BACKGROUND & AIMS: PURPOSE:Consistent condom use is critical to efforts to prevent sexually transmitted infections among adolescents, but condom use may decline as relationships and contraceptive needs change. The purpose of this research is to assess changes in condom non-use longitudinally in the context of changes in relationship quality, coital frequency and hormonal contraceptive choice. METHODS:Participants were women (aged 14-17 years at enrollment) recruited from three urban adolescent medicine clinics. Data were collected at three-month intervals using a face-to-face structured interview. Participants were able to contribute up to 10 interviews, but on average contributed 4.2 interviews over the 27-month period. Independent variables assessed partner-specific relationship quality (five items; scale range 5-25; alpha = .92, e.g., this partner is a very important person to me); and, number of coital events with a specific partner. Additional items assessed experience with oral contraceptive pills (OCP) use and injected depo medroxy-progesterone acetate (DMPA). The outcome variable was number of coital events without condom use during the past three months. Analyses were conducted as a three-level hierarchical linear growth curve model using HLM 6. The Level 1 predictor was time, to test the hypothesis that condom non-use increases over time. Level 2 predictors assessed relationship quality and coital frequency across all partners to assess hypotheses that participants' condom non-use increases over time as a function of relationship quality and coital frequency. Level 3 predictors assessed the participant-level influence of OCP or DMPA experience on time-related changes in condom non-use. RESULTS:A total of 176 women reported 279 sex partners and contributed 478 visits. Both average coital frequency and average condom non-use linearly increased during the 27-month follow-up. At any given follow-up, about 35% reported recent OCP use, and 65% reported DMPA use. HLM analyses showed that condom non-use increased as a function of time (beta = .12; p = .03, Level 1 analysis). Increased condom non-use over time was primarily a function of increased coital frequency (beta = .01; p = .00), although higher levels of relationship quality were associated with increased condom non-use at enrollment (beta = .44; p = .00, Level 2 analysis). The temporal rise in condom non-use significantly increased among DMPA users (beta = .06; p = .00) but not OCP users (Level 3 analysis) (beta = -.04; p = .06). CONCLUSIONS:Developmentally, relationship characteristics and coital frequency appear to have increasing weight in decisions about condom use. Hormonal contraceptive methods are not equivalently associated with the overall temporal decline in condom use. Future research associated with dual contraceptive/condom use should address differential factors associated condom use in combination with different hormonal methods.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Intrauterine devices (IUDs) provide highly effective contraception for women worldwide. Reluctance to insert IUDs in the primary care setting may relate to concern about potential difficulty and complications, particularly in nulliparous women. AIMS:To determine the practitioner, patient and procedural factors associated with abandoned IUD insertion, practitioner-reported difficulty of insertion and adverse events during IUD insertions in the family planning setting. METHODS:This was a prospective study over a 12-month period of consecutive IUD insertions in four family planning clinics across New South Wales and Queensland. Patient, practitioner and device-related factors associated with abandoned IUD insertion, practitioner-reported ease of insertion and immediate insertion-related adverse events were analysed using logistic regression. RESULTS:Of 996 insertion procedures, successful insertion occurred in 95%, and 90% were reported as easy by the inserting doctor, including 80% of those in nulliparous women. Patient characteristics associated with an abandoned insertion were nulliparity (AOR 5.19; 2.49-10.82) or caesarean section-only deliveries (AOR 5.38; 2.58-11.22) and with practitioner-reported difficult insertion, nulliparity alone (AOR 1.98; 1.11-3.54). Practitioners inserting fewer than 100 IUDs over the 12-month study period more frequently rated insertions as difficult (AOR 1.76; 1.08-2.88). Complications occurred in 34 women and were more likely in nulliparous women (AOR 4.51; 2.16-9.39). CONCLUSIONS:Most IUDs can be successfully inserted, even in nulliparous women, in a primary care setting. Referral to a specialist may be appropriate for some women who are nulliparous or had caesarean section-only deliveries, depending on the experience of the practitioner.

