit, Michigan. All participants were offered a multiplex genetic test that assessed risk for 8 common health conditions (e.g., type 2 diabetes). Data were collected from a baseline survey, a web-based survey, and at the time of testing.
Results
Averaging attitudes across diseases predicted test uptake but did not contribute beyond peak attitudes, the highest attitude toward testing for a single disease in the set. Peak attitudes were found sufficient to predict test uptake.
Limitations
The effects of set size and mode of presentation could not be examined because these factors were constant in the multiplex test offered.
Conclusions
These findings support theories suggesting that people use representative evaluations in attitude formation. The implication of these findings for further developments in genetic testing is that the communication and impact of multiplex testing may need to be considered in the light of a bias toward peak attitudes.
doi:10.1177/0272989X12464432
PMCID: PMC3799841  PMID: 23128581
cognitive psychology; judgment and decision psychology; patient choice modeling; social judgment theory
3.  Navigating a research partnership between academia and industry to assess the impact of personalized genetic testing 
Purpose
To describe the process of structuring a partnership between academic researchers and two personalized genetic testing companies that would manage conflicts of interest while allowing researchers to study the impact of this nascent industry.
Methods
We developed a transparent process of ongoing communication about the interests of all research partners to address challenges in establishing study goals, survey development, data collection, analysis, and manuscript preparation. Using the existing literature on conflicts of interest and our experience, we created a checklist for academic and industry researchers seeking to structure research partnerships.
Results
Our checklist includes questions about the risk to research participants, sponsorship of the study, control of data analysis, freedom to publish results, the impact of the research on industry customers, openness to input from all partners, sharing results before publication, and publication of industry-specific data. Transparency is critical to building trust between partners. Involving all partners in the research development enhanced the quality of our research and provided an opportunity to manage conflicts early in the research process.
Conclusion
Navigating relationships between academia and industry is complex and requires strategies that are transparent and responsive to the concerns of all. Employing a checklist of questions prior to beginning a research partnership may help to manage conflicts of interest.
doi:10.1038/gim.2011.59
PMCID: PMC3763722  PMID: 22241103
conflicts of interest; direct-to-consumer; partnership; personalized genetic testing; personalized medicine
4.  Effectiveness of a condensed protocol for disclosing APOE genotype and providing risk education for Alzheimer disease 
Purpose
Brief, effective models of patient genetic education are needed for common, complex diseases. Using Alzheimer disease as a model, we compared participants’ risk knowledge and recall in extended versus condensed education protocols.
Methods
A four-site randomized clinical trial enrolled 280 first-degree relatives of individuals with Alzheimer disease (mean age = 58 years, 71% female); each received lifetime Alzheimer disease risk information (range: 13–74%) that incorporated apolipoprotein E genotype. In the condensed protocol, participants received an educational brochure in place of an in-person education session. Outcomes were assessed at 6 weeks and 6 months following risk disclosure.
Results
The condensed protocol required less clinician time than the extended protocol (mean = 34 min vs. 77 min). The groups did not differ on recall of apolipoprotein E genotype or lifetime risk, and most participants in both groups recalled and retained this information over time. Both groups showed improvement from baseline in Alzheimer disease risk knowledge (e.g., understanding the magnitude of apolipoprotein E genotype effect on risk).
Conclusion
A condensed protocol for communicating genetic risk for Alzheimer disease achieved similar educational results as an extended protocol in this study. Further research should explore the efficacy of brief genetic education protocols for complex diseases in diverse populations.
doi:10.1038/gim.2012.37
PMCID: PMC3718049  PMID: 22498844
Alzheimer disease; APOE; genetic counseling; health education; risk communication
5.  Inhibition of transforming growth factor-β-activated kinase-1 blocks cancer cell adhesion, invasion, and metastasis 
British Journal of Cancer  2012;107(1):129-136.
Background:
Tumour cell metastasis involves cell adhesion and invasion, processes that depend on signal transduction, which can be influenced by the tumour microenvironment. N-6 polyunsaturated fatty acids, found both in the diet and in response to inflammatory responses, are important components of this microenvironment.
Methods:
We used short hairpin RNA (shRNA) knockdown of TGF-β-activated kinase-1 (TAK1) in human tumour cells to examine its involvement in fatty acid-stimulated cell adhesion and invasion in vitro. An in vivo model of metastasis was developed in which cells, stably expressing firefly luciferase and either a control shRNA or a TAK1-specific shRNA, were injected into the mammary fat pads of mice fed diets, rich in n-6 polyunsaturated fatty acids. Tumour growth and spontaneous metastasis were monitored with in vivo and in situ imaging of bioluminescence.
Results:
Arachidonic acid activated TAK1 and downstream kinases in MDA-MB-435 breast cancer cells and led to increased adhesion and invasion. Knockdown of TAK1 blocked this activation and inhibited both cell adhesion and invasion in vitro. Tumour growth at the site of injection was not affected by TAK1 knockdown, but both the incidence and extent of metastasis to the lung were significantly reduced in mice injected with TAK1 knockdown cells compared with mice carrying control tumour cells.
