The intrinsic vulnerability of networks to epidemics.

Contact networks are convenient models to investigate epidemics, with nodes and links representing potential hosts and infection pathways, respectively. The outcomes of outbreak simulations on networks are driven both by the underlying epidemic model, and by the networks' structural properties, so that the same pathogen can generate different epidemic dynamics on different networks. Here we ask whether there are general properties that make a contact network intrinsically vulnerable to epidemics (that is, regardless of specific epidemiological parameters). By conducting simulations on a large set of modelled networks, we show that, when a broad range of network topologies is taken into account, the effect of specific network properties on outbreak magnitude is stronger than that of fundamental pathogen features such as transmission rate, infection duration, and immunization ability. Then, by focusing on a large set of real world networks of the same type (potential contacts between field voles, Microtus agrestis), we showed how network structure can be used to accurately assess the relative, intrinsic vulnerability of networks towards a specific pathogen, even when those have limited topological variability. These results have profound implications for how we prevent disease outbreaks; in many real world situations, the topology of host contact networks can be described and used to infer intrinsic vulnerability. Such an approach can increase preparedness and inform preventive measures against emerging diseases for which limited epidemiological information is available, enabling the identification of priority targets before an epidemic event.

[Posterior lumbar interbody fusion implants. Software assisted planning--preliminary results]. / Posteriore lumbale interkorporelle Fusionscages. Softwarebasierte Operationsplanung--erste Ergebnisse.

BACKGROUND: Sagittal imbalance, adjacent segment degeneration, and loss of correction due to cage sintering are the main reasons for revision surgery after lumbar fusion. Based on the experience from hip and knee replacement surgery, preoperative software-assisted planning combined with the corresponding cages is helpful to achieve better long-term results. OBJECTIVES: Evaluation of the procedure regarding intraoperative application of preoperative planning and examination to what extent the planning was correct. MATERIALS AND METHODS: In all, 30 patients were included in the period from September 2012 to May 2013 in an observational study, planned preoperatively with the planning software, and treated with the corresponding PLIF cages. The radiological evaluation was performed by thin-layer CT after 3 months. RESULTS: A total of 24 (80%) patients were followed up after 3 months. In these 24 patients, the preoperative planning actually was correct in 17 cases with the intraoperatively implanted cage, which corresponds to a match of about 71%. The fusion rate for these 24 patients who underwent full examinations was 91.7%. CONCLUSION: The results of this observational study to evaluate the planning of intervertebral cages show positive experience with this novel therapeutic concept. Despite the limited number of participants, good results were observed for the intraoperative implementation of the planned cages and an adequate fusion rate was obtained. Irrespective of this, a software-based surgical planning must be questioned critically any time. Ultimately, it is the surgeon's responsibility to modify the planned procedure intraoperatively if necessary. Currently, the influence of this planning regarding the long-term course and the important question of adjacent segment instability remains unanswered.

[History of the German Spine Society]. / Geschichte der Deutschen Wirbelsäulengesellschaft.

The objective of this article is to summarize the history of the German Spine Society (DWG). This society resulted in the year 2006 after several attempts from the fusion of two established German societies, which were dealing with topics around the spine, der "German Society for Spine Research" founded in the year 1958 and the "German Society for Spine Surgery" founded in the year 1987. This fusion was the beginning of a success story, as from this time on the annual membership increased so much that the DWG became the largest spine society in Europe and one of all spine societies worldwide.

[Evaluation of the sagittal profile in patients with thoracic adolescent idiopathic scoliosis Lenke type 1 following posterior correction]. / Evaluation des sagittalen Profils nach operativer Therapie der thorakalen adoleszenten idiopathischen Skoliose Lenke Typ 1.

