BACKGROUND & AIMS: BACKGROUND:Abnormal respiratory rates are one of the first indicators of clinical deterioration in emergency department(ED) patients. Despite the importance of respiratory rate observations, this vital sign is often inaccurately recorded on ED observation charts, compromising patient safety. Concurrently, there is a paucity of research reporting why this phenomenon occurs. OBJECTIVE:To develop a substantive theory explaining ED registered nurses' reasoning when they miss or misreport respiratory rate observations. DESIGN:This research project employed a classic grounded theory analysis of qualitative data. PARTICIPANTS:Seventy-nine registered nurses currently working in EDs within Australia. Data collected included detailed responses from individual interviews and open-ended responses from an online questionnaire. METHODS:Classic grounded theory (CGT) research methods were utilised, therefore coding was central to the abstraction of data and its reintegration as theory. Constant comparison synonymous with CGT methods were employed to code data. This approach facilitated the identification of the main concern of the participants and aided in the generation of theory explaining how the participants processed this issue. RESULTS:The main concern identified is that ED registered nurses do not believe that collecting an accurate respiratory rate for ALL patients at EVERY round of observations is a requirement, and yet organizational requirements often dictate that a value for the respiratory rate be included each time vital signs are collected. The theory 'Rationalising Transgression', explains how participants continually resolve this problem. The study found that despite feeling professionally conflicted, nurses often erroneously record respiratory rate observations, and then rationalise this behaviour by employing strategies that adjust the significance of the organisational requirement. These strategies include; Compensating, when nurses believe they are compensating for errant behaviour by enhancing the patient's outcome; Minimalizing, when nurses believe that the patient's outcome would be no different if they recorded an accurate respiratory rate or not and; Trivialising, a strategy that sanctions negligent behaviour and occurs when nurses 'cut corners' to get the job done. Nurses' use these strategies to titrate the level ofemotional discomfort associated with erroneous behaviour, thereby rationalising transgression CONCLUSION: This research reveals that despite continuing education regarding gold standard guidelines for respiratory rate collection, suboptimal practice continues. Ideally, to combat this transgression, a culture shift must occur regarding nurses' understanding of acceptable practice methods. Nurses must receive education in a way that permeates their understanding of the relationship between the regular collection of accurate respiratory rate observations and optimal patient outcomes.

背景与目标：

BACKGROUND & AIMS: OBJECTIVES:Monochorionic (MC) twins are at increased risk of early fetal loss secondary to vascular complications such as twin-twin transfusion syndrome (TTTS). This study compared the early perinatal loss rates between MC and dichorionic (DC) twins in an era of invasive treatment for TTTS. METHODS:This was a retrospective study of all twin pregnancies of known chorionicity from a large regional cohort of nine hospitals over a 10-year period. Ultrasound data were matched to hospital delivery records and to a mandatory national register of pregnancy losses. Prospective risk of pregnancy loss from 14 to 24 weeks' gestation was calculated and the survival trend of MC and DC twins was analyzed using Kaplan-Meier survival analysis. RESULTS:The analysis included 3117 twin pregnancies (605 MC and 2512 DC). The total risk of early pregnancy loss (miscarriage and neonatal death) before 24 weeks was significantly higher in MC twins (60.3 per 1000 fetuses) than in DC twins (6.6 per 1000 fetuses), with a relative risk of 9.18 (95% CI, 6.0-13.9). Survival analysis showed a significant difference in overall and early mortality between MC and DC twins (log-rank test, P < 0.0001), while no difference was noted after 24 weeks' gestation (log-rank test, P = 0.08). CONCLUSIONS:Early pregnancy loss is significantly more common in MC than in DC twins, but no difference in the prospective risk of mortality between MC and DC twins is evident after 24 weeks' gestation. The observed early mortality rate has almost halved in comparison with previous studies in the published literature. Early detection and prompt treatment of complications in MC twins are likely to have contributed to this improvement in outcome.

背景与目标：

BACKGROUND & AIMS: :Fetal growth, birth weight specific mortality rates and effect of sick leave or hospitalization on the fetal growth were investigated in a material of 476 twin pregnancies managed at University Central Hospital of Turku in years 1970-81. Birth weights of twin babies at any gestational age were slightly but not significantly higher than in earlier materials. When compared to growth curve of singleton fetuses, the growth rate of both twins is equal to singletons up to 30th week of pregnancy, being thereafter slower than in singleton pregnancies. Although duration of sick leave and hospitalization increased considerably during the study period, no change in the duration of pregnancy nor in the weight of twin babies occurred. Instead perinatal mortality decreased from 101/per thousand to 36.2/per thousand. Birth weight specific mortality rates did not differ from those in singleton fetuses.