Conclusion:
These data demonstrate the importance of TAK1 signalling in tumour metastasis in vivo and suggest an opportunity for antimetastatic therapies.
doi:10.1038/bjc.2012.214
PMCID: PMC3389413  PMID: 22644295
adhesion; invasion; metastasis; fatty acid; TGF-β-activated kinase-1; breast cancer
6.  Eavesdropping and signal matching in visual courtship displays of spiders 
Biology Letters  2012;8(3):375-378.
Eavesdropping on communication is widespread among animals, e.g. bystanders observing male–male contests, female mate choice copying and predator detection of prey cues. Some animals also exhibit signal matching, e.g. overlapping of competitors' acoustic signals in aggressive interactions. Fewer studies have examined male eavesdropping on conspecific courtship, although males could increase mating success by attending to others' behaviour and displaying whenever courtship is detected. In this study, we show that field-experienced male Schizocosa ocreata wolf spiders exhibit eavesdropping and signal matching when exposed to video playback of courting male conspecifics. Male spiders had longer bouts of interaction with a courting male stimulus, and more bouts of courtship signalling during and after the presence of a male on the video screen. Rates of courtship (leg tapping) displayed by individual focal males were correlated with the rates of the video exemplar to which they were exposed. These findings suggest male wolf spiders might gain information by eavesdropping on conspecific courtship and adjust performance to match that of rivals. This represents a novel finding, as these behaviours have previously been seen primarily among vertebrates.
doi:10.1098/rsbl.2011.1096
PMCID: PMC3367748  PMID: 22219390
communication; eavesdropping; signal matching; spiders; Lycosidae
7.  Patient, Center and Geographic Characteristics of Nationally Placed Livers 
Once a liver offer has been refused locally and regionally, it is offered nationally. We characterized nationally (n = 1567) versus locally (n = 19 893) placed grafts from adult, nonfulminant, deceased donor liver transplants (LT) from 2/1/05 to 1/31/10. Donors of nationally versus locally placed livers differed by age (50 vs. 42 years), positive HCV antibody (11 vs. 2%) and death from stroke (51 vs. 42%) (p < 0.001 for all). Recipients of nationally versus locally placed livers differed by LT-MELD (20 vs. 24), rates of ascites (35 vs. 37%), encephalopathy (12 vs. 15%), hepatocellular (17 vs. 24%) and nonhepatocellular exceptions (6 vs. 11%) (p ≤ 0.03 for all). Six (5%) centers utilized 64% of the nationally placed grafts while 43 (38%) centers accepted zero during the 5-year period; all high volume centers used ≥1. Compared to local distribution, transplantation with a nationally placed liver was associated with a similar adjusted risk of graft (HR, 0.99; 95% CI, 0.86–1.14) and patient (HR, 0.98; 95% CI, 0.84–1.14; p = 0.77) survival. In conclusion, utilization of nationally placed livers is highly concentrated in very few centers, with no increased adjusted risk of graft loss. These findings provide the foundation for a more informed discussion about changing our current liver allocation and distribution policies.
doi:10.1111/j.1600-6143.2011.03962.x
PMCID: PMC3689311  PMID: 22300591
Distribution; extended criteria donor; geographic-disparity
8.  PI3K/Akt signalling is required for the attachment and spreading, and growth in vivo of metastatic scirrhous gastric carcinoma 
British Journal of Cancer  2012;106(9):1535-1542.
Background:
PI3K/Akt (PKB) pathway has been shown in several cell types to be activated by ligands to cell surface integrins, leading to the metastasis of tumour cells. The signalling pathways involved in the metastatic spread of human scirrhous gastric carcinoma cells have not been defined.
Methods:
The role of the PI3K/Akt pathway in an extensive peritoneal-seeding cell line, OCUM-2MD3 and a parental cell line, OCUM-2M, was investigated by assessing in vitro adhesion and spreading assay, and in vivo peritoneal metastatic model. We also examined the correlation of PI3K/Akt pathway with integrin signals by immunoprecipitations, using cells by transfection with mutant p85 (Δp85).
Results:
Adhesiveness and spreading of OCUM-2MD3 cells on collagen type IV was significantly decreased by PI3K inhibitors and expression of mutant p85, but not by inhibitors of protein kinase C (PKC) or extracellular signal-regulated kinase (ERK). Immunoprecipitation studies indicated that the PI3K/Akt pathway was associated with integrin signalling through Src and vinculin. In an in vivo experimental metastasis model, p85 inhibition reduced peritoneal metastasis of OCUM-2MD3 cells.
Conclusion:
PI3K/Akt signalling may be required for integrin-dependent attachment and spreading of scirrhous gastric carcinoma cells, and would be translated into generating better strategies to optimise their use in cancer clinical trials.
doi:10.1038/bjc.2012.107
PMCID: PMC3341864  PMID: 22531720
PI3 kinase; gastric carcinoma; adhesion; spreading: metastasis; integrin signalling
9.  Risk perceptions and worry about common diseases: A between- and within-subjects examination 
Psychology & health  2012;28(4):434-449.
Objective
To test the relationships between worry and perceptions of likelihood and severity (two indicators of risk perception) across eight common diseases, and to examine contributions of individual and disease variability in worry and risk perceptions.
