Zeitschriftenartikel zum Thema „Aggressiveness in adolescence – Mathematical models“

The aim of this study was to examine the relationship among aggressiveness, parenting practices, and attachment security in adolescents, assessing maternal and paternal effects separately. Two different subsamples of adolescents between 12 and 16 years old participated in the study (n = 157): 67 adopted adolescents (61.2% girls) and 90 non-adopted adolescents (56.7% girls). Partial and full mediation models were analyzed in multi-group structural equation models (using maximum likelihood estimates), allocating non-adoptive and adoptive adolescents into two different groups. Results showed that whereas acceptance/involvement of each parent predicted attachment security towards the corresponding parental figure, only the father’s coercion/imposition predicted aggressiveness, and only attachment security to the mother was a (negative) predictor of adolescent’s aggressiveness. The partial mediation model provided the most parsimonious explanation for the data, showing no differences between adopted and non-adopted subsamples and supporting a good model fit for both boys and girls in a multi-group invariance analysis. The implications of these results are discussed in light of the protective effects of care relationships in early adolescence (vs. late adolescence) as well as the differential role of parent figures.

The aggressiveness of an extensive collection of strains of Erwinia amylovora was analyzed using immature fruit and detached pear flower assays under controlled environmental conditions. The analysis was performed by means of a quantitative approach based on fitting data to mathematical models that relate infection incidence to pathogen dose and time. Probit and hyperbolic saturation models were used for disease-dose relationships and provided information on the median effective dose (ED50). Values of ED50 ranged from 103 to 106 CFU/ml (10 to 104 CFU per site of inoculation). A modified Gompertz model was used for disease-time relationships and provided information on the rate of infection incidence progression (rg) and time delayed to start of the incidence progress curve (t0). Values of rg ranged from near 0 to 1.90, and t0 varied from 1.3 to more than 10 days. The more aggressive strains showed high rg, low ED50 values, and short t0, whereas the less aggressive strains showed low rg, high ED50, and long t 0. The aggressiveness was dependent on plant material type and pear cultivars and was significantly different between strains of E. amylovora. Infectivity titration and kinetic analysis of progression of incidence of infections using the immature pear test and a standardized scale are proposed for assessment of strain aggressiveness. The implications of rg, ED50, and t0 for the epidemiology and management of fire blight are discussed, particularly the wide range of aggressiveness among strains, the degree of host specificity observed in pear isolates, the very high infective potential of this pathogen, the independent action of pathogen cells during infection, and the possible advantage of including aggressiveness parameters into fire blight risk forecasting systems.

Digital control of breeding process, creation of mathematical models of living objects and management of plant life cycle is an urgent problem of modern times. Сreation of technologies that ensure implementation of the concept of advanced digital "smart" agriculture is impossible without basic mathematical models of "mass interactions" of natural living objects. This primarily affects the spread of certain diseases in populations. In the plant world, such a convenient model object is the well-studied "host-pathogen" system by the example of the interaction of millet and its smut disease. At present, the knowledge of the patterns of development of this disease in the millet plant is of a qualitative nature (virulence), and the quantitative characteristics (aggressiveness) are approximate. Only mathematical modeling of this process can accurately describe the development of the disease. This paper examines a probabilistic model and certain aspects of mathematical modeling using the example of identifying the laws of horizontal resistance to smut in susceptible millet genotypes.

In São Paulo State, mainly in rural areas, the utilization of wooden poles is observed for different purposes. In this context, wood in contact with the ground presents faster deterioration, which is generally associated to environmental factors and, especially to the presence of fungi and insects. With the use of mathematical models, the useful life of wooden structures can be predicted by obtaining "climatic indexes" to indicate, comparatively among the areas studied, which have more or less tendency to fungi and insects attacks. In this work, by using climatological data of several cities at São Paulo State, a simplified mathematical model was obtained to measure the aggressiveness of the wood in contact with the soil.

Abstract Background Several cytomegalovirus (CMV) vaccine candidates are under development. To reduce the burden of congenital CMV infection, potential strategies under consideration include vaccination of adult women, adolescent girls, and/or young children (both sexes). Methods We reviewed 5 studies that used infectious disease modeling to assess the potential impact of vaccination for preventing congenital CMV infection. All models assumed CMV vaccination would prevent primary infection and 2 models also assumed prevention of reinfections and reactivations. Results Despite differences in structure, assumptions, and population data, infant vaccination (both sexes) was the optimal strategy in all models, but in 1 model vaccinating seronegative women at 19–21 years of age was also optimal (for duration of vaccine protection ≥8 years). In 3 models, infant vaccination increased average age at primary infection as a result of decreased secondary transmission (herd immunity) combined with waning vaccine-induced immunity. This effect could increase the risk of congenital CMV infections in populations where primary CMV infection occurs early in childhood but could be minimized by administering a second dose of vaccine during adolescence. Conclusions Understanding vaccine efficacy and duration of immunity, and how these might vary depending on CMV serostatus and age at vaccination, will be key to defining CMV vaccination strategies.

Abstract Background Gliomas manifest in a variety of histological phenotypes with varying aggressiveness. The etiology of glioma remains largely unknown. Taller stature in adulthood has been linked with glioma risk. The aim of this study was to discern whether this association can be detected in adolescence. Methods The cohort included 2 223 168 adolescents between the ages of 16 and 19 years. Anthropometric measurements were collected at baseline. Incident cases of glioma were extracted from the Israel National Cancer Registry over a follow-up period spanning 47 635 745 person-years. Cox proportional hazard models were used to estimate the hazard ratio (HR) for glioma and glioma subtypes according to height, body mass index (BMI), and sex. Results A total of 1195 patients were diagnosed with glioma during the study period. Mean (SD) age at diagnosis was 38.1 (11.7) years. Taller adolescent height (per 10-cm increase) was positively associated with the risk for glioma of any type (HR: 1.15; P = .002). The association was retained in subgroup analyses for low-grade glioma (HR: 1.17; P = .031), high-grade glioma (HR: 1.15; P = .025), oligodendroglioma (HR: 1.31; P = .015), astrocytoma (HR: 1.12; P = .049), and a category of presumed IDH-mutated glioma (HR: 1.17; P = .013). There was a trend toward a positive association between height and glioblastoma, however this had borderline statistical significance (HR: 1.15; P = .07). After stratification of the cohort by sex, height remained a risk factor for men but not for women. Conclusions The previously established association between taller stature in adulthood and glioma risk can be traced back to adolescence. The magnitude of association differs by glioma subtype.

We study a family of deterministic models for highway traffic flow which generalize cellular automaton rule 184. This family is parameterized by the speed limit m and another parameter k that represents a "degree of aggressiveness" in driving, strictly related to the distance between two consecutive cars. We compare two driving strategies with identical maximum throughput: "conservative" driving with high speed limit and "aggressive" driving with low speed limit. Those two strategies are evaluated in terms of accident probability. We also discuss fundamental diagrams of generalized traffic rules and examine limitations of maximum achievable throughput. Possible modifications of the model are considered.

PurposeThe purpose of this paper is to study the influence of the cutting conditions (cutting speed, feed rate and cutting depth) on the roughness (Ra) and on the flank wear (Vb) of the steel AISI 4140.Design/methodology/approachMixed ceramic (CC650) and polycrystalline cubic boron nitride (PCBN) have been used to carry out straight turning tests under dry conditions.FindingsThe results indicate that PCBN is more efficient than mixed ceramic (Al2O3+TiC) used in terms of wear resistance regardless of the aggressiveness of the AISI 4140 at 50 hardness rockwell (HRC). Consequently, it is the most powerful. Surface quality attained with PCBN tool considerably compares with that of grinding. Even when the tool wear VB reached 0.3 mm, the majority of the recorded Ra values did not exceed 1 m at the various speeds tested. The correlation of tool wear Vb and surface roughness Ra established allows obtaining experimental empirical data on the cutting tool wear from measured surface roughness for practical use in industry. The values of constants and the coefficient of determinationR2of this mathematical model will be calculated. Mathematical models expressing the relation between the elements of the cutting regime and technological parameters (tool life and roughness) are proposed.Originality/valueMany works have been already made in the similar manner, but this study of CC650 and PCBN wear is the first. Through this study, we propose a mathematical model expressing the relation between the elements of the cutting regime, tool life and roughness.