背景与目标： : 在图尔库大学中央医院1970-81年管理的476例双胎妊娠材料中，研究了胎儿生长，出生体重特定死亡率以及病假或住院对胎儿生长的影响。在任何胎龄的双胞胎婴儿的出生体重均略高于但不显着高于早期材料。与单胎胎儿的生长曲线相比，两个双胞胎的生长速度等于怀孕第30周的单胎，此后比单胎妊娠慢。尽管在研究期间病假和住院时间大大增加，但怀孕时间和双胞胎婴儿的体重没有变化。相反，围产期死亡率从101/每千下降到36.2/每千。出生体重特定死亡率与单胎胎儿没有差异。

BACKGROUND & AIMS: BACKGROUND:Hormone replacement therapy increases the number and quality of grafts recovered from brain-dead organ donors. Arginine vasopressin (AVP) has also been shown to have beneficial effects. The aim of this study was to determine the effect of AVP on recovery rates. METHODS:The Organ Procurement and Transplantation Network database was used. Donors treated with hormone replacement therapy and vasopressor agents who were successfully procured between January 1, 2009, and June 30, 2011, were studied. AVP-positive and AVP-negative donors were compared. The primary study end point was the rate of high-yield procurement (≥4 organs). RESULTS:A total of 10,431 donors were included. AVP was infused in 7,873 (75.5%) and was associated with an increased rate of high-yield procurement (50.5% vs 35.6%, P < .001). There was less overall graft refusal due to poor function (38.9% vs 45.6%, P < .001). AVP independently predicted high yield procurement. CONCLUSIONS:The use of AVP with hormone replacement therapy is independently associated with an increased rate of organ recovery. This strategy should be universally adopted in the management of donors progressing to neurologic death.

背景与目标：

BACKGROUND & AIMS: OBJECTIVES:To estimate the agreement between prenatal ultrasonography observations at 16 - 21 gestational weeks and fetal autopsy findings in pregnancies terminated because of fetal anomalies. STUDY DESIGN:This 4½ year retrospective study includes consecutive fetuses that were terminated because of fetal malformation and/or chromosomal anomaly diagnosed in the second trimester. Only fetuses that had undergone fetal anatomy scanning by an obstetrician trained in fetal ultrasound before the termination and with available fetal autopsy reports were included. The cases were identified through the malformation registry database of our ultrasound unit. The sensitivity and specificity of ultrasound were calculated per organ system. When estimating the agreement between ultrasound results and autopsy findings, the cases were allocated to one of four categories according to the degree of concordance between ultrasound and autopsy findings: full agreement, near match, partial agreement and unconfirmed ultrasound findings. RESULTS:71 of 95 pregnancy terminations due to fetal malformations met the inclusion criteria and constitute our study population. The sensitivity of ultrasonography with regard to malformations in the brain and spine was 100 % (27/27) and with regard to malformations in the internal organ system (including malformations in the urogenital and gastrointestinal systems and in the abdominal wall and diaphragm) was 91 % (30/33). The corresponding figures for malformations in the cardiovascular and skeletal organ systems were 63 % (17/27) and 71 % (25/35), respectively. The specificity was lowest for malformations in the central nervous system and internal organ system (33/38, 87 % and 39/44, 89 %, respectively). There was full agreement between the ultrasound and autopsy findings in 44 % (31/71) of all cases and a near match in 46 % (33/71) of cases. In almost 10 % (7/71) of the pregnancies, the ultrasound findings were only partially confirmed or not confirmed by autopsy. In one case the discrepancy between the ultrasound and autopsy findings suggests that the pregnant woman might have decided to terminate the pregnancy on the basis of incorrect interpretation of ultrasound findings. CONCLUSION:Even though the agreement between ultrasound and autopsy findings was acceptable from a clinical point of view, agreement with regard to the detailed description of malformations was far from perfect. The detection rates were suboptimal for the cardiovascular and skeletal organ systems. :ZIEL:: Bewertung, inwieweit bei Schwangerschaftsabbrüchen aufgrund fetaler Anomalien die Befunde der pränatalen Ultraschalluntersuchung in der 16.–21. SSW mit dem Autopsiebefund des Feten übereinstimmen. METHODEN:Diese 4½ jährige retrospektive Studie schließt fortlaufend Feten ein, bei denen im 2. Trimenon ein Schwangerschaftsabbruch (TOP) aufgrund fetaler Fehlbildungen und/oder aufgrund von diagnostizierten Chromosomenanomalien erfolgt ist. Es wurden nur Feten einbezogen, bei denen vor dem Abbruch eine anatomische Untersuchung durch einen in der Fetalsonografie geübten Geburtshelfer durchgeführt wurde und bei denen fetale Autopsiebefunde vorlagen. Die Fälle wurden durch die Datenbank unserer Sonografieabteilung zur „Registrierung von Fehlbildungen“ ermittelt. Die Sensitivität und Spezifität der Sonografie wurde für jedes Organsystem berechnet. Zur Abschätzung der Übereinstimmung von Ultraschall- und Autopsiebefunden wurden die Fälle einer der vier Kategorien zugewiesen, je nach Grad der Übereinstimmung der Befunde: Solche mit völliger, sich fast entsprechender und nur teilweiser Übereinstimmung sowie nicht bestätigte Ultraschallbefunde. ERGEBNISSE:Die Einschlusskriterien erfüllten 71 von 95 Schwangerschaftsabbrüchen aufgrund fetaler Anomalien und bildeten somit unsere Studienpopulation. Die Sensitivität der Sonografie in Bezug auf Malformationen des Gehirns und Wirbelsäule betrug 100 % (27/27) und in Bezug auf Anomalien der inneren Organe (einschließlich der Fehlbildungen des Urogenital- und Magen-Darm-Systems, der Bauchdecke und des Diaphragmas) 91 % (31/33). Die entsprechende Rate für Anomalien des Herz-Kreislauf-Systems betrug 63 % (17/27) und für die des Skelettsystems 71 % (25/35). Die niedrigste Spezifität wurde für Malformationen des zentralen Nervensystems (33/38, 87 %) und der inneren Organe (39/44, 89 %) ermittelt. Eine völlige Übereinstimmung von Ultraschall- und Autopsiebefunden wurde in 44 % (31/71) und eine sich fast entsprechende Übereinstimmung in 46 % (33/71) aller Fälle gefunden. Bei beinahe 10 % (7/71) der Schwangerschaften konnten die Ultraschallbefunde nur teilweise beziehungsweise gar nicht durch die Autopsie bestätigt werden. In einem Fall mit diskrepanten Ultraschall- und Autopsiebefunden kann angenommen werden, dass die Schwangere die Entscheidung für einen Abbruch vermutlich aufgrund der fehlerhaften Interpretation des Ultraschallbefundes fällte. SCHLUSSFOLGERUNG:Obwohl die Übereinstimmung von Ultraschall- und Autopsiebefunden vom klinischen Standpunkt betrachtet akzeptierbar schien, war sie bezüglich der genauen Beschreibung der Fehlbildungen bei weitem nicht perfekt. Die Trefferquoten beim Herz-Kreislauf- und Skelettsystem waren suboptimal.

