BACKGROUND & AIMS: :Spherical pellets containing theophylline, calcium acetate and microcrystalline cellulose were extruded and spheronized, before being coated with six different pectins or alginates by interfacial complexation. The aim of this study was to discover the effect of the coatings on physico-mechanical properties that will be crucial in determining the pellets' utility as sustained release systems. An insoluble, smooth and uniformly thick coat of calcium polysaccharide was formed around the core pellets. A factorial experiment was designed to investigate the effect of pellet size and polysaccharide type and concentration on the entrapment efficiency, mechanical properties and other physical characteristics. Coated pellets were observed by scanning electron microscopy and, depending on the particular polysaccharide used, the dry coats were found to be 30-80 microm thick. The size of pellet, the type and concentration of polysaccharide influenced the yield of theophylline in the coated pellets. Although the mechanical properties of the pellets were improved by applying any of the gel coats, use of an alginate with a high content of guluronic acid or an amidated pectin coating gave the best results. This is probably because both of these have significant potential to form very stable cross-links within the gel coats.

背景与目标： : 将含有茶碱，醋酸钙和微晶纤维素的球形颗粒挤出并球形化，然后通过界面络合用六种不同的果胶或藻酸盐包被。这项研究的目的是发现涂层对物理机械性能的影响，这对于确定颗粒作为持续释放系统的效用至关重要。在核心颗粒周围形成不溶性，光滑且均匀厚的钙多糖涂层。设计了析因实验，以研究颗粒大小，多糖类型和浓度对包封效率，机械性能和其他物理特性的影响。通过扫描电子显微镜观察到包被的颗粒，根据所用的特定多糖，发现干涂层的厚度为30-80微米。颗粒的大小，多糖的类型和浓度影响包衣颗粒中茶碱的产量。尽管通过施加任何凝胶涂层可以改善颗粒的机械性能，但使用具有高含量古罗糖醛酸的藻酸盐或酰胺化的果胶涂层可提供最佳结果。这可能是因为这两者都具有在凝胶涂层内形成非常稳定的交联的巨大潜力。

BACKGROUND & AIMS: :It is well-recognised that steady-state isometric muscle force is decreased following active shortening (force depression, FD) and increased following active stretch (force enhancement, FE). It has also been demonstrated that passive muscle force is increased following active stretch (passive FE). Several studies have reported that FD increases with shortening amplitude and that FE and passive FE increase with stretch amplitude. Here, we investigate whether these trends continue with further increases in shortening or stretch amplitude. Experiments were performed using in situ cat soleus muscles (n=8 for FD; n=7 for FE and passive FE). FD, FE and passive FE were measured after shortening or stretch contractions that covered as wide a range of amplitudes as practically possible without damaging the muscles. FD increased approximately linearly with shortening amplitude, over the full range of amplitudes investigated. This is consistent with the hypothesis that FD arises from a stress-induced inhibition of crossbridges. FE increased with stretch amplitude only up to a point, and then levelled off. Passive FE, and the transient increase in force at the end of stretch, showed relationships to stretch amplitude that were qualitatively very similar to the relationship for FE, increasing only until the same critical stretch amplitude had been reached. We conclude that FE and passive FE do not increase with stretch amplitude under all circumstances. This finding has important consequences for determining the mechanisms underlying FE and passive FE because any mechanism that is proposed to explain them must be able to predict it.

