从创新药物申报角度探讨中美新药评审制度的异同

创新药物研发是国家医药产业发展的原动力,美国作为全球新药研发能力最强的国家,这与其食品药品管理局在新药审批过程中给 予的技术支持和政策鼓励密不可分。通过分析比较我国与美国的新药评审相关政策的异同,学习和借鉴美国的成功经验,为我国创新药物 注册审评制度的调整与完善提供参考。     

以电子注册为手段, 推进高校学籍管理建设

学籍管理是高校教学管理工作的一项重要内容,是保证高校正常教学秩序,形成良好学风、教风和校风的重要保障。电子注册则是传统学籍管理工作在新形势下的延续和发展。实现电子注册,对保证高等教育质量,维护高校的社会形象和大学生的合法权益,起着很重要的保障作用。学籍管理是实施电子注册的基础,电子注册则是加强学籍管理的有效手段。     

The effectiveness of gadolinium MRI to improve target delineation for radiotherapy in hepatocellular carcinoma: A comparative study of rigid image registration techniques

To achieve consistent target delineation in radiotherapy for hepatocellular carcinoma (HCC), image registration between simulation CT and diagnostic MRI was explored.Twenty patients with advanced HCC were included. The median interval between MRI and CT was 11 days. CT was obtained with shallow free breathing and MRI at exhale phase. On each CT and MRI, the liver and the gross target volume (GTV) were drawn. A rigid image registration was taken according to point information of vascular bifurcation (Method[A]) and pixel information of volume of interest only including the periphery of the liver (Method[B]) and manually drawn liver (Method[C]). In nine cases with an indefinite GTV on CT, a virtual sphere was generated at the epicenter of the GTV. The GTV from CT (V_GTV[CT]) and MRI (V_GTV[MR]) and the expanded GTV from MRI (V_+GTV[MR]) considering geometrical registration error were defined. The underestimation (uncovered V[CT] by V[MR]) and the overestimation (excessive V[MR] by V[CT]) were calculated. Through a paired T-test, the difference between image registration techniques was analyzed.For method[A], the underestimation rates of V_GTV[MR] and V_+GTV[MR] were 16.4 ± 8.9% and 3.2 ± 3.7%, and the overestimation rates were 16.6 ± 8.7% and 28.4 ± 10.3%, respectively. For V_GTV[MR] and V_+GTV[MR], the underestimation rates and overestimation rates of method[A] were better than method[C]. The underestimation rates and overestimation rates of the V_GTV[MR] were better in method[B] than method[C]. By image registration and additional margin, about 97% of HCC could be covered. Method[A] or method[B] could be recommended according to physician preference.     

Fast and Accurate Registration of the Proximal Femurs in Bilateral Hip Joint Images by Using the Random Sub-Sample Points

Background and ObjectiveAs is known, point clouds representing the objects are frequently used in object registration. Although the objects can be registered by using all the points in the corresponding point clouds of the objects, the registration process can also be achieved with a smaller number of the landmark points selected from the entire point clouds of the objects. This paper introduces a research study focusing on the fast and accurate rigid registration of the bilateral proximal femurs in bilateral hip joint images by using the random sub-sample points. For this purpose, Random Point Sub-sampling (RPS) was analyzed and the reduced point sets were used for an accurate registration of the bilateral proximal femurs in coronal hip joint magnetic resonance imaging (MRI) slices.MethodsIn registration, bilateral proximal femurs in MRI slices were registered rigidly by performing a process consisting of three main phases named as MR image preprocessing, proximal femur registration over the random sub-sample points and MR image postprocessing. In the stage of the MR image preprocessing, segmentation maps of the bilateral proximal femurs are obtained as region of interest (RoI) images from the entire MRI slices and then, the edge maps of the segmented proximal femurs are extracted. In the registration phase, the edge maps describing the proximal femur surfaces are represented as point clouds initially. Thereafter, the RPS is performed on the proximal femur point clouds and the number of points representing the proximal femurs is reduced at different ratios. For the registration of the point clouds, the Iterative Closest Point (ICP) algorithm is performed on the reduced sets of points. Finally, the registration procedures are completed by performing MR image postprocessing on the registered proximal femur images.ResultsIn performance evaluation tests performed on healthy and pathological proximal femurs in 13 bilateral coronal hip joint MRI slices of 13 Legg-Calve-Perthes disease (LCPD) patients, bilateral proximal femurs were successfully registered with very small error rates by using the reduced set of points obtained via the RPS and promising results were achieved. The minimum error rate was observed at RPS rate of 30% as the value of 0.41 (±0.31)% on all over the bilateral proximal femurs evaluated. When the range of RPS rate of 20-30% is considered as the reference, the elapsed time in registration can be reduced by almost 30-40% compared to the case where all the proximal femur points were included in registration. Additionally, it was observed that the RPS rate should be selected as at least 25% to achieve a successful registration with an error rate below 1%.ConclusionIt was concluded from the observed results that a more successful and faster registration can be accomplished by selecting fewer points randomly from the point sets of proximal femurs instead of using all the points describing the proximal femurs. Not only an accurate registration with low error rates was performed, but also a faster registration process was performed by means of the limited number of points that are sub-sampled randomly from the whole point sets.     