背景与目标：

BACKGROUND & AIMS: :A 31-year-old woman complained of dyspnea and orthopnea at 38 weeks of gestation. A grade 3/6 pansystolic murmur was heard, and echocardiography revealed severe mitral regurgitation with a hyperechoic obstacle on the posterior mitral valve leaflet, consistent with a diagnosis of acute heart failure due to a ruptured chordae tendineae or an infectious endocarditis. An emergency cesarean section was performed under general anesthesia. A male infant was born weighing 2928 g with Apgar scores of 7 and 8 at 1 and 5 min, respectively. The patient was managed in the intensive care unit and underwent open-heart surgery for mitral valve repair on postpartum day 3. The two chordal tendineae appeared torn and frail, and a mitral annuloplasty was performed. No finding of infectious endocarditis was observed. Because it is a dramatic and life-threatening clinical situation, proper diagnosis and treatment in the intensive care unit assure a good outcome for both mother and fetus.

背景与目标： : 一名31岁的妇女在妊娠38周时抱怨呼吸困难和正呼吸。听到了3/6级的全收缩期杂音，超声心动图显示严重的二尖瓣反流，二尖瓣后叶上有高回声障碍，这与由于腱索破裂或感染性心内膜炎引起的急性心力衰竭的诊断一致。在全身麻醉下进行紧急剖宫产。出生时体重为2928  g的男婴，分别在1和5  min时Apgar评分为7和8。该患者在重症监护病房接受治疗，并于产后第3天接受心脏直视手术进行二尖瓣修复。两个腱索出现撕裂和脆弱，并进行了二尖瓣环成形术。未发现感染性心内膜炎。由于这是一个戏剧性的，危及生命的临床情况，因此在重症监护病房中进行适当的诊断和治疗可确保母亲和胎儿的良好结局。