Background Prior research has underscored negative impacts of perinatal parental depression on offspring cognitive performance in early childhood. However, little is known about the effects of parental depression during adolescence on offspring cognitive development. Methods and findings This study used longitudinal data from the nationally representative China Family Panel Studies (CFPS). The sample included 2,281 adolescents aged 10–15 years (the median age was 13 years with an interquartile range between 11 and 14 years) in 2012 when their parents were surveyed for depression symptoms with the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). The sample was approximately balanced by sex, with 1,088 females (47.7%). We examined the associations of parental depression in 2012 with offspring cognitive performance (measured by mathematics, vocabulary, immediate word recall, delayed word recall, and number series tests) in subsequent years (i.e., 2014, 2016, and 2018) using linear regression models, adjusting for various offspring (i.e., age, sex, and birth order), parent (i.e., parents’ education level, age, whether living with the offspring, and employment status), and household characteristics (i.e., place of residence, household income, and the number of offspring). We found parental depression during adolescence to be significantly associated with worse cognitive performance in subsequent years, in both crude and adjusted models. For example, in the crude models, adolescents whose mothers had depression symptoms in 2012 scored 1.0 point lower (95% confidence interval [CI]: −1.2 to −0.8, p < 0.001) in mathematics in 2014 compared to those whose mothers did not have depression symptoms; after covariate adjustment, this difference marginally reduced to 0.8 points (95% CI: −1.0 to −0.5, p < 0.001); the associations remained robust after further adjusting for offspring earlier cognitive ability in toddlerhood (−1.2, 95% CI: −1.6, −0.9, p < 0.001), offspring cognitive ability in 2012 (−0.6, 95% CI: −0.8, −0.3, p < 0.001), offspring depression status (−0.7, 95% CI: −1.0, −0.5, p < 0.001), and parents’ cognitive ability (−0.8, 95% CI: −1.2, −0.3, p < 0.001). In line with the neuroplasticity theory, we observed stronger associations between maternal depression and mathematical/vocabulary scores among the younger adolescents (i.e., 10–11 years) than the older ones (i.e., 12–15 years). For example, the association between maternal depression and 2014 vocabulary scores was estimated to be −2.1 (95% CI: −2.6, −1.6, p < 0.001) in those aged 10–11 years, compared to −1.2 (95% CI: −1.6, −0.8, p < 0.001) in those aged 12–15 years with a difference of 0.9 (95% CI: 0.2, 1.6, p = 0.010). We also observed a stronger association of greater depression severity with worse mathematical scores. The primary limitations of this study were the relatively high attrition rate and residual confounding. Conclusions In this study, we observed that parental depression during adolescence was associated with adverse offspring cognitive development assessed up to 6 years later. These findings highlight the intergenerational association between depression in parents and cognitive development across the early life course into adolescence.

Influenza is a major challenge to global healthcare due to its high transmissivity and ability to cause major epidemics. Influenza epidemics and pandemics are associated with changes in the society structure that contribute to the spread of new viral strains in certain environmental and social settings. Currently, influenza is one of the most common global diseases that results in annual epidemics or even pandemics, often leading to lethal outcome. Influenza viruses are uniquely prone to variability via point mutations, recombination and gene reassortment accompanied with changes in their biological properties considered as the main cause of uncontrolled infection spread. Hence, examining cohorts of predisposed individuals by using probability models provides not only additional information about viral outbreaks, but also allows monitoring dynamics of viral epidemics in controlled areas. Understanding influenza epidemiology is crucial for restructuring healthcare resources. Public healthcare service mainly relies on influenza vaccination. However, there are vulnerable cohorts such as elderly and immunocompromised individuals, which usually contain no protective antiinfluenza virus antibody level. Despite advances in the developing vaccines and chemotherapy, large-scale influenza epidemics still continue to emerge. Upon that, no reliable methods for disease prognosis based on rate of ongoing epidemic situation are currently available. Monitoring and predicting emerging epidemics is complicated due to discrepancy between dynamics of influenza epidemics that might be evaluated by using surveillance data as well as platform for tracking influenza incidence rate. However, it may be profoundly exacerbated by mutations found in the influenza virus genome by altering genuine morbidity dynamics. Use of probabilistic models for assessing parameters of stochastic epidemics would contribute to more accurately predicted changes in morbidity rate. Here, an SIR+A probabilistic model considering a relationship between infected, susceptible and protected individuals as well as the aggressiveness of external risks for predicting changes in influenza morbidity rate that allowed to evaluate and predict the 2016 ARVI influenza incidence rate in Moscow area. Moreover, introducing an intensity of infection parameter allows to conduct a reliable analysis of incidence rate and predict its changes.

AbstractNutritional geometry (NG) is a novel dietary analysis approach that considers nutrient balance, rather than single nutrient effects, on health and behaviour. Through NG, recent animal experiments have found that lifespan and reproduction are differentially altered by dietary macronutrient distribution. Epidemiological research using NG reports similar findings for human ageing. Yet, the relation of macronutrient balance to human reproduction, especially reproductive maturation, remains undefined. We studied the impact of childhood macronutrient intake on pubertal maturation, by applying NG to an Australian longitudinal adolescent dataset. Food records, collected at age 8 years from 142 pre-pubertal children (females, 92; males, 50), were analysed for absolute energy, percentage energy and energy-adjusted residuals from protein, carbohydrate and fat. Pubertal stage change (assessed at 8, 13 and 15 years) was modelled to obtain individual mathematical estimates of pubertal timing and tempo. Timing of menarche was recorded. The association of macronutrients to pubertal timing/tempo was assessed via NG, involving generalised additive models and heat maps to aid interpretation. Results showed lower dietary protein (relative to carbohydrate and fat) in girls consistently predicted earlier pubertal timing and menarche, and was related to faster pubertal tempo (all P &lt; 0·05). No significant associations were identified in boys for both timing and tempo. Results suggest a role of non-protein macronutrients in facilitating female maturation; corroborating feeding and reproductive behaviour patterns observed in earlier NG studies of primates. Application of NG to other adolescent datasets is required to confirm the present findings. Such work would advance understanding of how nutrient balance shapes human development and health.

Full-spinal radiographs (FRs) are often the first choice of imaging modality in the investigation of scoliosis. However, FRs are strongly related to breast cancer occurrence due to multiple large-field radiographic examinations taken during childhood and adolescence, which may increase the risk for breast cancer in adulthood among women with scoliosis. The purpose of this study was to consider various technical parameters to reduce the patient radiation dose of FRs for scoliosis. To evaluate breast surface doses (BSDs) in FRs, radio photoluminescence dosimeters were placed in contact with a child phantom. Using the PC-based Monte Carlo (PMC) program for calculating patient doses in medical X-ray examinations, the breast organ dose (BOD) and the effective dose were calculated by performing Monte Carlo simulations using mathematical phantom models. The BSDs in the posteroanterior (PA) view were 0.15–0.34-fold those in the anteroposterior (AP) view. The effective dose in the PA view was 0.4–0.61-fold that in the AP view. BSD measurements were almost equivalent to the BODs obtained using PMC at all exposure settings. During FRs, the PA view without an anti-scatter grid significantly reduced the breast dose compared to the AP view with an anti-scatter grid.

