人工髓核治疗颈椎间盘病变的动物实验研究

目的通过动物体内实验对生理状态下人工髓核在颈椎功能单位稳定性中的作用进行评估。方法实验动物为健康杂种犬30只,分为完整组（A组）、人工髓核组（B组）、颈椎间盘病变组（C组）,颈椎间盘病变组和人工髓核组分别经前路行髓核摘除术和人工髓核植入术,术后3个月处死动物,取标本固定,应用脊柱三维运动生物力学机测试时,施加最大载荷为1.0 N.m的6个方向上的力偶,使测试节段产生前屈、后伸、左右侧弯和左右轴向旋转运动,测量运动范围（ROM）和中性区（NZ）,然后施加0 N和100 N的轴向载荷下测量椎间隙高度变化。结果人工髓核组同完整组相比较,节段活动无显著差异（P〉0.05）;颈椎间盘病变组同完整组相比较,颈椎节段活动明显增加,稳定性下降（P〈0.05）。人工髓核组在0 N载荷下,椎间隙高度较完整组平均升高0.2 mm,100 N载荷下椎间隙高度较完整组平均升高0.1 mm。结论植入人工髓核能有效满足颈椎的稳定性和维持椎间隙高度,可考虑将其应用于治疗颈椎间盘病变。     

新型人工髓核植入对腰椎稳定性影响的生物力学研究

目的: 评价一种新型果胶/聚乙烯醇复合水凝胶人工髓核的生物力学性能, 为其临床应用提供科学依据。方法: 采用6具新鲜人体标本的 L4/5脊柱功能单元进行生物力学实验, 在轴向压缩、前屈后伸和左右侧弯等运动工况下, 观察正常椎间盘、髓核摘除以及新型人工髓核CoPP植入三种状态下活动度(ROM)、中性区(NZ)的变化以及在中立位轴向加载下椎间隙高度变化。结果: 髓核摘除后, L4/5椎间屈伸、旋转、侧弯的ROM和 NZ较正常组显著增加(P<0.05), 植入CoPP人工髓核后, L4/5椎间屈伸、侧弯、旋转的 ROM和 NZ与完整椎间盘无明显差异, 除右侧弯外其他方向的ROM和 NZ较髓核摘除组明显下降　(P<0.05)。髓核摘除组在 0和500N的负荷下椎间隙高度较相同情况下正常组平均下降1.08 mm和 1.77 　mm; CoPP人工髓核植入组较相同情况下髓核摘除组分别增加1.23 mm和1.95 mm。结论: 新型果胶/聚乙烯醇复合水凝胶人工髓核植入椎间隙可维持腰椎节段正常的三维运动稳定性,恢复椎间隙高度,可望进入临床应用。     

人工椎间盘植入术后颈椎邻近节段生物力学变化的有限元分析

目的研究人工椎间盘植入术后邻近节段的运动范围及椎间盘应力改变。方法将接触问题引入生物建模,建立正常全颈椎有限元模型,模拟C5/6椎间植骨融合和C5/6人工间盘植入,分析两种状态下其相邻节段的运动范围及椎间盘的应力改变。结果(1)所建立模型包含了韧带、关节囊及其他软组织结构,而且真实细腻,准确度高;(2)椎间植骨融合术后邻近椎间隙运动范围增加,相应椎间盘应力明显增大,上位节段髓核与纤维环的应力约增加70%,而下位节段髓核与纤维环应力约增加40%;(3)人工间盘植入后颈椎运动范围除仅后伸受限(P(0.05)外,邻近节段椎间盘应力增加不超过10%。结论植入的颈椎人工间盘可在一定程度上降低相邻椎体节段的应力,且有利于改善颈椎的活动度。     

