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1.
Genetic discrimination and the law.   总被引:16,自引:11,他引:5       下载免费PDF全文
The use of genetic tests can lead to genetic discrimination, discrimination based solely on the nature of an individual's genotype. Instances of the discriminatory uses of genetic tests by employers and insurance companies have already been reported. The recently enacted Americans with Disabilities Act of 1990 (ADA), together with other federal and state laws, can be used to combat some forms of this discrimination. In this article we define and characterize genetic discrimination, discuss the applicability of the various relevant federal and state laws, including the ADA, in the areas of employment and insurance discrimination, explore the limitations of these laws, and, finally, suggest some means of overcoming these limitations.  相似文献   

2.
3.

Introduction

Anti-TNF drugs have proven to be effective against spondyloarthritis (SpA), although 30% of patients fail to respond or experience adverse events leading to treatment discontinuation. In rheumatoid arthritis, the presence of anti-drug antibodies (ADA) against the first TNF inhibitor influences the outcome after switching. Our aim was to assess whether the response to a second anti-TNF drug is related to the previous development of ADA to the first anti-TNF drug SpA patients.

Methods

Forty-two SpA patients began a second anti-TNF drug after failing to respond to the first anti-TNF therapy. Clinical activity was assessed by the Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline (at the beginning of the first and second anti-TNF therapy) and at 6 months after switching. The drug and ADA levels were measured by ELISA before each administration.

Results

All patients were treated with anti-TNF drugs and mainly due to inefficacy were switched to a second anti-TNF drug. Eleven of 42 (26.2%) developed ADA during the first biologic treatment. At baseline, no differences in ASDAS were found in patients with or without ADA to the first anti-TNF drug (3.52 ± 1.03 without ADA vs. 3.14 ± 0.95 with ADA, p = 0.399) and to the second anti-TNF drug (3.36 ± 0.94 without ADA vs. 3.09 ± 0.91 with ADA, p = 0.466). At 6 months after switching, patients with previous ADA had lower disease activity (1.62 ± 0.93 with ADA vs. 2.79 ± 1.01 without ADA, p = 0.002) and most patients without ADA had high disease activity state by the ASDAS (25 out of 31 (80.6%) without ADA vs. 3 out of 11 (27.3%) with ADA, p = 0.002).

Conclusions

In SpA the failure to respond to the first anti-TNF drug due to the presence of ADA predicts a better clinical response to a second anti-TNF drug.  相似文献   

4.

Background

Individuals with lower socioeconomic status are at increased risk of involuntary exit from paid employment. To give sound advice for primary prevention in the workforce, insight is needed into the role of mediating factors between socioeconomic status and labour force participation. Therefore, it is aimed to investigate the influence of health status, lifestyle-related factors and work characteristics on educational differences in exit from paid employment.

Methods

14,708 Dutch employees participated in a ten-year follow-up study during 1999–2008. At baseline, education, self-perceived health, lifestyle (smoking, alcohol, sports, BMI) and psychosocial (demands, control, rewards) and physical work characteristics were measured by questionnaire. Employment status was ascertained monthly based on tax records. The relation between education, health, lifestyle, work-characteristics and exit from paid employment through disability benefits, unemployment, early retirement and economic inactivity was investigated by competing risks regression analyses. The mediating effects of these factors on educational differences in exit from paid employment were tested using a stepwise approach.

Results

Lower educated workers were more likely to exit paid employment through disability benefits (SHR:1.84), unemployment (SHR:1.74), and economic inactivity (SHR:1.53) but not due to early retirement (SHR:0.92). Poor or moderate health, an unhealthy lifestyle, and unfavourable work characteristics were associated with disability benefits and unemployment, and an unhealthy lifestyle with economic inactivity. Educational differences in disability benefits were explained for 40% by health, 31% by lifestyle, and 12% by work characteristics. For economic inactivity and unemployment, up to 14% and 21% of the educational differences could be explained, particularly by lifestyle-related factors.