背景与目标：

BACKGROUND & AIMS: PURPOSE:The purpose of this study was to assess demographic characteristics of women prescribed beta-blocker (beta-blocker) medication and compare to those not using beta-blocker medication, and to determine if there are differences in depression and fatigue among women who used beta-blockers compared to nonusers 6-12 months after myocardial infarction (MI). DATA SOURCES:This was a descriptive cross-sectional study of 84 women (61 using beta-blockers and 23 not using beta-blockers) aged 65 and older who were 6-12 months post-MI. Women had their height and weight measured and completed a Demographic Health Form, the Geriatric Depression Scale, and the Revised Piper Fatigue Scale (RPFS). CONCLUSIONS:While most of the women were taking beta-blockers after MI (74%), significantly fewer Black women were taking beta-blockers (chi(2) = 5.086, p = 0.032). Most of the beta-blocker users were overweight or obese. There were no significant differences in age, t(82) = 0.7, p = 0.486; body mass index, t(82) = 0.76, p = 0.445; income, chi(2)(df = 2) = 3.219, p = 0.075; mean depression, t(82) = 1.648, p = 0.103; or fatigue scores, t(82) = 0.993, p = 0.324, between beta-blocker users and nonusers. More of those not taking beta-blockers reported fatigue with significantly higher fatigue in the affective meaning dimension of the RPFS, t(82) = 2.272, p = 0.03. IMPLICATIONS FOR PRACTICE:beta-Blocker medication continues to be underutilized in older women. Because no difference was noted in fatigue and depression in the two groups, these may mean that these side effects are not barriers in prescribing this medication post-MI. Nurse practitioners are in pivotal positions to monitor the ongoing physiological and psychological sequelae post-MI and implement interventions to improve their outcomes.

背景与目标：

BACKGROUND & AIMS: :During chronic HIV-1 infection, continuing viral replication is associated with impaired proliferative capacity of virus-specific CD8+ T cells and with the expansion and persistence of oligoclonal T cell populations. TCR usage may significantly influence CD8+ T cell-mediated control of AIDS viruses; however, the potential to modulate the repertoire of functional virus-specific T cells by immunotherapy has not been explored. To investigate this, we analyzed the TCR Vbeta usage of CD8+ T cells populations which were expanded following vaccination with modified vaccinia virus Ankara expressing a HIV-1 gag/multiepitope immunogen (MVA.HIVA) in HIV-1-infected patients receiving highly active antiretroviral therapy. Vaccinations induced the re-expansion of HIV-1-specific CD8+ T cells and these showed broad TCR Vbeta usage which was maintained for at least 1 year in some individuals. By contrast, virus-specific CD8+ T cell populations in the same donors which failed to expand after vaccination and in unvaccinated controls were oligoclonal. Simultaneously, we observed that CD8+ T cells recognizing vaccine-derived HIV-1 epitopes displayed enhanced capacity to proliferate and to inhibit HIV-1 replication in vitro, following MVA.HIVA immunizations. Taken together, these data indicate that an attenuated viral-vectored vaccine can modulate adaptive CD8+ T cell responses to HIV-1 and improve their antiviral functional capacity. The potential therapeutic benefit of this vaccination approach warrants further investigation.

背景与目标： : 在慢性HIV-1感染期间，持续的病毒复制与病毒特异性CD8 + T细胞的增殖能力受损以及寡克隆T细胞群体的扩增和持续存在有关。TCR的使用可能会显着影响CD8 T细胞介导的AIDS病毒es的控制; 但是，尚未探索通过免疫疗法调节功能性病毒特异性T细胞库的潜力。为了研究这一点，我们分析了在接受高活性抗逆转录病毒治疗的HIV-1-infected患者中，用表达HIV-1 gag/多表位免疫原 (MVA.HIVA) 的改良痘苗病毒安卡拉疫苗接种后扩大的CD8 + T细胞群体的TCR Vbeta使用情况。疫苗接种诱导了HIV-1-specific CD8 + T细胞的再扩增，这些细胞显示了广泛的TCR Vbeta使用，在一些个体中维持了至少1年。相比之下，同一供体中的病毒特异性CD8 T细胞群体在疫苗接种后未能扩大，而未接种疫苗的对照则是寡克隆。同时，我们观察到识别疫苗衍生的HIV-1表位的CD8 + T细胞在MVA.HIVA免疫后表现出增强的体外增殖和抑制HIV-1复制的能力。综合起来，这些数据表明，减毒的病毒载体疫苗可以调节对HIV-1的适应性CD8 + T细胞反应并提高其抗病毒功能能力。这种疫苗接种方法的潜在治疗益处值得进一步研究。