新型人工髓核置换对邻近上节段三维运动与椎间盘内压影响的实验研究

目的评价果胶/聚乙烯醇复合水凝胶人工髓核植入对腰椎稳定性的影响;并通过与腰椎前路融合比较,探讨其对邻近节段运动范围和椎间盘内压的影响。方法采用6具新鲜人体腰椎标本(L3～L5)在机器人脊柱测试机上进行生物力学测试。观察正常椎间盘、CoPP人工髓核置换和腰椎前路cage植入3种状态下L4/5和L3/4的运动范围以及L3/4椎间盘内压的变化情况。结果在L4/5手术节段,CoPP组与完整椎间盘组的角位移除左侧屈运动方向差异有显著性外(P<0.05),其他方向两者之间差异均无显著性(P>0.05)。而cage组与完整椎间盘组或CoPP组之间,在所有的运动方向均有显著性差异(P<0.05)。而在相邻上节段L3/4,CoPP组与完整椎间盘组的运动范围除左侧屈运动方向差异有显著性外(P<0.05),其他方向两者之间差异均无显著性(P>0.05)。而cage组与完整椎间盘组或CoPP组之间,在所有的运动方向,L3/4运动范围的差异均有显著性(P<0.05)。CoPP组与完整椎间盘组的椎间盘内压在所有的运动方向两者之间的差异无显著性(P>0.05),而cage组与完整椎间盘组或CoPP组的椎间盘内压在前屈后伸及左右侧屈运动方向两者之间差异有显著性(P<0.05),而在轴向旋转方向,两者之间差异无显著性(P>0.05)。结论 CoPP人工髓核植入能保留手术节段的运动功能,稳定脊柱;相对腰椎融合手术,CoPP对相邻节段运动范围和椎间盘内压无明显影响,从而可降低或避免相邻节段退变的发生率。     

椎间孔镜下腰椎间盘髓核摘除治疗腰椎间盘突出症的生物力学优势

文题释义：腰椎间盘突出症的手术治疗：腰椎间盘突出症是脊柱外科常见病,手术方式较多。近年来,经皮椎间孔镜腰椎间盘髓核摘除术作为微创治疗方法迅速发展,具有创伤小、出血量少并能快速康复的优点,受到越来越多的关注。 背景：腰椎间盘突出症的手术方式较多,各有优缺点,通过有限元分析方法进行脊柱生物力学研究可以指导临床工作。 目的：建立L_3-5三维有限元模型,分析不同术式在椎间盘摘除后对脊柱力学的影响。方法：选择1名无腰椎病史的35岁男性志愿者,收集腰椎CT数据构建有限元模型并验证。在L₃/L₅脊柱正常模型(模型Ⅰ)的基础上建立L_4/5节段单纯开窗髓核摘除模型(模型Ⅱ)、椎间盘镜手术模型(模型Ⅲ)、经皮椎间孔镜腰椎间盘髓核摘除模型(模型Ⅳ)、关节突关节切除模型(模型Ⅴ),在7种加载工况下测定L₄/L₅节段椎体、椎间盘和左右关节软骨应力分布及L₄椎体位移。 结果与结论：①建立的三维有限元模型有效,方差分析模型有效;②L_4-5椎间盘两两比较后模型Ⅲ、Ⅳ在椎间盘应力集中最小;L₄椎体应力,模型Ⅳ对椎体影响最小;L₄椎体位移,模型Ⅲ和Ⅳ对椎体稳定影响最小;③从加载方式看,关节突关节损伤越小,椎间盘应力越小,模型Ⅳ最小;左侧关节突模型Ⅲ和Ⅳ均保持关节完整;右侧关节左右旋转加载下手术侧关节越完整,应力越大,故模型Ⅳ较大;左右侧倾加载下反而相反,模型Ⅴ最大;L₄椎体应力模型Ⅳ最小;椎体位移,模型Ⅲ和Ⅳ位移最小,接近模型Ⅰ;④提示经皮椎间孔镜腰椎间盘髓核摘除模型在椎体、椎间盘和关节突关节应力分布最小,有明显优势;椎间盘镜手术模型和经皮椎间孔镜腰椎间盘髓核摘除模型位移均较其他手术模型稳定,二者无差异;故经皮椎间孔镜腰椎间盘髓核摘除目前是较理想的术式。　 ORCID: 0000-0002-2604-0049(吐尔洪江·阿布都热西提) 中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程     

