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91.
We describe an extension to matched case-control studies of the parametric modelling framework developed by Diggle (1990) and Diggle and Rowlingson (1994) to investigate raised risk around putative sources of environmental pollution. We use a conditional likelihood approach for the family of risk functions considered in Diggle and Rowlingson (1994). We show that the likelihood surface that results from these models may be highly irregular, and provide a Bayesian analysis in which we investigate the posterior distribution using Markov chain Monte Carlo. An analysis of one-one matched data that were collected to investigate the relationship between respiratory disease and distance to roads in East London is presented. 相似文献
92.
Wakefield MA Chaloupka FJ Kaufman NJ Orleans CT Barker DC Ruel EE 《BMJ (Clinical research ed.)》2000,321(7257):333-337
ObjectiveTo determine the relation between extent of restrictions on smoking at home, at school, and in public places and smoking uptake and smoking prevalence among school students.DesignCross sectional survey with merged records of extent of restrictions on smoking in public places.SettingUnited States.Participants17 287 high school students.ResultsMore restrictive arrangements on smoking at home were associated with a greater likelihood of being in an earlier stage of smoking uptake (P<0.05) and a lower 30 day prevalence (odds ratio 0.79 (95% confidence interval 0.67 to 0.91), P<0.001). These findings applied even when parents were smokers. More pervasive restrictions on smoking in public places were associated with a higher probability of being in a earlier stage of smoking uptake (P<0.05) and lower 30 day prevalence (0.91 (0.83 to 0.99), P=0.03). School smoking bans were related to a greater likelihood of being in an earlier stage of smoking uptake (0.89 (0.85 to 0.99), P<0.05) and lower prevalence (0.86 (0.77 to 0.94), P<0.001) only when the ban was strongly enforced, as measured by instances when teenagers perceived that most or all students obeyed the rule.ConclusionsThese findings suggest that restrictions on smoking at home, more extensive bans on smoking in public places, and enforced bans on smoking at school may reduce teenage smoking. 相似文献
93.
Leptotrichia buccalis is rarely implicated in systemic disease. We report two patients with clinically significant L. buccalis bacteremia which developed during the neutropenia secondary to chemotherapy. Based upon our experience, L. buccalis bacteremia should be considered in certain high-risk immunocompromised patients with mucositis and/or gingivitis. 相似文献
94.
Marsupials and monotremes sort genome treasures from junk 总被引:1,自引:0,他引:1
A recent landmark paper demonstrates the unique contribution of marsupials and monotremes to comparative genome analysis, filling an evolutionary gap between the eutherian mammals (including humans) and more distant vertebrate species. 相似文献
95.
The objective of this research was to determine if ergotamine, an ergopeptine alkaloid isolated from Neotyphodium-infected grasses and associated with toxicoses in livestock, altered plasma concentrations of reproductive hormones in follicular phase heifers and in cows given a progestin implant. In Experiment 1, blood was sampled for 8h from four cycling heifers 2 days after synchronized luteolysis. Heifers were treated with ergotamine tartrate (19microg/kg) i.v. or saline vehicle in a simple cross-over design after 1h of pre-treatment blood sampling. Heifers received oxytocin (100USP units) i.v. 4h after ergotamine or saline treatment. Ergotamine reduced (P<0.01) prolactin concentrations from 1 to 4h post-treatment and increased (P<0.01) 13,14-dihydro-15-keto prostaglandin F2alpha (PGFM) concentrations from 2 to 5h post-treatment. A PGFM response to oxytocin was not detected. In Experiment 2, blood was sampled for 8h from six cycling cows 10 days after receiving a s.c. norgestomet implant. Cows were treated i.v. with ergotamine (20microg/kg) or saline in a simple cross-over design after 1h of pre-treatment blood sampling. Cows received gonadorelin (GnRH, 100microg) i.v. 1h after ergotamine or saline. Cows received oxytocin (100USP units) i.v. 4h after ergotamine or saline treatment. Ergotamine reduced (P<0.01) serum prolactin concentrations by 120min after treatment, with prolactin returning to pre-treatment concentrations by 200min after treatment. Saline-treated cows had lower (P<0.01) prolactin by 280min after treatment. Ergotamine-treated cows had higher (P<0.01) PGFM concentrations compared to saline-treated cows 120-240min after treatments, but the groups exhibited similar increases in PGFM after oxytocin. Plasma LH and FSH concentrations increased to peaks 100-120min after GnRH for both groups. However, the LH response to GnRH was greater (P<0.01) for ergotamine-treated cows. In summary, ergotamine lowered prolactin and elevated PGFM concentrations in follicular phase heifers and cows on norgestomet therapy. Ergotamine increased the LH response to exogenous GnRH in cows with norgestomet implants. These data highlight the potential of ergopeptine alkaloids to affect reproduction through altered endocrine function. 相似文献
96.
