Documentation of the Fourth Order Band Model

A general circulation model is presented which uses quadratically conservative, fourth order horizontal space differences on an unstaggered grid and second order vertical space differences with a forward-backward or a smooth leap frog time scheme to solve the primitive equations of motion. The dynamic equations for motion, finite difference equations, a discussion of the structure and flow chart of the program code, a program listing, and three relevent papers are given

Pain and autonomic dysfunction in patients with sarcoidosis and small fibre neuropathy

Small fibre neuropathy (SFN) has been demonstrated in sarcoidosis. However, a systematic analysis of neuropathic pain and autonomic symptoms, key features of SFN, has not been performed. Clinimetric evaluation of pain and autonomic symptoms using the neuropathic pain scale (NPS) and the modified Composite Autonomic Symptoms Scale (mCOMPASS) was used in sarcoidosis patients for this study. A total of 91 sarcoidosis patients (n = 23 without SFN symptoms, n = 43 with SFN symptoms but normal intraepidermal nerve fibre density (IENFD), n = 25 with SFN symptoms and reduced IENFD) were examined. NPS and mCOMPASS were assessed twice (reliability studies). Severity of pain was compared between the subgroups. Correlation between NPS and a visual analogue pain scale (VAS) was assessed (validity studies). Healthy controls (n = 105) completed the mCOMPASS for comparison with patients’ scores. Patients with sarcoidosis, SFN complaints, and reduced IENFD demonstrated more severe pain scores on the NPS. The mCOMPASS differentiated between subjects with and without SFN symptoms. A significant correlation was obtained between the NPS and VAS, indicating good construct validity. Good reliability values were obtained for all scales. The use of the NPS to evaluate SFN symptoms is suggested, as it shows differences between patients with SFN symptoms with normal or reduced IENFD values. The mCOMPASS might be used to select patients for further testing

Development and external validation study combining existing models and recent data into an up-to-date prediction model for evaluating kidneys from older deceased donors for transplantation

With a rising demand for kidney transplantation, reliable pre-transplant assessment of organ quality becomes top priority. In clinical practice, physicians are regularly in doubt whether suboptimal kidney offers from older donors should be accepted. Here, we externally validate existing prediction models in a European population of older deceased donors, and subsequently developed and externally validated an adverse outcome prediction tool. Recipients of kidney grafts from deceased donors 50 years of age and older were included from the Netherlands Organ Transplant Registry (NOTR) and United States organ transplant registry from 2006-2018. The predicted adverse outcome was a composite of graft failure, death or chronic kidney disease stage 4 plus within one year after transplantation, modelled using logistic regression. Discrimination and calibration were assessed in internal, temporal and external validation. Seven existing models were validated with the same cohorts. The NOTR development cohort contained 2510 patients and 823 events. The temporal validation within NOTR had 837 patients and the external validation used 31987 patients in the United States organ transplant registry. Discrimination of our full adverse outcome model was moderate in external validation (C-statistic 0.63), though somewhat better than discrimination of the seven existing prediction models (average C-statistic 0.57). The model's calibration was highly accurate. Thus, since existing adverse outcome kidney graft survival models performed poorly in a population of older deceased donors, novel models were developed and externally validated, with maximum achievable performance in a population of older deceased kidney donors. These models could assist transplant clinicians in deciding whether to accept a kidney from an older donor

Empathy in multiple sclerosis-correlates with cognitive, psychological and occupational functioning

Background Recent studies report deficits in social cognition in individuals with multiple sclerosis (MS). Social cognitive skills such as empathy are important for adequate social and occupational functioning. Our objectives are: (1) to examine whether empathy differs between individuals with MS and healthy controls, (2) to examine relations between empathy and cognitive, psychological and occupational functioning. Methods 278 individuals with MS (relapsing-remitting subtype) and 128 healthy controls from the MS@Work study participated in this investigation. The participants completed questionnaires about demographics, cognitive, psychological and occupational functioning, and underwent neurological and neuropsychological examinations. Mann-Whitney U-tests were used to examine group differences in empathy. Pearson and Spearman rank correlation analyses were used to examine relations between empathy and the other measures. Results Empathy did not differ between individuals with MS and healthy controls. In individuals with MS, higher empathy was correlated with a higher educational level (X2(df) = 13.2(2), p = 0.001), better verbal learning (r = 0.20, p = 0.001), less symptoms of depression (r=−0.21, p = 0.001), higher extraversion (r = 0.25, p ≤ 0.001), agreeableness (r = 0.55, p ≤ 0.001) and conscientiousness (r = 0.27, p ≤ 0.001) and better occupational functioning in terms of work scheduling and output demands (r = 0.23, p = 0.002) and less cognitive/psychological work barriers (r = −0.21, p = 0.001). In healthy controls, higher empathy was correlated with less symptoms of depression (r = −0.34, p ≤ 0.001), less fatigue (r = −0.37, p ≤ 0.001), higher agreeableness (r = 0.59, p ≤ 0.001) and better occupational functioning in terms of work ability as compared to lifetime best (r = 0.28, p = 0.001) and less cognitive/psychological work barriers (r = −0.34, p ≤ 0.001). Empathy did not differ between unemployed and employed individuals with MS or healthy controls. Conclusion Empathy did not differ between individuals with MS and healthy controls. Within both investigated groups, higher empathy was weakly to moderately correlated with less symptoms of depression, higher agreeableness and better occupational functioning. We also found unique correlations for empathy within the investigated groups. Longitudinal studies are needed to further examine social cognition in relation to cognitive, psychological and occupational functioning in both individuals with MS and healthy controls. It would be particularly interesting to concurrently examine changes in the brain network involved with social cognition