Modern dentistry requires the definition of individualized values of teleroentgenographic indicators. To solve such problems, methods of regression and correlation analysis are increasingly used, which help to establish not only the existence of various relationships between the anatomical structures of the head and the parameters of the dento-jaw system, but also allow more accurately predict the change in the contour of soft facial tissue in response to orthodontic treatment. The purpose of the study is to develop mathematical models for the determination of individual teleroentgenographic characteristics of the facial soft tissues by studying the cephalometric indices of young men and women of Ukraine with normal occlusion and balanced faces and conducting a direct stepwise regression analysis. With the use of Veraviewepocs 3D device, Morita (Japan) from 38 young men (17 to 21 years of age) and 55 young women (aged from 16 to 20 years) with occlusal close to the orthognathic bite and balanced faces received side teleroentgenograms. The cephalometric analysis was performed using OnyxCeph³™ licensed software. Cephalometric points and measurements were made according to the recommendations of Downs W. B., Holdway R. A., McNamara J., Schwarz A. M., Schmuth G. P. F., Steiner C. C. and Tweed C. H. With the help of direct stepwise regression analysis, in the licensed package “Statistica 6.0”, regression models of individual teleroentgenographic characteristics of the profile of soft facial tissues were constructed. In young men with normal occlusion close to the orthognathic bite of 19 possible models, 11 were constructed with a determination coefficient from 0.638 to 0.930, and in young women – 12 models with a determination coefficient from 0.541 to 0.927. The conducted analysis of models showed that in young men most often the regression equations included – angle N_POG, parameters of which indicate a linear interjaw relation in the anterior-posterior direction (14.0%); angle GL_SNPOG, or index of convexity of the soft tissue profile (8.8%); MAX maxillary length (7.0%), and GL_SN_S index, which defines vertical correlations in the facial profile (5.3%). The young women most often models included – the angle N_POG (12.5%); angle GL_SNPOG (7.5%); soft tissue front angle P_OR_N (6.25%); the reference angle ML_NL and the profile angle T (by 5.0%); the angle AB_NPOG, the angle NBA_PTGN, which defines the direction of development of the mandible and the distance PN_A (3.75%). Thus, in the work with the help of the method of stepwise regression with inclusion, among Ukrainians of adolescence age, based on the characteristics of teleroentgenographic indicators, reliable models of individual teleroentgenographic characteristics of the profile of soft facial tissues were developed and analyzed.

Long bone growth relies on the continuous bone formation from cartilaginous tissue (endochondral ossification). This process starts in the central region (diaphysis) of the forming bone and short before birth, ossification starts in bone extremes (epiphysis). A cartilaginous region known as the growth plate is maintained until adolescence between epiphysis and diaphysis to further contribute to longitudinal growth. Even though there are several biochemical factors controlling this process, there is evidence revealing an important regulatory role of mechanical stimuli. Up to now approaches to understand mechanical effects on ossification have been limited to epiphysis. In this work, based on Carter's mathematical model for epiphyseal ossification, we explored human growth plate response to mechanical loads. We analyzed growth plate stress distribution using finite element method for a generic bone considering different stages of bone development in order to shed light on mechanical contribution to growth plate function. Results obtained revealed that mechanical environment within the growth plate change as epiphyseal ossification progresses. Furthermore, results were compared with physiological behavior, as reported in literature, to analyze the role of mechanical stimulus over development. Our results suggest that mechanical stimuli may play different regulation roles on growth plate behavior through normal long bone development. However, as this approach only took into account mechanical aspects, failed to accurately predict biological behavior in some stages. In order to derive biologically relevant information from computational models it is necessary to consider biological contribution and possible mechanical–biochemical interactions affecting human growth plate physiology. Along these lines, we propose the dilatatorial parameter k used by Carter et al. should assume different values corresponding to the developmental stage in question. Thus, reflecting biochemical contribution changes over time.

RESUMEN: La adolescencia es una etapa, en la que la impulsividad y la búsqueda de sensaciones se presentan como dos factores que confluyen con un amplio abanico de cambios, inherentes al desarrollo adolescente. La impulsividad y la búsqueda de sensaciones han sido frecuentemente vinculadas a comportamientos de riesgo en adolescentes, y especialmente afines a la agresividad. Con el presente trabajo se pretende analizar el valor predictivo de variables relacionadas con la búsqueda de sensaciones y la impulsividad, en relación a la adopción de diferentes formas de agresión (agresión física, agresión verbal, ira y hostilidad), en adolescentes. Para ello, se seleccionó una muestra de 822 alumnos de secundaria, y se aplicaron la Escala de Búsqueda de Sensaciones, la Escala de Impulsividad Estado (EIE) y el Cuestionario de Agresión (AQ). Los resultados obtenidos, evidencian la existencia de correlaciones positivas entre los factores de búsqueda de sensaciones e impulsividad, con respecto a las modalidades de agresión analizadas. Por otro lado, los análisis de regresión múltiple evidencian el valor predictivo de los factores de búsqueda de sensaciones e impulsividad, para las diferentes manifestaciones de la conducta agresiva. Más concretamente, destaca la presencia de los componentes de la impulsividad en los modelos explicativos de la agresión física y verbal, y el factor Atencional como el mejor predictor de la ira y la hostilidad.Palabras clave: Impulsividad, búsqueda de sensaciones, agresión, predictores, adolescentes. Sensation seeking and impulsivity as predictors of aggression in adolescentsABSTRACT: Adolescence is a stage in which impulsivity and sensation seeking are presented as two factors that come together with a wide range of changes inherent to adolescent development. Impulsivity and sensation seeking have often been linked to risky behavior in adolescents, especially related to aggressiveness. With this paper is to analyze the predictive value of variables related to sensation seeking and impulsiveness, in relation to the adoption of different forms of aggression (physical aggression, verbal aggression, anger and hostility) in adolescents. To do this, a sample of 822 high school students were selected, and the Sensation Seeking Scale, the State Impulsivity Scale (EIE) and Aggression Questionnaire (AQ), were applied. The results obtained show the existence of positive correlations between factors of sensation seeking and impulsivity, regarding the modalities of aggression analyzed. On the other hand, multiple regression analysis shows the predictive value of factors sensation seeking and impulsiveness, for the different manifestations of aggressive behavior. More specifically, the presence of components of impulsivity in the explanatory models of physical and verbal aggression, and attentional factor, as the best predictor of anger and hostility.Keywords: Impulsiveness; sensation seeking; aggression; predictors; adolescents.

The lack of the ability to determine the individual standard angle characteristics of the position of the teeth and the technical provision of their control often does not lead to the expected result and in each case requires individualization, the vision of which is based, as a rule, on the experience and intuition of the doctor. In order to solve such a situation, in addition to improving the positioning protocols of the non-removable equipment, the physician should be able to clearly identify the individual angular characteristics of the tooth-jaw system. The purpose of the study – by studying computer tomography and cephalometric indices and conducting direct stepwise regression analysis to develop in Ukrainian adolescents with orthognathic bite mathematical models of individual angular positions of teeth. Using the Veraviewepocs 3D device, Morita (Japan) at 38 young men (aged from 17 to 21) and 55 young women (aged from 16 to 20 years) with normal occlusion close to orthognathic bite received and analyzed dental tomograms and lateral teleroentgenograms. Cephalometric points and measurements were performed according to recommendations of A. M. Schwarz, J. McNamara, W. B. Downs, R. A. Holdway, G. P. F. Schmuth, C. C. Steiner and C. H. Tweed. Anatomical points were determined taking into account the recommendations of A. E. Athanasiou and S. I. Doroshenko and Y. A. Kulginsky. The simulation of CT indexes describing the position of individual teeth relative to each other, to the bone cranial structures and the profile of adolescents with orthognathic bite, depending on the metric characteristics of the skull, which are usually unchanged during surgical and orthodontic treatment, as well as the width, lengths, angles and positions of the upper and lower jaws that may be altered by orthodontic surgery done. The statistical processing of the obtained results was carried out in the license package “Statistica 6.0” using a direct stepwise regression analysis. It was found that in young men of 40 possible models, 23 were constructed with a determination coefficient R2 of 0.557 to 0.832, while in young women, only 8 models with a determination coefficient R2 of 0.581 to 0.832. Moreover, in the young men – of 10 possible 9 models of vestibular-tongue inclination of corresponding teeth (R2 from 0.557 to 0.832) were constructed; out of 10 possible 5 models of mesio-distal inclination of corresponding teeth (R2 from 0.558 to 0.769) constructed; of the possible 14 constructed 6 models of rotation of the corresponding teeth (R2 from 0.579 to 0.737); and in young women - there are only 5 models of vestibular-tongue inclination of the corresponding teeth (R2 from 0.603 to 0.665). In addition, in both young men and young women, models of the size of the inter-incision angle (R2 0.748 in young men and 0.581 in young women) were constructed, the magnitude of the angle of inclination of the lower canine in the jet plane (R2 respectively 0.729 and 0.793), and the magnitude of the inclination of the closure planes relative to the palatal plane (R2 respectively 0.808 and 0.832). In the analysis it was found that in young men, most frequently models included - indicator WITS (7.0%); angle GL_SNPOG (5.4%); distance S_E, angle ММ, angle NSBA (by 4.7%); angle AB_NPOG, angle N_POG_, distance N_SE, coefficient N_SP_SP, angle P_OR_N (by 3.9%). In young women, most frequently models included – angle N_POG_ (14.3%); angle AB_NPOG (10.2%); indicator WITS (8.2%); angle ММ, angle ANB, length of the branch of the mandible R_ASC (by 6.1%). Thus, in the work with the help of the method of step-by-step regression with inclusion, among Ukrainian adolescence, on the basis of peculiarities of computer-tomographic and teleroentgenography indices, reliable models of computer-tomographic individual linear angular characteristics of the position of teeth necessary for constructing the correct three-dimensional geometry of dental arches are developed and analyzed.

