I did some of my training with Paul Bucy. He had a special interest in the surgical treatment of glioblastoma. Bucy believed, as did many “cancer surgeons” of his day, that tumors resulted from good cells becoming bad cells that formed a mass of tumor and that cells from the tumor’s periphery invaded the surrounding normal tissue. He correctly observed that malignant gliomas usually grew locally and rarely metastasized outside of the central nervous system. If there was any surgically curable “cancer”, he believed, it was a glioblastoma; all that was necessary for a cure was an aggressive enough resection with an adequate margin.Of course, his patients died right on schedule, just like anybody else’s patients. Bucy believed that this was because we just could not identify the true margin of the neoplasm at surgery and that the resection was rarely sufficiently adequate to provide a cure.The advent of computed tomography (CT scanning), magnetic resonance imaging (MRI) and image-guided neuronavigation would change all of this by potentially allowing us to accurately resect as much of a glioma as we chose to resect.Well, I have spent a career trying to cure gliomas with high technology-based surgery – in particular, imaging-based stereotactically guided volumetric resections – but the long-term survival in the vast majority of these patients is not much better than it was 60 years ago! We just do not hurt these patients as badly as we did 60 years ago. And what do we do? We keep throwing more and more expensive surgical high technology at the problem with marginal improvements in survival, if any.To be sure, there are some gliomas that we can cure with modern surgical techniques, such as pilocytic astrocytomas, the occasional oligodendroglioma, neurocytomas, gangliogliomas, subependymomas and a few xanthoastrocytomas and protoplasmic astrocytomas. But this is not a credit to neurosurgeons and our modern surgical methods. It is a function of the growth pattern of these particular tumors that lend themselves to complete and curative surgical excision. These tumors have a distinct boundary where tumor stops and normal brain begins. All that a surgeon has to do in these cases is identify the plane between tumor and surrounding brain tissue, develop that plane and remove the tumor. Image guidance helps a bit. But I will point out that Donald Matson claimed a 50% surgical cure rate in pilocytic astrocytomas over 50 years ago – without any “high technology”.Nonetheless, the “curable” tumors listed above are relatively rare compared to the overwhelmingly more common “fibrillary astrocytomas”, oligodendrogliomas and mixed gliomas. How are we doing with these tumors?Not so great!To be sure, there are many reports in the literature which show that patients having “total resection” and adjuvant therapy do better and live longer than those undergoing biopsy and adjuvant therapy. Comparisons to historical controls attempt to demonstrate the benefit of modern surgical techniques over methods used by past generations. An example of just such an exercise is shown in et al,[These life table survival curves compare my own experience with cases compiled in the years 1992 (published) and 2000et al, and RingAt first glance at Secondly, modern patients have had the benefit of more effective radiation therapy with linear accelerators instead of cobalt units and more specific chemotherapy. Indeed the improved 2-year survival noted in my 1992 and 2000 series more likely represents the efficacy of carboplatin in the 1980s and temazolamide in the 1990s and not necessarily “better surgery”.In low-grade gliomas, image-guided stereotactic surgical techniques allow us to resect any prospectively designated volume of tissue. Unlike surgery in high-grade gliomas, where we resect a volume of solid tumor tissue and necrosis that has replaced or displaced intact parenchyma and can be resected from just about anywhere in the CNS, resections of low-grade gliomas are restricted by anatomical location. Non-pilocytic astrocytomas, mixed gliomas and most low-grade oligodendrogliomas usually comprise a volume of sick brain tissue infiltrated by isolated tumor cells. Resecting the imaging defined tumor volume is, in fact, resecting intact and functional, albeit “diseased”, brain tissue. Figures de-jour is administered during the remaining course of their life as their tumors progress from low-grade gliomas to the high-grade tumors that eventually kill them. However, I have never submitted this material for publication for the following two reasons.This unpublished series suggests that patients undergoing resection clearly survive longer than those who had only biopsies plus whatever radiation or chemotherapy Experienced surgeons usually know which cases will do well with aggressive surgery and which will not. So, relatively compact tumors – especially those in non-eloquent brain areas – will be selected for resection, and diffuse infiltrating tumors in eloquent brain areas will undergo stereotactic biopsy only.So, studies like this basically compare survival in good surgical candidates to survival in poor surgical candidates rather than comparing the efficacy of aggressive resective surgery to less aggressive surgery. In fact, we may be comparing the natural history of two populations of gliomas, which may have the same histologic cell type but possibly different biologies.In order to prove the benefit of aggressive resection on survival in gliomas (both high and low grade) we would have to select the “good” surgical candidates and prospectively randomize these into “resection” and “biopsy” groups. However, considering that low-grade gliomas are relatively “rare” and their survival relatively long , a study of this nature would take many years to accrue enough cases with sufficient enough follow-up to justify any conclusions, and would probably require a multicenter effort and a time commitment that would be longer than most academic careers.And so these men of IndostanDisputed loud and long,Each in his own opinionExceeding stiff and strong,Though each was partly in the right,And all were in the wrong!From The Blind Men and the Elephant; John Godfrey Saxe; 1873oligodroastrocytoma or astro-oligodendroglioma). Most, however, do not. Serial stereotactic biopsy studies frequently show geographic phenotypic heterogeneity in the predominant cell type within individual tumors. In addition, review of surgical specimens by different neuropathologists usually results in different histologic diagnoses on the same surgical specimen! Some focus on the number of cells that stain positive with Glial fibrillary acidic protein (GFAP) and ignore other cells; others note the many oligodendroglial cells and feel that the many astrocytes are astrogliotic and most discount a neuronal component. I have had low-grade glioma surgical specimens reviewed by as many as eight different well-respected neuropathologists and received as many as eight different histologic diagnoses as regards cell type and grade. Diagnostic interobserver variability between neuropathologists in establishing predominant cell type and grade in gliomas in general and low-grade gliomas, in particular, is a well-recognized problem. This makes a mockery of cell type stratification in low-grade glioma follow-up studies.Many neurosurgeons and neuroncologists would like to believe that low-grade gliomas fall into clear-cut histologically homogeneous groups: astrocytomas, oligodendrogliomas and mixed gliomas , synaptophysin positive cells (primitive neurons), cells that stain with neither GFAP nor synaptophysin and are probably oligodendrocytes and perhaps even cells that stain with CD133 that is supposed to identify stem cells. Furthermore, microscopic examination of specimens obtained from the periphery of glial tumors at stereotactic serial biopsy procedures show isolated cells in the extracellular spaces within otherwise normal parenchyma. Time-lapse photography of cell cultures containing tissue from these biopsy specimens demonstrates amoeboid-like cells. They move by pseudopod propulsion – like stem cells which are also motile and also move by pseudopod propulsion .In normal organogenesis, cytokines bind to notch receptors that cause the stem cell to become a lineage specific progenitor which then progresses to the more specialized cells of the CNS: neurons, oligodendrocytes and astrocytes. In the developing nervous system, neurons need astrocytes, oligodendrocytes and a blood supply from endothelial cells that form capillaries. They signal this need to stem cells by growth factors (cytokines) that bind in the notch receptors of their cellular membrane which begins the intercellular cascade that transforms stem cells into the specialized cells required.All of this is fine in the developing nervous system, but what happens after the brain has developed?There are stem cells left over; what happens to them? Others retire