背景与目标： : 众所周知，主动缩短 (力降低，FD) 后，稳态等距肌肉力降低，主动拉伸 (力增强，FE) 后，稳态等距肌肉力增加。还已证明，主动拉伸 (被动FE) 后，被动肌肉力量会增加。一些研究报告说，FD随缩短幅度而增加，FE和被动FE随拉伸幅度而增加。在这里，我们研究这些趋势是否随着缩短或拉伸幅度的进一步增加而继续。使用原位猫比目鱼肌进行实验 (FD为n = 8; FE和被动FE为n = 7)。在缩短或拉伸收缩后测量FD，FE和被动FE，这些收缩实际上覆盖了尽可能宽的振幅范围，而不会损坏肌肉。在所研究的整个振幅范围内，FD随振幅的缩短而近似线性增加。这与FD由应力诱导的交叉桥抑制引起的假设是一致的。FE仅随拉伸幅度增加到一个点，然后趋于平稳。被动FE和拉伸结束时的瞬时力增加显示出与拉伸幅度的关系，在质量上与FE的关系非常相似，仅在达到相同的临界拉伸幅度之前才增加。我们得出的结论是，在所有情况下，FE和被动FE都不会随拉伸幅度而增加。这一发现对于确定FE和被动FE的潜在机制具有重要的影响，因为提出的任何解释它们的机制都必须能够预测它。

BACKGROUND & AIMS: :The purpose of this study was to test the hypothesis that runners having different running economies show differences in the mechanical and morphological properties of their muscle-tendon units (MTU) in the lower extremities. Twenty eight long-distance runners (body mass: 76.8+/-6.7 kg, height: 182+/-6 cm, age: 28.1+/-4.5 years) participated in the study. The subjects ran on a treadmill at three velocities (3.0, 3.5 and 4.0 m s(-1)) for 15 min each. The V(O(2)) consumption was measured by spirometry. At all three examined velocities the kinematics of the left leg were captured whilst running on the treadmill using a high-speed digital video camera operating at 250 Hz. Furthermore the runners performed isometric maximal voluntary plantarflexion and knee extension contractions at eleven different MTU lengths with their left leg on a dynamometer. The distal aponeuroses of the gastrocnemius medialis (GM) and vastus lateralis (VL) were visualised by ultrasound during plantarflexion and knee extension, respectively. The morphological properties of the GM and VL (fascicle length, angle of pennation, and thickness) were determined at three different lengths for each MTU. A cluster analysis was used to classify the subjects into three groups according to their V(O(2)) consumption at all three velocities (high running economy, N=10; moderate running economy, N=12; low running economy, N=6). Neither the kinematic parameters nor the morphological properties of the GM and VL showed significant differences between groups. The most economical runners showed a higher contractile strength and a higher normalised tendon stiffness (relationship between tendon force and tendon strain) in the triceps surae MTU and a higher compliance of the quadriceps tendon and aponeurosis at low level tendon forces. It is suggested that at low level forces the more compliant quadriceps tendon and aponeurosis will increase the force potential of the muscle while running and therefore the volume of active muscle at a given force generation will decrease.

背景与目标： : 这项研究的目的是检验以下假设: 具有不同跑步经济性的跑步者在下肢的肌肉肌腱单位 (MTU) 的机械和形态特性上存在差异。28名长跑运动员 (体重: 76.8 +/-6.7千克，身高: 182 +/-6厘米，年龄: 28.1 +/-4.5岁) 参加了这项研究。受试者在跑步机上以三种速度 (3.0、3.5和4.0 m s(-1)) 分别运行15分钟。通过肺活量测定法测量V(O(2)) 的消耗量。在所有三个检查的速度下，使用以250Hz运行的高速数字摄像机在跑步机上跑步时捕获左腿的运动学。此外，跑步者在测力计上的左腿以11种不同的MTU长度进行了等距最大的自愿plant屈和膝盖伸展收缩。在plant屈和膝关节伸展过程中，分别通过超声观察腓肠肌内侧 (GM) 和股外侧 (VL) 的远端腱膜。对于每个MTU，以三种不同的长度确定GM和VL的形态特性 (分束长度，顶角和厚度)。使用聚类分析根据受试者在所有三个速度下的V(O(2)) 消耗将受试者分为三组 (高运行经济，N = 10; 中等运行经济，N = 12; 低运行经济，N = 6)。GM和VL的运动学参数和形态特性均未在组之间显示出显着差异。最经济的跑步者在肱三头肌MTU中显示出更高的收缩强度和更高的归一化肌腱刚度 (肌腱力和肌腱应变之间的关系)，而在低水平的肌腱力下，股四头肌腱和腱膜的顺应性更高。建议在低水平的力下，更顺应性的股四头肌腱和腱膜会增加跑步时肌肉的力势，因此在给定的力产生下活动肌肉的体积会减少。