Abstract BACKGROUND Meningioma therapy efficiency is used to being assessed by 6 months progression survival rate (PFS6), which remains the most consensual criterion. Nevertheless, different patterns of meningiomas intrinsic aggressiveness and growth rates directly impact the PFS6 leading to unreliability of drug effect assessment. Moreover, therapeutic response remains rare in meningiomas. These points lead to consider classical and updated RANO criteria as not fully adapted to meningiomas. Based on phase II CEVOREM trial experience, we aim to improve the assessment of drugs efficiency in meningiomas via the determination of growth rate before and under treatment. MATERIAL AND METHODS Twenty patients were included in Cevorem trial which tested the combination of octreotide and everolimus as previously described. MRI assessment was performed in the 3 to 6 preinclusion months, at inclusion then every 3 months. Progression was assessed by investigators according to RANO criteria. An independent central review was performed with 2 reviewers and 1 adjudicator: largest diameter, 2D maximal area as 3D volume were assessed by autosegmentation software (Brainlab). Results from central review were correlated to investigators assessment. 3D volume growth rate (3DVGR) was calculated using 2 different processes (one simple and one complex). Comparison of 3DVGR before vs. under treatment was performed. Meningioma growth under treatment was compared to theoretical meningioma growth based on preinclusion data using a model of meningioma growth. RESULTS PFS6 assessed via the independent central review was in accordance with PFS6 assessed by investigators following RANO criteria. Then, we analyzed 3DVGR before and during therapy. Standard deviation was higher using the complex 3DVGR calculation process. A decrease of more than 50% of the 3DVGR was observed in 30/36 tumors at 3 months with the both calculation modes and could be considered as a threshold of drugs activity. Median volume growth rate decreased from 88.3 or 17.2%/3 months before inclusion to -2.2 or à -0.6 %/3mo at 3 months depending of the calculation mode (p <0.0002). Nevertheless, in our study, decrease in 3DVGR was associated with a prolonged free progression period when 3DVGR decreased around 0 or negative. Comparison of theoretical meningioma growth curve based on preinclusion data with under treatment growth curve is ongoing. Some limits remain: 3DVGR calculation remains directly related to the volume assessment accuracy and 3DVGR can be very high particularly in case of very small initial tumor which cannot be mitigated by current mathematical models. CONCLUSION 3DVGR measurement during versus before seems as a sensitive and reliable tool which provides valuable comparison in a phase 2 study to assess drugs activity in meningioma in complement to PFS6. 3DVGR assessment should be considered in future clinical trials.

Introduction. The relevance of the present research is determined by the need to create a system of measures to support and develop the institution of fatherhood, the formation of parental competence, effective models of paternal behaviour among modern youth and insufficient study of this phenomenon from psychological positions. The problem of the research is to resolve the contradiction between the requirement of modern society to form a value-positive attitude towards fatherhood among students’ youth and the need to identify psychological factors in the formation of ideas about fatherhood, parental attitudes, motivation for parenthood, and acceptance of the father’s role at the stage of entering adulthood.The aim of the research is to reveal the interrelation of ideas about fatherhood (“ideal father”, “I am an expectant father”) with gender, age and structure of valuable orientations among modern students.Methodology and research methods. The theoretical and methodological framework of the research is based on cultural-historical theory of development of the psyche and the doctrine of psychological age by L. S. Vygotsky; age-psychological approach to the analysis of mental development in ontogenesis (by L. S. Vygotsky, D. B. Elkonin, L. I. Bozhovich, O. A. Karabanova,E. I. Zakharova, G. V. Burmenskaya, et al.); the doctrine of the indicative activities by P. Y. Galperin. The research methods involve theoretical-methodological literature analysis, questionnaire method, psycho-diagnostic methods, and mathematical and statistical data processing methods.Results. The authors described and compared the content of ideas about fatherhood among young men and young women depending on the structure of valuable orientations at different stages of age development. Three homogeneous clusters were identifi using divisive clustering of an empirical sample:1) orientation towards the values of professional self-realisation (193 respondents, 17.8%); 2) orientation towards gnostic and aesthetic values (274 respondents, 25.2%); 3) orientation towards the values of personal life (619 respondents, 57%). The interrelation of ideas about fatherhood (“ideal father”, “I am an expectant father”) with gender, age, and structure of valuable orientations of modern students is revealed. The image of the ideal father is generally characterised by fragmentary and incomplete representations, and, in some cases, by cognitive distortions.Scientific novelty of the research is to reveal the interrelation of ideas about fatherhood with the structure of valuable orientations of young men and women in adolescence and early adulthood.Practical significance. The obtained results actualise the importance and necessity of psychological and pedagogical support of the process of family self-determination of students, the formation of complete and adequate ideas about fatherhood allowing for the development of its educational potential in the conditions of the educational environment of the university.

Introduction. The relevance of the present research is determined by the need to create a system of measures to support and develop the institution of fatherhood, the formation of parental competence, effective models of paternal behaviour among modern youth and insufficient study of this phenomenon from psychological positions. The problem of the research is to resolve the contradiction between the requirement of modern society to form a value-positive attitude towards fatherhood among students’ youth and the need to identify psychological factors in the formation of ideas about fatherhood, parental attitudes, motivation for parenthood, and acceptance of the father’s role at the stage of entering adulthood.The aim of the research is to reveal the interrelation of ideas about fatherhood (“ideal father”, “I am an expectant father”) with gender, age and structure of valuable orientations among modern students.Methodology and research methods. The theoretical and methodological framework of the research is based on cultural-historical theory of development of the psyche and the doctrine of psychological age by L. S. Vygotsky; age-psychological approach to the analysis of mental development in ontogenesis (by L. S. Vygotsky, D. B. Elkonin, L. I. Bozhovich, O. A. Karabanova,E. I. Zakharova, G. V. Burmenskaya, et al.); the doctrine of the indicative activities by P. Y. Galperin. The research methods involve theoretical-methodological literature analysis, questionnaire method, psycho-diagnostic methods, and mathematical and statistical data processing methods.Results. The authors described and compared the content of ideas about fatherhood among young men and young women depending on the structure of valuable orientations at different stages of age development. Three homogeneous clusters were identifi using divisive clustering of an empirical sample:1) orientation towards the values of professional self-realisation (193 respondents, 17.8%); 2) orientation towards gnostic and aesthetic values (274 respondents, 25.2%); 3) orientation towards the values of personal life (619 respondents, 57%). The interrelation of ideas about fatherhood (“ideal father”, “I am an expectant father”) with gender, age, and structure of valuable orientations of modern students is revealed. The image of the ideal father is generally characterised by fragmentary and incomplete representations, and, in some cases, by cognitive distortions.Scientific novelty of the research is to reveal the interrelation of ideas about fatherhood with the structure of valuable orientations of young men and women in adolescence and early adulthood.Practical significance. The obtained results actualise the importance and necessity of psychological and pedagogical support of the process of family self-determination of students, the formation of complete and adequate ideas about fatherhood allowing for the development of its educational potential in the conditions of the educational environment of the university.

