• 【基于放射性核素确定的肿瘤患者射血分数的临床决策。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Peng NJ,Advani R,Kopiwoda S,Fisher G,Strauss HW
    BACKGROUND & AIMS: UNLABELLED:Decreased left ventricular ejection fraction (LVEF) is a relative contraindication for the use of potentially cardiotoxic chemotherapy. A resting LVEF of 50% is usually used as the lower limit of normal values. The decision to change chemotherapy, however, is complex and is affected by many factors, including ejection fraction.

    METHODS:To determine how LVEF data were used by clinical oncologists in clinical decision making, we performed a retrospective analysis of patients referred for ejection fraction measurements from the hematology/oncology divisionS of Stanford University from March 1992 through March 1995. The records of 565 patients treated with potentially cardiotoxic chemotherapy were evaluated.

    RESULTS:LVEFs < 50% were found in 153 patients. The charts of patients with reduced ejection fractions were reviewed to determine if the radionuclide measurement resulted in either discontinuation of the cardiotoxic agent or substitution of a less cardiotoxic drug or mode of administration. These specific changes in therapy occurred in only 43 of the 153 (28%) patients with ejection fractions below 50%; 24 of the 43 (57%) had ejection fractions < or = 40%. Patients with lower ejection fraction values were more likely to have their therapy changed than those with LVEFs close to normal. Patients with ejection fractions < or = 30 generally had cardiotoxic agents discontinued. Of patients who had a resting LVEF < 50% and whose therapy was not changed, 81% had a normal increase in LVEF with exercise.

    CONCLUSION:In clinical practice at our institution, ejection fraction < 50% is not used as an absolute contraindication to cardiotoxic chemotherapy. When the LVEF is less than 40%, potentially cardiotoxic therapy is most often discontinued or omitted. Radionuclide evidence of cardiac reserve may account for decisions to continue cardiotoxic agents despite ejection fractions < 50% in the majority of patients. Further study will be needed to establish standard criteria. Reserve function, as measured by the change in ejection fraction from rest to stress may be an important parameter used by oncologists to help select patients for continued therapy in spite of a reduced ejection fraction. Our results argue that use of fixed criteria may be too restrictive.

    背景与目标: 未标记 : 左心室射血分数 (LVEF) 降低是使用潜在心脏毒性化学疗法的相对禁忌症。50% 的静息LVEF通常用作正常值的下限。然而,改变化疗的决定是复杂的,并且受到许多因素的影响,包括射血分数。
    方法 : 为了确定临床肿瘤学家如何在临床决策中使用LVEF数据,我们对1992年3月至1995年3月期间接受斯坦福大学血液学/肿瘤学部门射血分数测量的患者进行了回顾性分析。评估了565例接受潜在心脏毒性化学疗法治疗的患者的记录。
    结果 : 在153例患者中发现LVEFs <50%。回顾了射血分数降低的患者的图表,以确定放射性核素测量是否导致停用心脏毒性药物或替代心脏毒性较小的药物或给药方式。这些特定的治疗变化仅发生在射血分数低于50% 的153 (28%) 患者中; 43 (57%) 中的24的射血分数 <或 = 40%。射血分数值较低的患者比LVEFs接近正常的患者更有可能改变治疗。射血分数 <或 = 30的患者通常停用心脏毒性药物。在静息LVEF <50% 且治疗未改变的患者中,81% 的LVEF随运动而正常增加。
    结论 : 在我们机构的临床实践中,射血分数 <50% 不作为心脏毒性化疗的绝对禁忌症。当LVEF小于40% 时,潜在的心脏毒性治疗通常被停止或省略。尽管大多数患者的射血分数 <50%,但心脏储备的放射性核素证据可能解释了继续服用心脏毒性药物的决定。需要进一步研究以建立标准。储备功能 (通过从静息到压力的射血分数变化来衡量) 可能是肿瘤学家使用的重要参数,尽管射血分数降低,但可以帮助选择患者继续治疗。我们的结果认为,使用固定标准可能过于严格。
  • 【DAPK1通过使CaMKII/GluN2B结合LTP特异性来介导有限公司。】 复制标题 收藏 收藏
    DOI:10.1016/j.celrep.2017.05.068 复制DOI
    作者列表:Goodell DJ,Zaegel V,Coultrap SJ,Hell JW,Bayer KU
    BACKGROUND & AIMS: :The death-associated protein kinase 1 (DAPK1) is a potent mediator of neuronal cell death. Here, we find that DAPK1 also functions in synaptic plasticity by regulating the Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII). CaMKII and T286 autophosphorylation are required for both long-term potentiation (LTP) and depression (LTD), two opposing forms of synaptic plasticity underlying learning, memory, and cognition. T286-autophosphorylation induces CaMKII binding to the NMDA receptor (NMDAR) subunit GluN2B, which mediates CaMKII synaptic accumulation during LTP. We find that the LTP specificity of CaMKII synaptic accumulation is due to its LTD-specific suppression by calcineurin (CaN)-dependent DAPK1 activation, which in turn blocks CaMKII binding to GluN2B. This suppression is enabled by competitive DAPK1 versus CaMKII binding to GluN2B. Negative regulation of DAPK1/GluN2B binding by Ca2+/CaM results in synaptic DAPK1 removal during LTP but retention during LTD. A pharmacogenetic approach showed that suppression of CaMKII/GluN2B binding is a DAPK1 function required for LTD.