INTRODUCTION: The principle philosophy of posterior spinal instrumentation and fusion (PSIF) for the treatment of adolescent idiopathic scoliosis (AIS) has changed during recent decades. In the past the treatment of AIS mainly focused on correction of the major curve in the frontal plane while the sagittal profile and balancing were only of inferior interest in treatment planning. Various long-term outcome studies have demonstrated that many AIS patients developed a flatback syndrome (decrease of thoracic kyphosis and lumbar lordosis) associated with pain. It was concluded that treatment of AIS should consider the sagittal profile and balance; however, there are only few studies addressing additional procedures, which include the correction of the sagittal profile. MATERIAL AND METHODS: The purpose of this study was to evaluate the effects of different posterior correction techniques on sagittal profile and balance. A total of 36 consecutive patients with thoracic AIS, who were treated with selective thoracic posterior correction were included in this retrospective study. The patients were further assigned to three different subgroups according to different surgical strategies: A: pedicle screws, B: long-head pedicle screws and C: additional Ponte osteotomy. Standardized radiographs in the standing position of the whole spine in two planes were evaluated before and at least 2 years after correction for all patients and a subgroup analysis was done to identify differences between the three groups. RESULTS: A significant correction of the major curve was achieved in all three groups (p < 0.001). There was a significant difference between the groups with groups B and C showing significantly higher levels of major curve correction in comparison to group A (p < 0.001). Concerning the sagittal profile, there was a significant difference in the development of thoracic kyphosis (TK) and lumbar lordosis (LL). While a significant reduction of TK and LL was found in groups A and B after surgery, a significant increase of TK and LL was noted in group C which was associated with a decrease of pelvic tilt and an increase of sacral slope. The 2-year follow-up showed the lowest ODI-% value only in group C which was positively correlated with reduction in pelvic tilt. CONCLUSIONS: The results of this study underline that the PSIF technique alone using pedicle screws leads to a satisfactory correction in the frontal plane but is associated with adverse effects on the sagittal profile (flat back syndrome), corroborating previous studies. It was further shown that significant improvements of sagittal parameters were achieved by adding techniques for the lengthening of the dorsal thoracic column. This approach can therefore be recommended for the treatment of AIS Lenke type 1.

[Pyogenic spondylodiscitis: therapy algorithm and a new classification for therapeutic decision-making]. / Pyogene Spondylodiszitis : Therapiealgorithmus und neue Klassifikation zur therapeutischen Entscheidungsfindung.

The incidence of pyogenic spondylodiscitis is low but has been steadily increasing in recent years. To date there has been no consensus concerning selection of the appropriate treatment, management and strategies and the recommendations for an operative strategy are still a highly controversial issue. In the literature a few statements have been published concerning therapeutic decision-making in pyogenic spondylodiscitis. The classification given in this article is based on clinical experience and retrospective data analysis considering the degree of segmental bony destruction, grade of kyphosis and instability, epidural involvement of the disease and neurological deficits, which are pivotal for therapeutic decision-making. The therapeutic procedure can be defined based on this classification.

[The relevance of the sagittal profile in cervical artificial discs]. / Die Bedeutung des sagittalen Profils bei der zervikalen Endoprothetik.

We report on the results of 246 Bryan cervical discs, which were implanted between June 2002 and September 2010 in 146 patients. Of the patients 74 (128 prostheses) could be followed up for more than 1 year and the average follow-up period was 2.6 years. Of the patients 18 were operated on at one level (group 1), 77 prostheses were multilevel surgery (group 2) and with 33 patients arthroplasty was combined with fusion (hybrid, group 3). The global lordosis remained unchanged during follow-up and a recurrence of kyphosis was evident in group 3. The overall mobility improved in all 3 subgroups and 2 cases (group 3) fused. With 5 patients the prosthesis had to be removed and the segment had to be fused in the postoperative course. As a conclusion a meticulous preoperative planning as well as a subtle surgical technique is the main prerequisite for long-lasting mobility of the Bryan prosthesis.

[Effect of lumbar hybrid instrumentation and rigid fusion on the treated and the adjacent segments. A biomechanical study]. / Auswirkung der lumbalen Hybridinstrumentierung und der rigiden Fusion auf das versorgte und anschließende Segment. Eine biomechanische Untersuchung.