BACKGROUND & AIMS: BACKGROUND:Currently, there is little data available regarding the role of gender-specific gene expression on synonymous codon usage (translational selection) in most organisms, and particularly plants. Using gender-specific EST libraries (with > 4000 ESTs) from Zea mays and Triticum aestivum, we assessed whether gender-specific gene expression per se and gender-specific gene expression level are associated with selection on codon usage. RESULTS:We found clear evidence of a greater bias in codon usage for genes expressed in female than in male organs and gametes, based on the variation in GC content at third codon positions and the frequency of species-preferred codons. This finding holds true for both highly and for lowly expressed genes. In addition, we found that highly expressed genes have greater codon bias than lowly expressed genes for both female- and male-specific genes. Moreover, in both species, genes with female-specific expression show a greater usage of species-specific preferred codons for each of the 18 amino acids having synonymous codons. A supplemental analysis of Brassica napus suggests that bias in codon usage could also be higher in genes expressed in male gametophytic tissues than in heterogeneous (flower) tissues. CONCLUSION:This study reports gender-specific bias in codon usage in plants. The findings reported here, based on the analysis of 1,497,876 codons, are not caused either by differences in the biological functions of the genes or by differences in protein lengths, nor are they likely attributable to mutational bias. The data are best explained by gender-specific translational selection. Plausible explanations for these findings and the relevance to these and other organisms are discussed.

背景与目标：

BACKGROUND & AIMS: OBJECTIVES:To investigate which characteristics of women and healthcare professionals (HCPs) were associated with changing to another combined hormonal contraceptive (CHC) method after contraceptive counselling. METHODS:CHOICE was a cross-sectional survey in which 18,787 women were counselled about combined hormonal contraceptives, during which their contraceptive methods preferred both prior to and after counselling were recorded. In this subanalysis, characteristics associated with changing the method after counselling were determined using logistic regression models. RESULTS:The probability of intending to change from the pill to another method was associated with being older; university-educated; being in a steady relationship; a prior unintended pregnancy; a younger HCP or one who recommended methods other than the pill. Changing to the patch was associated with a female HCP or a HCP who recommended the patch or an injectable. Changing to the ring was associated with being over 21 years; university-educated; being in a relationship; previous hormonal method use; and counselling by a female HCP, a HCP < 60 years old, or a HCP who recommended the ring or an implant. The country of residence influenced these changes in a complex pattern. CONCLUSIONS:Women's choice of CHC methods after contraceptive counselling are influenced by their age, educational background, relationship status, prior unplanned pregnancies and country of residence, as well as age, gender and preferences of their HCP.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Excess opioid use after surgery contributes to opiate misuse and diversion. Understanding opioid prescribing and utilization patterns after sinonasal surgery is critical in designing effective practice protocols. In this study we aim to identify factors associated with variable opioid usage and further delineate optimal prescription patterns for sinonasal surgery. METHODS:All patients undergoing sinonasal surgery within a single health-care system from March 2017 to August 2018 were sent electronic postoperative surveys. Data were collected on the amount of opioid required, pain control, presurgical opiate use, and narcotic disposal. Additional data collected from the electronic medical record included demographics, type of surgery performed, and total amount of opioid prescribed, including refills. RESULTS:Three-hundred sixty four patients were included. A mean number of 25.3 tablets were prescribed per patient, yet the mean taken was just 11.8 tablets. Excess opioids were prescribed 84.9% of the time with a mean excess narcotic in oral morphine equivalents of 152.5. Among patients, 11.8% reported using no opioids, whereas 52.1% used <50% and 36.1% used >50% of their narcotic prescription. Patients used 9.3% of their full prescription and only 2.6% required a refill. The amount used was not associated with complexity of endoscopic sinus surgery, type of opiate prescribed, gender, distance living from hospital, or current opioid usage before surgery (p > 0.05). The addition of septoplasty and/or turbinoplasty was associated with variation in opioid usage (p < 0.001). A total of 76.1% of patients incorrectly discarded/stored excess opiates. CONCLUSION:Opioids are overprescribed after sinonasal surgery. The amount of postoperative opiate prescribed should be greatly reduced and may be based on the specific procedures performed. Improved patient education regarding disposal of excess narcotics may help to curtail future opioid diversion.