BACKGROUND & AIMS: :The aim of this study was to investigate alterations in the leukocyte and differential leukocyte counts in different trimesters of pregnancy and the initial postpartum period. The study population consisted of 40,325 pregnant women. A full blood count and automated differential leukocyte count were performed and all the haemogram results in the different trimesters of pregnancy were recorded. Percentiles were calculated using statistical software. A total of 82,786 complete blood count evaluations were performed in 40,325 subjects from the 6th to 41st week of pregnancy and in the initial postpartum period. The leukocyte counts increased from the 1st to the 3rd trimester and peaked in the initial postpartum period. Our reference values for the total and differential leukocyte counts may assist clinicians in distinguishing between leukocytosis and pathological elevation of the white blood cell count during pregnancy and the initial postpartum period. Impact statement Pregnancy requires profound adaptation by multiple systems to accommodate the demands of the developing foetus. Similar to all other systems, many haematological changes occur during pregnancy. Studies of normal variation in leukocyte counts were insufficient to distinguish normal from abnormal leukocyte counts during pregnancy and in the initial postpartum period, due to small numbers of patients and a lack of differential leukocyte counts. Without reference leukocyte levels, infections may be more difficult to assess during pregnancy and in the postpartum period. In this study, we report the 3rd, 5th, 10th, 50th, 95th and 99th percentile values for the total and differential leukocyte counts according to trimester in normal pregnancy and the initial postpartum period. Our reference values for the total and differential leukocyte counts in each trimester and the initial postpartum period may assist clinicians in distinguishing between normal leukocytosis and pathological elevation of the white blood cell count during pregnancy and the initial postpartum period. Our results may prevent misdiagnosis of physiological elevated leukocytes as bacterial infection that leads to unnecessary medication use that may compromise the foetus.

背景与目标： : 这项研究的目的是调查妊娠不同三个月和产后初期白细胞和白细胞计数差异的变化。研究人群由40,325名孕妇组成。进行了全血细胞计数和自动差异白细胞计数，并记录了妊娠不同三个月的所有血象结果。使用统计软件计算百分位数。从怀孕的第6周至第41周和产后初期，对40,325名受试者进行了总共82,786次全血细胞计数评估。白细胞计数从第1个月到第3个月增加，并在产后初期达到峰值。我们的总白细胞计数和差异白细胞计数参考值可以帮助临床医生区分白细胞增多和妊娠和产后初期白细胞计数的病理升高。影响声明怀孕需要多个系统进行深刻的适应，以适应发育中的胎儿的需求。与所有其他系统相似，许多血液学变化发生在怀孕期间。由于患者人数少且缺乏差异的白细胞计数，对白细胞计数正常变化的研究不足以区分妊娠期间和产后初期的正常白细胞计数与异常白细胞计数。如果没有参考白细胞水平，则在怀孕期间和产后期间可能更难评估感染。在这项研究中，我们根据正常妊娠和产后初期的三个月报告了总白细胞计数和差异白细胞计数的第3、5、10、50、95和99个百分位数值。我们在每个孕期和产后初期的总白细胞计数和差异白细胞计数的参考值可以帮助临床医生区分正常的白细胞增多和妊娠和产后初期的白细胞计数的病理升高。我们的结果可以防止将生理性白细胞升高误诊为细菌感染，从而导致不必要的药物使用，从而可能损害胎儿。

BACKGROUND & AIMS: BACKGROUND:The recent spread of avian influenza in wild birds and poultry may be a precursor to the emergence of a 1918-like human pandemic. Therefore, stockpiles of human pre-pandemic vaccine (targeted at avian strains) are being considered. For many countries, the principal constraint for these vaccine stockpiles will be the total mass of antigen maintained. We tested the hypothesis that lower individual doses (i.e., less than the recommended dose for maximum protection) may provide substantial extra community-level benefits because they would permit wider vaccine coverage for a given total size of antigen stockpile. METHODS AND FINDINGS:We used a mathematical model to predict infection attack rates under different policies. The model incorporated both an individual's response to vaccination at different doses and the process of person-to-person transmission of pandemic influenza. We found that substantial reductions in the attack rate are likely if vaccines are given to more people at lower doses. These results are applicable to all three vaccine candidates for which data are available. As a guide to the magnitude of the effect, we simulated epidemics based on historical studies of immunogenicity. For example, for one of the vaccines for which data are available, the attack rate would drop from 67.6% to 58.7% if 160 out of the total US population of 300 million were given an optimal dose rather than 20 out of 300 million given the maximally protective dose (as promulgated in the US National Pandemic Preparedness Plan). Our results are conservative with respect to a number of alternative assumptions about the precise nature of vaccine protection. We also considered a model variant that includes a single high-risk subgroup representing children. For smaller stockpile sizes that allow vaccine to be offered only to the high-risk group at the optimal dose, the predicted benefits of using the homogenous model formed a lower bound in the presence of a risk group, even when the high-risk group was twice as infective and twice as susceptible. CONCLUSIONS:In addition to individual-level protection (i.e., vaccine efficacy), the population-level implications of pre-pandemic vaccine programs should be considered when deciding on stockpile size and dose. Our results suggest that a lower vaccine dose may be justified in order to increase population coverage, thereby reducing the infection attack rate overall.