BACKGROUND & AIMS: In the initial stages of crystallization of proteins, monomers aggregate rapidly and form nuclei and large fractal clusters, as previously shown by dynamic light scattering experiments (Georgalis, Y., J. Schüler, J. Frank, D. M. Soumpasis, and W. Saenger. 1995. Protein crystallization screening through scattering techniques. Adv. Colloid Interface Sci. 5857-86). In this communication we initiate an effort to understand the effective interactions controlling charged protein aggregation and crystallization using the potential of mean force (PMF) theory. We compute the PMFs of the system lysozyme-water-NaCl within the framework of the hypernetted chain approximation for a wide range of protein and salt concentrations. We show that the computed effective interactions can rationalize the experimentally observed aggregation behavior of lysozyme under crystallization conditions.

背景与目标： 在蛋白质结晶的初始阶段，单体迅速聚集并形成核和大的分形簇，如先前的动态光散射实验所示 (Georgalis，Y.，J. Sch ü ler，J. Frank，d.m.Sompasis，和W. Saenger。1995。通过散射技术进行蛋白质结晶筛选。胶体界面科学。5857-86)。在此交流中，我们开始努力使用平均力 (PMF) 理论来了解控制带电蛋白质聚集和结晶的有效相互作用。我们在各种蛋白质和盐浓度的超净链近似框架内计算系统溶菌酶-水-NaCl的pmf。我们证明，计算出的有效相互作用可以使结晶条件下实验观察到的溶菌酶的聚集行为合理化。

BACKGROUND & AIMS: OBJECTIVE:To review the findings and discuss the implications of mechanical ventilator weaning protocols in children. DESIGN:A critical appraisal of Randolph et al. Effect of mechanical ventilator weaning protocols on respiratory outcomes in infants and children: A randomized controlled trial. JAMA 2002;288:2561-2568, and literature review. FINDINGS:There was no difference in ventilator weaning times between children randomized to a ventilator weaning protocol (pressure support, volume support, or no protocol). However, the study did show that increased sedative use during the first 24 hrs of weaning (the only time during which these data were collected) was an important predictor of weaning duration (p < .001) and weaning failure (p = .04). CONCLUSIONS:The majority of children are weaned from mechanical ventilation over a short period of time. Weaning protocols may not shorten this brief duration of weaning but may have other advantages such as improved collaboration between healthcare team members. Future research into the effects of sedation on weaning from mechanical ventilation is needed in children.

背景与目标：

BACKGROUND & AIMS: :In the present account it is proposed that in smokers the transition from peripheral airway disease to COPD is characterized by three sequential stages: Stage I, during which the closing volume eventually exceeds the functional residual capacity; Stage II, during which tidal expiratory flow limitation (EFL) is eventually exhibited; and Stage III, during which dynamic hyperinflation progressively increases leading to dyspnea and exercise limitation, which may be considered as markers of overt disease. Presence of airway closure (Stage I) and EFL (Stage II) in the tidal volume range may promote peripheral airway injury and accelerate the abnormalities of lung function. It is such injury that may determine which smoker is destined to develop COPD.