背景与目标：

BACKGROUND & AIMS: :This paper examines the association between social networks and contraceptive use. Using data from a survey of women belonging to voluntary associations in Yaoundé, Cameroon, we find that the behavior and characteristics of the members of a respondent's personal networks are associated with her contraceptive use, over and above a set of her own individual characteristics that are usually found to be important. Respondents who report that their network partners approve of contraception, use it, and encourage the respondent to use are more likely to use contraception themselves; the association with encouragement is particularly strong. Moreover, there is a strong association between the specific methods of contraception used by a respondent and those used by her network partners, suggesting that members of personal networks exchange and evaluate specific methods. Because most of the respondent's network partners were interviewed, we are able to compare the respondent's perceptions of contraceptive use by her network partners with the network partner's actual use. We find that it is perceptions of use that matter, even if those perception are incorrect.

背景与目标： : 本文研究了社交网络与避孕药具使用之间的关联。使用来自喀麦隆雅温得自愿协会的妇女的调查数据，我们发现受访者个人网络成员的行为和特征与她的避孕药具使用有关，超出了她自己的一系列个人特征，通常被发现很重要。报告自己的网络伴侣赞成避孕，使用避孕并鼓励受访者使用避孕的受访者更有可能自己使用避孕措施; 与鼓励的联系特别强烈。此外，受访者使用的特定避孕方法与她的网络合作伙伴使用的避孕方法之间存在很强的联系，这表明个人网络成员交换和评估特定方法。由于大多数受访者的网络合作伙伴都接受了采访，因此我们能够将受访者对其网络合作伙伴使用避孕药具的看法与网络合作伙伴的实际使用情况进行比较。我们发现，重要的是对使用的感知，即使这些感知是不正确的。

BACKGROUND & AIMS: BACKGROUND:The study was conducted to compare the antifertility effectiveness and side effects of the copper/low-density polyethylene nanocomposite IUD (experimental group) and the copper T220C IUD (control group). STUDY DESIGN:One hundred females were randomly divided into two groups (experimental group and control group, n = 50 in each group). Clinical observation and comparative study were performed on the two groups for 12 months. RESULTS:Follow-up rate was 100% at the 12th month. In the experimental group and control group, the cumulative continuation rates were both 92.0 per 100 women at the 12th month and there was no difference between them (p > .05). The pregnancy rate, removal rate and expulsion rate were low with the difference being not statistically significant (p>.05). The most common side effects were excessive menstrual bleeding, spotting and pain. The rates of side effects were lower in the experimental group than in control group, especially during the initial 3 months after insertion with the differences being statistically significant (p < .05). CONCLUSION:The new design of the copper/low-density polyethylene nanocomposite IUD showed low pregnancy rate, high contraceptive efficacy and satisfactory acceptability. The study suggested that the TCu220C IUD also had high contraceptive efficacy, but had relatively more side effects.