to stem cell clusters of 50–100 cells that self-renew and die. Some are probably called up for brain repair in the case of injury or to simply maintain failing cells in the mature brain. Specific growth factors may provide a “call to action”. Or perhaps, these stem cells leave the cluster on their own and wander through the extracellular spaces of the white matter and neuropil. Somewhere, some stop wandering, start reproducing and form neural, oligodendroglia and astrocytic progenitors that also reproduce and this is the genesis of a glioma that contains astrocytic, oligodendroglial and neuronal phenotype – a “mixed glioma”.All cells have a cell cycle. New cells are born (mitosis) and others die (apoptosis). Undoubtedly, many nascent “tumors” reach a “steady state” where the mitotic rate equals the apoptotic rate and the tumor never grows, never becomes symptomatic and simply exists as a heterogeneous collection of cells co-existing with normal cells in the extracellular fluid of the interstitial spaces. However, occasionally, the mitotic rate exceeds the apoptotic rate and the early tumor begins to add cells. As their numbers increase, their metabolic by-products increase the local osmotic gradient of the extracellular fluid. This results in the ingress of fluid from the intravascular space, and if the spatial volume of this process is large enough, an MRI may now detect a small region of T2 prolongation.The mitotic and apototic rates differ in the neuronal, astrocytic and oligodendroglial populations of these young gliomas. The cellular clone with the highest mitotic and lowest apoptotic rates will eventually become the dominant cell type. Thus, mixed gliomas containing primitive neurons, astrocytes and oligodendrocytes will eventually become whatever phenotype has the highest mitotic and lowest apoptotic rate as those phenotypic cells can eventually overwhelm and replace the other two cell types in the neoplasm.The vast majority of gliomas may start out as mixed gliomas having neuronal, astrocytic and oligodendroglial components, but with sufficient time, cellular clones with the highest mitotic rate become the dominant phenotypic cell type from which offspring with even higher mitotic rates evolve.Low-grade mixed gliomas become high-grade gliomas with a predominant cell type that ultimately kills the patient. The transition from low-grade mixed glioma to malignant glioma of a single cell type, e.g. glioblastoma, malignant oligodendroglioma or very rarely a malignant neurocytoma can occur in weeks, months or many years. Also, it is possible that some early gliomas reach a steady state in which a low mitotic rate is matched by a similar apoptotic rate and the lesion never progresses or possibly even regresses over time.In the USA, about 19,500 new gliomas are diagnosed each year. Considering that the US population in 2008 was 306 million people, this works out to a glioma incidence rate of 0.00064. That is, 0.0064% or 6.4 cases per 100,000 population. There are some data showing that the incidence of gliomas in the US has increased slightly in the recent years, probably because we are finding more of them due to increased awareness and the easy availability of diagnostic imaging. However, this is just the tip of the iceberg; the actual number of gliomas in the USA is probably 40–50 times greater than the reported incidence.Journal of the American Medical Association (JAMA), found three gliomas in those 1000 individuals.[Over the years, there have been about 16 reported studies focusing on the incidence of CNS disease detected by CT and MRI within the “normal” asymptomatic population.[ividuals.Extrapolating to the entire population of the USA, three in a thousand works out to over 900 thousand Americans harboring asymptomatic gliomas! Only a small number of these will become symptomatic, diagnosed and recorded in any given year. We know that number, which is about 19,500. We do not know how many of these will become symptomatic, diagnosed and treated in a lifetime.Also, there is the possibility that many more people may harbor microscopic gliomas that have not yet sufficiently influenced the parenchymal interstitial microenvironment to be detectable by MRI.Nonetheless, those 900 thousand or so individuals may represent a “population at risk” for developing a symptomatic, and most likely incurable, glioma in their lifetime even though only a small percentage becomes symptomatic in any given year.By the time a glioma becomes symptomatic, it is almost always too late in its biological course. Motile isolated tumor/stem cells would have migrated far beyond the imaging-defined tumor mass. These will ultimately start another tumor nidus in the margin of the resection, at some distance from the margin or, indeed, even in the opposite hemisphere. Also, this is purely a function of time, with or without the benefit of surgery.Radiation therapy and chemotherapy may have some effect on some of these cells but there will always be individual cells or even a small population of cells that will not be affected by these modalities – just like the normal cells of the brain that, we hope, are not affected by treatment.The real culprits are not necessarily the “cancer” cells. The real culprits are the cells that are mostly like “normal” cells – the stem cells. By the time a glioma is diagnosed – by the time it becomes symptomatic and an imaging study is performed – the vast majority are incurable.nd floor who calls out: “How are you doing?”Some neurosurgeons might recall a case or two which presented with an MRI showing a significant glioblastoma but also happened to have had an earlier MRI done for some other reason, a headache or minor trauma, etc., and the earlier MRI being perfectly normal. I have had a few cases like this also. I submit that in these cases the transition from low-grade mixed glioma to, say, malignant astrocytoma occurred much more rapidly than most – over a few weeks or months, perhaps. I believe that such cases are relatively rare. In fact, I have seen many more cases where physicians have watched a T2 abnormality on MRI getting larger and larger over several years but feel that they must wait for symptoms before recommending surgery. This reminds me of my friend Thor Sundt’s joke about the man jumping off the top of the Empire State Building, passing someone on the 42The Jumper calls back: “I’m doing fine so far!”Many studies have shown that current therapies  expand survival in gliomas beyond the natural history of the disease. However, in the vast majority of cases, gliomas are ultimately incurable. Most low-grade gliomas kill patients by becoming high-grade gliomas. Even low-grade gliomas are incurable because by the time they are diagnosed, the disease process has extended far beyond the limits of surgical resectability. Also, no treatment that I know of will prevent a low-grade glioma from ultimately becoming a high-grade glioma – except, perhaps, surgical total excision of a small low-grade lesion.In my opinion, gliomas are incurable because we are finding them far too late in their clinical course. It is like finding breast cancer after it has spread to the regional nodes, lung, liver, skeletal system or brain, prostate cancer after it has spread to the pelvis and spine, colon cancer after it has metastasized to the liver, skin melanoma after it has spread to lymph nodes and beyond, etc. However, there are screening programs for the early detection of all of these “cancers”: self-examination and mammography for breast cancer, PSA blood tests for prostate cancer, colonoscopy for colon cancer, dermatological examinations for skin cancer, etc. Why not screen for brain tumors?Unlike these other “cancers”, brain tumors grow by local invasion. Brain tumors rarely metastasize outside of the central nervous system. If the concept of early detection has any merit at all, it should be in the early detection of gliomas: find them when they are small, find them before they turn malignant and find them when they may still be curable by some minimally invasive surgical method or even by stereotactic radiation methods such as brachytherapy or radiosurgery.In addition, it is much easier and safer to operate on a small lesion, be it a glioma, meningioma, acoustic neurinoma or whatever, than a big one!In the 1950s, clinics and mobile X-ray units offered free or low-cost screening chest X-rays for the early detection of tuberculosis. This was probably one of the most effective public screening programs ever. Early detection of pre-clinical disease and isoniazid wiped out tuberculosis in the USA in a few years. What screening tools are available for gliomas?Perhaps, a blood test and genetic screening for brain tumors may be possible some day. However, since 1973, we have had an excellent tool for brain tumor screening, i.e. MRI. And what do we use it for? We use it to make a diagnosis in symptomatic patients who, by the time