背景与目标： : 在本报告中，建议吸烟者从外周气道疾病到COPD的转变以三个连续阶段为特征: 阶段I，在此期间闭合量最终超过功能剩余容量; 阶段II，在此期间最终表现出呼气流量限制 (EFL); 第三阶段，在此期间，动态过度通货膨胀逐渐增加，导致呼吸困难和运动受限，这可能被认为是明显疾病的标志。潮气量范围内存在气道关闭 (I期) 和EFL (II期) 可能会促进周围气道损伤并加速肺功能异常。正是这种伤害可能决定了哪个吸烟者注定会发展为COPD。

BACKGROUND & AIMS: :To study the force-velocity characteristics of human knee-hip extension movement, a dynamometer, in which force was controlled by a servo system, was developed. Seated subjects pressed either bilaterally or unilaterally a force plate, a horizontal position of which was servo-controlled so as to equalize the measured force and a force command generated by a computer at a time resolution of 2 ms (force clamp). The force command was based on the relation between maximum isometric force and foot position within the range between 70% and 90% of "leg length" (LL: longitudinal distance between the sole of the foot and the hip joint), so that the same force relative to the maximum isometric force was consistently applied regardless of the foot position. By regulating the force according to this function, the force-velocity relation was determined. The force-velocity relation obtained was described by a linear function (n=17, r=-0.986 for 80% LL, r=-0.968 for 85% LL) within a range of force between 0.1 and 0.8F(0) (maximum isometric force). The maximum force extrapolated from the linear regression (F(max)) coincided with F(0) (n=17, F(0)/F(max)=1.00+/-0.09 for 80% LL and 1.00+/-0.20 for 85% LL). Also, the velocity at zero force (V(max)) was obtained from the extrapolation. When compared to the bilateral movements, unilateral movements gave rise to a smaller F(max) but the same V(max), suggesting that V(max) is independent of force and therefore represents the proper unloaded velocity. It is suggested that some neural mechanisms may be involved in the force-velocity relation of the knee-hip extension movement, and make it exhibit a linear appearance rather than a hyperbola.

背景与目标： : 为了研究人体膝关节-髋关节伸展运动的力-速度特性，开发了一种测力计，该测力计由伺服系统控制。就座的对象在两侧或一侧按压一个测力板，其水平位置受到伺服控制，以使测得的力和计算机以2 ms的时间分辨率 (力夹) 产生的力命令相等。力命令基于最大等距力和足部位置之间的关系，范围在 “腿长” 的70% 和90% 之间 (LL: 脚底和髋关节之间的纵向距离)，因此，无论脚的位置如何，都始终施加相对于最大等距力的相同力。通过根据此函数调节力，确定了力-速度关系。在0.1和0.8F(0) (最大等距力) 之间的力范围内，通过线性函数 (n = 17，对于80% LL，r =-0.986，对于85% LL，r =-0.968) 描述获得的力-速度关系。从线性回归外推的最大力 (F(max)) 与F(0) 一致 (对于80% LL，n = 17，F(0)/F(max)= 1.00 +/-0.09，对于85% LL，1.00 +/-0.20)。此外，通过外推获得了零力 (V(max)) 的速度。与双边运动相比，单边运动产生的F(max) 较小，但V(max) 相同，这表明V(max) 与力无关，因此代表适当的空载速度。建议某些神经机制可能参与膝髋伸展运动的力-速度关系，并使其表现出线性外观而不是双曲线。

BACKGROUND & AIMS: :This report is a study of structure, castability, mechanical properties as well as corrosion behaviour of titanium doped with up to 5 weight percentage (wt%) of a series of alloy elements, including Ta, Mo, Nb, Hf, Zr, Sn, Bi and Ag. The results indicate that, with addition of 1 wt% alloy element, Bi and Mo were most effective in enhancing the castability of titanium. With more alloy elements added, the castability values of most alloys more or less decreased. Except Ti-Mo system, all Ti alloys with a fine acicular morphology had the same crystal structure (hcp) as that of c.p. Ti with a typical lath type morphology. When 3 wt% or more Mo was added, a finer orthorhombic alpha'' phase was formed. The microhardness and bending strength values of Ti alloys were all higher than those of c.p. Ti. Among all alloys, Ti-Mo system exhibited the highest hardness and strength level. For a certain alloy, the bending strength did not necessarily increase with its alloy content. Except Ti-5Zr and Ti-Mo alloys, the bending moduli of most alloy systems were not much different from that of c.p. Ti. All alloys showed an excellent resistance to corrosion in Hanks' solution at 37 degrees C.