    背景与目标: 死亡相关蛋白激酶1 (DAPK1) 是神经元细胞死亡的有效介质。在这里,我们发现DAPK1还通过调节Ca2/钙调蛋白 (CaM) 依赖性蛋白激酶II (CaMKII) 在突触可塑性中起作用。长期增强 (LTP) 和抑郁 (LTD) 都需要CaMKII和T286自磷酸化,这是学习,记忆和认知基础的突触可塑性的两种相反形式。T286-autophosphorylation诱导CaMKII与NMDA受体 (NMDAR) 亚基GluN2B结合,后者在LTP期间介导CaMKII突触积累。我们发现CaMKII突触积累的LTP特异性是由于钙调神经磷酸酶 (CaN) 依赖性DAPK1激活对其LTD特异性的抑制,这反过来又阻止了CaMKII与GluN2B的结合。通过竞争性DAPK1与CaMKII结合GluN2B来实现这种抑制。Ca2 +/CaM对DAPK1/GluN2B结合的负调节导致LTP期间突触DAPK1去除,但在LTD.期间保留。药物遗传学方法表明,抑制CaMKII/GluN2B结合是LTD所需的DAPK1功能。
  • 【前列腺素类血栓素A2受体-和前列环素受体-g蛋白偶联结构决定因素的新见解.】 复制标题 收藏 收藏
    DOI:10.1128/MCB.00725-12 复制DOI
    作者列表:Chakraborty R,Pydi SP,Gleim S,Bhullar RP,Hwa J,Dakshinamurti S,Chelikani P
    BACKGROUND & AIMS: :G protein-coupled receptors (GPCRs) interact with heterotrimeric G proteins and initiate a wide variety of signaling pathways. The molecular nature of GPCR-G protein interactions in the clinically important thromboxane A2 (TxA(2)) receptor (TP) and prostacyclin (PGI(2)) receptor (IP) is poorly understood. The TP activates its cognate G protein (Gαq) in response to the binding of thromboxane, while the IP signals through Gαs in response to the binding of prostacyclin. Here, we utilized a combination of approaches consisting of chimeric receptors, molecular modeling, and site-directed mutagenesis to precisely study the specificity of G protein coupling. Multiple chimeric receptors were constructed by replacing the TP intracellular loops (ICLs) with the ICL regions of the IP. Our results demonstrate that both the sequences and lengths of ICL2 and ICL3 influenced G protein specificity. Importantly, we identified a precise ICL region on the prostanoid receptors TP and IP that can switch G protein specificities. The validities of the chimeric technique and the derived molecular model were confirmed by introducing clinically relevant naturally occurring mutations (R60L in the TP and R212C in the IP). Our findings provide new molecular insights into prostanoid receptor-G protein interactions, which are of general significance for understanding the structural basis of G protein activation by GPCRs in basic health and cardiovascular disease.