BACKGROUND: Degeneration of the upper adjacent segment after operative treatment of degenerative spinal diseases of the lumbar spine (degenerative disc disease DDD) is an unsolved problem. There is also no consensus on whether a rigid or dynamic treatment of DDD should be carried out to protect the segments. This study was carried out to evaluate the effect of bisegmental rigid 360° fusion and bisegmental hybrid fusion on the treated segment as well as on the upper adjacent segment under the aspect of segment protection. MATERIAL AND METHODS: A total of six human spinal column preparations (L2-5) were tested under native conditions (NAT), with bisegmental rigid fusion (RIG 360°) and with hybrid fusion (Hybrid) in all three movement directions under physical load and with an preload. The range of motion (ROM) and neutral zone (NZ) were evaluated. The intradiscal pressure (IDP) was measured in the upper adjacent segment (OAS). RESULTS: The RIG 360° led to a significant reduction in movement in all directions compared to NAT but Hybrid only in lateral bending (LB). In the OAS the NZ was showed a much greater increase than the ROM. The RIG 360° showed an increase of the NZ in flexion-extension of 86.8% and in LB of 49.6% as well as a significant increase in axial rotation of 52.5%. The increase in the Hybrid was not significant compared to NAT in all directions. Pressure measurements in OAS showed no significant differences for RIG 360° and for Hybrid compared to NAT for both load scenarios. DISCUSSION: The range of motion of the treated segments for Hybrid were close to NAT in comparison to RIG 360° indicating a segment-protective effect. The hypothesis that rigid fusion has a significant effect on intersegmental mobility and the increase in intradiscal pressure in the upper adjacent segment could not be confirmed. The data indicate that the primary effect of fusion on the adjacent segment is very low but the fusion-linked increased frequency of extreme loads of the OAS falling within the significance level leads to degeneration. Even if the NZ values for Hybrid and RIG 360° do not significantly differ from NAT, the NZ alterations between the instrumentations tend to be strongly shifted in favor of Hybrid. CONCLUSIONS: The data confirm that the clear and sometimes significant alterations of the NZ can be an essential factor for development of adjacent segment degeneration. A dynamic conclusion of instrumentation in the sense of a topping-off would appear to be useful if pathoanatomical indications for an intervertebral disc prosthesis are present.

[Pyogenic spondylodiscitis of the thoracic and lumbar spine : a new classification and guide for surgical decision-making]. / Pyogene Spondylodiszitis der Brust- und Lendenwirbelsäule : Eine neue Klassifikation zur Entscheidungsfindung bei der Wahl der operativen Therapie.

Despite modern diagnostic imaging options pyogenic infections of the spine are often detected tardily and therefore accompanied by a high mortality rate. To ensure an efficient and adequate therapy it is necessary to identify and treat the focus of inflammation. The recommendations for the operative strategy are still a highly controversial issue. On the other hand no classification and guidelines for surgical treatment and treatment strategies of pyogenic spinal infection have yet been published.Pyogenic spinal infections are often underestimated in frequency of occurrence and severity of symptoms. From 1994 until 2008, 269 patients suffering from an infection of the thoracic and lumbar spine were treated in the Department of Orthopedic Surgery Heidelberg and 221 patients underwent surgery. Within the scope of a clinical trial clinical aspects and therapeutic consequences of patients with pyogenic spinal infections were retrospectively investigated. Based on the study data a classification of pyogenic spinal infections of the thoracic and lumbar spine and a guide for surgical decision-making was developed.

[Kyphectomy in myelomeningocele patients. Longterm results, complications and risk analysis]. / Gibbusresektion bei Myelomeningozelepatienten. Langzeitergebnisse, Komplikationen und Risikoanalyse.

BACKGROUND: The conservative and surgical management of lumbar kyphosis is difficult and is a challenge for the orthopaedic surgeon. A kyphotic deformity of the lumbar spine is present in 8% to 20% of these patients. Most curves have very rigid components, often exceed 80 degrees at birth. The options for conservative management are limited. Bracing is extremely difficult, rarely effective, and in advanced stages impossible. We have been using the Warner and Fackler kyphectomy technique at our institution since 1994 as a standard procedure for treating children with lumbar kyphosis due to myelomeningocele. RESULTS: This study was performed for a better understanding of the cause of the complications and optimizing the surgical technique. AIM: The aim of this study was to evaluate the longterm results, technical problems, early and late complications and the complication associated risk factors.

[Urogenic spondylodiscitis]. / Urogene Spondylodiszitis.

Despite modern diagnostic investigations, pyogenic infections of the spine are often detected late and are therefore associated with a high lethality. To ensure efficient and adequate therapy, it is necessary to identify and treat the focus of the inflammation. Urogenic spinal infections are often underestimated in their frequency of occurrence and severity of symptoms. From 1994 to 2006, 209 patients suffering a spinal infection were treated in the Department of Orthopedic Surgery. In 13 of them (6.2%), a urogenital inflammation caused the spondylodiscitis. In the context of a retrospective clinical trial, we investigated the risk factors, clinical aspects, and therapeutic consequences of patients with urogenic spinal infections and those with another genesis. The two data sets were compared, and therapeutic differences were extracted.

[Current short- and long-term results of lumbar disc replacement : update 2008]. / Lumbale Bandscheibenendoprothetik - Update 2008 : Metaanalyse der Kurz- und Langzeitergebnisse.