背景与目标： : 本报告研究了掺有高达5重量百分比 (wt %) 的一系列合金元素 (包括Ta，Mo，Nb，Hf，Zr，Sn，Bi和Ag) 的钛的结构，可铸造性，机械性能以及腐蚀行为。结果表明，添加1 wt % 合金元素时，Bi和Mo最有效地提高了钛的可铸造性。随着添加更多的合金元素，大多数合金的可铸造性值或多或少会降低。除Ti-Mo体系外，所有具有细针状形态的Ti合金均具有与c.p.相同的晶体结构 (hcp)。具有典型板条型形态的Ti。当添加3 wt % 或更多Mo时，形成了更细的正交晶型 α'' 相。Ti合金的显微硬度和弯曲强度值均高于c.p.Ti。在所有合金中，Ti-Mo体系表现出最高的硬度和强度水平。对于某种合金，弯曲强度不一定随其合金含量而增加。除Ti-5Zr和Ti-Mo合金外，大多数合金体系的弯曲模量与c.p.没有太大差异。Ti。所有合金在汉克斯溶液中在37 ℃ 下均表现出优异的耐腐蚀性。

BACKGROUND & AIMS: :In this study, the distribution, transfer and fate of both polychlorinated biphenyls (PCBs) and cyanotoxins via phytoplankton routes were systematically investigated in two Chinese lakes. Results indicated that PCB adsorption/bioaccumulation dynamics has significantly positive correlations with the biomass of green alga and diatoms. Total lipid content of phytoplankton is the major factor that influences PCB adsorption/bioaccumulation. Cyanobacterial blooms with relatively lower lipid content could also absorb high amount of PCBs due to their high cell density in the water columns, and this process was proposed as major route for the transfer of PCBs in Chinese eutrophic freshwater. According to these findings, a novel route on fates of PCBs via phytoplankton and a green bioadsorption concept were proposed and confirmed. In the practice of mechanical collections of bloom biomass from Lake Taihu, cyanotoxin/cyanobacteria and PCBs were found to be removed simultaneously very efficiently followed this theory.

背景与目标： : 在这项研究中，系统地研究了两个中国湖泊中通过浮游植物路线的多氯联苯 (pcb) 和氰基毒素的分布，转移和命运。结果表明，PCB的吸附/生物蓄积动力学与绿藻和硅藻的生物量呈显着正相关。浮游植物的总脂质含量是影响PCB吸附/生物积累的主要因素。由于水柱中细胞密度高，脂质含量相对较低的蓝藻水华也可以吸收大量的多氯联苯，这一过程被认为是中国富营养化淡水中多氯联苯转移的主要途径。根据这些发现，提出并证实了通过浮游植物获得多氯联苯命运的新途径和绿色生物吸附概念。在机械收集太湖盛开生物质的实践中，发现根据该理论同时非常有效地去除了氰基毒素/蓝细菌和多氯联苯。

BACKGROUND & AIMS: OBJECTIVES:The purposes of this study included the following: (1) to predict L3 contact force during side-lying lumbar manipulation by combining direct and indirect measurements into a single mathematical framework and (2) to assess the accuracy and confidence of predicting L3 contact force using common least squares (CLS) and weighted least squares (WLS) methods. METHODS:Five participants with no history of lumbar pain underwent 10 high-velocity, low-amplitude lumbar spinal manipulations at L3 in a side-lying position. Data from 5 low-force criterion standard trials where the L3 contact force was directly measured were used to generate participant-specific force prediction algorithms. These algorithms were used to predict L3 contact force in 5 experimental trials performed at therapeutic levels. The accuracy and effectiveness of CLS and WLS methods were compared. RESULTS:Differences between the CLS-predicted forces and the criterion standard-measured forces were 621.0 ± 193.5 N. Differences between the WLS-predicted forces and the criterion standard-measured forces were -3.6 ± 9.1 N. The 95% limits of agreement ranged from 234.0 to 1008.0 N for the CLS and -21.9 to 14.7 N for the WLS. During both the criterion standard and experimental trials, the CLS overestimated contact forces with larger variance than the WLS. CONCLUSION:This novel method to predict spinal contact force combines direct and indirect measurements into a single framework and preserves clinically relevant practitioner-participant contacts. As advanced instrumentation becomes available, this framework will enable advancements in training and high-quality research on mechanisms of spinal manipulative therapy.