    背景与目标: : g蛋白偶联受体 (gpcr) 与异三聚体g蛋白相互作用,并启动多种信号通路。临床上重要的血栓烷A2 (TxA(2)) 受体 (TP) 和前列环素 (PGI(2)) 受体 (IP) 中gpcr-g蛋白相互作用的分子性质知之甚少。TP响应血栓烷的结合而激活其同源g蛋白 (G α q),而IP响应前列环素的结合而通过G α s发出信号。在这里,我们结合了由嵌合受体,分子建模和定点诱变组成的方法来精确研究g蛋白偶联的特异性。通过用IP的ICL区域替换TP细胞内环 (ICL) 来构建多个嵌合受体。我们的结果表明,ICL2和ICL3的序列和长度均影响g蛋白的特异性。重要的是,我们在前列腺素受体TP和IP上确定了一个精确的ICL区域,可以切换g蛋白特异性。通过引入临床相关的自然发生突变 (TP中的R60L和IP中的R212C),证实了嵌合技术和衍生分子模型的有效性。我们的发现为前列腺素受体-g蛋白相互作用提供了新的分子见解,这对于理解GPCRs在基础健康和心血管疾病中激活g蛋白的结构基础具有普遍意义。
  • 【关于生育治疗的生育知识和信念: 国际生育决策研究的结果。】 复制标题 收藏 收藏
    DOI:10.1093/humrep/des402 复制DOI
    作者列表:Bunting L,Tsibulsky I,Boivin J
    BACKGROUND & AIMS: STUDY QUESTION:How good is fertility knowledge and what are treatment beliefs in an international sample of men and women currently trying to conceive? SUMMARY ANSWER:The study population had a modest level of fertility knowledge and held positive and negative views of treatment. WHAT IS KNOWN ALREADY:Few studies have examined general fertility treatment attitudes but studies of specific interventions show that attitudes are related to characteristics of the patient, doctor and context. Further, research shows that fertility knowledge is poor. However, the majority of these studies have examined the prevalence of infertility, the optimal fertile period and/or age-related infertility in women, in university students and/or people from high-resource countries making it difficult to generalize findings. STUDY DESIGN, SIZE, DURATION:A cross-sectional sample completed the International Fertility Decision-making Study (IFDMS) over a 9-month period, online or via social research panels and in fertility clinics. PARTICIPANTS/MATERIALS, SETTING, METHODS:Participants were 10 045 people (8355 women, 1690 men) who were on average 31.8 years old, had been trying to conceive for 2.8 years with 53.9% university educated. From a total of 79 countries, sample size was >100 in 18 countries. All 79 countries were assigned to either a very high Human Development Index (VH HDI) or a not very high HDI (NVH HDI). The IFDMS was a 45-min, 64-item English survey translated into 12 languages. The inclusion criteria were the age between 18 and 50 years and currently trying to conceive for at least 6 months. Fertility knowledge was assessed using a 13-item correct/incorrect scale concerned with risk factors, misconceptions and basic fertility facts (range: 0-100% correct). Treatment beliefs were assessed with positive and negative statements about fertility treatment rated on a five-point agree/disagree response scale. MAIN RESULTS AND THE ROLE OF CHANCE:Average correct score for Fertility Knowledge was 56.9%, with greater knowledge significantly related to female gender, university education, paid employment, VH HDI and prior medical consultation for infertility (all P < 0.001). The mean agreement scores for treatment beliefs showed that agreement for positive items (safety, efficacy) was correlated with agreement for negative items (short/long-term physical/emotional effects) (P > 0.001). People who had given birth/fathered a child, been trying to conceive for less than 12 months, who had never consulted for a fertility problem and who lived in a country with an NVH HDI agreed less with negative beliefs. HDI, duration of trying to conceive and help-seeking were also correlates of higher positive beliefs, alongside younger age, living in an urban area and having stepchildren. Greater fertility knowledge was associated with stronger agreement on negative treatment beliefs items (P < 0.001) but was unrelated to positive treatment beliefs items. LIMITATIONS, REASONS FOR CAUTION:There was volunteer bias insofar as more women, people of higher education and people with fertility problems (i.e. met criteria for infertility, had consulted a medical doctor, had conceived with fertility treatment) participated and this was true in VH and NVH HDI countries. The bias may mean that people in this sample had better fertility knowledge and less favourable treatment beliefs than is the case in the general population. WIDER IMPLICATIONS OF THE FINDINGS:Educational interventions should be directed at improving knowledge of fertility health. Future prospective research should be aimed at investigating how fertility knowledge and treatment beliefs affect childbearing and help-seeking decision-making.
    背景与目标:
  • 【身体吸引力对获得酒精的影响: 当社会政策符合社会决策时。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:McCall M
    BACKGROUND & AIMS: Despite numerous legal interventions, minors continue to purchase and consume alcohol. Prior research had suggested that the decision to request identification to prove legal age was susceptible to various judgement and decision heuristics. This research examined whether the physical attractiveness of the potential consumer and the presence or absence of others were significant predictors of alcohol accessibility. Bartenders (n = 130) rated a target individual who was either high or low in attractiveness. Results indicated that attractiveness was a significant predictor of "proofing likelihood". High levels of attractiveness were associated with a decrease in the likelihood of being asked to provide proof of legal age for the purchase of alcohol. Individuals presented alone were seen as significantly older than when grouped with others. Implications of these findings for the restriction of alcohol availability among minors are considered.