Abstract Abstract 544 Introduction: Conventional dosing of FVIII prophylaxis in adults with hemophilia is based on 3 weekly or alternate day regimes of 20–40IU/kg, aiming for a trough level above 1IU/dL. However, pharmacokinetics of FVIII widely varies between individuals, thus the amount of factor concentrate required to maintain trough levels above 1IU/dL is also disparate. Mathematical modeling indicates that half-life has a significant influence over trough level. An individualized dose based on FVIII half-life may therefore allow for more appropriate dosing of prophylaxis in adults. For this approach to be effective, half-life results obtained from pharmacokinetic studies need to be consistent and representative of an individual's steady state. Although it is recognised that half-life increases from early childhood until adolescence, intra-individual variation of half-life in adults has not been examined. Hypotheses: We hypothesized that for patients >18years significant inter-individual variation, but minimal intra-individual variation, in half-life would be detected. Method: This single center study investigated inter- and intra-individual variation in FVIII half-life based on 140 pharmacokinetic studies conducted in 73 individuals with severe hemophilia A (FVIII:C < 1IU/dL). Data for all FVIII pharmacokinetic studies performed over a 5-year period were extracted from an in-house database. Patient demographics and laboratory results were verified against electronic patient records. All half-life studies were performed according to a set protocol and analyzed within the same clinical pathology accredited reference laboratory. Results were tested using the non-parametric Wilcoxin signed rank test. Data is presented as median and range and p-values < 0.001 were considered significant. Results: The median age of patients was 17.5 years (range 5.0– 54.0). The wide range in FVIII half-life data indicated substantial inter-individual variation within the complete population (median 9.9hrs, range 2.3–19hrs), replicated upon division of data into age specific categories (Fig. 1). 36 patients had undergone multiple studies over the 5-year period. Of these, 21 had at least 3 data sets. FVIII half-life showed considerable intra-individual variation with 17 patients (81%) demonstrating a range of half-life greater than 2hrs. FVIII half-life data was normalized to nullify the effect of extensive inter-individual variation in half-life within the population. Figure 2 demonstrates mean difference in normalized FVIII half-life for all patients with multiple half-life results. Testing against a null hypothesis of no variation, we found significant intra-individual variation upon examination of the entire population (n= 36, p<0.0001). Following exclusion of data from children less than 6 years, significant intra-individual variation could still be detected for children 6–18 years (n=19, p< 0.0001), and adults (n= 16, p<0.0001). Discussion: This study verifies expected inter-individual variation of pharmacokinetic profiles and appears to support the concept of individualized prophylaxis regimes in adults based on half-life data. However, considerable intra-individual variation in FVIII half-life in adult patients was registered. Mathematical models have indicated that even modest changes in half-life influence dosing requirements for FVIII prophylaxis. Intra-individual fluctuations in FVIII half-life will necessitate regular pharmacokinetic studies to ensure appropriate dosing. This will naturally affect the cost, utility and acceptability of treatment. Disclosures: No relevant conflicts of interest to declare.

Abstract Despite extensive research and aggressive therapies, glioblastoma (GBM) remains a central nervous system malignancy with poor prognosis. The varied histopathology of GBM suggests a landscape of differing microenvironments and clonal expansions, which may influence metabolism, driving tumor progression. Indeed, GBM metabolic plasticity in response to differing nutrient supply within these microenvironments has emerged as a key driver of aggressiveness. Additionally, emergent biophysical and biochemical interactions in the tumor microenvironment (TME) are offering new perspectives on GBM metabolism. Perivascular and hypoxic niches exert crucial roles in tumor maintenance and progression, facilitating metabolic relationships between stromal and tumor cells. Alterations in extracellular matrix and its biophysical characteristics, such as rigidity and topography, regulate GBM metabolism through mechanotransductive mechanisms. This review highlights insights gained from deployment of bioengineering models, including engineered cell culture and mathematical models, to study the microenvironmental regulation of GBM metabolism. Bioengineered approaches building upon histopathology measurements may uncover potential therapeutic strategies that target both TME-dependent mechanotransductive and biomolecular drivers of metabolism to tackle this challenging disease. Longer term, a concerted effort integrating in vitro and in silico models predictive of patient therapy response may offer a powerful advance toward tailoring of treatment to patient-specific GBM characteristics.

Social behavior in mammals is often studied in pairs under artificial conditions, yet groups may rely on more complicated social structures. Here, we use a novel system for tracking multiple animals in a rich environment to characterize the nature of group behavior and interactions, and show strongly correlated group behavior in mice. We have found that the minimal models that rely only on individual traits and pairwise correlations between animals are not enough to capture group behavior, but that models that include third-order interactions give a very accurate description of the group. These models allow us to infer social interaction maps for individual groups. Using this approach, we show that environmental complexity during adolescence affects the collective group behavior of adult mice, in particular altering the role of high-order structure. Our results provide new experimental and mathematical frameworks for studying group behavior and social interactions.

The facial image analysis for classifying human age has a vital role in Image processing, Pattern recognition, Computer vision, Cognitive science and Forensic science. The various computational and mathematical models, for classifying facial age includes Principal Component Analysis (PCA) and Wavelet Transforms and Local Binary Pattern (LBP). A more sophisticated method is introduced to improve the performance of the system by decomposing the face image using 2-level linear wavelet transforms and classifying the human age group using Artificial Neural Network. This approach needs normalizing the facial image at first and then extracting the face features using linear wavelet transforms. The distance of the features is measured using Euclidean distance and given as input to Adaptive Resonance Theory (ART). The network is trained with an own dataset consisting of 70 facial images of various age group. The goal of the proposed work is to classify the human age group into four categories as Child, Adolescence, Adult and Senior Adult.

Abstract Background Epstein-Barr virus (EBV) is an important human pathogen which causes lifelong infection of > 90% people globally and is linked to infectious mononucleosis (arising from infection in the later teenage years) and several types of cancer. Vaccines against EBV are in development. In order to determine the most cost-effective public health strategy for vaccine deployment, setting-specific data on the age at EBV acquisition and risk factors for early infection are required. Such data are also important to inform mathematical models of EBV transmission that can determine the required target product profile of vaccine characteristics. We thus aimed to examine risk factors for EBV infection in young people in England, in order to improve our understanding of EBV epidemiology and guide future vaccination strategies. Methods The Health Survey for England (HSE) is an annual, cross-sectional representative survey of households in England during which data are collected via questionnaires and blood samples. We randomly selected individuals who participated in the HSE 2002, aiming for 25 participants of each sex in each single year age group from 11 to 24 years. Stored samples were tested for EBV and cytomegalovirus (CMV) antibodies. We undertook descriptive and regression analyses of EBV seroprevalence and risk factors for infection. Results Demographic data and serostatus were available for 732 individuals. EBV seroprevalence was strongly associated with age, increasing from 60.4% in 11–14 year olds throughout adolescence (68.6% in 15–18 year olds) and stabilising by early adulthood (93.0% in those aged 22–24 years). In univariable and multivariable logistic regression models, ethnicity was associated with serostatus (adjusted odds ratio for seropositivity among individuals of other ethnicity versus white individuals 2.33 [95% confidence interval 1.13–4.78]). Smoking was less strongly associated with EBV seropositivity. Conclusions By the age of 11 years, EBV infection is present in over half the population, although age is not the only factor associated with serostatus. Knowledge of the distribution of infection in the UK population is critical for determining future vaccination policies, e.g. comparing general versus selectively targeted vaccination strategies.

Abstract Objectives Quantifying the long-term effects of nutritional or drug treatments on bone is challenging due to the delay in time between treatment and changes in bone mass. The objective of this study was to develop a dynamic (non-steady state) mathematical model of calcium metabolism in young growing rats as an analogue for human adolescents and to use that model to predict the effects of treatments on calcium mass in bone. Methods A dynamic model of calcium metabolism was developed using kinetic data collected from Sprague-Dawley male rats (n = 54) dosed intraperitoneally with 50 μCi of 45Ca at 4 wk of age. Total calcium and 45Ca levels measured in serum and 24-h urine samples collected periodically for 45 d after treatment were analyzed by compartmental modeling using WinSAAM software. Concurrently, tracer (45Ca) and tracee (total calcium) models, together called the ‘dynamic model’, were developed. Growth of the rats was modeled using a formula based on body weight. Calcium absorption was decreased by about 50% at wk 6 to account for the reduction in bone mineral accretion in late puberty. During the first 40 d after weaning, the model included a 4-fold decrease in bone resorption and a 20-fold decrease in bone formation, consistent with previous findings of studies conducted in growing rats. Data were fitted by iterative least squares regression analysis. To mimic the effects of dietary and drug interventions during adolescence, the absorption efficiency was manipulated in terms of degree, timing, and duration and the subsequent changes in bone mass were quantified. Results The dynamic model predicted that, if absorption decreased by 25% instead of 50% during growth, the rate of bone accretion would be 32% higher and the bone mineral mass at d 50 would be 24% larger, suggesting that a dietary or drug intervention that minimizes the drop in absorption, would result in a higher bone mineral mass. Conclusions A dynamic model of calcium metabolism during growth was developed and used to predict the effect of interventions on bone mass. These predictions would be tested in future studies. Funding Sources Purdue University Graduate School and Amgen, Inc., Thousand Oaks, CA.