背景与目标：

BACKGROUND & AIMS: :A three-dimensional static model is described to evaluate the forces on low-back muscles and on the spine during manual handling tasks and other forceful activities. It is simple to use either with a calculator or programmed onto a micro-computer, whilst being more accurate than existing simple models. Comparisons are made with a more sophisticated model that requires mathematical libraries and programming skills. As predictions are similar, so is the area of validity: the proposed model's accuracy is good for light tasks but poorer for strenuous ones.

背景与目标： : 描述了一个三维静态模型，以评估在手动处理任务和其他有力活动期间对下背部肌肉和脊柱的作用力。它可以简单地与计算器一起使用或编程到微型计算机上，同时比现有的简单模型更准确。使用需要数学库和编程技能的更复杂的模型进行比较。由于预测是相似的，因此有效性领域也是相似的: 所提出的模型的准确性对于轻型任务是好的，而对于繁重的任务则较差。

BACKGROUND & AIMS: :Healing of the rat Achilles tendon is sensitive to mechanical loading, and the callus strength is reduced by 3/4 after 14 days, if loading is prevented. Exogenous GDFs stimulate tendon healing. This response is influenced by loading: without loading, cartilage and bone formation is initiated. This implies BMP signaling is crucial during tendon healing and influenced by mechanical loading. We therefore asked if mechanical loading influences the gene expression of the BMP signaling system in intact and healing tendons, and how the BMP signaling system changes during healing. The genes were four BMPs (OP-1/BMP-7, GDF-5/CDMP-1/BMP-14, GDF-6/CDMP-2/BMP-13, and GDF-7/CDMP-3/BMP-12), two receptors (BMPR1b and BMPR2), and the antagonists follistatin and noggin. The Achilles tendon was transected in rats and left to heal. Half of the rats had one Achilles tendon unloaded by injection of Botox in the calf muscles. Ten tendons were analyzed before transection and for each of four time points. All genes except noggin were expressed at all time points, but followed different patterns during healing. Loading strongly decreased the expression of follistatin, which could lead to increased signaling. The BMP system appears involved in tendon maintenance and healing, and may respond to mechanical loading.

背景与目标： : 大鼠跟腱的愈合对机械负荷敏感，如果防止负荷，则在14天后愈伤组织强度降低3/4。外源性GDFs刺激肌腱愈合。这种反应受负荷影响: 在没有负荷的情况下，开始软骨和骨形成。这意味着BMP信号在肌腱愈合过程中至关重要，并受到机械负荷的影响。因此，我们询问机械负荷是否会影响完整和愈合肌腱中BMP信号系统的基因表达，以及BMP信号系统在愈合过程中如何变化。基因是四个bmp (OP-1/BMP-7，GDF-5/CDMP-1/BMP-14，GDF-6/CDMP-2/BMP-13和GDF-7/CDMP-3/BMP-12)，两个受体 (BMPR1b和BMPR2) 以及拮抗剂follistatin和noggin。在大鼠中横切跟腱并使其愈合。通过在小腿肌肉中注射肉毒杆菌毒素，一半的大鼠的跟腱被卸载。在横切之前和四个时间点中的每一个都分析了十根肌腱。除noggin外，所有基因均在所有时间点表达，但在愈合过程中遵循不同的模式。负载强烈降低了卵泡抑素的表达，这可能导致信号传导增加。BMP系统似乎参与肌腱的维护和愈合，并且可能对机械负荷做出反应。