    背景与目标: 尽管有许多法律干预,未成年人仍继续购买和消费酒精。先前的研究表明,要求证明合法年龄的决定容易受到各种判断和决策启发式的影响。这项研究检查了潜在消费者的身体吸引力以及其他人的存在与否是否是酒精可及性的重要预测因素。调酒师 (n = 130) 对吸引力高或低的目标个体进行了评分。结果表明,吸引力是 “打样可能性” 的重要预测指标。高吸引力与被要求提供购买酒精的法定年龄证明的可能性降低有关。单独出现的人被认为比与他人分组时要大得多。考虑了这些发现对限制未成年人饮酒的影响。
  • 【食品加工行为的灵活表达: 巴巴多斯野生加勒比grackles中扣篮率的决定因素。】 复制标题 收藏 收藏
    DOI:10.1016/j.beproc.2007.05.005 复制DOI
    作者列表:Morand-Ferron J,Lefebvre L
    BACKGROUND & AIMS: :Dunking, the softening of dry food in water to speed up consumption time, is normally a very rare behaviour in wild Carib grackles (Quiscalus lugubris) of Barbados. Its frequency can be experimentally increased when large numbers of dry items are repeatedly placed near a standing source of water in conditions that minimize intraspecific competition and risk of theft. To reconcile the normally low frequency of the behaviour in the wild with the high rates obtained in previous experiments, we tested three conditions where dunking varied between 0 and 70%. Dunking was very rare when it had been made unnecessary by pre-soaking the food, water was far from the dry items offered and only one food item was given, focusing all competitive interactions and theft attempts on a single individual. In contrast, dunking rate was high when food was not pre-soaked, water was close to dry food and more than one item (and hence target for competition and theft) was given. These experiments confirm that dunking rates, like other proto-tool-like food-processing techniques, depend on the costs and benefits of the situation where they are used.
    背景与目标: : 在巴巴多斯的野生加勒比grackles (Quiscalus lugubris) 中,浸泡是将干粮在水中软化以加快食用时间的行为,通常是非常罕见的行为。当在最大程度地减少种内竞争和盗窃风险的条件下将大量干燥物品反复放置在站立的水源附近时,可以通过实验提高其频率。为了使野外行为的正常频率与先前实验中获得的高比率相协调,我们测试了三个条件,其中扣篮在0到70% 之间变化。当预先浸泡食物而变得不必要时,扣篮是非常罕见的,水远离提供的干物品,只提供了一种食物,将所有竞争互动和盗窃企图集中在一个人身上。相反,当未预先浸泡食物,水接近干粮并且给出了多个物品 (因此是竞争和盗窃的目标) 时,扣篮率很高。这些实验证实,与其他类似原始工具的食品加工技术一样,灌篮率取决于使用它们的情况的成本和收益。
  • 【关于心脏病预防的决策辅助工具对患者与医生的讨论及其预防计划的影响: 一项随机试验。】 复制标题 收藏 收藏
    DOI:10.1186/1472-6963-6-121 复制DOI
    作者列表:Sheridan SL,Shadle J,Simpson RJ Jr,Pignone MP
    BACKGROUND & AIMS: BACKGROUND:Low utilization of effective coronary heart disease (CHD) prevention strategies may be due to many factors, but chief among them is the lack of patient involvement in prevention decisions. We undertook this study to test the effectiveness of an individually-tailored, computerized decision aid about CHD on patients' discussions with their doctor and their plans for CHD prevention. METHODS:We conducted a pilot randomized trial in a convenience sample of adults with no previous history of cardiovascular disease to test the effectiveness of an individually-tailored, computerized decision aid about CHD prevention against a risk factor list that patients could present to their doctor. RESULTS:We enrolled 75 adults. Mean age was 53. 59% were female, 73% white, and 23% African-American. 66% had some college education. 43% had a 10-year CHD risk of 0-5%, 25% a risk of 6-10%, 24% a risk of 11-20%, and 5% a risk of > 20%. 78% had at least one option to reduce their CHD risk, but only 45% accurately identified the strategies best supported by evidence. 41 patients received the decision aid, 34 received usual care. In unadjusted analysis, the decision aid increased the proportion of patients who discussed CHD risk reduction with their doctor from 24% to 40% (absolute difference 16%; 95% CI -4% to +37%) and increased the proportion who had a specific plan to reduce their risk from 24% to 37% (absolute difference 13%; 95% CI -7% to +34%). In pre-post testing, the decision aid also appeared to increase the proportion of patients with plans to intervene on their CHD risk (absolute increase ranging from 21% to 47% for planned medication use and 5% to 16% for planned behavioral interventions). CONCLUSION:Our study confirms patients' limited knowledge about their CHD risk and effective risk reduction options and provides preliminary evidence that an individually-tailored decision aid about CHD prevention might be expected to increase patients' discussions about CHD prevention with their doctor and their plans for CHD risk reduction. These findings should be replicated in studies with a larger sample size and patients at overall higher risk of CHD.