they are diagnosed, have essentially an incurable disease! Why not use MRI to screen for brain tumors in an early detection program? We screen for other tumors; why not brain tumors?Radiologists who are used to mammograms and chest X-rays usually raise the issue of “false positives.” But unlike X-ray based procedures, MRI provides various imaging sequences to non-invasively investigate abnormalities. In particular, MR spectoscopy (MRS) is very useful in the determining whether a unidentified bright object (UBO) is a glioma instead of a demyelinating plaque, microinfarction or some other non-neoplastic process. However, what do we do when an abnormality suspicious for a glioma is found?As we have seen above, the clinical incidence of gliomas is orders of magnitude lower than the assumed prevalence in an asymptomatic population. It is possible that many incidentally found gliomas will never grow. Indeed, some smaller lesions may even regress. Most may never require treatment in the near future. Some may never need treatment.Those with an MRI defined abnormality, in whom MRS suggested glioma, would represent a “population at risk”. These would require follow-up imaging. Treatment would be recommended for those having lesions larger than, say, 2 cm in diameter or those in whom documented growth or change in a small lesion is noted on follow-up imaging or the lesion becomes symptomatic.Many point out that screening is not “cost effective”. I agree. It is certainly less expensive to treat a small number of afflicted people with ineffective and expensive therapies than it is to screen a large healthy population. But this argument could be made for screening, in general. Nonetheless, a screening MRI for the detection of early gliomas only requires two or three imaging sequences . Contrast enhancement would not be necessary – it would be a very rare tumor that would exhibit contrast enhancement and not show an abnormality on T2 or Flair images. The cost of a diagnostic MRI with multiple sequences and contrast enhancement in New York City, at least, is about $1000 and the entire examination takes about 45–60 minutes. A screening MRI would require about 3–5 minutes scanning time, and as a proportion of the cost of a diagnostic examination, should cost only $60–80 which would compare favorably to the cost of a colonoscopy (average: $2000–3734), total PSA blood test (between $70 and 400), mammography ($140–320), skin screening (about $150 plus), etc. Of course, someone would have to read the MRIs but computer-assisted diagnosis (CAD) systems should reduce the tedium and costs.Over the past 30 years, we have seen real progress in the development of sophisticated surgical technology. Computer-based medical imaging combined with stereotactic navigation techniques for minimally invasive surgical or non-invasive radiosurgical methods, intraoperative imaging, mapping procedures, etc., all of these combine to make tumor neurosurgery less invasive, more effective and safer. However, in the resection of gliomas, we are fighting a war that would be easier and more likely to win if we begin before the enemy becomes extensive and well entrenched in the “civilian population”. We need a screening program for the early detection of gliomas.http://www.roadtoearlydetection.org). A General Electric 1.5 Tesla MRI unit, housed in a truck, makes the rounds of the five boroughs of New York City offering free screening head MRI scans to anybody who wants one [see About two years ago, the Manhattan based Brain Tumor Foundation began such a program in New York City ( one see . The res


Catastrophic and sudden collapses of ecosystems are sometimes preceded by early warning signals that potentially could be used to predict and prevent a forthcoming catastrophe. Universality of these early warning signals has been proposed, but no formal proof has been provided. Here, we show that in relatively simple ecological models the most commonly used early warning signals for a catastrophic collapse can be silent. We underpin the mathematical reason for this phenomenon, which involves the direction of the eigenvectors of the system. Our results demonstrate that claims on the universality of early warning signals are not correct, and that catastrophic collapses can occur without prior warning. In order to correctly predict a collapse and determine whether early warning signals precede the collapse, detailed knowledge of the mathematical structure of the approaching bifurcation is necessary. Unfortunately, such knowledge is often only obtained after the collapse has already occurred. As catastrophic shifts can cause substantial loss of biodiversity and ecosystem functioning, reliably predicting such catastrophes would be of crucial importance. Recently, it has been proposed that there exist generic early warning signs, based on a phenomenon that is coined “critical slowing down” near the bifurcation Catastrophic regime shifts can occur in many ecosystems, and often such shifts cause substantial loss of biodiversity and ecosystem functioning J), adult (A), and predator density (P): In this paper, we investigate a simple ecological model for the interaction between a predator and a stage-structured prey species. The model distinguishes between juvenile and adult prey individuals, and the predator only attacks adult prey. The model, in its most general form, consists of three ordinary differential equations for, respectively, juvenile (f(A) is a function that specifies the reproduction rate of adults, g(J) specifies the maturation rate of juveniles, and h is the predation rate on adults. Parameters Jµ, Aµ and Pµ are death rates, and c is a conversion factor. We use a realization of this model with f(A) = bA, g(J)  = 2)J/  = AP. For a description of the ecological setting of the model we refer to an earlier paper by van Kooten et al.b represents adult reproduction rate. Environmental noise is added to this model by randomly varying death rates every time unit, applying random (white), or correlated (pink) noise. This method of adding noise to the per capita death rates is giving similar results to directly perturbing population numbers after every time unit. For numerical integration we used the Cash-Karp Runge-Kutta method Here, Pµ≈0.553 (corresponding to point 1T in In Pµ = 0.5528). In Apparently, the early warning signals are not generic at all, as a fold catastrophe can occur without prior warning. So, what is flawed in the argument that “critical slowing down” is a generic property of all fold bifurcations? In fact, the statement is completely correct, but the slowing down only occurs in the direction of the dominant eigenvector. In our system, this eigenvector, near the bifurcation, almost exclusively points in the direction of the axis corresponding to the juvenile population. 2T in P≈0.038. In We extensively tested robustness of the silent collapse phenomenon, e.g. by varying the type of noise. In We have shown three examples where catastrophic collapse can occur without prior early warning signals in autocorrelation or variance. Although critical slowing down is a universal property of fold bifurcations, this does not mean that the increased sensitivity will necessarily manifest itself in the system variables. Instead, whether the population numbers will display early warning will depend on the direction of the dominant eigenvector of the system, that is, the direction in which the system is destabilizing. This theoretical point also applies to other proposed early warning signals, such as skewness We want to stress that we have used ecological models that have been proposed before We have focused on catastrophic regime shifts that are caused by an underlying fold bifurcation, as this cause of bistability has received most attention in the ecological literature. However, catastrophic shifts can also be induced by other underlying mathematical structures, such as a subcritical Hopf bifurcation or a bifurcation to a chaotic attractor. For this latter possibility it has recently been demonstrated that also in this case early warning signals can be absent Movie S1Animated rotation of . White noise is added to the juvenile prey death rate, which induces excursions of the system state in the direction of the dominant eigenvector (indicated by the red arrow). As a result, the system only responds along this eigenvector (trajectory in blue), leading to an early warning signal that only appears in the juvenile population.(MOV)Click here for additional data file.Movie S2Animated rotation of . White noise is added to the adult prey death rate, which induces excursions of the system state in the direction of the surface (indicated in grey) corresponding to the second and third eigenvector (black arrows). As a result, the system responds with damped oscillations (trajectory in blue), leading to a total absence of early warning signals.(MOV)Click here for additional data file.