97.
John Wakefield R. Yule Alwyn Smith A. M. Adelstein 《BMJ (Clinical research ed.)》1973,2(5859):142-143
An analysis of the cytological records of almost 300,000 women in the Manchester area shows that the rates of positive/suspicious findings from population screening are highly correlated with the rates of mortality from cancer of the cervix when both are distributed according to the occupation of the husband. The correlation holds for various occupational groupings and for all the individual occupation units in which there are more than 1,000 women. This evidence strengthens the case for believing that the condition revealed by a positive smear is a stage in the development of invasive cancer of the uterine cervix. 相似文献
98.
Misako Sato Tsutomu Matsubara Jun Adachi Yuuki Hashimoto Kazuna Fukamizu Marina Kishida Yu-an Yang Lalage M. Wakefield Takeshi Tomonaga 《PloS one》2015,10(5)
Transforming growth factor-β (TGF-β) has a dual role in tumorigenesis, acting as either a tumor suppressor or as a pro-oncogenic factor in a context-dependent manner. Although TGF-β antagonists have been proposed as anti-metastatic therapies for patients with advanced stage cancer, how TGF-β mediates metastasis-promoting effects is poorly understood. Establishment of TGF-β-related protein expression signatures at the metastatic site could provide new mechanistic information and potentially allow identification of novel biomarkers for clinical intervention to discriminate TGF-β oncogenic effects from tumor suppressive effects. In the present study, we found that systemic administration of the TGF-β receptor kinase inhibitor, SB-431542, significantly inhibited lung metastasis from transplanted 4T1 mammary tumors in Balb/c mice. The differentially expressed proteins in the comparison of lung metastases from SB-431542 treated and control vehicle-treated groups were analyzed by a quantitative LTQ Orbitrap Velos system coupled with stable isotope dimethyl labeling. A total of 36,239 peptides from 6,694 proteins were identified, out of which 4,531 proteins were characterized as differentially expressed. A subset of upregulated proteins in the control group was validated by western blotting and immunohistochemistry. The eukaryotic initiation factor (eIF) family members constituted the most enriched protein pathway in vehicle-treated compared with SB-43512-treated lung metastases, suggesting that increased protein expression of specific eIF family members, especially eIF4A1 and eEF2, is related to the metastatic phenotype of advanced breast cancer and can be down-regulated by TGF-β pathway inhibitors. Thus our proteomic approach identified eIF pathway proteins as novel potential mediators of TGF-β tumor-promoting activity. 相似文献
99.
Xin Chen Yuan Yang Qiong Zhou Jonathan M. Weiss OlaMae Zack Howard John M. McPherson Lalage M. Wakefield Joost J. Oppenheim 《PloS one》2014,9(1)
TGFβ is reportedly responsible for accumulation of CD4+Foxp3+ regulatory T cells (Tregs) in tumor. Thus, we treated mouse 4T1 mammary carcinoma with 1D11, a neutralizing anti-TGFβ (1,2,3) antibody. The treatment delayed tumor growth, but unexpectedly increased the proportion of Tregs in tumor. In vitro, 1D11 enhanced while TGFβ potently inhibited the proliferation of Tregs. To enhance the anti-tumor effects, 1D11 was administered with cyclophosphamide which was reported to eliminate intratumoral Tregs. This combination resulted in long term tumor-free survival of up to 80% of mice, and the tumor-free mice were more resistant to re-challenge with tumor. To examine the phenotype of tumor infiltrating immune cells, 4T1-tumor bearing mice were treated with 1D11 and a lower dose of cyclophosphamide. This treatment markedly inhibited tumor growth, and was accompanied by massive infiltration of IFNγ-producing T cells. Furthermore, this combination markedly decreased the number of splenic CD11b+Gr1+ cells, and increased their expression levels of MHC II and CD80. In a spontaneous 4T1 lung metastasis model with resection of primary tumor, this combination therapy markedly increased the survival of mice, indicating it was effective in reducing lethal metastasis burden. Taken together, our data show that anti-TGFβ antibody and cyclophosphamide represents an effective chemoimmunotherapeutic combination. 相似文献
100.
Ahmi Ben-Yehudah Becki M Campanaro Laura M Wakefield Tia N Kinney Jill Brekosky Vonya M Eisinger Carlos A Castro Diane L Carlisle 《Respiratory research》2013,14(1):119