Toxicity and context-dependent repellency of temporarily granted repellents under new biocidal products regulations in South Korea against Drosophila melanogaster (Diptera: Drosophilidae)

In South Korea, control agents for small flying insects are subjected to approval under newly enforced Act on biocidal products by the Ministry of Environment starting from 2019, along with other conventional household insecticides. The present study aimed to evaluate 18 compounds for their toxicity and repellency in various contexts. A tube assay revealed the greatest toxicity of synthetic repellent DEET. Interestingly, spatial repellency of several plant essential oils was greater than those of conventional repellent, indicating their suitability for temporal grants. Meanwhile, unlike conventional repellents, botanical oils often lost their choice repellency in gaseous unsaturable condition. Spatial repellency was positively correlated to the evaporation rate of the compounds while choice repellencies were negatively correlated regardless of their gaseous saturability. Our results are expected to provide implications for both the regulation process and product development.     

A quantitative evaluation of deformable image registration based on MV cone beam CT images: Impact of deformation magnitudes and image modalities

Background and purposeTo evaluate the impact of deformation magnitude and image modality on deformable-image-registration (DIR) accuracy using Halcyon megavoltage cone beam CT images (MVCBCT).Materials and methodsPlanning CT images of an anthropomorphic Head phantom were aligned rigidly with MVCBCT and re-sampled to achieve the same resolution, denoted as pCT. MVCBCT was warped with twenty simulated pre-known virtual deformation fields (T_i, i = 1–20) with increasing deformation magnitudes, yielding warped CBCT (wCBCT). The pCT and MVCBCT were registered to wCBCT respectively (Multi-modality and Uni-modality DIR), generating deformation vector fields V_i and V_i′ (i = 1–20). V_i and V_i′ were compared with T_i respectively to assess the DIR accuracy geometrically. In addition, V_i, T_i, and V_i′ were applied to pCT, generating deformed CT (dCT_i), ground-truth CT (G_i) and deformed CT′ (dCT_i′) respectively. The Hounsfield Unit (HU) on these virtual CT images were also compared.ResultsThe mean errors of vector displacement increased with the deformation magnitude. For deformation magnitudes between 2.82 mm and 7.71 mm, the errors of uni-modality DIR were 1.16 mm ~ 1.73 mm smaller than that of multi-modality (p = 0.0001, Wilcoxon signed rank test). DIR could reduce the maximum signed and absolute HU deviations from 70.8 HU to 11.4 HU and 208 HU to 46.2 HU respectively.ConclusionsAs deformation magnitude increases, DIR accuracy continues to deteriorate and uni-modality DIR consistently outperformed multi-modality DIR. DIR-based adaptive radiotherapy utilizing the noisy MVCBCT images is only conditionally applicable with caution.     