人工颈椎间盘置换与融合治疗颈椎病:中短期疗效的比较

背景:近年来,以人工颈椎间盘置换为代表的非融合技术不断改进,在重建受累节段间盘结构和功能的基础上,使得术区节段颈椎结构显著接近天然生理系统所要求的动静态负荷应力分布,在保护退变节段椎间小关节及邻近节段颈椎结构功能及维持颈椎动态稳定性方面作用显著,表现出较节段融合技术明显的方法学优势。目的:评价颈前路椎间盘切除融合与Bryan人工颈椎椎间盘置换治疗单节段间盘退变性脊髓或神经根型颈椎病的临床效果。方法:纳入2010年3月至2012年3月收治的43例单节段退变的脊髓或神经根型颈椎病中老年患者,随机分为前路颈椎间盘切除加椎间植骨融合组(融合组)和Bryan人工椎间盘置换组。治疗前后通过X射线影像学检查观察颈椎整体及目标间隙上下邻近椎间活动度的变化;随访期间应用日本骨科协会评分、颈痛目测类比评分和颈椎功能障碍指数进行术后神经功能恢复评估。结果与结论:所有患者术中及术后未出现神经血管损伤的并发症。人工椎间盘置换组术后整体颈椎及邻近关节活动度较融合组有所改善;术后各组患者神经功能均较术前明显改善,术后3个月人工椎间盘置换组日本骨科协会评分、颈痛目测类比评分及颈椎功能障碍指数均较融合组明显改善(P0.05),末次随访时除颈痛目测类比评分两组间有差异外,其余神经功能两组恢复情况相同。随访期间未见假体下沉、偏移及异位骨化现象。提示人工颈椎间盘置换能有效保持颈椎节段活动度,并对邻近节段间盘退变有一定的保护作用,中期随访可取得与融合手术相当的神经功能改善效果,非融合技术在单节段颈椎病的中短期疗效优于融合技术。     

人工髓核

椎间盘源性疼痛作为慢性下腰痛的主要原因之一, 近来受到越来越多的重视。既往对间盘源性疼痛经保守治疗无效的患者,椎间融合术是标准的手术方式。但随着对脊柱生物力学了解的不断深入,这一有悖正常生理的外科治疗屡被质疑,从而使“保留节段活动度”的“非融合性”技术得到了发展。其中,人工髓核的概念及其应用显示出了一定的前景。     

一种新型人工颈椎间盘置换的生物力学研究

目的研究新型人工颈椎间盘(Pretic-I)置换和颈椎前路椎间固定对颈椎活动范围(Range of motion,ROM)及邻近节段椎间盘髓核内压力(Intradiscal Pressures,IDPs)的影响。方法新鲜尸体颈椎标本6具,先后依次作为完整组(A组)、C_(5/6)人工椎间盘置换组(B组)和C5/6前路椎间固定组(C组)进行生物力学测试。给予75N跟随载荷,前屈/后伸、左/右侧弯及左/右轴向旋转均施加2.0Nm的纯力矩载荷,在0.2Nm/S的变化条件下测量手术节段及邻近节段ROM,以及邻近节段IDPs。结果 B组与A组在手术节段及邻近节段的ROM相比均无显著性差异(0.05)。在C_(5/6)节段,C组的ROM明显小于A组和B组(0.05)。在C_(4/5)、C_(6/7)节段,C组的ROM则明显大于其他两组(0.05)。B组和A组的C_(4/5)及C_(6/7)节段IDPs相比均无显著性差异(0.05),而C组的C_(4/5)和C_(6/7)节段IDPs均较其他两组显著增加(0.05)。结论 Pretic-I人工颈椎间盘置换术较好的维持了手术节段及邻近节段的活动范围,并保持了邻近节段椎间盘髓核内压力。     