This paper details the study on the changes in riding behaviour, such as changes in speed as well as the brake force and throttle force applied, when motorcyclists ride over a curve section road using an instrumented motorcycle. In this study, an instrumented motorcycle equipped with various types of sensors, on-board cameras, and data loggers, was developed in order to collect the riding data on the study site. Results from the statistical analysis showed that riding characteristics, such as changes in speed, brake force, and throttle force applied, are influenced by the distance from the curve entry, riding experience, and travel mileage of the riders. A structural equation modeling was used to study the impact of these variables on the change of riding behaviour in curve entry section. Four regression equations are formed to study the relationship between four dependent variables, which are speed, throttle force, front brake force, and rear brake force applied with the independent variables. It is well recognized that road safety is a public health problem as road traffic accidents are among the eight leading causes of death worldwide, according to Loo et al. . MalaysiMotorcycle crashes continue to be a problem in both developing and developed countries. According to Radin Umar et al. , a preliMixed traffic that contains motorized and nonmotorized vehicles becomes more common in urban area. Mixed traffic flow contains standard vehicle types such as passenger cars, buses, and trucks and also nonstandard vehicles such as motorcycles and bicycles. Cho and Wu  have donIn a more detailed study on Malaysia motorcycle accident data  and on curve entry point on the virtual route map for analysis purposes. The traffic data were collected starting at the 100 m point before the curve entry till the curve entry point. The reason for taking 100 m before the curve entry as a starting point is because this is an appropriate distance to cover for riders travelling at a free speed and a good distance to observe when a curve section starts to take an impact on reducing riders' speed and influencing riding behaviour in response to the entering of the curve section.Each experimental riding session was conducted according to the following protocol: on arrival at the starting point, the subjects were briefed on the route map. Subjects were instructed to ride on a motorway route within the campus of University of Malaya, Malaysia. The subjects were asked to ride with their usual and natural riding behaviour. All the riding sessions were performed in the morning period, when the weather was clear and the roadway was in dry condition. Upon completion of the journey, the subjects were asked to complete a simple questionnaire. Subjective measures, such as age, riding experience, and others, were taken from the simple questionnaire for record and analysis purposes. The traffic data collected in the experimental run was recorded and stored in a compact flash memory card. The data was then further analysed using system manufacturer analysis software. From the analysis software, data such as travel speed, throttles applied, brakes applied, and GPS positions of the motorcycle were extracted.refer to , where rZ = −11.566, N = 641. A two-tailed analysis was carried out and found P < 0.001, which is significant at P < 0.05. In short, one can conclude that the rear brake and front brake force applied are significantly different. Besides, both braking lines show similar trends as the braking values were constant at the beginning 50 m and experience a similar rate of change when they ride approaching the curve entry point. This indicated that the closer the riders approached the curve, the higher the brake force applied as riders tended to reach a comfortable speed when they enter the curve section. Two regression equations were formed to study the change in brake intensity with the distances from curve entry for both braking systems and were shown as follows:In the brake behaviour study, there are two braking data collected through the instrumented motorcycle, which are rear brake intensity value and front brake intensity value. Generally, as shown in A model was developed on the basis of structural equation modeling (SEM). Structural equation modeling is a multivariate technique that can be described as a combination of both factor analysis and path analysis. It is a statistical technique that allows the analyst to examine a series of dependence relationships between exogenous variables and endogenous variables simultaneously. An exogenous variable is one whose variability is assumed to be determined by causes outside the causal model under consideration. An endogenous variable, on the other hand, is one whose variation is to be explained by exogenous and other endogenous variables in the causal model.Model testing via path analysis can be carried out with the conventional multiple regression technique. That is, path coefficients can be estimated by regressing the endogenous variable (the dependent variable) onto the exogenous variables (the predictor variables) and then repeating the procedure by treating the exogenous variables as endogenous variables. Such a method, however, is typically piecemeal in nature and does not provide information regarding the hypothesized model's goodness-of-fit. Without information about the model's goodness-of-fit, it is difficult to assess the adequacy of the theory underlying the hypothesized model. SEM, on the other hand, is able to estimate the multiple and interrelated dependence relationships simultaneously. Because it tests the model as a whole, rather than in a piecemeal fashion, statistics can be calculated to show the goodness-of-fit of the data to the hypothesized model. Besides, conventional multiple regression technique assumes that the variables in the analysis are error-free while SEM improves statistical estimation by accounting for measurement error in the estimation process. In short, SEM analysis removed the potential biasing effects of the measurement error on the results and thus improved the statistical estimation process. The process of development of SEM path model for the study is shown in χ2 = 399.157, P < 0.05. Although the hypothesized model did not fit the observed variance-covariance matrix well by the chi-square test, the baseline comparisons fit indices of NFI, IFI, and CFI are all above 0.9 (range: 0.921-0.922). These indices compare the fit of the hypothesized model to the null or independence model. Given the range of the computed baseline comparisons fit indices, the remaining possible improvement in fit for the hypothesized model (range: 0.078 to 0.079) appears so small as to be of little practical significance. In short, the model is sufficiently fit for the data. Since the original path model consists of four regression models, it is easier to study if we discuss and explain the model separately.The input covariance matrix generated from the model's eight observed variables contains 44 sample moments. For the hypothesized model , there aP < 0.001). The standardized correlation coefficient is found at 0.972, as shown in The covariance between “age” and “riding experience” is found highly significant by C.R. test (β) are independent of the units in which all variables are measured. These standardized coefficients allow us to compare directly the relative relationship between each independent variable and the dependent variable. In the speed regression model, it was found that the standardized regression weights are all significant by the critical ratio test  . From β = 0.315; β = 0.392, resp.) while “age” is found negatively correlated to “speed.” Thus, it can be concluded that the speed reduced when they rode approaching the curve entry. Besides, it was found that the greater the riding experience is and the younger a rider is, the higher the riding speed is. In the throttle regression model, the standardized regression weights are all significant by the critical ratio test . Based on this criterion, the variables “distance before curve,” “speed,” “age,” “riding experience,” and “travel mileage” are highly significant predictors of throttle. The ratings on two variables of “distance before curve” and “age” are both significantly and positively correlated to “throttle”  while “speed,” “riding experience,” and “travel mileage” are found negatively related to “throttle” . In conclusion, the smaller the distance from the curve entry and rider's age, the lower the throttle force applied. In contrast, the greater the speed, riding experience, and travel mileage are, the smaller the throttle force applied by the riders will be.Standardized coefficient estimates (.05) see , except P < 0.05) that range from −0.567 to 0.269. These values indicate that the rear brake is significantly represented by “distance before curve,” “speed,” “age,” “riding experience,” and “travel mileage.” From β = −0.567; β = −0.502, resp.) while other variables are found positively correlated to rear brake. From this model, it was found that more rear brake force was applied when riding approaching curve and during higher riding speed. Meanwhile in the front brake regression model, the standardized regression weights are all significant by the critical ratio test , except for variables “age” and “travel mileage” and range from −0.586 to 0.093. These values indicate that the front brake is significantly represented by “distance before curve,” “speed,” and “riding experience.” As observed from β = −0.586; β = −0.217, resp.) while “speed” is positively correlated to front brake. In conclusion, more front brake force was applied in higher riding speed and at a distance closer to the curve entry point. The standardized regression equations for these models were shown as follows:In the rear brake regression model, the standardized regression weights are all significant by the critical ratio test  analysis is used to develop a model which suits the collected data in our case study. It is justified that “age” and “riding experience” are two correlated factors with the coefficient of correlation as 0.972. Multiple regression equation is formed for each of the regression models. Generally, it was found that distance from curve entry was the most significant and dominant factor that causes the change of throttle and brake force applied, which recorded high impact values, ranging from absolute value of 0.567 to 0.641. Other exogenous variables are found to have various rates of impact towards endogenous variables in each model set.In the riding study presented in this paper, it was found that the speed reduced in a different rate as riders ride approaching the curve section. The speed reduction rate can be expressed in a linear equation of With the help of the instrumented motorcycle, the findings from this study should provide us with a brief idea on how riders would react and respond to the riding towards the curve section. The instrumented motorcycle is a very powerful tool as it provided a robust, accurate, and reliable way of collecting such important motorcycle riding data in this study of motorcyclist riding behaviour. By conducting such motorcycle accident and riders' behaviour studies, traffic engineers, law enforcers, and policy makers may take effective actions to reduce the number of accidents and therefore save valuable human life.