Methods
Participants were 294 people recruited through the Multiplex Initiative, in which a genetic susceptibility test for 8 common diseases was offered to healthy adults. Participants completed a baseline telephone survey and Web-based surveys measuring the variables for this ancillary study, without a commitment to be tested.
Results
Between- and within-subjects analyses yielded the following findings: 1) worry is more related to likelihood perceptions than to severity perceptions; 2) severity perceptions add significantly to explained worry variances above and beyond likelihood perceptions; 3) the likelihood × severity perception does not add to explained variance in worry above its components; 4) risk perceptions and worries form two identifiable clusters: cancer diseases and cardiovascular-metabolic diseases; 5) there are significant differences in risk perceptions and worry among diseases; 6) there are significant gender differences in risk perceptions and worry about common diseases; 7) variance in risk perception and worry is explained by a combination of between- and within-subjects variances, with the latter being more powerful.
Conclusions
Risk perception research should pay attention to severity perceptions, within-subjects variability and inter-disease differences should not be ignored, gender perspectives on illness perceptions should be acknowledged, and health psychologists must prepare for considering groups of illnesses in addition to single diseases.
doi:10.1080/08870446.2012.737464
PMCID: PMC3566271  PMID: 23121110
risk perception; worry; severity; likelihood; within-subjects
10.  Recruitment and retention monitoring: facilitating the mission of the National Institute of Neurological Disorders and Stroke (NINDS) 
It is commonly accepted that inefficient recruitment and inadequate retention continue to threaten the completion of clinical trials intended to reduce the public health burden of neurological disease. This article will discuss the scientific, economic, and ethical implications of failure to recruit and retain adequate samples in clinical trials, including the consequences of failing to recruit adequately diverse samples. We will also discuss the more common challenges and barriers to efficient and effective recruitment and retention, and the impact these have on successful clinical trial planning. We will explain the newly established efforts within National Institute of Neurological Disorders and Stroke (NINDS) to monitor recruitment and retention with well-defined metrics and implementation of grant awards that include feasibility milestones for continued funding. Finally, we will describe our efforts to address some of the common challenges to recruitment and retention through assistance to investigators and coordinators with evidence-based support, tools, and resources for planning and strategizing recruitment and retention as well as a trans-NIH effort to improve awareness of clinical research in the general public.
PMCID: PMC3517027  PMID: 23230460
12.  Evaluation of the national Cleanyourhands campaign to reduce Staphylococcus aureus bacteraemia and Clostridium difficile infection in hospitals in England and Wales by improved hand hygiene: four year, prospective, ecological, interrupted time series study 
Objective To evaluate the impact of the Cleanyourhands campaign on rates of hospital procurement of alcohol hand rub and soap, report trends in selected healthcare associated infections, and investigate the association between infections and procurement.
Design Prospective, ecological, interrupted time series study from 1 July 2004 to 30 June 2008.
Setting 187 acute trusts in England and Wales.
Intervention Installation of bedside alcohol hand rub, materials promoting hand hygiene and institutional engagement, regular hand hygiene audits, rolled out nationally from 1 December 2004.
Main outcome measures Quarterly (that is, every three months) rates for each trust of hospital procurement of alcohol hand rub and liquid soap; Staphylococcus aureus bacteraemia (meticillin resistant (MRSA) and meticillin sensitive (MSSA)) and Clostridium difficile infection for each trust. Associations between procurement and infection rates assessed by mixed effect Poisson regression model (which also accounted for effect of bed occupancy, hospital type, and timing of other national interventions targeting these infections).
Results Combined procurement of soap and alcohol hand rub tripled from 21.8 to 59.8 mL per patient bed day; procurement rose in association with each phase of the campaign. Rates fell for MRSA bacteraemia (1.88 to 0.91 cases per 10 000 bed days) and C difficile infection (16.75 to 9.49 cases). MSSA bacteraemia rates did not fall. Increased procurement of soap was independently associated with reduced C difficile infection throughout the study (adjusted incidence rate ratio for 1 mL increase per patient bed day 0.993, 95% confidence interval 0.990 to 0.996; P<0.0001). Increased procurement of alcohol hand rub was independently associated with reduced MRSA bacteraemia, but only in the last four quarters of the study (0.990, 0.985 to 0.995; P<0.0001). Publication of the Health Act 2006 was strongly associated with reduced MRSA bacteraemia (0.86, 0.75 to 0.98; P=0.02) and C difficile infection (0.75, 0.67 to 0.84; P<0.0001). Trust visits by Department of Health improvement teams were also associated with reduced MRSA bacteraemia (0.91, 0.83 to 0.99; P=0.03) and C difficile infection (0.80, 0.71 to 0.90; P=0.01), for at least two quarters after each visit.
Conclusions The Cleanyourhands campaign was associated with sustained increases in hospital procurement of alcohol rub and soap, which the results suggest has an important role in reducing rates of some healthcare associated infections. National interventions for infection control undertaken in the context of a high profile political drive can reduce selected healthcare associated infections.
doi:10.1136/bmj.e3005
PMCID: PMC3343183  PMID: 22556101

Results 1-12 (12)