背景与目标：

BACKGROUND & AIMS: :Currently developed progesterone receptor modulators (PRMs) are steroid-derived compounds with mild or potent antiprogestin activity. PRMs may exert a contraceptive activity by different mechanisms such as blockade of ovulation and endometrial desynchronization. Their potential clinical applications are manifold and are very promising in major public health areas, including emergency contraception, long term oestrogen-free contraception (administered alone, or in association with a progestin-only pill to improve bleeding patterns), endometriosis and myoma treatment. The mechanisms of their anti-ovulatory effects and of the endometrial modifications elicited during long term PRM treatment are still not fully elucidated. In future clinical applications, PRMs will be administered orally, via intrauterine systems or vaginal rings.

背景与目标： : 目前开发的孕激素受体调节剂 (prm) 是具有温和或有效抗孕激素活性的类固醇衍生化合物。PRMs可能通过不同的机制 (例如排卵阻断和子宫内膜失步) 发挥避孕活性。它们的潜在临床应用是多方面的，并且在主要公共卫生领域非常有前途，包括紧急避孕，长期无雌激素避孕 (单独使用或与仅孕激素药联合使用以改善出血模式)，子宫内膜异位症和肌瘤治疗。在长期PRM治疗期间，其抗排卵作用和子宫内膜修饰的机制仍未完全阐明。在未来的临床应用中，PRMs将通过宫内系统或阴道环口服。

BACKGROUND & AIMS: PURPOSE:Pregnancy rates among adolescents have declined in the U.S. and Britain but remain high compared with other high-income countries. This comparison describes trends in pregnancy rates, recent sexual activity, and contraceptive use among women aged 16-19 years in the U.S. and Britain to consider the contribution of these two behavioral factors to the decline in pregnancy rates in the two countries and the differences between them. METHODS:We use data from two rounds of the U.S. National Survey of Family Growth, conducted 2002-2003 and 2011-2015, and the British National Survey of Sexual Attitudes and Lifestyles, conducted 2000-2001 and 2010-2012, to describe population-level differences between countries and over time in sexual activity and contraceptive use. We calculate pregnancy rates using national births and abortions data. RESULTS:Pregnancy rates declined in both countries; this began earlier in the U.S. and was steeper. There was no change in sexual activity in Britain, but in the U.S., the proportion reporting recent sex declined. In both countries, there was a shift toward more effective contraception. A higher proportion in Britain than the U.S. reported ever having had sex (65% vs. 49%) and sex in the last year (64% vs. 45%), 6 months (59% vs. 39%), and 4 weeks (48% vs. 29%). A higher proportion in Britain reported using more effective contraception (68% vs. 52%). CONCLUSIONS:In both countries, improvements in contraceptive use have contributed substantially to declines in pregnancy rates; however, the steeper decline in the U.S. likely also reflects declines in recent sex occurring only in that country.

背景与目标：

BACKGROUND & AIMS: :Euphorbiaceae plants are important as suppliers of biodiesel. In the current study, the codon usage patterns and sources of variance in chloroplast genome sequences of six different Euphorbiaceae plant species have been systematically analyzed. Our results revealed that the chloroplast genomes of six Euphorbiaceae plant species were biased towards A/T bases and A/T-ending codons, followed by detection of 17 identical high-frequency codons including GCT, TGT, GAT, GAA, TTT, GGA, CAT, AAA, TTA, AAT, CCT, CAA, AGA, TCT, ACT, TAT and TAA. It was found that mutation pressure was a minor factor affecting the variation of codon usage, however, natural selection played a significant role. Comparative analysis of codon usage frequencies of six Euphorbiaceae plant species with four model organisms reflected that Arabidopsis thaliana, Populus trichocarpa, and Saccharomyces cerevisiae should be considered as suitable exogenous expression receptor systems for chloroplast genes of six Euphorbiaceae plant species. Furthermore, it is optimal to choose Saccharomyces cerevisiae as the exogenous expression receptor. The outcome of the present study might provide important reference information for further understanding the codon usage patterns of chloroplast genomes in other plant species.