N = 18). Nineteen categories of classroom misbehaviors were identified, with talking out of turn, disrespecting teacher, and doing something in private being most frequently mentioned. Findings revealed that students tended to perceive misbehaviors as those actions inappropriate in the classroom settings and even disrupting teachers' teaching and other students' learning. Among various misbehaviors, talking out of turn and disrespecting teacher were seen as the most disruptive and unacceptable. These misbehaviors were unacceptable because they disturbed teaching and learning, and violated the values of respect, conformity, and obedience in the teacher-student relationship within the classroom. The frequency and intensity of misbehaviors would escalate if students found it fun, no punishment for such misbehaviors, or teachers were not authoritative enough in controlling the situations. Implications for further research and classroom management are discussed.Using individual interviews, this study investigated perceptions of classroom misbehaviors among secondary school students in Hong Kong ( There are numerous studies examining the definitions and range of student misbehaviors. For example, in the United Kingdom and Australia, researchers defined classroom misbehaviors as behaviors which are disruptive to classroom order and cause trouble to teachers, such as making nonverbal noise, disobedience, talking out of turn, idleness/slowness, nonpunctuality, hindering others, physical aggression, untidiness, out of seat, and verbal abuse –3. In thWhile classroom misbehavior is generally interpreted as disruptive and improper behavior that adversely affects the order, teaching, and learning in classroom, it is noteworthy that the range of student misbehavior varies across cultures , 7. PartAgainst the above background, a recent study was conducted in Hong Kong Chinese schools by Sun and Shek , which sOne serious limitation of the research on student misbehavior is that most of the existing studies on school misbehavior were primarily based on teachers' perceptions and ratings, The overarching goal of this study was to examine classroom misbehavior from the perspective of students in junior secondary school settings in Hong Kong. In this study, classroom misbehavior was regarded as a kind of problem behavior –22. It iA qualitative research method was adopted in this study. This method can enrich our understanding of the problem area because most of the studies in this area are quantitative in nature. By listening to the voices of the students, it is expected that the findings can help generate findings that cannot be adequately captured by those based on the teachers. A general qualitative study orientation  was adopted, with the following elements intrinsic to the study. First, voices of the students instead of the “experts” or “adults” were heard. Second, narratives of the students were focused upon. Third, individual interviews were conducted in nonartificial setting. As it is an exploratory study, a general qualitative orientation close to a postpositivistic tradition  was sufficient for this purpose.The informants were 18 junior secondary school students from three schools, with each school admitting students having low, medium, or high academic competencies. In each school, six students  were randomly selected by their teachers and they were invited to join an individual interview on a voluntary basis. The informants comprised nine boys and nine girls, with a mean age of 13.9 years old (range = 12–17 years old). Although there is no “sacred number” in qualitative research, an engagement of 18 participants could be regarded as on the high side. Also, recruitment of students from schools with different academic abilities and gender could ensure that a wide range of experiences would be examined. Written consent from the school principals and the informants, as well as passive parental consent from the student informants, were obtained prior to data collection. At the beginning of each interview, anonymity and confidentiality of the study were clearly explained to the informants. Before conducting this research, ethical approval was obtained from the Human Research Ethics Committee, The University of Hong Kong.A self-constructed semi-structured interview guide was used for each individual interview. In the interview guide, questions and prompts were used to explore the informants' perceptions of students' problem behaviors and teachers' management strategies in the classroom and school contexts. The informants were asked to define “problem behaviors” based on their own understanding and interpretation. They were invited to use real-life examples to further illustrate their views. The average time for an interview was 48 minutes (range = 33–71 minutes). Each interview was conducted by two trained interviewers in Cantonese (the mother tongue of both the interviewers and interviewees). The interviews were audio-taped with informants' prior consent and transcribed in verbatim after the interviews. As many open-ended questions were covered in the interview guide, only data related to the following questions were analyzed in this paper. Interested readers can write to the first author to obtain the full list of interview questions. In the classroom, what student problem behaviors are there? Please list out as many as possible and describe them. Among these problem behaviors, which one(s) is/are the most common? Among these problem behaviors, which one(s) is/are the most disruptive to teaching and learning? Among these problem behaviors, which one(s) is/are the most unacceptable? Please illustrate.The data were analyzed by general qualitative analyses techniques , in whicThe researchers were aware of their possible biases in their conceptions of student misbehavior because they had worked in the education field for some time. Therefore, checking procedures were carried out to look at the consistency in the coding process without the involvement of the authors. Both intra- and interrater reliability on the coding were calculated to ensure the credibility of the findings. Intrarater reliability tests were conducted by the two coders independently, whereas interrater reliability tests were conducted by two colleagues  independently. In each reliability test, 20 raw responses were randomly selected for each rater to code without referring to the original codes. Results of the reliability analyses were on the high side: intrarater agreement percentages were both 100% for both coders; interrater agreement percentages were 80% and 90% for each coder when they coded the analyses of the counterpart. To enhance the quality of the research, audit trails were developed and data analyses processes were systematically documented.“do not put up their hands before answering questions” and “shout the answer out” (Student A05). This kind of calling out, as well as asking nonsense questions without teacher permission, were regarded as disturbing. As mentioned by Student B08:The informants perceived that students usually talked out of turn, such as “No one likes to hear people speaking too loudly. It will affect the learning environment. The class is often distracted by this kind of noise. Also the noise will largely affect each student psychologically. I mean student may be annoyed by the noise. They will become more agitated, easy to lose their temper and becomes inattentive in class. It is fine if you make noise but you should not disturb others”.They also revealed that “conversation among students” was the most common and annoying. Student B10 described:“When the teacher is teaching, students at the back talk to each other… Sometimes they are not too excessive, but sometimes they speak too loudly that we can hardly hear what the teacher is saying… There are not just two (students) but sometimes a cluster… just like to kick up a fuss, because sometimes you won't sit next to your friend. Your friend may sit far away from you at the diagonal corner. You have to speak out loudly in order to let your friend hear you. Then, other students will hear you and all of them will laugh together. This is like ripple effect”.“Talking out of turn”, especially chatting among students, was perceived as most disruptive to teachers' teaching and students' learning. Student C10 explained:“Chatting will disturb teaching. If they chat very loudly or do not listen to the teacher, they and other students will miss some new knowledge. Also the teacher may think that you do not have motivation to learn which may make him/her unhappy”.: It was perceived as unacceptable when the misbehavior becomes so noisy and uncontrollable that it adversely affects other students' learning. Student A10 revealed“It is acceptable if you chat in a low voice. But the point is you chat louder and louder despite being asked to stop. This is the most distracting behavior which makes others unable to concentrate in class”.Behaviors that were disrespectful to teachers, such as disobedience, refusing to follow instructions, rudeness, talking back, arguing with teacher, offending, or attacking teachers, were reported as an obvious problem behavior in the classroom. Student B08 described how students used some subtle ways to offend their teachers:“The students do not respect their teacher. Sometimes they do not treat their teacher as a person. Generally speaking, they do not care about him/her. They may pretend to be good, but in fact, they behave differently at the back of their teacher”.On the other hand, some students would attack teachers directly. Student A06 recalled:“Such as our class teacher, when teaching, some boys offended him/her for no reason. It is because the teacher does not know how to scold the students. That's why those boys like to assault him/her”.