BACKGROUND & AIMS: BACKGROUND AND PURPOSE:Effects of imatinib mesylate, a Kit receptor tyrosine kinase inhibitor, on spontaneous activity of interstitial cells of Cajal (ICC) and smooth muscles in the stomach were investigated. EXPERIMENTAL APPROACH:Effects of imatinib on spontaneous electrical and mechanical activity were investigated by measuring changes in the membrane potential and tension recorded from smooth muscles of the guinea-pig stomach. Its effects on spontaneous changes in intracellular concentration of Ca(2+) ([Ca(2+)](i)) (Ca(2+) transients) were also examined in fura-2-loaded preparations. KEY RESULTS:Imatinib (1-10 microM) suppressed spontaneous contractions and Ca(2+) transients. Simultaneous recordings of electrical and mechanical activity demonstrated that imatinib (1 microM) reduced the amplitude of spontaneous contractions without suppressing corresponding slow waves. In the presence of nifedipine (1 microM), imatinib (10 microM) reduced the duration of slow waves and follower potentials in the antrum and accelerated their generation, but had little affect on their amplitude. In contrast, imatinib reduced the amplitude of antral slow potentials and slow waves in the corpus. CONCLUSIONS AND IMPLICATIONS:Imatinib may suppress spontaneous contractions of gastric smooth muscles by inhibiting pathways that increase [Ca(2+)](i) in smooth muscles rather than by specifically inhibiting the activity of ICC. A high concentration of imatinib (10 microM) reduced the duration of slow waves or follower potentials in the antrum, which reflect activity of ICC distributed in the myenteric layers (ICC-MY), and suppressed antral slow potentials or corporal slow waves, which reflect activity of ICC within the muscle bundles (ICC-IM), presumably by inhibiting intracellular Ca(2+) handling.

背景与目标：

BACKGROUND & AIMS: :The NCCN HER2 Testing in Breast Cancer Task Force was convened to critically evaluate the ability of the level of HER2 expression or gene amplification in breast cancer tumors to serve as a prognostic and a predictive factor in the metastatic and adjuvant settings, to assess the reliability of the methods of measuring HER2 expression or gene amplification in the laboratory, and to make recommendations regarding the interpretation of test results. The Task Force is a multidisciplinary panel of 24 experts in breast cancer representing the disciplines of medical oncology, pathology, radiation oncology, surgical oncology, epidemiology, and patient advocacy. Invited members included members of the NCCN Breast Cancer Panel and other needed experts selected solely by the NCCN. During a 2-day meeting, individual task force members provided didactic presentations critically evaluating important aspects of HER2 biology and epidemiology: HER2 as a prognostic and predictive factor; results from clinical trials in which trastuzumab was used as a targeted therapy against HER2 in the adjuvant and metastatic settings; the available testing methodologies for HER2, including sensitivity, specificity, and ability to provide prognostic and predictive information; and the principles on which HER2 testing should be based. Each task force member was charged with identifying evidence relevant to their specific expertise and presentation. Following the presentations, an evidence-based consensus approach was used to formulate recommendations relating to the pathologic and clinical application of the evidence to breast cancer patient evaluation and care. In areas of controversy, this process extended beyond the meeting to achieve consensus. The Task Force concluded that accurate assignment of the HER2 status of invasive breast cancer is essential to clinical decision making in the treatment of breast cancer in both adjuvant and metastatic settings. Formal validation and concordance testing should be performed and reported by laboratories performing HER2 testing for clinical purposes. If appropriate quality control/assurance procedures are in place, either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) methods may be used. A tumor with an IHC score of 0 or 1+, an average HER2 gene/chromosome 17 ratio of less than 1.8, or an average number of HER2 gene copies/cell of 4 or less as determined by FISH is considered to be HER2 negative. A tumor with an IHC score of 3+, an average HER2 gene/chromosome 17 ratio of greater than 2.2 by FISH, or an average number of HER2 gene copies/cell of 6 or greater is considered HER2 positive. A tumor with an IHC score of 2+ should be further tested using FISH, with HER2 status determined by the FISH result. Tumor samples with an average HER2 gene/chromosome ratio of 1.8 to 2.2 or average number of HER2 gene copies/cell in the range of greater than 4 to less than 6 are considered to be borderline, and strategies to assign the HER2 status of such samples are proposed.