Conclusions

There are educational differences in exit from paid employment, which are partly mediated by health, lifestyle and work characteristics, particularly for disability benefits. Health promotion and improving working conditions seem important measures to maintain a productive workforce, particularly among workers with a low education.  相似文献   

5.

Background

Murine retroviral vectors have been used in several hundred gene therapy clinical trials, but have fallen out of favor for a number of reasons. One issue is that gene expression from viral or internal promoters is highly variable and essentially unregulated. Moreover, with retroviral vectors, gene expression is usually silenced over time. Mammalian genes, in contrast, are characterized by highly regulated, precise levels of expression in both a temporal and a cell-specific manner. To ascertain if recapitulation of endogenous adenosine deaminase (ADA) expression can be achieved in a vector construct we created a new series of Moloney murine leukemia virus (MuLV) based retroviral vector that carry human regulatory elements including combinations of the ADA promoter, the ADA locus control region (LCR), ADA introns and human polyadenylation sequences in a self-inactivating vector backbone.

Methods

A MuLV-based retroviral vector with a self-inactivating (SIN) backbone, the phosphoglycerate kinase promoter (PGK) and the enhanced green fluorescent protein (eGFP), as a reporter gene, was generated. Subsequent vectors were constructed from this basic vector by deletion or addition of certain elements. The added elements that were assessed are the human ADA promoter, human ADA locus control region (LCR), introns 7, 8, and 11 from the human ADA gene, and human growth hormone polyadenylation signal. Retroviral vector particles were produced by transient three-plasmid transfection of 293T cells. Retroviral vectors encoding eGFP were titered by transducing 293A cells, and then the proportion of GFP-positive cells was determined using fluorescence-activated cell sorting (FACS). Non T-cell and T-cell lines were transduced at a multiplicity of infection (MOI) of 0.1 and the yield of eGFP transgene expression was evaluated by FACS analysis using mean fluorescent intensity (MFI) detection.

Results

Vectors that contained the ADA LCR were preferentially expressed in T-cell lines. Further improvements in T-cell specific gene expression were observed with the incorporation of additional cis-regulatory elements, such as a human polyadenylation signal and intron 7 from the human ADA gene.

Conclusion

These studies suggest that the combination of an authentically regulated ADA gene in a murine retroviral vector, together with additional locus-specific regulatory refinements, will yield a vector with a safer profile and greater efficacy in terms of high-level, therapeutic, regulated gene expression for the treatment of ADA-deficient severe combined immunodeficiency.  相似文献   

6.

Objective:

The effectiveness of group‐based comprehensive, multidisciplinary (stage 3) pediatric weight management programs is backed by a growing body of literature, yet insurance coverage of these programs is scarce to nonexistent, limiting their reach and long‐term survival. The objective of this study was to better understand the perspectives of insurers and large employers on the issue of group‐based treatment coverage.

Design and Methods:

The authors performed a qualitative study utilizing structured interviews with these stakeholders, following accepted techniques.

Results:

Six major themes emerged: cost, program effectiveness, corporate social responsibility, secondary parental (employee) benefits, coverage options and new benefit determination.

Conclusion:

Future efforts to secure payment for group‐based pediatric weight management programs should address these key themes.  相似文献   

7.

Objective

The efficacy and reliability of prognostic scores has been described extensively for intensive care, but their role for predicting mortality in intermediate care patients is uncertain. To provide more information in this field, we have analyzed the performance of the Simplified Acute Physiology Score (SAPS) II and SAPS 3 in a single center intermediate care unit (ImCU).

Materials and Methods

Cohort study with prospectively collected data from all patients admitted to a single center ImCU in Pamplona, Spain, from April 2006 to April 2012. The SAPS II and SAPS 3 scores with respective predicted mortality rates were calculated according to standard coefficients. Discrimination was evaluated by calculating the area under receiver operating characteristic curve (AUROC) and calibration with the Hosmer-Lemeshow goodness of fit test. Standardized mortality ratios (SMR) with 95% confidence interval (95% CI) were calculated for each model.