“if the teacher scolds us, we will argue back, and then the teacher will scold us even much more. It uses up all the time”. Student B08 also considered it as an unacceptable behavior: “I think politeness of a student is very important. Sometimes if the teacher asks you to do something, you need to show your politeness in addition to respect… A person's virtue is more important than his/her knowledge”.Arguing with teachers could disrupt teaching and learning because it was time consuming. Student C07 commented that “some students use mobile phone to text when the teacher is not looking at them… Actually, I think using mobile phone or pushing classmates are not problematic. It will not affect the learning atmosphere… playing mobile phone only affects the individual…a person's learning attitude… and usually the teacher do not see them so that it affects nothing”.Students liked to do something unrelated to classroom learning, such as doing homework of other subjects, dealing with personal stuff, having irrelevant drawing, or using mobile phone. However, not all informants would regard “doing something in private” as a kind of problem behavior. For example, Student C09 explained: The informants also pointed out that “out of seat” (including changing seats and wandering around the classroom) and “sleeping” were other problem behaviors in the classroom. Moreover, these problem behaviors would become more serious and spread over if without proper teacher control. Some students also considered that both of these behaviors would affect classroom teaching and learning. As two students described:“The teacher sometimes is not aware of students who are out of seat, and also he/she may be dealing with the students who are making noise…so he/she is not able to handle those who leave their seats”.  (Student A06)“When the students, who are very tired but try to endure the sleepiness, find their classmate is sleeping, they will begin to lay on the table, sleep or do other things because they realize that the sleeping student will not be punished, that means they are allowed to do so”.    (Student A09)“I feel hurt when I saw my classmate was struck by others… We are classmates, we are friends… I don't dare to stop them because I'm afraid that they will strike me too”.“Verbal aggression”  and “physical aggression”  were reported as problem behaviors. Student might feel bad and even threatening when there was hostility. As Student C09 expressed, As shown in The present study attempted to examine classroom misbehaviors perceived by junior secondary school students in Hong Kong. A total of 19 problem behaviors were mentioned by the students, including talking out of turn, disrespecting teachers, doing something in private, verbal aggression, out of seat, sleeping, playing, clowning/making fun,  failure in submitting assignments, nonattentiveness/looking out of window, nonverbal communication, physical aggression, isolating classmates, making noise, copying homework, forget to bring textbook and other learning materials to class, disturbing other classmates, invasion of privacy, and intimate physical contact see . The preIn conjunction with the previous study conducted by the authors , the preThere are two explanations for the discrepancies in the conceptions of misbehavior between teachers and students. First, some misbehaviors may be more easily identified among students than by teachers such as those misbehaviors performed at the back of the teacher inside the classroom. It was mentioned by the students that teachers were not aware of some misbehaviors when they were concentrated in teaching or dealing with other problem behaviors in the classroom. Second, the discrepancies might be due to different levels of tolerance between the students and teachers. For example, some students did not perceive some off-task behaviors as problematic as they considered that these behaviors would not cause disturbances to others. Moreover, students and teachers might view the same thing through different lens. For example, students who had not brought textbook to class were perceived as “forgetfulness” in the eyes of the students but perceived as “unprepared for learning” by the teachers. Both “forgetfulness” and “unpreparedness” refer to a lack of responsibility in the expected role of students, but the level of accusation for “unprepared for learning” seemed to be more serious than that for “forgetfulness”. Obviously, the present study shows that collecting students' views can help provide a more comprehensive picture in describing various types of student misbehaviors.In the present findings, all the reported misbehaviors were actually off-task and inappropriate behaviors inside classrooms. This observation is in line with the assertion that misbehavior is behavior “students either did what they were not supposed to do or did not do what they were supposed to do” , page 9.Among various misbehaviors reported in this study, both talking out of turn and disrespecting teachers were rated as the most unacceptable problem behaviors. Obviously, these behaviors, particularly if uncontrollable, are disruptive to classroom learning and thus unacceptable. Moreover, it is interesting to note that some students found these misbehaviors as intolerable, when they upheld the personal virtues of politeness and respect, and the Chinese values of conformity and obedience, in the teacher-student relationship within the school context . TherefoSome students also mentioned that the frequency and intensity of misbehaviors, such as chatting, sleeping, and out of seat, would escalate if they found it fun, or no punishment for such misbehaviors, or teachers were not authoritarian enough in controlling the situations. Dreikurs  stated tThe present findings underscore the importance to view student misbehavior through the lens of students. Practically, they shed lights on managing student behavior and enhancing student learning and development via identifying students' needs and matching up with the classroom context. It is equally important for future research to further explore the reasons behind student misbehaviors and the effective means of managing student behaviors from both students' and teachers' perspectives. As mentioned above, there are few studies looking at both the perspectives of the teachers and students. Theoretically, it is important to look at the discrepancies between teachers and students on student misbehavior and understand how such differences may affect school policies on school discipline and counseling. For researchers adopting an interpretive perspective, the social reality is fluid in nature. Hence, it is important to look at things from different angles and hear voices of different parties. For critical theories, it is even more important to understand the views of different stakeholders so that we can empower them.There are several limitations in this study. First, it was a small-scale exploratory study with 18 students from three secondary schools recruited via convenience sampling. Hence, representativeness of the findings should be viewed with caution. However, it is noteworthy that the informants were randomly selected from the students. Second, as the informants were junior secondary school students, generalization of the findings to other age groups, like upper secondary or elementary school students, needs further validation. Third, only a one-shot interview was conducted for each informant. It would be ideal if more interviews over a longer period of time can be conducted. Finally, it may be criticized that the students may share the ideologies of the teachers. However, as the students were randomly selected, this possibility is not too high. Regardless of these limitations, this study is a good endeavor to understand the issue of classroom misbehavior from the perspectives of students, which helps to give a fuller picture of the phenomenon of classroom misbehavior, particularly in Hong Kong Chinese school context.To what extent the present study is an acceptable qualitative study? Based on the criteria proposed by Shek et al.  to evalu


Comparatively few studies address the problems related to multimorbidity. This is surprising, since multimorbidity is a particular challenge for both general practitioners and patients. This study focuses on the latter, analyzing the way patients aged 65–85 cope with multimorbidity.19 narrative in-depth interviews with multimorbid patients were conducted. The data was analysed using grounded theory. Of the 19 interviewed patients 13 were female and 6 male. Mean age was 75 years. Participating patients showed a relatively homogeneous socio-economic status. Patients were recruited from the German city of Hamburg and the state of North Rhine-Westphalia.Despite suffering from multimorbidity, interviewees held positive attitudes towards life: At the social level, patients tried to preserve their autonomy to the most possible extent. At the emotional level, interviewees oscillated between anxiety and strength - having, however, a positive approach to life. At the practical level, patients aimed at keeping their diseases under control. The patients tended to be critical in regards to medication.These findings might have implications for the treatment of multimorbid patients in primary care and further research: The generally presumed passivity of older individuals towards medical treatment, which can be found in literature, is not evident among our sample of older patients. In future, treatment of these patients might take their potential for pro-active cooperation more strongly into account than it is currently the case. Today, multimorbidity is a common problem among the elderly and its occurrence rises with age -3. Reseaprocess that is concerned with what a person within a specific context thinks or does. The authors distinguish between emotion-focused forms of coping and problem-focused forms of coping. Whereas the former are likely to occur whenever individuals appraise that nothing can be done to modify “harmful, threatening, or challenging environmental conditions”  the core category around which the other developed categories can be grouped and by which they are integrated”  I tell you, the diseases are all bearable. Even if I can’t comb my own hair – well, that’s not so bad. I get my hair combed in the mornings so now my doctor suggests that we apply for nursing allowance. So I tell her, ‘No, why should we? I’m still able to talk; I can still talk to other people. And everything else I can do by myself. No,’ I tell her, ‘It’s not that bad yet. I really don’t need any nursing allowance.’ […] Good thing I have a good family, right?