Treatment of Brain Metastases of Non-Small Cell Lung Carcinoma

Lung cancer is one of the most common malignant neoplasms. As a result of the disease’s progression, patients may develop metastases to the central nervous system. The prognosis in this location is unfavorable; untreated metastatic lesions may lead to death within one to two months. Existing therapies—neurosurgery and radiation therapy—do not improve the prognosis for every patient. The discovery of Epidermal Growth Factor Receptor (EGFR)—activating mutations and Anaplastic Lymphoma Kinase (ALK) rearrangements in patients with non-small cell lung adenocarcinoma has allowed for the introduction of small-molecule tyrosine kinase inhibitors to the treatment of advanced-stage patients. The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein with tyrosine kinase-dependent activity. EGFR is present in membranes of all epithelial cells. In physiological conditions, it plays an important role in the process of cell growth and proliferation. Binding the ligand to the EGFR causes its dimerization and the activation of the intracellular signaling cascade. Signal transduction involves the activation of MAPK, AKT, and JNK, resulting in DNA synthesis and cell proliferation. In cancer cells, binding the ligand to the EGFR also leads to its dimerization and transduction of the signal to the cell interior. It has been demonstrated that activating mutations in the gene for EGFR-exon19 (deletion), L858R point mutation in exon 21, and mutation in exon 20 results in cancer cell proliferation. Continuous stimulation of the receptor inhibits apoptosis, stimulates invasion, intensifies angiogenesis, and facilitates the formation of distant metastases. As a consequence, the cancer progresses. These activating gene mutations for the EGFR are present in 10–20% of lung adenocarcinomas. Approximately 3–7% of patients with lung adenocarcinoma have the echinoderm microtubule-associated protein-like 4 (EML4)/ALK fusion gene. The fusion of the two genes EML4 and ALK results in a fusion gene that activates the intracellular signaling pathway, stimulates the proliferation of tumor cells, and inhibits apoptosis. A new group of drugs—small-molecule tyrosine kinase inhibitors—has been developed; the first generation includes gefitinib and erlotinib and the ALK inhibitor crizotinib. These drugs reversibly block the EGFR by stopping the signal transmission to the cell. The second-generation tyrosine kinase inhibitor (TKI) afatinib or ALK inhibitor alectinib block the receptor irreversibly. Clinical trials with TKI in patients with non-small cell lung adenocarcinoma with central nervous system (CNS) metastases have shown prolonged, progression-free survival, a high percentage of objective responses, and improved quality of life. Resistance to treatment with this group of drugs emerging during TKI therapy is the basis for the detection of resistance mutations. The T790M mutation, present in exon 20 of the EGFR gene, is detected in patients treated with first- and second-generation TKI and is overcome by Osimertinib, a third-generation TKI. The I117N resistance mutation in patients with the ALK mutation treated with alectinib is overcome by ceritinib. In this way, sequential therapy ensures the continuity of treatment. In patients with CNS metastases, attempts are made to simultaneously administer radiation therapy and tyrosine kinase inhibitors. Patients with lung adenocarcinoma with CNS metastases, without activating EGFR mutation and without ALK rearrangement, benefit from immunotherapy. This therapeutic option blocks the PD-1 receptor on the surface of T or B lymphocytes or PD-L1 located on cancer cells with an applicable antibody. Based on clinical trials, pembrolizumab and all antibodies are included in the treatment of non-small cell lung carcinoma with CNS metastases.     

Incidence and costs of bicycle-related traumatic brain injuries in the Netherlands

The main cause of death and serious disability in bicycle accidents is traumatic brain injury (TBI). The aim of this population-based study was to assess the incidence and costs of bicycle-related TBI across various age groups, and in comparison to all bicycle-related injuries, to identify main risk groups for the development of preventive strategies.Data from the National Injury Surveillance System and National Medical Registration were used for all patients with bicycle-related injuries and TBI who visited a Dutch emergency department (ED) between 1998 and 2012. Demographics and national, weighted estimates of injury mechanism, injury severity and costs were analysed per age group. Direct healthcare costs and indirect costs were determined using the incidence-based Dutch Burden of Injury Model.Between 1998 and 2012, the incidence of ED treatments due to bicycle-related TBI strongly increased with 54%, to 43 per 100,000 persons in 2012. However, the incidence of all bicycle-related injuries remained stable, from 444 in 1998 to 456/100,000 in 2012. Incidence of hospital admission increased in both TBI (92%) and all injuries from cycling (71%). Highest increase in incidence of both ED treatments and hospital admissions was seen in adults aged 55+. The injury rate of TBI per kilometre travelled increased (44%) except in children, but decreased (−4%) for all injuries, showing a strong decrease in children (−36%) but an increase in men aged 25+, and women aged 15+. Total costs of bicycle-related TBI were €74.5 million annually. Although bicycle-related TBI accounted for 9% of the incidence of all ED treatments due to cycling, it accounted for 18% of the total costs due to all bicycle-related injuries (€410.7 million). Children and adolescents (aged 0–24) had highest incidence of ED treatments due to bicycle-related injuries. Men in the working population (aged 15–64) had highest indirect costs following injuries from cycling, including TBI. Older cyclists (aged 55+) were identified as main risk group for TBI, as they had highest ED attendance, injury rate, injury severity, admission to hospital or intensive care unit, and costs.Incidence of ED treatments due to cycling are high and often involve TBI, imposing a high burden on individuals and society. Older cyclists aged 55+ were identified as main risk group for TBI to be targeted in preventive strategies, due to their high risk for (serious) injuries and ever-increasing share of ED visits and hospital admissions.     