Results

The study included 607 patients. The observed in-hospital mortality was 20.1% resulting in a SMR of 0.87 (95% CI 0.73-1.04) for SAPS II and 0.56 (95% CI 0.47-0.67) for SAPS 3. Both scores showed acceptable discrimination, with an AUROC of 0.76 (95% CI 0.71-0.80) for SAPS II and 0.75 (95% CI 0.71- 0.80) for SAPS 3. Calibration curves showed similar performance based on Hosmer-Lemeshow goodness of fit C-test: (X2=12.9, p=0.113) for SAPS II and (X2=4.07, p=0.851) for SAPS 3.

Conclusions

Although both scores overpredicted mortality, SAPS II showed better discrimination for patients admitted to ImCU in terms of SMR.  相似文献   

8.

Background

A total of six Neocalanus species inhabit the oceans of the world. Of these, three species plus form variants (N. cristatus, N. plumchrus, N. flemingeri large form, and N. flemingeri small form), which constitute a monophyletic group among Neocalanus copepods, occur in the Northwestern Pacific off Japan. In the present study, we have tried to discriminate the three species plus form variants of Neocalanus copepods based on sequences of four DNA marker regions.

Methodology/Principal Findings

Discrimination was performed based on the DNA sequence information from four genetic markers, including the mitochondrial COI, 12S, nuclear ITS, and 28S gene regions. Sequence dissimilarity was compared using both distance- and character-based approaches. As a result, all three species were confirmed to be distinct based on the four genetic marker regions. On the contrary, distinction of the form variants was only confirmed based on DNA sequence of the mitochondrial COI gene region.

Conclusions/Significance

Although discrimination was not successful for the form variants based on the mitochondrial 12S, nuclear ITS, and 28S genes, diagnostic nucleotide sequence characters were observed in their mitochondrial COI gene sequences. Therefore, these form variants are considered to be an important unit of evolution below the species level, and constitute a part of the Neocalanus biodiversity.  相似文献   

9.

Background

Intermediate Care Units (ImCU) have become an alternative scenario to perform Non-Invasive Ventilation (NIV). The limited number of prognostic studies in this population support the need of mortality prediction evaluation in this context.

Objective

The objective of this study is to analyze the performance of Simplified Acute Physiology Score (SAPS) II and 3 in patients undergoing NIV in an ImCU. Additionally, we searched for new variables that could be useful to customize these scores, in order to improve mortality prediction.

Design

Cohort study with prospectively collected data from all patients admitted to a single center ImCU who received NIV. The SAPS II and 3 scores with their respective predicted mortality rates were calculated. Discrimination and calibration were evaluated by calculating the area under the receiver operating characteristic curve (AUC) and with the Hosmer-Lemeshow goodness of fit test for the models, respectively. Binary logistic regression was used to identify new variables to customize the scores for mortality prediction in this setting.

Patients

The study included 241 patients consecutively admitted to an ImCU staffed by hospitalists from April 2006 to December 2013.

Key Results

The observed in-hospital mortality was 32.4% resulting in a Standardized Mortality Ratio (SMR) of 1.35 for SAPS II and 0.68 for SAPS 3. Mortality discrimination based on the AUC was 0.73 for SAPS II and 0.69 for SAPS 3. Customized models including immunosuppression, chronic obstructive pulmonary disease (COPD), acute pulmonary edema (APE), lactic acid, pCO2 and haemoglobin levels showed better discrimination than old scores with similar calibration power.

Conclusions

These results suggest that SAPS II and 3 should be customized with additional patient-risk factors to improve mortality prediction in patients undergoing NIV in intermediate care.  相似文献   

10.

Background

Adenosine Deaminase Activity (ADA) is a commonly used marker for the diagnosis of tuberculous pleural effusion. There has been concern about its usefulness in immunocompromised patients, especially HIV positive patients with very low CD4 counts. The objective of this study was to evaluate the sensitivity of ADA in pleural fluid in patients with low CD4 counts.

Materials and Methods

This was a retrospective case control study. Medical files of patients with tuberculous pleuritis and non-tuberculous pleuritis were reviewed. Clinical characteristics, CD4 cell counts in blood and biochemical markers in pleural fluid, including ADA were recorded.