背景与目标：

BACKGROUND & AIMS: :This study examined the effects of human pregnancy and advancing gestation on the intensity of respiratory discomfort (dyspnea) during cycle exercise. Fourteen pregnant women (PG) performed a progressive cycle ergometer exercise test involving 20 W/min increases in work rate to symptom limitation and/or a heart rate of 170-175 beats/min at 19.7+/-1.2 weeks (ENTRY), 28.2+/-0.3 weeks (TM2) and 36.3+/-0.3 weeks (TM3) gestation. Eight, age-matched, sedentary non-pregnant women (CG) were also studied for comparison purposes. Measurements included dyspnea intensity (Borg scale), minute ventilation (VE), breathing pattern and other cardiorespiratory parameters. At peak exercise, neither pregnancy nor advancing gestation had an effect on dyspnea, VE, breathing pattern, oxygen uptake or work rate (p>0.05). VE was significantly greater (by 11 L/min at 100 W) in the PG at TM3 versus CG (p<0.05) at all submaximal work rates. VE also increased progressively from ENTRY to TM2 and TM3 during submaximal exercise. Dyspnea was not significantly different at any submaximal work rate in the PG at TM3 versus CG or with advancing gestation in the PG. In addition, dyspnea at a standardized exercise VE of 40 L/min was not different at TM3 versus ENTRY or in the PG at TM3 versus CG. Neither pregnancy nor advancing gestation were associated with increased respiratory discomfort during strenuous non-weight bearing cycle ergometer exercise, despite substantial increases in VE and progressive mechanical adaptations of the respiratory system to accommodate the increasing size of the gravid uterus.

背景与目标： : 这项研究检查了人类怀孕和妊娠对周期运动期间呼吸不适 (呼吸困难) 强度的影响。14名孕妇 (PG) 进行了渐进式循环测力计运动测试，包括在19.7周 +/-1.2周 (进入) 时，工作速率增加20 W/min，以达到症状限制和/或心率170-175次/min，28.2 +/-0.3周 (TM2) 和36.3 +/-0.3周 (TM3)。为了比较目的，还研究了八名年龄匹配的久坐不动的非孕妇 (CG)。测量包括呼吸困难强度 (Borg量表)，分钟通气量 (VE)，呼吸模式和其他心肺参数。在运动高峰时，怀孕和妊娠均不会影响呼吸困难，VE，呼吸方式，摄氧量或工作效率 (p>0.05)。在所有次最大工作速率下，TM3的PG相对于CG (p<0.05) 的VE显着更高 (在100 W下为11 l/min)。在次最大运动期间，VE也从进入TM2和TM3逐渐增加。在TM3相对于CG的PG中，在任何亚最大工作速率下，或在PG中进行妊娠时，呼吸困难均无显着差异。此外，在标准化运动VE为40 l/min时的呼吸困难在TM3与ENTRY或PG在TM3与CG时没有差异。尽管VE的显着增加和呼吸系统的进行性机械适应以适应妊娠子宫的增加，但在剧烈的非负重循环测力计运动中，怀孕和妊娠都不会增加呼吸不适。

BACKGROUND & AIMS: :Infection with Listeria monocytogenes elicits expansion in numbers of Ag-specific CD8+ T cells, which then undergo programmed contraction. The remaining cells undergo further phenotypic and functional changes with time, eventually attaining the qualities of memory CD8+ T cells. In this study, we show that L. monocytogenes-specific CD8+ T cell populations primed in antibiotic-pretreated mice undergo brief effector phase, but rapidly develop phenotypic (CD127(high), CD43(low)) and functional (granzyme B(low), IL-2-producing) characteristics of memory CD8+ T cells. These early memory CD8+ T cells were capable of substantial secondary expansion in response to booster challenge at day 7 postinfection, resulting in significantly elevated numbers of secondary effector and memory CD8+ T cells and enhanced protective immunity compared with control-infected mice. Although early expansion in numbers is similar after L. monocytogenes infection of antibiotic-pretreated and control mice, the absence of sustained proliferation coupled with decreased killer cell lectin-like receptor G-1 up-regulation on responding CD8+ T cells may explain the rapid effector to memory CD8+ T cell transition. In addition, antibiotic treatment 2 days post-L. monocytogenes challenge accelerated the generation of CD8+ T cells with memory phenotype and function, and this accelerated memory generation was reversed in the presence of CpG-induced inflammation. Together, these data show that the rate at which Ag-specific CD8+ T cell populations acquire memory characteristics after infection is not fixed, but rather can be manipulated by limiting inflammation that will in turn modulate the timing and extent to which CD8+ T cells proliferate and up-regulate killer cell lectin-like receptor G-1 expression.