Omega-6支撑身体，Omega-3支撑大脑：均衡摄入对儿童大脑发育的影响（网络首发、推荐阅读）

人体大脑和身体的发育，需要从食物中摄取均衡的营养物质。人类大脑是区分人类和其他动物的特征。食物中的必需脂肪酸是机体组织结构和功能的必要组成部分。Omega-6（O6）亚油酸（LA6）是皮肤组织的组成成分，且是炎症、血栓形成、免疫和其他信号分子的前体；Omega-3（O3）α-亚麻酸（ALA3），特别是其长链代谢产物——二十二碳六烯酸（DHA3），是大脑、视网膜和部分神经组织中的关键组分。从富含LA6脂肪酸（缺乏O3脂肪酸）的植物籽中提取出的廉价而优质油脂，是20世纪的西方国家食品工业生产的主要脂肪来源。在代谢通路中，高浓度的LA6脂肪酸可拮抗O3脂肪酸代谢，造成O3脂肪酸不足，因此，在给怀孕动物的饲料中，只提供富含LA6但缺乏O3脂肪酸的油脂作为唯一的脂肪来源，会导致幼崽大脑发育不良。过去20~30年的研究表明，低含量LA6且含DHA3的油脂可改善大脑的功能。近年来的研究较多集中在营养因素对大脑发育的影响，最新研究数据表明，脂肪酸平衡对营养不良儿童的大脑发育尤为重要。世界卫生组织（WHO）越来越重视大脑的营养健康，通过其下属的食品法典委员会，建议用于治疗严重急性营养不良儿童的即食治疗食品中，使用含有均衡脂肪酸组成/构成的脂肪。同样，脂肪酸均衡对老年人可能也很重要。目前，业界已经有了调整油脂成分的方法，以确保脂肪酸均衡，从而维持人体整个生命周期的大脑健康。     

Comparative analysis on performance of vertical drain improved clay deposit under vacuum or surcharge loading

This paper presents two well-instrumented large-scale field tests of PVD-improved soft soil with vacuum and surcharge preloading, respectively. The two large-scale field tests were conducted adjacent to each other with the same preload. A comparative analysis was performed to investigate the performance of subsoil (i.e., the ground settlement, the layered settlement, the lateral displacement of subsoil and pore water pressure) under vacuum preloading and equivalent surcharge preloading. Some design methods were verified based on the field data. Cone Penetration Tests (CPT) and Vane Shear Tests (VST) were conducted to assess the improvement effects on subsoil after preloading. The results showed that as compared with surcharge preloading, vacuum preloading mitigated the differential settlement of the ground. The vacuum pressure transmitted into the soil with a minor loss through the PVD length. From a practical point of view, the improvement effects by vacuum preloading and surcharge preloading were similar in terms of influence depth and soil strength based on the in-situ tests.     

Fast Positive Feedback Between the Adrenocortical Stress Response and a Brain Mechanism Involved in Aggressive Behavior.

Aggressive behavior induces an adrenocortical stress response, and sudden stressors often precipitate violent behavior. Experiments in rats revealed a fast, mutual, positive feedback between the adrenocortical stress response and a brain mechanism controlling aggression. Stimulation of the aggressive area in the hypothalamus rapidly activated the adrenocortical response, even in the absence of an opponent and fighting. Hypothalamic aggression, in turn, was rapidly facilitated by a corticosterone injection in rats in which the natural adrenocortical stress response was prevented by adrenalectomy. The rapidity of both effects points to a fast, mutual, positive feedback of the controlling mechanisms within the time frame of a single conflict. Such a mutual facilitation may contribute to the precipitation and escalation of violent behavior under stressful conditions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

LDD方法在提高电路工作电压中的应用研究

研究了利用轻掺杂漏结构来制作高电源电压器件的工艺方法。分析了ＬＤＤ结构参数对器件击穿特性的影响，并结合实验结果对Ｎ＾－区的注入剂量，长度及引入的串联电阻进行了优化设计。     

Effects of stimulus emotionality and sentence generation on memory for words in adults with unilateral brain damage.

Does sentence generation and/or stimulus emotionality enhance verbal memory in patients with neurological impairment? This question was addressed by testing 40 patients with unilateral stroke (20 with left-brain and 20 with right-brain damage) and 20 healthy control participants for recall and recognition of 48 target words. During encoding, emotional and nonemotional words were either presented in sentences (read condition) or used to form sentences (generate condition). Both word emotionality and generative processing improved memory performance in all groups. The authors suggest that a similar influence (i.e., cognitive activation) underlies both of these memory-enhancing effects, although the putative origins of the 2 effects are quite different. Neuropsychological underpinnings and clinical implications of these phenomena are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned facilitation of brain reward function after repeated cocaine administration.

Cocaine lowers brain reward thresholds, reflecting increased brain reward function. The authors investigated whether, similar to acute cocaine administration, cocaine-predictive conditioned stimuli would lower intracranial self-stimulation (ICSS) thresholds. Rats received a saline injection for 5 days, a cocaine injection (10 mg/kg) for 20 consecutive days, then saline for 5 additional days. Thresholds were measured immediately before and 10 min after each injection. The initial 5 saline injections had no effect on thresholds, whereas cocaine significantly lowered thresholds for 20 days. There was no tolerance or sensitization to this effect of cocaine over days. During the last 5 days when cocaine administration was substituted with saline, rats demonstrated a conditioned lowering of thresholds during the 2nd daily ICSS session. These data demonstrate that cocaine-predictive conditioned stimuli induce a conditioned facilitation of brain reward function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

300MW机组高压加热器结构特点

简要介绍了哈锅300MW机组高压加热器发展概况及给水入口管端、过热蒸气冷却段出口部、疏水冷却段入口部、上级疏水入口等部件的结构特点。