Results

One ninety seven tuberculous pleuritis and 40 non- tuberculous pleuritis patients were evaluated. Using the cut-off value of 30 U/L, the overall sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of ADA was 94%, 95%, 19, and 0.06 respectively. The mean CD4 cell counts among TB pleuritis patients was 29 and 153 cells/microL in patients with CD4 <50 cells/microL and >50 cells/microL, (p<0.05) respectively. The corresponding mean ADA values for these patients were 76 U/L and 72 U/L respectively (p>0.5). There was no correlation between ADA values and CD4 cell counts (r = −0.120, p = 0.369).

Conclusion

ADA analysis is a sensitive marker of tuberculous pleuritis even in HIV patients with very low CD4 counts in a high TB endemic region. The ADA assay is inexpensive, rapid, and simple to perform and is of great value for the immediate diagnosis of tuberculous pleuritis while waiting for culture result and this has a positive impact on patient outcome.  相似文献   

11.

Background  

Enteropathogenic Campylobacter jejuni and C. coli are presently the most common cause of acute bacterial gastroenteritis in the developed world. An understanding of sources and means of transmission of Campylobacter is an essential factor in order to reduce the incidence of Campylobacter-related gastroenteritis in man. Consequently a reproducible, sensitive and well-standardised typing scheme is critical in the successful discrimination of strains and in the subsequent investigations of outbreaks. For this purpose, a phenotypic typing scheme based on quantitative antibiogram determination based on Euclidean distance (QATED), was developed.  相似文献   

12.
The Government of Canada is considering a recommendation by the Committee on the Status of Endangered Wildlife in Canada to list shortjaw cisco (Coregonus zenithicus) as “Threatened” throughout its range under the Species At Risk Act (SARA). If the listing is approved, shortjaw cisco will receive legal protection, including protection for its ‘critical habitat.’ This study focused on habitat characteristics associated with specimens identified as shortjaw cisco collected with targeted sampling in Lake Huron of the Laurentian Great Lakes. Competing habitat-use models were developed using available data for three physical habitat variables: Water Depth, Substrate Slope, and Cliff Distance, and the models were evaluated using binary logistic regression and ranking of Akaike information criteria. For the habitat factors examined, Water Depth was the most important variable for explaining the observed distribution of identified shortjaw cisco, although this factor alone was not sufficient to adequately represent habitat for this taxonomically uncertain and rare animal. Future habitat discrimination for this hypothesized species at risk must be based on (a) reduction of taxonomic uncertainty, (b) expansion of sampling effort, and (c) consideration of additional physical and ecological habitat factors.  相似文献   

13.

Background

Taking care of children diagnosed with cancer affects parents’ professional life. The impact in the long-term however, is not clear. We aimed to compare the employment situation of parents of long-term childhood cancer survivors with control parents of the general population, and to identify clinical and socio-demographic factors associated with parental employment.

Methods

As part of the Swiss Childhood Cancer Survivor Study, we sent a questionnaire to parents of survivors aged 5–15 years, who survived ≥5 years after diagnosis. Information on control parents of the general population came from the Swiss Health Survey (restricted to men and women with ≥1 child aged 5–15 years). Employment was categorized as not employed, part-time, and full-time employed. We used generalized ordered logistic regression to determine associations with clinical and socio-demographic factors. Clinical data was available from the Swiss Childhood Cancer Registry.

Results

We included 394 parent-couples of survivors and 3’341 control parents (1’731 mothers; 1’610 fathers). Mothers of survivors were more often not employed (29% versus 22%; ptrend = 0.007). However, no differences between mothers were found in multivariable analysis. Fathers of survivors were more often employed full-time (93% versus 87%; ptrend = 0.002), which remained significant in multivariable analysis. Among parents of survivors, mothers with tertiary education (OR = 2.40, CI:1.14–5.07) were more likely to be employed. Having a migration background (OR = 3.63, CI: 1.71–7.71) increased the likelihood of being full-time employed in mothers of survivors. Less likely to be employed were mothers of survivors diagnosed with lymphoma (OR = 0.31, CI:0.13–0.73) and >2 children (OR = 0.48, CI:0.30–0.75); and fathers of survivors who had had a relapse (OR = 0.13, CI:0.04–0.36).