背景与目标： : 单核细胞增生李斯特菌感染引起Ag特异性CD8 + T细胞数量的扩增，然后进行程序性收缩。其余细胞随时间发生进一步的表型和功能变化，最终达到记忆CD8 T细胞的质量。在这项研究中，我们显示在抗生素预处理的小鼠中引发的单核细胞增生李氏菌特异性CD8 + T细胞群体经历了短暂的效应子期，但迅速发展为表型 (CD127 (高)，CD43 (低)) 和功能性 (颗粒酶B (低)，IL-2-producing) 记忆CD8 + T细胞的特点。与对照感染的小鼠相比，这些早期记忆CD8 + T细胞能够在感染后第7天响应增强攻击而大量二次扩增，导致次级效应子和记忆CD8 + T细胞的数量显着增加，并增强了保护性免疫。尽管在抗生素预处理和对照小鼠的单核细胞增生李氏菌感染后，早期数量的增加是相似的，但缺乏持续增殖以及杀伤细胞凝集素样受体G-1在应答CD8 + T细胞上的上调降低可能解释了对记忆CD8 + T细胞转变的快速效应子。此外，单核细胞增生李氏菌攻击后2天的抗生素治疗加速了具有记忆表型和功能的CD8 T细胞的生成，并且在CpG诱导的炎症存在下，这种加速的记忆生成被逆转。总之，这些数据表明，感染后Ag特异性CD8 + T细胞群体获得记忆特征的速率不是固定的，而是可以通过限制炎症来操纵，炎症反过来将调节CD8 + T细胞增殖的时间和程度，并上调杀伤细胞凝集素样受体G-1表达。

BACKGROUND & AIMS: The response to activated protein C (APC) was investigated in 28 healthy women, non-carriers of the Arg506-Gln mutation in factor V, throughout pregnancy (gestation weeks 12, 20, 28, 32 and 37) and after the delivery. A suppression of APC response was observed which reached lowest values by week 28 (nAPC-ratio 0.78 +/- 0.13), sustained low up to the end of pregnancy and rose after delivery (1.11 +/- 0.22; P < 0.05). APC resistance (nAPC ratio < 0.75) was registered in 16 of the 28 women (57%). A reduction of APC ratio was directly related to its value in the non-pregnant state, being most pronounced in the women with the highest APC ratio. Factor VIII increased during pregnancy and correlated inversely to APC ratio (Z coefficient = -0.645, P < 0.0001). The correlation became weaker in the course of pregnancy, losing significance by week 32. This was explained by the differences in profiles of the two variablesthe lowest measured APC ratio preceded the peak of factor VIII in most cases. The most pronounced rise of factor VIII was found in the women with minimal levels of APC ratio between 0.8 and 0.7. These results allowed us to speculate that APC response is closely regulated during pregnancy, aiming to maintain a certain relevant level. Transitory reduction of APC response is connected to factor VIII and discussed as a prevalent mechanism of functional APC resistance during pregnancy.

背景与目标： 在整个妊娠期间 (妊娠第12、20、28、32和37周) 和分娩后，对28名健康妇女 (非因子V Arg506-Gln突变携带者) 的活化蛋白C (APC) 的反应进行了研究。观察到APC反应的抑制，其在第28周达到最低值 (nAPC比0.78 +/- 0.13)，持续到妊娠结束并在分娩后上升 (1.11 +/- 0.22; P <0.05)。28名女性中有16名 (57% 名) 出现APC耐药 (nAPC比值 <0.75)。APC比率的降低与其在非怀孕状态下的价值直接相关，在APC比率最高的女性中最为明显。因子VIII在怀孕期间增加，并与APC比率成反比 (Z系数 = -0.645，P <0.0001)。相关性在怀孕过程中变弱，到第32周失去意义。这可以通过两个变量的分布差异来解释，在大多数情况下，最低的APC比率先于因子VIII的峰值。在0.8和0.7之间APC比率最低的女性中发现了因子VIII的最明显升高。这些结果使我们能够推测APC反应在怀孕期间受到密切调节，旨在维持一定的相关水平。APC反应的暂时性降低与因子VIII有关，并被认为是怀孕期间功能性APC抵抗的普遍机制。