背景与目标： : 大戟科植物作为生物柴油的供应商很重要。在当前的研究中，已经对六种不同大戟科植物物种的叶绿体基因组序列的密码子使用模式和变异来源进行了系统分析。我们的结果表明，六个大戟科植物的叶绿体基因组偏向A/T碱基和A/T结尾密码子，随后检测到17个相同的高频密码子，包括GCT，TGT，GAT，GAA，TTT，GGA，CAT，AAA，TTA，AAT，CCT，CAA、AGA、TCT、ACT、TAT和TAA。发现突变压力是影响密码子使用变化的次要因素，但是自然选择起着重要作用。6种大戟科植物与4种模式生物密码子使用频率的比较分析表明，拟南芥，毛白杨和酿酒酵母应被视为六种大戟科植物叶绿体基因的合适外源表达受体系统。此外，选择酿酒酵母作为外源表达受体是最佳的。本研究的结果可能为进一步了解其他植物物种中叶绿体基因组的密码子使用模式提供重要的参考信息。

BACKGROUND & AIMS: :We examined the effect of menstrual cycle (MC) phase on acid-base regulation and ventilatory control at rest in monophasic oral contraceptive (OC) users. Twelve healthy women (25+/-1 years; mean+/-S.E.) were tested during the inactive (IP; 5.1+/-0.2 days) and active (AP; 21.1+/-0.7 days) pill phase of the MC. Central and peripheral chemoreflex responsiveness was examined using a modified CO(2) rebreathing procedure. Minute ventilation (V E), breathing pattern and metabolic rate were measured during 10 min of quiet, resting breathing. Blood for the determination of arterial P(CO2) (Pa(CO2)) and hydrogen ion concentration ([H(+)]); plasma concentrations of the strong ion difference ([SID]) and total weak acid ([A(tot)]); serum concentrations of progesterone ([P(4)]) and 17beta-estradiol ([E(2)]) were also obtained. Although [E(2)] (p<0.05) and [A(tot)] (p=0.05) were increased in the IP versus AP, MC phase had no significant effect on resting V E, breathing pattern, metabolic rate, [H(+)], Pa(CO2), [SID], [P(4)] and central or peripheral chemoreflex characteristics. Overall, OC had no significant physiological effect on acid-base regulation or ventilatory control at rest in healthy women. This may reflect suppression of endogenous fluctuations in circulating [P(4)] typically observed across the MC in healthy, eumenorrheic non-OC users.

背景与目标： : 我们检查了单相口服避孕药 (OC) 使用者的月经周期 (MC) 阶段对静息时酸碱调节和通气控制的影响。在MC的非活性 (IP; 5.1 +/-0.2天) 和活性 (AP; 21.1 +/-0.7天) 药丸期测试了12名健康女性 (25 +/-1岁; 平均 +/-S.E.)。使用改良的CO(2) 再呼吸程序检查了中枢和外周化学反射的反应性。在安静的静息呼吸10分钟内，测量分钟通气 (V E)，呼吸方式和代谢率。血液测定动脉P(CO2) (Pa(CO2)) 和氢离子浓度 ([H(+)]); 血浆浓度的强离子差 ([SID]) 和总弱酸 ([A(tot)]); 还获得了孕酮 ([P(4)]) 和17β-雌二醇 ([E(2)]) 的血清浓度。尽管与AP相比，IP中 [E(2)] (p<0.05) 和 [A(tot)] (p = 0.05) 增加，但MC期对静息V E，呼吸方式，代谢率，[H(+)]，pa (CO2)，[SID]，[P(4)] 和中央或外围化学反射特性。总体而言，OC对健康女性休息时的酸碱调节或通气控制没有显着的生理作用。这可能反映了在健康的，正常的非OC用户中，通常在MC中观察到的循环 [P(4)] 内源性波动的抑制。