The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology

Small fibre neuropathy (SFN), a condition dominated by neuropathic pain, is frequently encountered in clinical practise either as prevalent manifestation of more diffuse neuropathy or distinct nosologic entity. Aetiology of SFN includes pre-diabetes status and immune-mediated diseases, though it remains frequently unknown. Due to their physiologic characteristics, small nerve fibres cannot be investigated by routine electrophysiological tests, making the diagnosis particularly difficult. Quantitative sensory testing (QST) to assess the psychophysical thresholds for cold and warm sensations and skin biopsy with quantification of somatic intraepidermal nerve fibres (IENF) have been used to determine the damage to small nerve fibres. Nevertheless, the diagnostic criteria for SFN have not been defined yet and a ‘gold standard’ for clinical practise and research is not available. We screened 486 patients referred to our institutions and collected 124 patients with sensory neuropathy. Among them, we identified 67 patients with pure SFN using a new diagnostic ‘gold standard’, based on the presence of at least two abnormal results at clinical, QST and skin biopsy examination. The diagnosis of SFN was achieved by abnormal clinical and skin biopsy findings in 43.3% of patients, abnormal skin biopsy and QST findings in 37.3% of patients, abnormal clinical and QST findings in 11.9% of patients, whereas 7.5% patients had abnormal results at all the examinations. Skin biopsy showed a diagnostic efficiency of 88.4%, clinical examination of 54.6% and QST of 46.9%. Receiver operating characteristic curve analysis confirmed the significantly higher performance of skin biopsy comparing with QST. However, we found a significant inverse correlation between IENF density and both cold and warm thresholds at the leg. Clinical examination revealed pinprick and thermal hypoesthesia in about 50% patients, and signs of peripheral vascular autonomic dysfunction in about 70% of patients. Spontaneous pain dominated the clinical picture in most SFN patients. Neuropathic pain intensity was more severe in patients with SFN than in patients with large or mixed fibre neuropathy, but there was no significant correlation with IENF density. The aetiology of SFN was initially unknown in 41.8% of patients and at 2-year follow-up a potential cause could be determined in 25% of them. Over the same period, 13% of SFN patients showed the involvement of large nerve fibres, whereas in 45.6% of them the clinical picture did not change. Spontaneous remission of neuropathic pain occurred in 10.9% of SFN patients, while it worsened in 30.4% of them

Development and external validation study combining existing models and recent data into an up-to-date prediction model for evaluating kidneys from older deceased donors for transplantation

With a rising demand for kidney transplantation, reliable pre-transplant assessment of organ quality becomes top priority. In clinical practice, physicians are regularly in doubt whether suboptimal kidney offers from older donors should be accepted. Here, we externally validate existing prediction models in a European population of older deceased donors, and subsequently developed and externally validated an adverse outcome prediction tool. Recipients of kidney grafts from deceased donors 50 years of age and older were included from the Netherlands Organ Transplant Registry (NOTR) and United States organ transplant registry from 2006-2018. The predicted adverse outcome was a composite of graft failure, death or chronic kidney disease stage 4 plus within one year after transplantation, modelled using logistic regression. Discrimination and calibration were assessed in internal, temporal and external validation. Seven existing models were validated with the same cohorts. The NOTR development cohort contained 2510 patients and 823 events. The temporal validation within NOTR had 837 patients and the external validation used 31987 patients in the United States organ transplant registry. Discrimination of our full adverse outcome model was moderate in external validation (C-statistic 0.63), though somewhat better than discrimination of the seven existing prediction models (average C-statistic 0.57). The model's calibration was highly accurate. Thus, since existing adverse outcome kidney graft survival models performed poorly in a population of older deceased donors, novel models were developed and externally validated, with maximum achievable performance in a population of older deceased kidney donors. These models could assist transplant clinicians in deciding whether to accept a kidney from an older donor.Clinical epidemiolog

Evaluation of spelt germplasm for polyphenol oxidase activity and aluminium resistance

Kidney transplantation is the best treatment option for patients with end-stage renal failure. At present, approximately 800 Dutch patients are registered on the active waiting list of Eurotransplant. The waiting time in the Netherlands for a kidney from a deceased donor is on average between 3 and 4years. During this period, patients are fully dependent on dialysis, which replaces only partly the renal function, whereas the quality of life is limited. Mortality among patients on the waiting list is high. In order to increase the number of kidney donors, several initiatives have been undertaken by the Dutch Kidney Foundation including national calls for donor registration and providing information on organ donation and kidney transplantation. The aim of the national PROCARE consortium is to develop improved matching algorithms that will lead to a prolonged survival of transplanted donor kidneys and a reduced HLA immunization. The latter will positively affect the waiting time for a retransplantation. The present algorithm for allocation is among others based on matching for HLA antigens, which were originally defined by antibodies using serological typing techniques. However, several studies suggest that this algorithm needs adaptation and that other immune parameters which are currently not included may assist in improving graft survival rates. We will employ a multicenter-based evaluation on 5429 patients transplanted between 1995 and 2005 in the Netherlands. The association between key clinical endpoints and selected laboratory defined parameters will be examined, including Luminex-defined HLA antibody specificities, T and B cell epitopes recognized on the mismatched HLA antigens, non-HLA antibodies, and also polymorphisms in complement and Fc receptors functionally associated with effector functions of anti-graft antibodies. From these data, key parameters determining the success of kidney transplantation will be identified which will lead to the identification of additional parameters to be included in future matching algorithms aiming to extend survival of transplanted kidneys and to diminish HLA immunization. Computer simulation studies will reveal the number of patients having a direct benefit from improved matching, the effect on shortening of the waiting list, and the decrease in waiting time

Self-reported occupational functioning in persons with relapsing-remitting multiple sclerosis: does personality matter?

Health and self-regulatio