背景与目标： : 乳腺癌工作组的NCCN HER2测试是为了严格评估乳腺癌肿瘤中HER2表达或基因扩增水平在转移和辅助环境中作为预后和预测因素的能力，评估实验室中测量HER2表达或基因扩增方法的可靠性，并就测试结果的解释提出建议。该工作组是由24位乳腺癌专家组成的多学科小组，代表医学肿瘤学，病理学，放射肿瘤学，外科肿瘤学，流行病学和患者倡导等学科。受邀成员包括NCCN乳腺癌小组的成员以及NCCN单独挑选的其他所需专家。在为期2天的会议中，个别工作组成员提供了教学报告，批判性地评估了HER2生物学和流行病学的重要方面: HER2作为预后和预测因素; 曲妥珠单抗在辅助和转移环境中被用作针对HER2的靶向治疗的临床试验结果; HER2可用的测试方法，包括敏感性，特异性以及提供预后和预测信息的能力; 以及HER2测试应基于的原则。每个工作队成员都负责确定与其特定专业知识和陈述相关的证据。演讲结束后，使用基于证据的共识方法来制定有关证据在乳腺癌患者评估和护理中的病理和临床应用的建议。在有争议的领域，这一进程超出了会议的范围，以达成共识。工作组得出结论，准确分配浸润性乳腺癌的HER2状态对于辅助和转移性乳腺癌治疗的临床决策至关重要。正式验证和一致性测试应由进行HER2测试的实验室进行并报告，以用于临床目的。如果有适当的质量控制/保证程序，则可以使用免疫组织化学 (IHC) 或荧光原位杂交 (FISH) 方法。IHC评分为0或1 + 、平均HER2基因/染色体17比率小于1.8、或平均HER2基因拷贝数/细胞数为4或更少 (由FISH测定) 的肿瘤被认为是HER2阴性。IHC评分为3 + 、FISH平均HER2基因/17号染色体比率大于2.2或HER2基因拷贝/细胞平均数为6或更大的肿瘤被认为是HER2阳性。IHC评分为2 + 的肿瘤应使用FISH进一步检测，HER2状态由FISH结果确定。具有1.8至2.2的平均HER2基因/染色体比率或HER2基因拷贝/细胞的平均数在大于4至小于6的范围内的肿瘤样品被认为是临界的，并且提出了分配此类样品的HER2状态的策略。

BACKGROUND & AIMS: :In 1998 the Society for Academic Emergency Medicine's (SAEM's) Board of Directors asked the SAEM Public Health and Education Task Force to develop recommendations for prevention, screening, and counseling activities to be conducted in emergency departments (EDs). The Task Force's work was divided into two phases: 1) a discussion of the rationale for preventive services in the ED, along with generation of a preliminary list of prevention activities that could be studied for ED implementation; and 2) a formal evidence-based review of topics chosen from the preliminary list, along with recommendations for ED implementation and further study. This paper represents Phase I of the project. Phase II, the formal evidence-based review and recommendations, is published separately in this issue.

背景与目标： : 1998年，学术急诊医学协会 (SAEM's) 董事会要求SAEM公共卫生和教育工作组为在急诊科 (EDs) 进行的预防，筛查和咨询活动制定建议。专责小组的工作分为两个阶段: 1) 讨论在ED中提供预防服务的理由，并生成可研究用于ED实施的预防活动的初步清单; 2) 对从初步清单中选择的主题进行正式的循证审查，以及对ED实施和进一步研究的建议。本文代表了该项目的第一阶段。第二阶段，正式的循证审查和建议，在本期单独发表。