“"can-do-approach to life”: They activated all their resources for the continuation of a meaningful and autonomous life.In general, patients were characterized by a “However, some patients faced stronger barriers in coping with the social dimension of their situation. This was particularly true for patients suffering from uncommon disorders or from diseases people could not relate to, e.g. vegetative problems. A distinctive case is Mrs. D. At the age of 63 she was afflicted – among other disorders – with food intolerance. She felt abandoned by her social surrounding:"“Should I be straightforward with you?! You’re left all to yourself. (pause) You’re all alone. It’s, well, the other people listen to your problem but basically they don’t really know how to deal with it and some don’t even want to. Even within the family – they know I’ve got this problem and then later we don’t even talk ‘bout it. […]“"This category includes patients’ ways of dealing emotionally with the challenges involved in multimorbidity. Interviewees experienced an interplay of anxiety, desperation, and dolefulness on the one side and strength and euphoria on the other side. Patients’ quality of life was highly influenced by the way patients coped with their multiple chronic conditions. A typical example of hopelessness and desperation is Mrs. E. She was aged 77 and suffering from arthritis, COPD, and vascular obliteration of one eye. The latter was the reason for fearing the loss of her eyesight:"“[I’m worried] that I might not be able to do anything here anymore, that’s … my son, he was so sad.  When he was here with me last week, I told him, well, that when I can’t see him anymore, please not have me go to a nursing home. I really only want to be here and maybe that’s… My partner also knows about it and I told him that, don’t you dare leave me anywhere by myself, that’s horrible. That’s what I fear most – but I keep trying to face it, really (speaking sobbingly)”"Another patient, Mr. F, aged 69, reported some kind of calming down during the period of sustaining a serious atrioventricular block and receiving a cardiac pacemaker:"“However, you suddenly become very calm and very serene. I felt instinctively that, if this isn’t fixed, right, you’ll die, you know? And then I also thought, well, this guy that they nailed to the cross, right – I’ll lay my fate in his hands. There’s nothing more you can do then – nobody can.”"positive approach to life” was also evident in the interview with Mrs. G. Being aged 75 and treated for aortic valve calcification, hypertension, and musculoskeletal disorders. She stated, “there are people that are much, much worse off. That’s what I always keep in mind.” Daily mastering the difficulties of chronic diseases and multimorbidity without capitulating was the prevailing pattern among interviewees. This was also true for Mrs. H. Having experienced several serious disorders and surgeries, at the age of 83 Mrs. H suffered a herniated disc. She remembered the effort she put into living a normal life again:After recovery, Mr. F put an effort into actualizing his desires and dreams: He arranged holidays at the Mediterranean Sea and flying with a hot air balloon. This “"“But basically I can feel as lousy as may be – I simply don’t give up. Last year it got so bad, I had to pull myself up the stairs. I really wasn’t able to place one foot in front of the other. And I always kept thinking, ‘Lord almighty, is this the way you’re supposed to end?’ But as it kept getting better, I used the stairs as a kind of exercise. So I sometimes went up and down those stairs 25 times a day. But, you know, I did it.”"keeping their diseases under control”. Patients reported, for instance, about storing and comparing blood values. Mr. I is a typical example of this pattern. He was aged 77 and treated for type 2 diabetes, hypertension, and gout. His wife, who was present during the interview, stated the following:Coping at the practical level refers to patients’ efforts in dealing with their multiple chronic diseases from a practical point of view, including management of physical examinations, therapies, medication and so forth. Interviewees looked very intensively into the subject of treating and medicating their conditions. Also, they put much effort into “"“These checkups every three months … that’s good for everyone. It’s good for us because we control it. We get to take the results home with us. Whenever we ask for it at the doctor’s office, we get a copy of the blood test results, right? Then we compare them with the last time and in case something is wrong, then we somewhat try to adjust, if possible.“"In general, patients were well informed about their diseases and disorders. They used to seek advice from books, journals, pharmacies, or the internet. A patient suffering, among other disorders, from migraine stated:"“I read a lot of magazines and newspapers and quite often they include reports about migraine and I know 100% certain how I need to react.”; “I read a lot about my sickness in books.”."Some patients turned to their GP whenever they had questions or doubts. Nonetheless, patients believed that you need to help yourself, otherwise “nobody helps” and “you are lost”. This was the case also for Mr. J. Being aged 74 and suffering from coronary heart disease, type 2 diabetes, and osteoarthritis he believed:"“And that proves once again that you need to listen to your own body and decide all for yourself. What is good for me? And if I didn’t do that, no doctor would be able to help me.”"As far as adherence to lifestyle recommendations was concerned, almost all patients stated to stick to the general advice of their GPs. Patients were aware of and complied with dietary needs and exercised. However, with respect to medication, patients showed a lower level of adherence. They tended to be rather critical and emphasized the dual nature of drugs: Mitigating symptoms and improving quality of life on the one side and leading to adverse reactions and new symptoms on the other side. Mrs. K is a typical example of a patient who is critical towards medication. At the same time, however, she prioritizes which pills are necessary to take and which not. She was aged 75 and treated for type 2 diabetes, arthritis, gastro-esophageal reflux disease, and hypertension. She reported:"“That’s some really strong stuff, these diabetes pills, but I know I need to take them. And what I always umh, that was this [pill] the urologist gave me, like I said, but they go right to your stomach, so I didn’t take them, because I, I told myself, and my conscience told me, leave them, they make you sick. You see, it’s an antipathy that I’ve got against these pills. I’ve never got a clear conscience when I take something. I’m even really sad, now that I have to treat my diabetes like that. I also don’t take sleeping pills. I’d lie awake for three hours rather […] I’d have a really guilty conscience sneaking through life on sleeping pills.”"A similar view was held by Mrs. L, aged 69 and suffering from COPD and several musculoskeletal disorders. She ignored her GPs recommendation to vary her daily amount of cortisone and continued to take the same little dosage."“Yeah, she [her GP] reckoned I'd feel better if I increased the dosage. But I'd rather suffer two or three days – then I've got it under control again.”"The belief that drugs would impair health as a matter of principle recurred among our interviewees: A 78 years old female patient suffering from gonarthrosis, metabolic disorder, depression, and chronic cough stated: “And if you just keep taking those pills (…) all you do is harm yourself“; “I'm not a big fan of this constant pill-taking, because my stomach can't handle it.”Given the age of the interviewed patients, the trend towards controlling existing diseases, informing oneself actively about disorders, and being critical about medication is rather surprising: Interviewees had much less paternalistic expectations toward their GP than one would expect.In Figure can-do approach to life”. At the emotional level, interviewees oscillated between anxiety and strength – having, however, a “positive approach to life”. And finally, at the practical level, patients aimed at “keeping their diseases under control”. Astonishingly, the patients we interviewed were not part of an intellectual elite, but belonged to the middle class and represented ‘ordinary people’. Also, patients were concordant with their GPs’ recommendations concerning lifestyle changes, complied with dietary needs and exercised. However, patients tended to be critical in regards to medication and emphasized the dual nature of drugs: Mitigating symptoms and improving quality of life on the one side, and leading to adverse reactions and new symptoms on the other side. This finding supports Horne and Weinman’s framework on the relationship between necessity of medication and concerns related to medication. Conducting a cross-sectional study, the authors found that higher necessity scores correlate with higher reported adherence, whereas higher concerns correlate with lower reported adherence [This paper focuses on the question, how old aged multimorbid patients cope with their multiple chronic diseases. The interviews provide evidence that despite multimorbidity interviewees held positive attitudes towards life: At the social level, patients tried to keep their social role and to preserve their autonomy to the most possible extent. This was evident in their “dherence . The facdherence .pro-active in seeking information, adhering to GP’s lifestyle recommendations and questioning the benefit of drugs. Further research is necessary to evaluate whether this pro-active behaviour is an emerging phenomenon and if so, how it relates to relevant outcomes e.g. quality of life. One might suggest, that pro-active behaviour is related to increasing levels of life satisfaction and quality of life.Our findings give some evidence that today’s generation of seventy-year-old people might be different from previous generations of this age: Literature shows that earlier generations of older adults were less likely than others to cope by information seeking or by engaging in wish fulfilling fantasies ,38. Our With respect to existing approaches on coping, the emerging categories of coping at the social, emotional and practical level might be integrated into Lazarus and Folkman’s differentiation between emotion-focused forms of coping and problem-focused forms of coping. Both frameworks might be understood as one dimension in a diagram, where coping at each level might be distinguished with respect to emotion-focused forms and problem-focused forms of coping. Among our interviewees, we find both forms of coping in all of the three categories. For instance, at the social level Mr. B employed a problem-focused form of coping by purchasing a tricycle. Mrs. D, though, used an emotion-focused form of coping: She accepted that people are indifferent towards her