BACKGROUND & AIMS: The kinetics of flash-induced H+ ion binding by isolated reaction centers (RCs) of Rhodobacter sphaeroides, strain R-26, were measured, using pH indicators and conductimetry, in the presence of terbutryn to block electron transfer between the primary and secondary quinones (QA and QB), and in the absence of exogenous electron donors to the oxidized primary donor, P+, i.e., the P+QA-state. Under these conditions, proton binding by RCs is to the protein rather than to any of the cofactors. After light activation to form P+QA-, the kinetics of proton binding were monoexponential at all pH values studied. At neutral pH, the apparent bimolecular rate constant was close to the diffusional limit for proton transfer in aqueous solution (approximately 10(11) M-1 s-1), but increased significantly in the alkaline pH range (e.g., 2 x 10(13) M-1 s-1 at pH 10). The average slope of the pH dependence was -0.4 instead of -1.0, as might be expected for a H+ diffusion-controlled process. High activation energy (0.54 eV at pH 8.0) and weak viscosity dependence showed that H+ ion uptake by RCs is not limited by diffusion. The salt dependence of the H+ ion binding rate and the pK values of the protonatable amino acid residues of the reaction center implicated surface charge influences, and Gouy-Chapman theory provided a workable description of the ionic effects as arising from modulation of the pH at the surface of the RC. Incubation in D2O caused small increases in the pKs of the protonatable groups and a small, pH (pD)-dependent slowing of the binding rate. The salt, pH, temperature, viscosity, and D2O dependences of the proton uptake by RCs in the P+QA- state were accounted for by three considerations1) parallel pathways of H+ delivery to the RC, contributing to the observed (net) H+ disappearance; 2) rate limitation of the protonation of target groups within the protein by conformational dynamics; and 3) electrostatic influences of charged groups in the protein, via the surface pH.

背景与目标： 在特布林存在下，使用pH指示剂和电导法，测量了球形红球菌 (R-26菌株) 的分离反应中心 (RCs) 对闪光诱导的H + 离子结合的动力学，以阻断一级和二级醌之间的电子转移 (QA和QB)，并且在没有外源电子供体的情况下，氧化的主供体P，即P QA态。在这些条件下，RCs的质子结合是与蛋白质结合，而不是与任何辅因子结合。光激活形成P QA-后，在所有研究的ph值下，质子结合的动力学都是单指数的。在中性pH下，表观双分子速率常数接近于水溶液中质子转移的扩散极限 (约10(11) M-1 s-1)，但在碱性pH范围内显著增加 (例如，2 × 10(13) M-1在ph10 s-1)。pH依赖性的平均斜率为-0.4而不是-1.0，这对于H + 扩散控制的过程可能是预期的。高活化能 (pH 8.0时0.54 eV) 和弱粘度依赖性表明，RCs对H + 离子的吸收不受扩散的限制。H离子结合率的盐依赖性和反应中心的可质子化氨基酸残基的pk值涉及表面电荷的影响，Gouy-Chapman理论提供了对离子效应的可行描述，该离子效应是由pH的调节引起的。RC的表面。在D2O中孵育会导致可质子化基团的pKs小幅增加，并导致结合速率的pH (pD) 依赖性减慢。在P + QA状态下，RCs吸收质子的盐、酸碱度、温度、粘度和D2O依赖性由三个因素解释。1) H + 递送到RC的平行途径，有助于观察到的 (净) H + 消失; 2) 通过构象动力学限制蛋白质内目标基团质子化的速率; 3) 通过表面pH对蛋白质中带电基团的静电影响。

BACKGROUND & AIMS: :The present study evaluated whether the luteal phase elevation of body temperature would be offset during exercise by increased sweating, when women are normally hydrated. Eleven women performed 60 min of cycling exercise at 60% of their maximal work load at 32 degrees C and 80% relative air humidity. Each subject participated in two identical experimental sessions: one during the follicular phase (between days 5 and 8) and the other during the luteal phase (between days 22 and 25). Women with serum progesterone >3 ng/mL, in the luteal phase were classified as group 1 (N = 4), whereas the others were classified as group 2 (N = 7). Post-exercise urine volume (213 +/- 80 vs 309 +/- 113 mL) and specific urine gravity (1.008 +/- 0.003 vs 1.006 +/- 0.002) changed (P < 0.05) during the luteal phase compared to the follicular phase in group 1. No menstrual cycle dependence was observed for these parameters in group 2. Sweat rate was higher (P < 0.05) in the luteal (3.10 +/- 0.81 g m-2 min-1) than in the follicular phase (2.80 +/- 0.64 g m(-2) min(-1)) only in group 1. During exercise, no differences related to menstrual cycle phases were seen in rectal temperature, heart rate, rate of perceived exertion, mean skin temperature, and pre- and post-exercise body weight. Women exercising in a warm and humid environment with water intake seem to be able to adapt to the luteal phase increase of basal body temperature through reduced urinary volume and increased sweating rate.