Lumbar total disc replacement is an increasingly common way of treating degenerative lumbar disc disease while preserving mobility. The aim of this analysis was to survey evidence-based data to classify the procedure. Based on a MEDLINE inquiry, 38 clinical trials dealing with lumbar total disc replacement were selected and analyzed by the criteria of indication, preoperative procedure, and clinical follow-up. These data represent 3,180 patient-related evaluations with follow-up of 5.9 to 204 months. We also included ten retrospective studies. Patient satisfaction was a mean of 90.73%, and the Oswestry Disability Index and Visual Analog Scale were significantly lower. High rates of revision surgery, explantation surgery, and secondary fusions are linked to wrong preoperative indication. According to evidence criteria, the results show that lumbar total disc replacement is a safe procedure with a high rate of success. There is clear evidence that both imprecise indication and the choice of too-small implants significantly reduce the prospect of surgical success and increase the rates of reintervention.

CBP/cycA, a CCAAT-binding protein necessary for adhesion-dependent cyclin A transcription, consists of NF-Y and a novel Mr 115,000 subunit.

Cells of most tissues, with the exception of hematopoietic cells, require adhesion to an appropriate surface to grow. Cyclin A is needed for cell cycle progression at the G1-S transition, and appearance of cyclin A mRNA and protein in late G1 has been shown to be dependent on adhesion-initiated signals in normal rat kidney fibroblasts. Previously, we have reported that the adhesion-dependent activation of cyclin A transcription in late G1 is mediated by CBP/cycA (CCAAT-binding protein for cyclin A gene), a novel CCAAT-binding protein. Specific binding of CBP/cycA, a Mr 30,000/40,000/115,000 heterotrimeric protein complex, to the CCAAT element of the cyclin A promoter was detectable in growing but not in G0-arrested or nonadherent normal rat kidney cells. Here, we demonstrate that the Mr 30,000/40,000 subunits of CBP/cycA are identical with NF-YA and NF-YB, the two subunits of NF-Y. In addition, we show that, aside from CBP/cycA, NF-Y itself also binds to the CCAAT element of the cyclin A promoter. But, whereas the binding of CBP/cycA is adhesion and cell cycle dependent and correlates with the expression of cyclin A in late G1 phase, NF-Y itself seems to bind in a cell cycle-independent manner.

Erratum: Proof of uniform sampling of binary matrices with fixed row sums and column sums for the fast Curveball algorithm [Phys. Rev. E 91, 042812 (2015)].

This corrects the article DOI: 10.1103/PhysRevE.91.042812.

Continuous passive motion versus immobilisation in a cast after surgical treatment of idiopathic club foot in infants: a prospective, blinded, randomised, clinical study.

Continuous passive motion has been shown to be effective in the conservative treatment of idiopathic club foot. We wished to determine whether its use after operation could improve the results in resistant club feet which required an extensive soft-tissue release. There were 50 feet in the study. Posteromedial lateral release was performed in 39 feet but two were excluded due to early relapse. The mean age at surgery was eight months (5 to 12). Each foot was assigned a Dimeglio club foot score, which was used as a primary outcome measure, before operation and at 6, 12, 18 and 44 months after. Nineteen feet were randomly selected to receive continuous passive motion and 18 had standard immobilisation in a cast. After surgery and subsequent immobilisation in a cast the Dimeglio club foot score improved from 10.3 before to 4.17 by 12 months and to 3.89 at 48 months. After operation followed by continuous passive motion the score improved from 9.68 before to 3.11 after 12 months, but deteriorated to 4.47 at 48 months. Analysis of variance adjusted for baseline values indicated a significantly better score in those having continuous passive motion up to one year after surgery, but after 18 and 48 months the outcomes were the same in both groups.

Proof of uniform sampling of binary matrices with fixed row sums and column sums for the fast Curveball algorithm.

Randomization of binary matrices has become one of the most important quantitative tools in modern computational biology. The equivalent problem of generating random directed networks with fixed degree sequences has also attracted a lot of attention. However, it is very challenging to generate truly unbiased random matrices with fixed row and column sums. Strona et al. [Nat. Commun. 5, 4114 (2014)] introduce the innovative Curveball algorithm and give numerical support for the proposition that it generates truly random matrices. In this paper, we present a rigorous proof of convergence to the uniform distribution. Furthermore, we show the Curveball algorithm must include certain failed trades to ensure uniform sampling.