Conclusion

Employment situation of parents of long-term survivors reflected the more traditional parenting roles. Specific support for parents with low education, additional children, and whose child had a more severe cancer disease could improve their long-term employment situation.  相似文献   

14.
Expression of murine adenosine deaminase (ADA) in transgenic maize   总被引:1,自引:0,他引:1  
A murine adenosine deaminase (ADA) gene, driven by the maize ubi-1 promoter and intron region, was transformed into embryogenic maize callus, along with a bar and gusA gene-containing plasmid, using microparticle bombardment. Selection in the presence of either the herbicide Basta® or the adenosine analogue 2-deoxyadenosine resulted in transgenic cultures that expressed GUS and accumulated a 41kD protein that immunoprecipated with an ADA-specific polyclonal antibody. ADA enzyme activity was observed in extracts from transgenic callus as well as regenerated plants and progeny. Cultures expressing ADA grew in the presence of 200mg/l 2-deoxyadenosine, a concentration which completely inhibited the growth of non-transgenic cultures. ADA activity appeared to segregate in progeny of regenerated plants as a single, dominant Mendelian trait. These results suggest that ADA, in combination with adenosine analogue selection, represents a potentially viable selectable marker system for transgenic maize production.  相似文献   

15.

Background  

Enterobacter aerogenes and Klebsiella pneumoniae are common isolates in clinical microbiology and important as producers of extended spectrum β-lactamases (ESBL). The discrimination between both species, which is routinely based on biochemical characteristics, is generally accepted to be straightforward. Here we report that genotypically unrelated strains of E. aerogenes can be misidentified as K. pneumoniae by routine laboratories using standard biochemical identification and using identification automates.  相似文献   

16.

Objective:

Better weight loss outcomes are achieved in adults and youth who adhere to obesity treatment regimens (i.e., session attendance and prescribed changes in weight control behaviors). However, more research is needed regarding children's adherence to a range of behaviors relevant for weight maintenance over long‐term follow‐up.

Design and Methods:

Overweight children (N = 101, aged 7‐12 years), along with an overweight parent, participated in a 20‐week family‐based behavioral weight loss treatment (FBT) and were then assigned to either a behaviorally focused or socially focused 16‐week weight maintenance treatment (MT). Treatment attendance and child and parent adherence (i.e., reported use of skills targeted within treatment) were examined in relation to child percent overweight change from baseline to post‐FBT, post‐MT, and 2‐year follow‐up.

Results:

Higher attendance predicted better child weight outcomes at post‐MT, but not at 2‐year follow‐up. Adherence to self‐regulatory skills/goal‐setting skills predicted child weight outcomes at 2‐year follow‐up among the behaviorally focused MT group.

Conclusions:

Future research is needed to examine mediators of change within family‐based weight control interventions, including behavioral and socially based targets. Incorporating self‐regulatory weight maintenance skills into a comprehensive MT may maximize children's sustained weight control.  相似文献   