Application of Dual Modality Contrast Agent Combined with Multi-Scale Representation in Ultrasound-Magnetic Resonance Imaging Registration Scheme

To achieve the image registration/fusion and perfect the quality of theintegration, with dual modality contrast agent (DMCA), a novel multi-scale representation registration method between ultrasound imaging (US) and magneticresonance imaging (MRI) is presented in the paper, and how DMCA influenceon registration accuracy is chiefly discussed. Owing to US’s intense speckle noise,it is a tremendous challenge to register US with any other modality images. Howto improve the algorithms for US processing has become the bottleneck, and inthe short term it is difficult to have a breakthrough. In that case, DMCA isemployed in both US and MRI to enhance the region of interest. Then, becausemulti-scale representation is a strategy that attempts to diminish or eliminate several possible local minima and lead to convex optimization problems to be solvedquickly and more efficiently, a multi-scale representation Gaussian pyramid basedaffine registration (MRGP-AR) scheme is constructed to complete the US-MRIregistration process. In view of the above-mentioned method, the comparison testsindicate that US-MRI registration/fusion may be a remarkable method for gaininghigh-quality registration image. The experiments also show that it is feasible thatnovel nano-materials combined with excellent algorithm are used to solve somehard tasks in medical image processing field.     

Dose warping performance in deformable image registration in lung

PurposeIt is unclear that spatial accuracy can reflect the impact of deformed dose distribution. In this study, we used dosimetric parameters to compare an in-house deformable image registration (DIR) system using NiftyReg, with two commercially available systems, MIM Maestro (MIM) and Velocity AI (Velocity).MethodsFor 19 non-small-cell lung cancer patients, the peak inspiration (0%)-4DCT images were deformed to the peak expiration (50%)-4DCT images using each of the three DIR systems, which included computation of the deformation vector fields (DVF). The 0%-gross tumor volume (GTV) and the 0%-dose distribution were also then deformed using the DVFs. The agreement in the dose distributions for the GTVs was evaluated using generalized equivalent uniform dose (gEUD), mean dose (D_mean), and three-dimensional (3D) gamma index (criteria: 3 mm/3%). Additionally, a Dice similarity coefficient (DSC) was used to measure the similarity of the GTV volumes.ResultsD_mean and gEUD demonstrated good agreement between the original and deformed dose distributions (differences were generally less than 3%) in 17 of the patients. In two other patients, the Velocity system resulted in differences in gEUD of 50.1% and 29.7% and in D_mean of 11.8% and 4.78%. The gamma index comparison showed statistically significant differences for the in-house DIR vs. MIM, and MIM vs. Velocity.ConclusionsThe finely tuned in-house DIR system could achieve similar spatial and dose accuracy to the commercial systems. Care must be taken, as we found errors of more than 5% for D_mean and 30% for gEUD, even with a commercially available DIR tool.     

Point-cloud registration using adaptive radial basis functions

Non-rigid registration is a common part of bioengineering model-generation workflows. Compared to common mesh-based methods, radial basis functions can provide more flexible deformation fields due to their meshless nature. We introduce an implementation of RBF non-rigid registration with iterative knot-placement to adaptively reduce registration error. The implementation is validated on surface meshes of the femur, hemi-pelvis, mandible, and lumbar spine. Mean registration surface errors ranged from 0.37 to 0.99?mm, Hausdorff distance from 1.84 to 2.47?mm, and DICE coefficients from 0.97 to 0.99. The implementation is available for use in the free and open-source GIAS2 library.     

Factors affecting the robustness of metabolite fingerprinting using 1H NMR spectra

1H NMR spectroscopy is one of the techniques whose potential is currently being explored in the emerging field of metabolomics. It is a non-targeted method, producing signals for all proton-containing chemical species. For crude plant materials the spectra are always complex, with many signals overlapping. Hence a most suitable approach for analysing them is 'metabolite fingerprinting', which is aimed at highlighting compositional similarities and exploring the overall natural variability in a population of samples. The most commonly used method for this is principal component analysis (PCA), as it allows the whole spectral trace to be analysed and the vast quantity of information to be simplified. In this paper we investigate whether there are factors which may affect the NMR spectra in a way that subsequently decreases the robustness of the metabolite fingerprinting by PCA. Imperfections in the signal registration (i.e. inconsistency of the peak position) are generally detrimental to analysing whole traces by multivariate methods. The sources of such problems are illustrated through specially designed repeatability studies using potato and tomato samples, and the analysis of a tea dataset containing many samples. Careful sample preparation can help to limit peak shifts; for instance here by attempting to control the pH of the extracts. In addition, some compounds are susceptible to interactions affecting their chemical shifts and mathematical alignment of peaks may be necessary. Lastly factors such as resolution can also affect analyses and must be carefully adjusted. Our choice of examples aims to raise awareness of potential problems. We do not question the validity of the NMR approach, but point out those areas where special care may need to be taken.