背景与目标： : 本研究评估了在运动过程中，当女性正常水分充足时，出汗增加是否会抵消体温的黄体期升高。11名妇女在32摄氏度和80% 相对空气湿度的最大工作负荷的60% 下进行60分钟的骑自行车运动。每个受试者都参加了两个相同的实验课程: 一个在卵泡期 (第5天和第8天之间)，另一个在黄体期 (第22天和第25天之间)。黄体期血清孕酮> 3 ng/mL的妇女被归类为第1组 (N = 4)，而其他妇女被归类为第2组 (N = 7)。与卵泡期相比，运动后的尿量 (213 +/- 80 vs 309 +/- 113 mL) 和比尿重力 (1.008 +/- 0.003 vs 1.006 +/- 0.002) 在黄体期发生了变化 (P < 0.05) 在组1中。在第2组中，这些参数未观察到月经周期依赖性。仅在第1组中，黄体 (3.10/- 0.81g m-2 min-1) 的汗液率高于卵泡期 (2.80/- 0.64g m(-2) min(-1)) 的汗液率 (P <0.05)。在运动过程中，直肠温度，心率，感知的劳累率，平均皮肤温度以及运动前后的体重未发现与月经周期阶段有关的差异。在温暖潮湿的环境中进行运动并摄入水分的女性似乎能够通过减少尿量和增加出汗率来适应黄体期基础体温的升高。

BACKGROUND & AIMS: :Cortisol is used in research as a biomarker of psychological stress. Logistical considerations argue for collecting as few samples as possible, balanced against diurnal rhythms and intra-individual variations. 100 pregnant women gave five saliva samples a day for 3 days, at waking, 30 min after waking, and 11:00 a.m., 5:00 p.m., and 9:00 p.m. Timing of collection was confirmed by monitors. Another sample was taken during a clinic visit. Using the 15 measures as the gold standard, correlations and mean area under the curve (AUC) were compared with subsets and the single clinic sample to evaluate alternate collection protocols. Five samples in 1 day, or protocols involving morning and night samples, had the highest correlations with mean AUC (correlation coefficient ranging from 0.82 to 0.88). Standardizing the clinic measurement to a single time of day did not substantially improve correlations with mean AUC. Correlations with measures of reported stress were also not strong.

背景与目标： : 皮质醇在研究中被用作心理压力的生物标志物。后勤方面的考虑主张收集尽可能少的样本，并与昼夜节律和个体内部变化保持平衡。100名孕妇每天在醒来时，醒来后30分钟以及上午11:00，下午5:00和下午9:00时每天提供五个唾液样本收集时间由监视器确认。在诊所就诊时采集了另一个样本。使用15项措施作为金标准，将相关性和曲线下平均面积 (AUC) 与子集和单个临床样本进行比较，以评估替代收集方案。1天内的5个样品或涉及早晨和夜间样品的方案与平均AUC的相关性最高 (相关系数范围从0.82到0.88)。将临床测量标准化为一天中的单个时间并没有显着改善与平均AUC的相关性。与报告的压力度量的相关性也不强。

BACKGROUND & AIMS: :It has been shown that the generalized F-statistics can give satisfactory performances in identifying differentially expressed genes with microarray data. However, for some complex diseases, it is still possible to identify a high proportion of false positives because of the modest differential expressions of disease related genes and the systematic noises of microarrays. The main purpose of this study is to develop statistical methods for Affymetrix microarray gene expression data so that the impact on false positives from non-expressed genes can be reduced. I proposed two novel generalized F-statistics for identifying differentially expressed genes and a novel approach for estimating adjusting factors. The proposed statistical methods systematically combine filtering of non-expressed genes and identification of differentially expressed genes. For comparison, the discussed statistical methods were applied to an experimental data set for a type 2 diabetes study. In both two- and three-sample analyses, the proposed statistics showed improvement on the control of false positives.

背景与目标： : 已经表明，广义F统计量可以在用微阵列数据鉴定差异表达基因方面提供令人满意的性能。然而，对于一些复杂的疾病，由于疾病相关基因的适度差异表达和微阵列的系统噪声，仍然有可能识别出高比例的假阳性。这项研究的主要目的是开发Affymetrix微阵列基因表达数据的统计方法，以便可以减少对非表达基因假阳性的影响。我提出了两种新颖的通用F统计量来识别差异表达的基因，以及一种估计调整因子的新方法。所提出的统计方法系统地结合了非表达基因的过滤和差异表达基因的鉴定。为了进行比较，将讨论的统计方法应用于2型糖尿病研究的实验数据集。在两样本和三样本分析中，建议的统计数据均显示出对假阳性的控制有所改善。