    背景与目标:
  • 【消费者和政策制定者如何利用系统审查进行决策。】 复制标题 收藏 收藏
    DOI:10.7326/0003-4819-127-1-199707010-00007 复制DOI
    作者列表:Bero LA,Jadad AR
    BACKGROUND & AIMS: Systematic reviews can be a very useful decision-making tool because they objectively summarize large amounts of information, identify gaps in medical research, and identify beneficial or harmful interventions. Consumers can use systematic reviews to help them make health care decisions. Policymakers can use systematic reviews to help them make decisions about what types of health care to provide. Despite the potential value of systematic reviews, little evidence of their direct impact on the decisions made by consumers and policymakers is available. We discuss strategies for optimizing the use of systematic reviews by increasing the awareness and identification of reviews, learning to critically evaluate the findings of reviews, and overcoming barriers to the incorporation of reviews into the decision-making process. In addition, the participation of consumers and policymakers in the design, conduct, and reporting of systematic reviews can help to produce reviews that are relevant and understandable to target audiences. Because decisions that involve health care policies and issues are complex processes in which information (such as that provided by systematic reviews) plays only a part, strategies for increasing the use of systematic reviews should be evaluated for their usefulness in the decision-making process.

    背景与目标: 系统评价可以是一个非常有用的决策工具,因为它们客观地总结了大量信息,确定了医学研究中的差距,并确定了有益或有害的干预措施。消费者可以使用系统的评论来帮助他们做出医疗保健决策。政策制定者可以使用系统的审查来帮助他们决定提供哪些类型的医疗保健。尽管系统审查具有潜在的价值,但几乎没有证据表明它们对消费者和政策制定者做出的决定有直接影响。我们讨论了通过提高对评论的认识和识别,学会批判性地评估评论的结果以及克服将评论纳入决策过程的障碍来优化系统评论使用的策略。此外,消费者和政策制定者参与系统审查的设计,进行和报告可以帮助产生与目标受众相关且易于理解的评论。由于涉及医疗保健政策和问题的决策是复杂的过程,其中信息 (例如由系统审查提供的信息) 仅起一部分作用,因此应评估增加使用系统审查的策略在决策过程中的有用性。
  • 【省卫生服务局的优先事项设定: 关键决策者调查。】 复制标题 收藏 收藏
    DOI:10.1186/1472-6963-7-84 复制DOI
    作者列表:Teng F,Mitton C,Mackenzie J
    BACKGROUND & AIMS: BACKGROUND:In recent years, decision makers in Canada and elsewhere have expressed a desire for more explicit, evidence-based approaches to priority setting. To achieve this aim within health care organizations, knowledge of both the organizational context and stakeholder attitudes towards priority setting are required. The current work adds to a limited yet growing body of international literature describing priority setting practices in health organizations. METHODS:A qualitative study was conducted using in-depth, face-to-face interviews with 25 key decision makers of the Provincial Health Services Authority (PHSA) of British Columbia. Major themes and sub-themes were identified through content analysis. RESULTS:Priorities were described by decision makers as being set in an ad hoc manner, with resources generally allocated along historical lines. Participants identified the Strategic Plan and a strong research base as strengths of the organization. The main areas for improvement were a desire to have a more transparent process for priority setting, a need to develop a culture which supports explicit priority setting, and a focus on fairness in decision making. Barriers to an explicit allocation process included the challenge of providing specialized services for disparate patient groups, and a lack of formal training in priority setting amongst decision makers. CONCLUSION:This study identified factors important to understanding organizational context and informed next steps for explicit priority setting for a provincial health authority. While the PHSA is unique in its organizational structure in Canada, lessons about priority setting should be transferable to other contexts.