'He did what the cipher could not, he rescued himself.' -- Alfred Bester, The Stars My Destination (23) On many levels, the new Nine Inch Nails album The Fragile is a gritty meditation about different types of End: the eternal relationship cycle of 'fragility, tension, ordeal, fragmentation' (adapted, with apologies to Wilhelm Reich); fin-de-siècle anxiety; post-millennium foreboding; a spectre of the alien discontinuity that heralds an on-rushing future vastly different from the one envisaged by Enlightenment Project architects. In retrospect, it's easy for this perspective to be dismissed as jargon-filled cyber-crit hyperbole. Cyber-crit has always been at its best too when it invents pre-histories and finds hidden connections between different phenomena (like the work of Greil Marcus and early Mark Dery), and not when it is closer to Chinese Water Torture, name-checking the canon's icons (the 'Deleuze/Guattari' tag-team), texts and key terms. "The organization of sound is interpreted historically, politically, socially ... . It subdues music's ambition, reins it in, restores it to its proper place, reconciles it to its naturally belated fate", comments imagineer Kodwo Eshun (4) on how cyber-crit destroys albums and the innocence of the listening experience. This is how official histories are constructed a priori and freeze-dried according to personal tastes and prior memes: sometimes the most interesting experiments are Darwinian dead-ends that fail to make the canon, or don't register on the radar. Anyone approaching The Fragile must also contend with the music industry's harsh realities. For every 10 000 Goth fans who moshed to the primal 'kill-fuck-dance' rhythms of the hit single "Closer" (heeding its siren-call to fulfil basic physiological needs and build niche-space), maybe 20 noted that the same riff returned with a darker edge in the title track to The Downward Spiral, undermining the glorification of Indulgent hedonism. "The problem with such alternative audiences," notes Disinformation Creative Director Richard Metzger, "is that they are trying to be different -- just like everyone else." According to author Don Webb, "some mature Chaos and Black Magicians reject their earlier Nine Inch Nails-inspired Goth beginnings and are extremely critical towards new adopters because they are uncomfortable with the subculture's growing popularity, which threatens to taint their meticulously constructed 'mysterious' worlds. But by doing so, they are also rejecting their symbolic imprinting and some powerful Keys to unlocking their personal history." It is also difficult to separate Nine Inch Nails from the commercialisation and colossal money-making machine that inevitably ensued on the MTV tour circuit: do we blame Michael Trent Reznor because most of his audience are unlikely to be familiar with 'first-wave' industrial bands including Cabaret Voltaire and the experiments of Genesis P. Orridge in Throbbing Gristle? Do we accuse Reznor of being a plagiarist just because he wears some of his influences -- Dr. Dre, Daft Punk, Atari Teenage Riot, Pink Floyd's The Wall (1979), Tom Waits's Bone Machine (1992), David Bowie's Low (1977) -- on his sleeve? And do we accept no-brain rock critic album reviews who quote lines like 'All the pieces didn't fit/Though I really didn't give a shit' ("Where Is Everybody?") or 'And when I suck you off/Not a drop will go to waste' ("Starfuckers Inc") as representative of his true personality? Reznor evidently has his own thoughts on this subject, but we should let the music speak for itself. The album's epic production and technical complexity turned into a post-modern studio Vision Quest, assisted by producer Alan Moulder, eleventh-hour saviour Bob Ezrin (brought in by Reznor to 'block-out' conceptual and sonic continuity), and a group of assault-technicians. The fruit of these collaborations is an album where Reznor is playing with our organism's time-binding sense, modulating strange emotions through deeply embedded tonal angularities. During his five-year absence, Trent Reznor fought diverse forms of repetitious trauma, from endogenous depression caused by endless touring to the death of his beloved grandmother (who raised him throughout childhood). An end signals a new beginning, a spiral is an open-ended and ever-shifting structure, and so Reznor sought to re-discover the Elder Gods within, a shamanic approach to renewal and secular salvation utilised most effectively by music PR luminary and scientist Howard Bloom. Concerned with healing the human animal through Ordeals that hard-wire the physiological baselines of Love, Hate and Fear, Reznor also focusses on what happens when 'meaning-making' collapses and hope for the future cannot easily be found. He accurately captures the confusion that such dissolution of meaning and decline of social institutions brings to the world -- Francis Fukuyama calls this bifurcation 'The Great Disruption'. For a generation who experienced their late childhood and early adolescence in Reagan's America, Reznor and his influences (Marilyn Manson and Filter) capture the Dark Side of recent history, unleashed at Altamont and mutating into the Apocalyptic style of American politics (evident in the 'Star Wars'/SDI fascination). The personal 'psychotic core' that was crystallised by the collapse of the nuclear family unit and supportive social institutions has returned to haunt us with dystopian fantasies that are played out across Internet streaming media and visceral MTV film-clips. That such cathartic releases are useful -- and even necessary (to those whose lives have been formed by socio-economic 'life conditions') is a point that escapes critics like Roger Scruton, some Christian Evangelists and the New Right. The 'escapist' quality of early 1980s 'Rapture' and 'Cosmocide' (Hal Lindsey) prophecies has yielded strange fruit for the Children of Ezekiel, whom Reznor and Marilyn Manson are unofficial spokes-persons for. From a macro perspective, Reznor's post-human evolutionary nexus lies, like J.G. Ballard's tales, in a mythical near-future built upon past memory-shards. It is the kind of worldview that fuses organic and morphogenetic structures with industrial machines run amok, thus The Fragile is an artefact that captures the subjective contents of the different mind produced by different times. Sonic events are in-synch but out of phase. Samples subtly trigger and then scramble kinaesthetic-visceral and kinaesthetic-tactile memories, suggestive of dissociated affective states or body memories that are incapable of being retrieved (van der Kolk 294). Perhaps this is why after a Century of Identity Confusion some fans find it impossible to listen to a 102-minute album in one sitting. No wonder then that the double album is divided into 'left' and 'right' discs (a reference to split-brain research?). The real-time track-by-track interpretation below is necessarily subjective, and is intended to serve as a provisional listener's guide to the aural ur-text of 1999. The Fragile is full of encrypted tones and garbled frequencies that capture a world where the future is always bleeding into a non-recoverable past. Turbulent wave-forms fight for the listener's attention with prolonged static lulls. This does not make for comfortable or even 'nice' listening. The music's mind is a snapshot, a critical indicator, of the deep structures brewing within the Weltanschauung that could erupt at any moment. "Somewhat Damaged" opens the album's 'Left' disc with an oscillating acoustic strum that anchor's the listener's attention. Offset by pulsing beats and mallet percussion, Reznor builds up sound layers that contrast with lyrical epitaphs like 'Everything that swore it wouldn't change is different now'. Icarus iconography is invoked, but perhaps a more fitting mythopoeic symbol of the journey that lies ahead would be Nietzsche's pursuit of his Ariadne through the labyrinth of life, during which the hero is steadily consumed by his numbing psychosis. Reznor fittingly comments: 'Didn't quite/Fell Apart/Where were you?' If we consider that Reznor has been repeating the same cycle with different variations throughout all of his music to date, retro-fitting each new album into a seamless tapestry, then this track signals that he has begun to finally climb out of self-imposed exile in the Underworld. "The Day the World Went Away" has a tremendously eerie opening, with plucked mandolin effects entering at 0:40. The main slashing guitar riff was interpreted by some critics as Reznor's attempt to parody himself. For some reason, the eerie backdrop and fragmented acoustic guitar strums recalls to my mind civil defence nuclear war films. Reznor, like William S. Burroughs, has some powerful obsessions. The track builds up in intensity, with a 'Chorus of the Damned' singing 'na na nah' over apocalyptic end-times imagery. At 4:22 the track ends with an echo that loops and repeats. "The Frail" signals a shift to mournful introspectiveness with piano: a soundtrack to faded 8 mm films and dying memories. The piano builds up slowly with background echo, holds and segues into ... "The Wretched", beginning with a savage downbeat that recalls earlier material from Pretty Hate Machine. 