A system utilizing Epstein-Barr virus-based expression vectors for the functional cloning of human fibroblast growth regulators.

The acquired ability of adherent mammalian cells to grow in suspension is closely linked to tumorigenic transformation. The anchorage-independence phenotype is likely to result from bypassing an adherence-responsive cell-cycle check-point at the G1/S boundary of the cell cycle. In order to identify genes that are part of or act upon the anchorage signal transduction pathway, we have developed a system which allows functional cloning of regulatory genes by expression of libraries of cDNA inserts either in the sense or antisense direction. The system is comprised of two components: (i) the library expression vectors, CMV-EL and C1E-EL, containing EBoriP for replication in EBN A-1-expressing cells, an expression cassette with a multiple cloning site suitable for directional insertion of cDNA libraries generated by standard protocols, and loxP sites which allow rapid manipulation of recovered vectors without the use of restriction enzymes and (ii) the EBNA-1-producing cell line, BB-5, a derivative of the immortalized, non-tumorigenic and anchorage-dependent human fibroblast cell line, MSU1.1. The growth characteristics of BB-5 cells did not differ from its parental cell line. BB-5 cells supported the episomal replication of CMV-EL and C1E-EL and allowed recovery of the vector from Hirt lysates of transfected BB-5 cells. BB-5 cells transformed to anchorage-independent growth by transfection with a mutant c-Ha-ras gene inserted into CMV-EL could be accurately and efficiently identified in a background of non-transfected BB5 cells by screening for anchorage-independent colonies with the aid of computer-assisted image analysis.

Human KRAS oncogene expression in meningioma.

Expression of 16 oncogenes was investigated in a series of human meningiomas showing a normal chromosome complement or the characteristic monosomy 22 but no structural aberrations detectable by banding analysis. By dot hybridization, the only expressed sequence detected was KRAS. The expression was elevated approximately 6--8-fold in comparison to matrix tissue (meninges) and to fibroblasts of the corresponding patient. Northern blot analysis displayed the typical banding pattern and an 8--10-fold overexpression. DNA analysis did not reveal gene amplification or major rearrangements in the KRAS gene structure.

Enhanced expression of four cellular oncogenes in a human glioblastoma cell line.

Examination of a human glioblastoma cell line displaying a relatively stable karyotype and absence of both copies of chromosome #13 (HeRo) as well as of a SV-40 transformed subline (HeRo-SV) using analysis on the DNA and RNA level showed that both cell lines express high levels of abl, erb B, myc, and Ha-ras mRNA. Neither gene amplification nor gene rearrangement at the loci concerned nor abnormal transcription account for this activation of expression. The possible influence of the deleted sequences in the context of a suppressor gene hypothesis is discussed.

The role of hydroxyl radicals in tetrachlorohydroquinone induced DNA strand break formation in PM2 DNA and human fibroblasts.

Tetrachlorohydroquinone (TCHQ), which has previously been identified as a metabolite of pentachlorophenol, induces DNA strand breaks in isolated DNA and in human fibroblasts. Strand break formation in PM2 DNA is prevented by the addition of catalase and the hydroxyl radical scavengers DMSO, ethanol and mannitol, whereas addition of SOD reduced SSB only slightly. Oxygen radicals are formed by the autoxidation of TCHQ to the tetrachlorosemiquinone radical. Desferrioxamine (0.2 mM) completely abolished strand break formation, whereas the metal chelator DETAPAC (1 mM) reduced SSB by only 8.5%. The formation of the semiquinone radical at physiological conditions is shown by ESR spectroscopy. Exposure of human fibroblasts to TCHQ also leads to DNA single strand breaks measured by the alkaline elution assay. These were reduced by addition of 5% DMSO. This indicates that at least part of the strand break formation in human cells is also due to the action of hydroxyl radicals.

Long-term review of the lumbar spine in javelin throwers.

We studied 21 former top-class competitive javelin throwers to investigate radiological and clinical symptoms in the lumbar spine many years after the end of their athletic careers. The athletes underwent clinical and radiological examinations at an average of 20 years after retiring from athletics. The Hannover questionnaire was used to evaluate functional restrictions in daily living. Degenerative changes in the lumbar spine were more marked towards the caudal aspect of the spine. Ten athletes also had spondylolisthesis, but with little progression (< 15%) throughout the observation period. Athletes both with and without radiologically demonstrated spondylolisthesis, complained of no more back problems than the normal population (93% for athletes v 86% for controls). Slight progression followed their retirement from athletics.