    背景与目标:
  • 【二尖瓣置换术后存活和瓣膜衰竭的决定因素。】 复制标题 收藏 收藏
    DOI:10.1016/0003-4975(90)90316-x 复制DOI
    作者列表:Teoh KH,Ivanov J,Weisel RD
    BACKGROUND & AIMS: :A prospective evaluation of 333 consecutive patients undergoing isolated mitral valve replacement between 1982 and 1985 was performed to identify the predictors of survival and valve failure. Follow-up between 2 and 6 years postoperatively (mean, 32 +/- 17 months) was 98% complete. Four prostheses were inserted to permit a prospective evaluation of alternative valves: Björk-Shiley mechanical (n = 118), Ionescu-Shiley pericardial (n = 146), Carpentier-Edwards porcine (n = 38), and Hancock pericardial (n = 31). Hospital mortality was 6%, and actuarial survival at 5 years was 74% +/- 5%. Multivariate Cox regression analysis identified advancing age (less than 40 years, 88% +/- 7%; greater than 70 years, 50% +/- 14%) and poor left ventricular function (ejection fraction less than 0.20, 62% +/- 17%; ejection fraction greater than 0.60, 80% +/- 7%) as independent predictors of postoperative survival. Freedom from structural valve dysfunction, prosthetic valve endocarditis, reoperation, and valve-related mortality and morbidity were 86% +/- 4%, 91% +/- 4%, 81% +/- 4%, and 72% +/- 5%, respectively, at 5 years. The actuarial incidence of valve failure was inordinately high with the Hancock pericardial valve (p less than 0.05). Freedom from thromboembolic events (78% +/- 8% at 5 years) was significantly lower in patients with poor ventricular function (ejection fraction (less than 0.20, 54% +/- 20%; ejection fraction greater than 0.60, 73% +/- 11%; p less than 0.05). Survival after mitral valve replacement was determined by age and left ventricular function. Premature failure of the Hancock pericardial valve resulted in an unacceptable rate of valve-related complications.
    背景与目标: : 对333例接受单独二尖瓣置换1982年和1985的连续患者进行了前瞻性评估,以确定生存和瓣膜衰竭的预测因素。术后2至6年 (平均32/- 17个月) 的随访98% 完成。插入四个假体以对替代瓣膜进行前瞻性评估: bj ö rk-Shiley机械 (n = 118),Ionescu-Shiley心包 (n = 146),Carpentier-Edwards猪 (n = 38) 和Hancock心包 (n = 31)。医院死亡率为6%,5年时的精算生存率为74% +/- 5%。多因素Cox回归分析发现年龄 (小于40岁,88% +/- 7%; 大于70岁,50% +/- 14%) 和左心室功能差 (射血分数小于0.20,62% +/- 17%; 射血分数大于0.60,80% +/- 7%) 作为术后生存率的独立预测因子。在5年时,免于结构瓣膜功能障碍,人工瓣膜心内膜炎,再次手术以及瓣膜相关的死亡率和发病率分别为86%/- 4%,91%/- 4%,81%/- 4% 和72%/- 5%。汉考克心包瓣膜的精算发生率过高 (p小于0.05)。无血栓栓塞事件 (5年时78% +/- 8%) 在心室功能差的患者中显著降低 (射血分数小于0.20,54% +/- 20%; 射血分数大于0.60,73% +/- 11%; p小于0.05)。二尖瓣置换后的存活率取决于年龄和左心室功能。汉考克心包瓣膜过早衰竭导致瓣膜相关并发症的发生率不可接受。
  • 【打破灵长类动物的决策层次结构。】 复制标题 收藏 收藏
    DOI:10.7554/eLife.16650 复制DOI
    作者列表:Hyafil A,Moreno-Bote R
    BACKGROUND & AIMS: :Possible options in a decision often organize as a hierarchy of subdecisions. A recent study concluded that perceptual processes in primates mimic this hierarchical structure and perform subdecisions in parallel. We argue that a flat model that directly selects between final choices accounts more parsimoniously for the reported behavioral and neural data. Critically, a flat model is characterized by decision signals integrating evidence at different hierarchical levels, in agreement with neural recordings showing this integration in localized neural populations. Our results point to the role of experience for building integrated perceptual categories where sensory evidence is merged prior to decision.