'The Far Aways/Forget It' intones Reznor -- it's becoming clear that despite some claims to the contrary, there is redemption in this album, but it is one borne out of a relentless move forward, a strive-drive. 'You're finally free/You could be' suggest Reznor studied Existentialism during his psychotherapy visits. This song contains perhaps the ultimate post-relationship line: 'It didn't turn out the way you wanted it to, did it?' It's over, just not the way you wanted; you can always leave the partner you're with, but the ones you have already left will always stain your memories. The lines 'Back at the beginning/Sinking/Spinning' recall the claustrophobic trapped world and 'eternal Now' dislocation of Post-Traumatic Stress Disorder victims. At 3:44 a plucked cello riff, filtered, segues into a sludge buzz-saw guitar solo. At 5:18 the cello riff loops and repeats. "We're in This Together Now" uses static as percussion, highlighting the influence of electricity flows instead of traditional rock instrument configurations. At 0:34 vocals enter, at 1:15 Reznor wails 'I'm impossible', showing he is the heir to Roger Waters's self-reflective rock-star angst. 'Until the very end of me, until the very end of you' reverts the traditional marriage vow, whilst 'You're the Queen and I'm the King' quotes David Bowie's "Heroes". Unlike earlier tracks like "Reptile", this track is far more positive about relationships, which have previously resembled toxic-dyads. Reznor signals a delta surge (breaking through barriers at any cost), despite a time-line morphing between present-past-future. At 5:30 synths and piano signal a shift, at 5:49 the outgoing piano riff begins. The film-clip is filled with redemptive water imagery. The soundtrack gradually gets more murky and at 7:05 a subterranean note signals closure. "The Fragile" is even more hopeful and life-affirming (some may even interpret it as devotional), but this love -- representative of the End-Times, alludes to the 'Glamour of Evil' (Nico) in the line 'Fragile/She doesn't see her beauty'. The fusion of synths and atonal guitars beginning at 2:13 summons forth film-clip imagery -- mazes, pageants, bald eagles, found sounds, cloaked figures, ruined statues, enveloping darkness. "Just like You Imagined" opens with Soundscapes worthy of Robert Fripp, doubled by piano and guitar at 0:39. Drums and muffled voices enter at 0:54 -- are we seeing a pattern to Reznor's writing here? Sonic debris guitar enters at 1:08, bringing forth intensities from white noise. This track is full of subtle joys like the 1:23-1:36 solo by David Bowie pianist Mike Garson and guitarist Adrian Belew's outgoing guitar solo at 2:43, shifting back to the underlying soundscapes at 3:07. The sounds are always on the dissipative edge of chaos. "Just like You Imagined" opens with Soundscapes worthy of Robert Fripp, doubled by piano and guitar at 0:39. Drums and muffled voices enter at 0:54 -- are we seeing a pattern to Reznor's writing here? Sonic debris guitar enters at 1:08, bringing forth intensities from white noise. This track is full of subtle joys like the 1:23-1:36 solo by David Bowie pianist Mike Garson and guitarist Adrian Belew's outgoing guitar solo at 2:43, shifting back to the underlying soundscapes at 3:07. The sounds are always on the dissipative edge of chaos. "Pilgrimage" utilises a persistent ostinato and beat, with a driving guitar overlay at 0:18. This is perhaps the most familiar track, using Reznor motifs like the doubling of the riff with acoustic guitars between 1:12-1:20, march cries, and pitch-shift effects on a 3:18 drumbeat/cymbal. Or at least I could claim it was familiar, if it were not that legendary hip-hop producer and 'edge-of-panic' tactilist Dr. Dre helped assemble the final track mix. "No, You Don't" has been interpreted as an attack on Marilyn Manson and Hole's Courntey Love, particularly the 0:47 line 'Got to keep it all on the outside/Because everything is dead on the inside' and the 2:33 final verse 'Just so you know, I did not believe you could sink so low'. The song's structure is familiar: a basic beat at 0:16, guitars building from 0:31 to sneering vocals, a 2:03 counter-riff that merges at 2:19 with vocals and ascending to the final verse and 3:26 final distortion... "La Mer" is the first major surprise, a beautiful and sweeping fusion of piano, keyboard and cello, reminiscent of Symbolist composer Debussy. At 1:07 Denise Milfort whispers, setting the stage for sometime Ministry drummer Bill Reiflin's jazz drumming at 1:22, and a funky 1:32 guitar/bass line. The pulsing synth guitar at 2:04 serves as anchoring percussion for a cinematic electronica mindscape, filtered through new layers of sonic chiaroscuro at 2:51. 3:06 phase shifting, 3:22 layer doubling, 3:37 outgoing solo, 3:50-3:54 more swirling vocal fragments, seguing into a fading cello quartet as shadows creep. David Carson's moody film-clip captures the end more ominously, depicting the beauty of drowning. This track contains the line 'Nothing can stop me now', which appears to be Reznor's personal mantra. This track rivals 'Hurt' and 'A Warm Place' from The Downward Spiral and 'Something I Can Never Have' from Pretty Hate Machine as perhaps the most emotionally revealing and delicate material that Reznor has written. "The Great Below" ends the first disc with more multi-layered textures fusing nostalgia and reverie: a twelve-second cello riff is counter-pointed by a plucked overlay, which builds to a 0:43 washed pulse effect, transformed by six second pulses between 1:04-1:19 and a further effects layer at 1:24. E-bow effects underscore lyrics like 'Currents have their say' (2:33) and 'Washes me away' (2:44), which a 3:33 sitar riff answers. These complexities are further transmuted by seemingly random events -- a 4:06 doubling of the sitar riff which 'glitches' and a 4:32 backbeat echo that drifts for four bars. While Reznor's lyrics suggest that he is unable to control subjective time-states (like The Joker in the Batman: Dark Knight series of Kali-yuga comic-books), the track constructions show that the Key to his hold over the listener is very carefully constructed songs whose spaces resemble Pythagorean mathematical formulas. Misdirecting the audience is the secret of many magicians. "The Way Out Is Through" opens the 'Right' disc with an industrial riff that builds at 0:19 to click-track and rhythm, the equivalent of a weaving spiral. Whispering 'All I've undergone/I will keep on' at 1:24, Reznor is backed at 1:38 by synths and drums coalescing into guitars, which take shape at 1:46 and turn into a torrential electrical current. The models are clearly natural morphogenetic structures. The track twists through inner storms and torments from 2:42 to 2:48, mirrored by vocal shards at 2:59 and soundscapes at 3:45, before piano fades in and out at 4:12. The title references peri-natal theories of development (particularly those of Stanislav Grof), which is the source of much of the album's imagery. "Into the Void" is not the Black Sabbath song of the same name, but a catchy track that uses the same unfolding formula (opening static, cello at 0:18, guitars at 0:31, drums and backbeat at 1:02, trademark industrial vocals and synth at 1:02, verse at 1:23), and would not appear out of place in a Survival Research Laboratories exhibition. At 3:42 Reznor plays with the edge of synth soundscapes, merging vocals at 4:02 and ending the track nicely at 4:44 alone. "Where Is Everybody?" emulates earlier structures, but relies from 2:01 on whirring effects and organic rhythms, including a flurry of eight beat pulses between 2:40-2:46 and a 3:33 spiralling guitar solo. The 4:26 guitar solo is pure Adrian Belew, and is suddenly ended by spluttering static and white noise at 5:13. "The Mark Has Been Made" signals another downshift into introspectiveness with 0:32 ghostly synth shimmers, echoed by cello at 1:04 which is the doubled at 1:55 by guitar. At 2:08 industrial riffs suddenly build up, weaving between 3:28 distorted guitars and the return of the repressed original