半限制型人工颈椎间盘置换与植骨融合术后下颈椎生物力学特性的有限元分析

目的研究Discover、Prodisc-C人工椎间盘置换术与植骨融合术后下颈椎活动度(range of motion,ROM)、椎间盘应力、韧带张力的生物力学特性以及植入假体力学性能的改变。方法建立C5~6椎间盘退变3种手术方案:Discover、Prodisc-C人工椎间盘置换和自体髂骨植骨融合有限元模型,同时建立C4~7节段下颈椎原始模型。分析术后下颈椎C4~7节段在矢状面、冠状面及横断面上椎体的生物力学特性变化。结果术后手术节段关节ROM变化:Discover模型增加12.7%~73.1%,Prodisc-C模型增加74%~98%,植骨融合模型下降55.8%~71.8%。Discover置换后上邻近椎间盘应力无明显增加,下邻近椎间盘应力在前屈、后伸、轴向旋转工况下减少33.2%~54.2%,囊韧带张力增幅比Prodisc-C置换后减少30%~40%。Discover假体最大应力(36.72 MPa)出现在前屈工况下,小于Prodisc-C假体的最大应力(42.66 MPa)。结论人工椎间盘置换术可以保留手术节段的运动性能,Discover作为新一代人工椎间盘假体,在减少韧带负担和维持脊柱稳定性方面有所进步。研究结果可为颈椎前路融合手术和人工颈椎间盘置换术的临床研究提供理论依据。     

颈前路钢板置入内固定加椎间植骨治疗Ⅱ型Hangman骨折的生物力学评价

背景:C2/3椎间盘切除,钢板置入内固定加椎间植骨是治疗Hangman骨折的常用术式。该术式在临床应用广泛,但目前尚缺乏相关实验评价钢板置入内固定治疗Hangman骨折的生物力学特点研究。目的:评价钢板置入内固定+椎间植骨治疗Ⅱ型Hangman骨折的生物力学稳定性。方法:6具正常成人新鲜冷冻颈椎,每一标本依次制作成以下3种状态组:即正常对照组、Ⅱ型Hangman骨折模型组、椎间植骨+钢板内固定组。按以上顺序应用脊柱三维运动试验机和三维激光扫描仪测试每一状态C2/3节段的三维运动范围。结果与结论:与正常对照组比较,Ⅱ型Hangman骨折模型组C2/3节段前屈、后伸、旋转及侧弯关节活动度均显著增大(P0.05),钢板内固定+椎间植骨组旋转方向关节活动度显著增大(P0.05);与Ⅱ型Hangman骨折模型组相比,钢板内固定+椎间植骨组C2/3节段前屈、后伸及侧弯关节活动度均显著减小(P0.05)。结果提示钢板置入内固定能够在前屈、后伸及侧弯方向恢复Ⅱ型Hangman骨折的稳定性,然而在旋转方向缺乏稳定作用,术后需辅以外固定以确保融合。     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

The universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.     

Der Einfluß von Nahrungsmitteln und Rauchen auf die klinisch-chemische Diagnostik von Phäochromozytom,Neuroblastom und Karzinoid-Syndrom

Zusammenfassung Der Einfluß von verschiedenen Nahrungsmitteln auf Methoden zur Bestimmung von Adrenalin (AD), Noradrenalin (NA), Vanillinmandelsäure (VMS), Metanephrinen (MN), Homovanillinsäure (HVS) und 5-Hydroxyindolessigsäure (5-HIE) im 24 h-Harn zur Diagnose des Phäochromozytoms bzw. Karzinoid-Syndroms wurde untersucht. Die in die Untersuchung einbezogenen Nahrungsmittel waren: Tee, Kaffee, Mandeln, Ananas, Käse, Walnüsse, Vanillepudding, Bananen, Tomaten und Milchschokolade. Außerdem wurde der Einfluß des Zigarettenrauchens auf die Bestimmung von AD, NA, VMS und MN untersucht.Walnüsse führten zu einer starken Erhöhung der 5-HIE-Ausscheidung. Bananen erhöhten die Ausscheidung von AD, NA, VMS, MN und 5-HIE. Kaffee und Ananas bewirkten eine geringe Zunahme der MN-Werte. Rauchen von 20–30 Zigaretten/Tag beeinflußte keine der vier Variablen.Wenn die beschriebenen Methoden benutzt werden, sollte lediglich auf den Verzehr von Bananen und Walnüssen vor und während der Harnsammelperioden verzichtet werden, da die oberen Normgrenzen im Harn überschritten werden könnten. Ein Verzicht auf Kaffee und Ananas in normalen Mengen ist nicht erforderlich. Es besteht kein Anlaß, weiterhin die bisherigen umfangreichen Restriktionen der übrigen Nahrungsmittel beizubehalten.