    背景与目标: : 决策中的可能选项通常组织为子决策的层次结构。最近的一项研究得出的结论是,灵长类动物的感知过程模仿了这种层次结构,并并行执行子决策。我们认为,直接在最终选择之间进行选择的平面模型对报告的行为和神经数据更为宽容。至关重要的是,扁平模型的特征是决策信号在不同的层次级别上集成了证据,与神经记录一致,表明这种集成在局部神经种群中。我们的结果指出了经验在建立综合感知类别中的作用,在这些类别中,感官证据在做出决定之前就已合并。
  • 【在决策辅助工具中引入阈值是否对患者有益?: 基于发现的诊断决策辅助工具与基于阈值的诊断决策辅助工具之间的比较。】 复制标题 收藏 收藏
    DOI:10.1177/0272989X12461854 复制DOI
    作者列表:Bisig B,Moreira J,Combes M,Asiimwe A,Bisoffi Z,Haegeman F,Bottieau E,Van den Ende J
    BACKGROUND & AIMS: PURPOSE:To assess how different diagnostic decision aids perform in terms of sensitivity, specificity, and harm. METHODS:Four diagnostic decision aids were compared, as applied to a simulated patient population: a findings-based algorithm following a linear or branched pathway, a serial threshold-based strategy, and a parallel threshold-based strategy. Headache in immune-compromised HIV patients in a developing country was used as an example. Diagnoses included cryptococcal meningitis, cerebral toxoplasmosis, tuberculous meningitis, bacterial meningitis, and malaria. Data were derived from literature and expert opinion. Diagnostic strategies' validity was assessed in terms of sensitivity, specificity, and harm related to mortality and morbidity. Sensitivity analyses and Monte Carlo simulation were performed. RESULTS:The parallel threshold-based approach led to a sensitivity of 92% and a specificity of 65%. Sensitivities of the serial threshold-based approach and the branched and linear algorithms were 47%, 47%, and 74%, respectively, and the specificities were 85%, 95%, and 96%. The parallel threshold-based approach resulted in the least harm, with the serial threshold-based approach, the branched algorithm, and the linear algorithm being associated with 1.56-, 1.44-, and 1.17-times higher harm, respectively. Findings were corroborated by sensitivity and Monte Carlo analyses. CONCLUSION:A threshold-based diagnostic approach is designed to find the optimal trade-off that minimizes expected harm, enhancing sensitivity and lowering specificity when appropriate, as in the given example of a symptom pointing to several life-threatening diseases. Findings-based algorithms, in contrast, solely consider clinical observations. A parallel workup, as opposed to a serial workup, additionally allows for all potential diseases to be reviewed, further reducing false negatives. The parallel threshold-based approach might, however, not be as good in other disease settings.
    背景与目标:
  • 【2,3-二磷酸甘油酸和细胞内pH是脱氧血红蛋白S的生理溶解度的相互决定因素。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Poillon WN,Kim BC
    BACKGROUND & AIMS: :We have established that 2,3-diphosphoglycerate (2,3-DPG) content and intracellular pH exert separate, but interdependent, effects on the equilibrium solubility (csat) of deoxyhemoglobin S (deoxy-Hb S) that act in concert to modulate intraerythrocytic polymer formation. In a nonphysiologic csat assay system, a steep dependence of csat on pH in the physiologic range 7.0 to 7.6 was shown for both stripped (Hb) and DPG-saturated deoxy-Hb S (Hb-DPG). The solubility-pH profile for Hb under near-physiologic buffer conditions also showed that csat increased steeply in the same pH range (6.8 to 7.6). The effect of 2,3-DPG on csat under near-physiologic conditions was evaluated separately. At pH 7.20, the pH of the human red blood cell, csat values for Hb and Hb-DPG were 19.56 +/- 0.14 and 17.95 +/- 0.45 g/dL, respectively, indicating that the solubility of Hb-DPG is lower than that of Hb by 8.2% +/- 2.3%. Thus, binding of 2,3-DPG in the beta-cleft promotes the polymerization of deoxy-Hb S, the ultimate determinant of cell sickling. Furthermore, because of the abnormal Bohr effect of sickle blood (approximately double that of normal blood), the intracellular pH of deoxygenated sickle erythrocytes should be approximately 0.28 pH unit higher than that of oxygenated cells (ie, 7.41 v 7.13). At the higher pH, the corresponding csat for Hb-DPG is 20.22 g/dL, which is the best estimate of the intrinsic solubility of T-state Hb S under conditions that approximate closely those of pH, temperature, ionic strength, and 2,3-DPG saturation in the fully desaturated sickle erythrocyte.