layer at 4:16. The surprise is a mystery 32 second soundscape at the end with Reznor crooning 'I'm getting closer, all the time' like a zombie devil Elvis. "Please" highlights spacious noise at 0:48, and signals a central album motif at 1:04 with the line 'Time starts slowing down/Sink until I drown'. The psychic mood of the album shifts with the discovery of Imagination as a liberating force against oppression. The synth sound again is remarkably organic for an industrial album. "Starfuckers Inc" is the now infamous sneering attack on rock-stardom, perhaps at Marilyn Manson (at 3:08 Reznor quotes Carly Simon's 'You're So Vain'). Jungle beats and pulsing synths open the track, which features the sound-sculpting talent of Pop Will Eat Itself member Clint Mansell. Beginning at 0:26, Reznor's vocals appear to have been sampled, looped and cut up (apologies to Brion Gysin and William S. Burroughs). The lines 'I have arrived and this time you should believe the hype/I listened to everyone now I know everyone was right' is a very savage and funny exposure of Manson's constant references to Friedrich Nietzsche's Herd-mentality: the Herd needs a bogey-man to whip it into submission, and Manson comes dangerous close to fulfilling this potential, thus becoming trapped by a 'Stacked Deck' paradox. The 4:08 lyric line 'Now I belong I'm one of the Chosen Ones/Now I belong I'm one of the Beautiful Ones' highlights the problem of being Elect and becoming intertwined with institutionalised group-think. The album version ditches the closing sample of Gene Simmons screaming "Thankyou and goodnight!" to an enraptured audience on the single from KISS Alive (1975), which was appropriately over-the-top (the alternate quiet version is worth hearing also). "The danger Marilyn Manson faces", notes Don Webb (current High Priest of the Temple of Set), "is that he may end up in twenty years time on the 'Tonight Show' safely singing our favourite songs like a Goth Frank Sinatra, and will have gradually lost his antinomian power. It's much harder to maintain the enigmatic aura of an Evil villain than it is to play the clown with society". Reznor's superior musicianship and sense of irony should keep him from falling into the same trap. "Complication" juggernauts in at 0:57 with screaming vocals and a barrage of white noise at 1:56. It's clear by now that Reznor has read his psychological operations (PSYOP) manuals pertaining to blasting the hell out of his audiences' psyche by any means necessary. Computer blip noise and black light flotation tank memories. Dislocating pauses and time-bends. The aural equivalent of Klein bottles. "Complication" juggernauts in at 0:57 with screaming vocals and a barrage of white noise at 1:56. It's clear by now that Reznor has read his psychological operations (PSYOP) manuals pertaining to blasting the hell out of his audiences' psyche by any means necessary. Computer blip noise and black light flotation tank memories. Dislocating pauses and time-bends. The aural equivalent of Klein bottles. "The Big Come Down" begins with a four-second synth/static intro that is smashed apart by a hard beat at 0:05 and kaleidoscope guitars at 0:16. Critics refer to the song's lyrics in an attempt to project a narcissistic Reznor personality, but don't comment on stylistic tweaks like the AM radio influenced backing vocals at 1:02 and 1:19, or the use of guitars as a percussion layer at 1:51. A further intriguing element is the return of the fly samples at 2:38, an effect heard on previous releases and a possible post-human sub-text. The alien mythos will eventually reign over the banal and empty human. At 3:07 the synths return with static, a further overlay adds more synths at 3:45 as the track spirals to its peak, before dissipating at 3:1 in a mesh of percussion and guitars. "Underneath It All" opens with a riff that signals we have reached the album's climatic turning point, with the recurring theme of fragmenting body-memories returning at 0:23 with the line 'All I can do/I can still feel you', and being echoed by pulsing static at 0:42 as electric percussion. A 'Messiah Complex' appears at 1:34 with the line 'Crucify/After all I've died/After all I've tried/You are still inside', or at least it appears to be that on the surface. This is the kind of line that typical rock critics will quote, but a careful re-reading suggests that Reznor is pointing to the painful nature of remanifesting. Our past shapes us more than we would like to admit particularly our first relationships. "Ripe (With Decay)" is the album's final statement, a complex weaving of passages over a repetitive mesh of guitars, pulsing echoes, back-beats, soundscapes, and a powerful Mike Garson piano solo (2:26). Earlier motifs including fly samples (3:00), mournful funeral violas (3:36) and slowing time effects (4:28) recur throughout the track. Having finally reached the psychotic core, Reznor is not content to let us rest, mixing funk bass riffs (4:46), vocal snatches (5:23) and oscillating guitars (5:39) that drag the listener forever onwards towards the edge of the abyss (5:58). The final sequence begins at 6:22, loses fidelity at 6:28, and ends abruptly at 6:35. At millennium's end there is a common-held perception that the world is in an irreversible state of decay, and that Culture is just a wafer-thin veneer over anarchy. Music like The Fragile suggests that we are still trying to assimilate into popular culture the 'war-on-Self' worldviews unleashed by the nineteenth-century 'Masters of Suspicion' (Charles Darwin, Sigmund Freud, Friedrich Nietzsche). This 'assimilation gap' is evident in industrial music, which in the late 1970s was struggling to capture the mood of the Industrial Revolution and Charles Dickens, so the genre is ripe for further exploration of the scarred psyche. What the self-appointed moral guardians of the Herd fail to appreciate is that as the imprint baseline rises (reflective of socio-political realities), the kind of imagery prevalent throughout The Fragile and in films like Strange Days (1995), The Matrix (1999) and eXistenZ (1999) is going to get even darker. The solution is not censorship or repression in the name of pleasing an all-saving surrogate god-figure. No, these things have to be faced and embraced somehow. Such a process can only occur if there is space within for the Sadeian aesthetic that Nine Inch Nails embodies, and not a denial of Dark Eros. "We need a second Renaissance", notes Don Webb, "a rejuvenation of Culture on a significant scale". In other words, a global culture-shift of quantum (aeon or epoch-changing) proportions. The tools required will probably not come just from the over-wordy criticism of Cyber-culture and Cultural Studies or the logical-negative feeding frenzy of most Music Journalism. They will come from a dynamic synthesis of disciplines striving toward a unity of knowledge -- what socio-biologist Edward O. Wilson has described as 'Consilience'. Liberating tools and ideas will be conveyed to a wider public audience unfamiliar with such principles through predominantly science fiction visual imagery and industrial/electronica music. The Fragile serves as an invaluable model for how such artefacts could transmit their dreams and propagate their messages. For the hyper-alert listener, it will be the first step on a new journey. But sadly for the majority, it will be just another hysterical industrial album promoted as selection of the month. References Bester, Alfred. The Stars My Destination. London: Millennium Books, 1999. Eshun, Kodwo. More Brilliant than the Sun: Adventures in Sonic Fiction. London: Quartet Books, 1998. Van der Kolk, Bessel A. "Trauma and Memory." Traumatic Stress: The Effects of Overwhelming Experience on Mind, Body, and Society. Eds. Bessel A. van der Kolk et al. New York: Guilford Press, 1996. Nine Inch Nails. Downward Spiral. Nothing/Interscope, 1994. ---. The Fragile. Nothing, 1999. ---. Pretty Hate Machine. TVT, 1989. Citation reference for this article MLA style: Alex Burns. "'This Machine Is Obsolete': A Listeners' Guide to Nine Inch Nails' The Fragile." M/C: A Journal of Media and Culture 2.8 (1999). [your date of access] <http://www.uq.edu.au/mc/9912/nine.php>. Chicago style: Alex Burns, "'This Machine Is Obsolete': A Listeners' Guide to Nine Inch Nails' The Fragile," M/C: A Journal of Media and Culture 2, no. 8 (1999), <http://www.uq.edu.au/mc/9912/nine.php> ([your date of access]). APA style: Alex Burns. (1999) 'This machine is obsolete': a listeners' guide to Nine Inch Nails' The fragile. M/C: A Journal of Media and Culture 2(8). <http://www.uq.edu.au/mc/9912/nine.php> ([your date of access]).