BACKGROUND & AIMS: :T cells specific for a single viral epitope, but using different T cell receptors, should have flexibility in their epitope recognition to protect the infected host against the emergence of viral escape mutants. Therefore, polyclonality of the hepatitis B virus (HBV)-specific cytotoxic T lymphocyte response has been hypothesized to be a major determinant in the control of infection. We analyzed the Vbeta chain composition of the core 18-27-specific CD8 cells in acute and persistently HBV-infected patients using HLA-A2 tetrameric complexes and a panel of Vbeta antibodies. Different T cell receptors were utilized by core 18-27-specific CD8 cells both in patients with acute and chronic infection. The functional ability of these epitope-specific T cells to respond to potential viral mutations was then tested. The polyclonal HBV-specific CD8 response present in patients with acute hepatitis displayed a limited efficiency to recognize mutations introduced within the epitope. The ability of core 18-27-specific CD8 to tolerate epitope mutations was found only during persistent HBV infection. The data suggest that although a clonally heterogeneous CD8 response can be largely inhibited by the occurrence of single epitope mutations in primary HBV infection, preferential selection of T cells able to counteract the emergence of viral mutations can occur during persistent infection.

背景与目标： : 对单个病毒表位特异的T细胞，但使用不同的T细胞受体，应在其表位识别方面具有灵活性，以保护受感染的宿主免受病毒逃逸突变体的出现。因此，乙型肝炎病毒 (HBV) 特异性细胞毒性T淋巴细胞反应的多克隆性被认为是控制感染的主要决定因素。我们使用HLA-A2四聚体复合物和一组Vbeta抗体分析了急性和持续HBV感染患者中核心18-27特异性CD8细胞的Vbeta链组成。在急性和慢性感染患者中，核心18-27特异性CD8细胞都利用了不同的T细胞受体。然后测试了这些表位特异性T细胞对潜在病毒突变的响应能力。急性肝炎患者中存在的多克隆HBV特异性CD8反应显示出识别表位内引入的突变的有限效率。仅在持续性HBV感染期间发现核心18-27特异性CD8耐受表位突变的能力。数据表明，虽然克隆异质性CD8反应可以在很大程度上抑制原发性HBV感染中发生单表位突变，但能够抵消病毒突变出现的T细胞的优先选择可以在持续感染期间发生。

BACKGROUND & AIMS: CONTEXT:Oral contraceptive (OC) use is weakly associated with breast cancer risk in the general population, but the association among women with a familial predisposition to breast cancer is less clear. OBJECTIVE:To determine whether the association between OC use and risk of breast cancer is influenced by family history of the disease. DESIGN AND SETTING:Historical cohort study of 426 families of breast cancer probands diagnosed between 1944 and 1952 at the Tumor Clinic of the University of Minnesota Hospital. Follow-up data on families were collected by telephone interview between 1991 and 1996. PARTICIPANTS:A total of 394 sisters and daughters of the probands, 3002 granddaughters and nieces, and 2754 women who married into the families. MAIN OUTCOME MEASURE:Relative risk (RR) of breast cancer associated with history of OC use by relationship to proband. RESULTS:After accounting for age and birth cohort, ever having used OCs was associated with significantly increased risk of breast cancer among sisters and daughters of the probands (RR, 3.3; 95% confidence interval [CI], 1.6-6.7), but not among granddaughters and nieces of the probands (RR, 1.2; 95% CI, 0.8-2.0) or among marry-ins (RR, 1.2; 95% CI, 0.8-1.9). Results were essentially unchanged after adjustment for parity, age at first birth, age at menarche, age at menopause, oophorectomy, smoking, and education. The elevated risk among women with a first-degree family history of breast cancer was most evident for OC use during or prior to 1975, when formulations were likely to contain higher dosages of estrogen and progestins (RR, 3.3; 95% CI, 1.5-7.2). A small number of breast cancer cases (n = 2) limited the statistical power to detect risk among women with a first-degree relative with breast cancer and OC use after 1975. CONCLUSIONS:These results suggest that women who have ever used earlier formulations of OCs and who also have a first-degree relative with breast cancer may be at particularly high risk for breast cancer. Further studies of women with a strong family history who have used more recent lower-dosage formulations of OCs are needed to determine how women with a familial predisposition to breast cancer should be advised regarding OC use today. JAMA. 2000;284:1791-1798.

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