    背景与目标: : 我们已经确定,2,3-二磷酸甘油酸 (2,3-dpg) 含量和细胞内pH对脱氧血红蛋白S (脱氧-Hb S) 的平衡溶解度 (csat) 产生独立但相互依存的影响,而脱氧血红蛋白S (脱氧-Hb S) 协同作用调节红细胞内聚合物的形成。在非生理性csat测定系统中,对于汽提 (Hb) 和DPG饱和脱氧-Hb S (hb-dpg),显示出csat对7.0至7.6的生理范围内的pH的急剧依赖性。Hb在近生理缓冲条件下的溶解度-pH曲线也表明,在相同的pH范围内 (6.8至7.6),csat急剧增加。分别评估了近生理条件下2,3-dpg对csat的影响。在pH 7.20时,人红细胞的pH、Hb和hb-dpg的csat值分别为19.56 +/- 0.14和17.95 +/- 0.45g/dL,表明hb-dpg的溶解度比Hb的溶解度低8.2% +/- 2.3%。因此,在 β-裂隙中结合2,3-dpg会促进脱氧-Hb S的聚合,脱氧-Hb S是细胞镰状的最终决定因素。此外,由于镰状血液的异常玻尔效应 (大约是正常血液的两倍),脱氧镰状红细胞的细胞内pH应该比氧合细胞的pH高约0.28 pH单位 (即7.41 v 7.13)。在较高的pH下,hb-dpg的相应csat为20.22g/dL,这是在非常接近pH、温度、离子强度和完全去饱和镰刀红细胞中2,3-DPG饱和度的条件下,T-态Hb S固有溶解度的最佳估计值。
  • 【通过健康促进方案支持决策: 移民背景下老龄人的经验。】 复制标题 收藏 收藏
    DOI:10.1080/17482631.2017.1337459 复制DOI
    作者列表:Barenfeld E,Gustafsson S,Wallin L,Dahlin-Ivanoff S
    BACKGROUND & AIMS: :This study is part of the Promoting Aging Migrants' Capabilities programme that applied person-centred group meetings and one individual home visit to prolong independence in daily activities among people ≥70 years who had migrated to Sweden from Finland or the Western Balkan region. With the purpose to understand programme outcomes, the study aimed to explore the participants' everyday experiences of using health-promoting messages exchanged during the programme. Using a grounded theory approach, 12 persons aged 70-83 years were interviewed six months to one year after their participation in the programme. The participants experienced how using health-promoting messages was a dynamic process of how to make decisions on taking action to satisfy health-related needs of oneself or others immediately or deferring action. Five sub-processes were also identified: gaining inner strength, meeting challenges in available resources, being attentive to what is worth knowing, approaching health risks, and identifying opportunities to advocate for others. The results suggest that the programme could develop personal skills to support older people who have migrated to overcome health-related challenges. They further demonstrate the importance of supporting their health literacy before personal resources hinder action, and call for research on programmes to overcome environmental barriers to health.
    背景与目标: : 这项研究是 “促进老龄移民能力” 计划的一部分,该计划采用以人为中心的小组会议和一次个人家访,以延长从芬兰或西巴尔干地区移民到瑞典的70岁以上人群的日常活动独立性。为了了解计划的结果,该研究旨在探索参与者在计划中使用健康促进信息的日常经验。采用扎根理论的方法,对12名年龄在70-83岁的人参加该计划六个月至一年后进行了采访。参与者体验了如何使用促进健康的信息是一个动态的过程,如何决定立即采取行动以满足自己或他人的健康相关需求或推迟采取行动。还确定了五个子过程: 获得内在力量,应对可用资源的挑战,关注值得了解的内容,应对健康风险以及确定为他人辩护的机会。结果表明,该计划可以发展个人技能,以支持为克服健康相关挑战而移民的老年人。他们进一步证明了在个人资源阻碍行动之前支持其健康素养的重要性,并呼吁研究克服环境对健康的障碍的方案。
  • 【科学技术中的联觉: 不仅仅是让看不见的东西可见。】 复制标题 收藏 收藏
    DOI:10.1016/j.cbpa.2012.10.030 复制DOI
    作者列表:Suslick KS
    BACKGROUND & AIMS: :Much of our science and technology relies on the visualization of complex data, and chemical biology, more than most fields, often deals with complex datasets. There are, however, other ways of making information available to our senses beyond the visual. Rare individuals naturally have sensory crossover, whose synesthesia permits them, for example, to see colors or shapes when hearing sounds or to sense a specific taste with a specific word. Many scientists, technologists and inventors, however, make a conscious attempt to convert one type of sensory-like input to a different sensory output. A laser light show, for example, converts sound to sight; infrared imaging converts heat to sight. Two recent examples of such intentional synesthesia are discussed in this context: sight-tasting and smell-seeing.
    背景与目标: : 我们的许多科学技术都依赖于复杂数据的可视化,而化学生物学比大多数领域更多地处理复杂数据集。但是,还有其他方法可以使我们的感官获得视觉以外的信息。稀有个体自然具有感觉交叉,例如,其联觉使他们能够在听到声音时看到颜色或形状,或者用特定的单词感知特定的味道。但是,许多科学家,技术人员和发明家都有意识地尝试将一种类似感觉的输入转换为不同的感觉输出。例如,激光表演将声音转换为视线; 红外成像将热量转换为视线。在这种情况下,讨论了这种故意联觉的两个最近的例子: 视觉品尝和嗅觉观察。

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