food intolerance and all problems related to that.The study goes beyond previous studies on disease coping as we focus on multimorbidity instead of a single chronic disease. The active disease management that we found among interviewees might be highly related to multimorbidity: Since the co-existence of multiple chronic diseases requires careful and coordinated treatment and care, patients might have learnt to put priorities with regard to their health, and to act actively.As far as limitations are concerned, our study is not based upon theoretical sampling as mentioned above, but upon 2 randomized samples, which were compiled in two different regions. After the first interviews were discussed within the team of researchers, we decided to further pursue this path as our data included cases of high contrast. Nonetheless, this procedure does not allow for a completely theory-driven approach of data generation and analysis as it is aimed at by grounded theory.These findings might have implications for the treatment of multimorbid and chronically ill patients in primary care: Our data suggests that the generally presumed passivity of older individuals towards medical treatment might no longer be prevalent in today’s generation of older patients. In future, treatment of these patients might take their potential for pro-active cooperation more strongly into account than it is currently the case.However, in order to do so, patients will require possibilities to express their emotions and concerns. GPs, on the other side, will need concepts that allow for identifying the different resources patients have. Future research might follow this path by developing concepts that allow for the integration of patients’ pro-active attitudes and behaviour. Our findings support the chronic care model ,40 with a In Germany, nursing allowance is a social benefit for patients in need of care. Since 1995, nursing care insurance is statutory. Depending on the patient’s level of nursing care dependency, nursing allowances for care-giving expenses are remitted.The authors declare that they have no competing interest.HK and AA initiated and designed the study. Fieldwork was carried out by WS, COS, HK and Carsten A. Reich. Coding and categorising of the interviews was done by CL and FS and discussed with all authors continuously in the process of the analysis. All authors drafted memos and discussed them regularly. The paper was drafted by CL. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2296/13/45/prepub


Eric Kandel wrote in his intriguing paper titled “A new intellectual framework for psychiatry”  and the challenge of so-called “situatedness”  about “what is it like to be a bat”  and attempts to incorporate the body and its imprinted neural representation into a genuine, more holistic understanding of the field. One could interpret it as a new esteem of anciently quirky psychosomatics in biological psychiatry that overcomes its centro-centric monodimensionality.Second is the rediscovery of the body in biological psychiatry.  Walter, . However Damsio, . These sDamasio,  apparenta Wiens, . The fan” Nagel,  currentlhyperscanning ,” and it is perhaps the most integrating framework covering cognitive and affective neurosciences that will give rise to emerging social neurosciences , is ultimately the first step into a new era of real cooperativeness among neuroscientists and brains (Markram, the brain of my conspecific, and psychiatry and psychosomatics grow together, entities that belong together grow together. We have the opportunity to see the emergence of a new, non-reductionist science of fractal brains, as we examine mental orders and disorders differently, in a “brainy way,” with more cooperation and integration than ever before. In one word, in accordance with Henry Markram (Kandel et al., Finally, after three waves, a fourth wave seems inevitable. I would venture to predict that this “new wave” will belong to the computational neurosciences (Wen et al.,  Tononi, . The HumMarkram,  which waMarkram, . Unfortu


Recently, individualized or personalized medicine (PM) has become a buzz word in the academic as well as public debate surrounding health care. However, PM lacks a clear definition and is open to interpretation. This conceptual vagueness complicates public discourse on chances, risks and limits of PM. Furthermore, stakeholders might use it to further their respective interests and preferences. For these reasons it is important to have a shared understanding of PM. In this paper, we present a sufficiently precise as well as adequate definition of PM with the potential of wide acceptance.For this purpose, in a first step a systematic literature review was conducted to understand how PM is actually used in scientific practice. PubMed was searched using the keywords “individualized medicine”, “individualised medicine”, “personalized medicine” and “personalised medicine” connected by the Boolean operator OR. A data extraction tabloid was developed putting forward a means/ends-division. Full-texts of articles containing the search terms in title or abstract were screened for definitions. Definitions were extracted; according to the means/ends distinction their elements were assigned to the corresponding category. To reduce complexity of the resulting list, summary categories were developed inductively from the data using thematic analysis. In a second step, six well-known criteria for adequate definitions were applied to these categories to derive a so-called precising definition.We identified 2457 articles containing the terms PM in title or abstract. Of those 683 contained a definition of PM and were thus included in our review. 1459 ends and 1025 means were found in the definitions. From these we derived the precising definition: PM seeks to improve stratification and timing of health care by utilizing biological information and biomarkers on the level of molecular disease pathways, genetics, proteomics as well as metabolomics.Our definition includes the aspects that are specific for developments labeled as PM while, on the other hand, recognizing the limits of these developments. Furthermore, it is supported by the quantitative analysis of PM definitions in the literature, which suggests that it it is widely acceptable and thus has the potential to avoid the above mentioned issues. Promising to make health care more effective and efficient by tailored medical interventions it has become one of the core areas of public research funding and pharmaceutical research investment . Furthermore, we had no reason to suspect that our sample was significantly different from the general population of papers.Third, one may criticize our exclusion decisions. To derive a precising definition we had to interpret terms like “tailored”, “health care” or “adequately distinctive”. For example, we define health care as being constituted by preventive and therapeutic measures. Naturally, those assumptions can be discussed critically as most terms are not as clearly delineated as would be desirable for the construction of a definition. However, as these terms are well-established in scientific discourse and interpretation only becomes necessary at the margin, this should not weaken our analysis in any significant way. Our definition can therefore help to re-focus the discourse on PM by reducing its conceptual vagueness.not medicine with a special focus on the interests and preferences of the individual patient. For instance, PM does not include any reference to an adequate doctor-patient relationship. Hence, PM as such is not related to the term patient-centered medicine. Moving towards a more patient-centered medicine may be desirable, but cannot be achieved by solely furthering PM technology. To forestall false hopes attached to the concept and accordingly wrong decisions regarding investments, it might be reasonable to adapt terminology. Stratifying medicine, for example, would be a more appropriate term than personalized medicine to describe the developments currently labeled as PM.Fourth, as mentioned above, people debating PM hold understandings that diverge from what PM technology actually can achieve. As our results show, PM is a For pragmatic reasons we will only use the acronym PM to refer to both individualized as well as personalized medicine in the following. Besides, individualized and personalized medicine are often used synonymously in public discourse.b See Additional file c By medical context we refer to medicine as in medical care. This results from the insight that PM is generally discussed as a means to improve medical care.d Of course, “medical decision making” would belong to the genus “medicine”. The rather general reference to “decision making”, however, does not necessarily belong to the genus “medicine”. Therefore, we refrained from including “decision making” in our definition.e By “health care” we understand medical care both on the population and on the individual level.f We will return to that category later.g Cf. [sufficiently precise, we want to point out that it obviously cannot be perfectly precise. The construction of a perfectly precise definition would demand defining every element of the definiendum, e.g. the terms “biomarker”, “proteomics” or “metabolomics”. It is sufficiently precise in the sense that it can decrease the chances of misusing the term PM. For this purpose, it is not necessary to provide an exact definition of terms like proteomics or metabolomics. Rather, it is sufficient to point out that certain biological sub-disciplines are decisive for PM’s development and implementation.g Cf.  for an aThe authors declare that they have no competing interests.SS initiated the study and contributed to conception and design, acquisition of data, analysis and  interpretation of data. He was involved in drafting the manuscript and revised it. CK contributed to data analysis and interpretation and was involved in drafting the manuscript as well as revision. TB contributed to acquisition of data and revised the manuscript. WHR contributed to conception and design and was involved in drafting and revising the manuscript. GM contributed to data interpretation and was involved in drafting and revising the manuscript. All authors gave final approval of the paper.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6939/14/55/prepubEnds and Means of PM in the Literature (Long).Click here for fileSearched Papers Containing PM in Title/Abstract.Click here for file