17.
18.
Photosynthetic gas exchange characteristics of two common boreal forest mosses, Sphagnum (section acutifolia) and Pleurozium schreberi, were measured continuously during the time required for the moss to dry out from full hydration. Similar patterns of change in CO2 assimilation with variation in water content occurred for both species. The maximum rates of CO2 assimilation for Sphagnum (approx. 7 mol m–2 s–1) occurred at a water content of approximately 7 (fresh weight/dry weight) while for Pleurozium the maximum rate (approx. 2 mol m–2 s–1) occurred at a water content of approximately 6 (fresh weight/dry weight). Above and below these water contents CO2 assimilation declined. In both species total conductance to water vapour (expressed as a percentage of the maximum rates) remained nearly constant at a water content above 9 (fresh weight/dry weight), but below this level declined in a strong linear manner. Short-term, on-line 13CO2 and C18O16O discrimination varied substantially with changes in moss water content and associated changes in the ratio of chloroplast CO2 to ambient CO2 partial pressure. At full hydration (maximum water content) both Sphagnum and Pleurozium had similar values of 13CO2 discrimination (approx. 15). Discrimination against 13CO2 increased continuously with reductions in water content to a maximum of 27 in Sphagnum and 22 in Pleurozium. In a similar manner C18C16O discrimination increased from approximately 30 at full hydration in both species to a maximum of 150 in Sphagnum and 90 in Pleurozium, at low water content. The observed changes in C18O16O were strongly correlated to predictions of a mechanistic model of discrimination processes. Field measurements of moss water content suggested that photosynthetic gas exchange by moss in the understory of a black spruce forest was regularly limited by low water content.  相似文献   

19.

Background

Tissue-specific stable isotope signatures can provide insights into the trophic ecology of consumers and their roles in food webs. Two parameters are central for making valid inferences based on stable isotopes, isotopic discrimination (difference in isotopic ratio between consumer and its diet) and turnover time (renewal process of molecules in a given tissue usually measured when half of the tissue composition has changed). We investigated simultaneously the effects of age, sex, and diet types on the variation of discrimination and half-life in nitrogen and carbon stable isotopes (δ15N and δ13C, respectively) in five tissues (blood cells, plasma, muscle, liver, nail, and hair) of a top predator, the arctic fox Vulpes lagopus.

Methodology/Principal Findings

We fed 40 farmed foxes (equal numbers of adults and yearlings of both sexes) with diet capturing the range of resources used by their wild counterparts. We found that, for a single species, six tissues, and three diet types, the range of discrimination values can be almost as large as what is known at the scale of the whole mammalian or avian class. Discrimination varied depending on sex, age, tissue, and diet types, ranging from 0.3‰ to 5.3‰ (mean  = 2.6‰) for δ15N and from 0.2‰ to 2.9‰ (mean  = 0.9‰) for δ13C. We also found an impact of population structure on δ15N half-life in blood cells. Varying across individuals, δ15N half-life in plasma (6 to 10 days) was also shorter than for δ13C (14 to 22 days), though δ15N and δ13C half-lives are usually considered as equal.

Conclusion/Significance

Overall, our multi-factorial experiment revealed that at least six levels of isotopic variations could co-occur in the same population. Our experimental analysis provides a framework for quantifying multiple sources of variation in isotopic discrimination and half-life that needs to be taken into account when designing and analysing ecological field studies.  相似文献   

20.

Objective

Think Health! ¡Vive Saludable! evaluated a moderate‐intensity, lifestyle behavior‐change weight‐loss program in primary care over 2 years of treatment. Final analyses examined weight‐change trajectories by treatment group and attendance.

Methods

Adult primary care patients (n = 261; 84% female; 65% black; 16% Hispanic) were randomly assigned to Basic Plus (moderate intensity; counseling by primary care clinician and a lifestyle coach) or Basic (clinician counseling only). Intention‐to‐treat analyses used all available weight measurements from data collection, treatment, and routine clinical visits. Linear mixed‐effects regression models adjusted for treatment site, gender, and age, and sensitivity analyses evaluated treatment attendance and the impact of loss to follow‐up.

Results

Model‐based estimates for 24‐month mean (95% CI) weight change from baseline were ?1.34 kg (?2.92 to 0.24) in Basic Plus and ?1.16 kg (?2.70 to 0.37) in Basic (net difference ?0.18 kg [?2.38 to 2.03]; P = 0.874). Larger initial weight loss in Basic Plus was attenuated by a ~0.5‐kg rebound at 12 to 16 months. Each additional coaching visit was associated with a 0.37‐kg greater estimated 24‐month weight loss (P = 0.01).

Conclusions

These findings in mostly black and Hispanic female primary care patients suggest that strategies to improve treatment attendance may improve weight loss resulting from moderate‐intensity counseling.
  相似文献   

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