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People with severe or profound intellectual disabilities (IDs) are believed to experience low levels of self-determination, which negatively affects their quality of life. This systematic review describes existing interventions aimed to support self-determination or components thereof and synthesises evidence on the interventions' effects. Eight databases were searched, turning in 76 articles for the final inclusion. The studies included 631 people with severe or profound IDs of whom 81% had multiple disabilities. The studies had quantitative (k = 63), qualitative (k = 7) and mixed study designs (k = 6). Sample sizes ranged from 1 to 95 and a study quality index ranged from 40% to 100%. While many studies included several self-determination components and intervention elements, overall, 53 studies focused on the self-determination components choice making, independence and problem solving. Other studies included increased assistance (k = 14); engagement in meaningful activities and relationships (k = 10); community and societal participation (k = 5); supporting the basic psychological needs autonomy, competence and relatedness (k = 4); individuality and dignity (k = 3); supportive decision-making (k = 2); self-advocacy (k = 2); and motivation (k = 1). Intervention elements included technology (k = 33); multiple-component training packages, goal setting, empowerment tactics and applied behaviour principles (k = 17); training of caretakers (k = 17); changes in policies and living arrangements (k = 9); supporter responsiveness (k = 1); drama therapy and storytelling (k = 1); electrical wheelchair training (k = 1); joint painting procedure (k = 1); youth advocacy project (k = 1); and multiliteracies training (k = 1). Reflecting the heterogeneity of the field, only four studies tested a similar intervention for this population and were eligible for the meta-analysis, which combined showed a small effect size of 2.69. Further research is needed to explore relationships between individuals with severe or profound IDs and their relatives and health care professionals and create supportive environments that meet their basic psychological needs.

BackgroundThe high support needs of persons with profound intellectual and multiple disabilities hamper their possibilities for self-determination. To support their self-determination understanding of what this means for this group is necessary.MethodA three-round Delphi procedure with international experts was undertaken to operationalise self-determination for persons with profound intellectual and multiple disabilities. The quantitative output of Likert scales guided us in finding consensus or differences in the qualitative data. First round qualitative data were analysed thematically.ResultsThe analysis revealed four topics: (1) statements regarding the characteristics of the person with profound intellectual and multiple disabilities, (2) statements regarding characteristics of the social environment, (3) statements regarding the concept of self-determination, and (4) statements regarding the definition and operationalisation of concepts.ConclusionConsensus was found on the assumption that persons with profound intellectual and multiple disabilities can live a self-determined life and on the importance of the interplay between persons with profound intellectual and multiple disabilities and the environment in order to experience self-determination.

Medical imaging as method to assess the longitudinal process of a SARS-CoV-2 infection in non-human primates is commonly used in research settings. Bronchoalveolar lavage (BAL) is regularly used to determine the local virus production and immune effects of SARS-CoV-2 in the lower respiratory tract. However, the potential interference of those two diagnostic modalities is unknown in non-human primates. The current study investigated the effect and duration of BAL on computed tomography (CT) in both healthy and experimentally SARS-CoV-2-infected female rhesus macaques (Macaca mulatta). In addition, the effect of subsequent BALs was reviewed. Thorax CTs and BALs were obtained from four healthy animals and 11 experimentally SARS-CoV-2-infected animals. From all animals, CTs were obtained just before BAL, and 24 hours post-BAL. Additionally, from the healthy animals, CTs immediately after, and four hours post-BAL were obtained. Thorax CTs were evaluated for alterations in lung density, measured in Hounsfield units, and a visual semi-quantitative scoring system. An increase in the lung density was observed on the immediately post-BAL CT but resolved within 24 hours in the healthy animals. In the infected animals, a significant difference in both the lung density and CT score was still found 24 hours after BAL. Furthermore, the differences between time points in CT score were increased for the second BAL. These results indicate that the effect of BAL on infected lungs is not resolved within the first 24 hours. Therefore, it is important to acknowledge the interference between BAL and CT in rhesus macaques.

Medical imaging as method to assess the longitudinal process of a SARS-CoV-2 infection in non-human primates is commonly used in research settings. Bronchoalveolar lavage (BAL) is also regularly used to determine the local virus production and immune effects of SARS-CoV-2 in the lower respiratory tract. However, the potential interference of those two diagnostic modalities with each other is unknown in non-human primates. The current study investigated the effect and duration of BAL on computed tomography (CT) in both healthy and experimentally SARS-CoV-2-infected female rhesus macaques (Macaca mulatta). In addition, the effect of subsequent BALs was reviewed. Thorax CTs and BALs were obtained from four healthy animals and 11 experimentally SARS-CoV-2-infected animals. From all animals, CTs were obtained just before BAL, and 24 hours post-BAL. Additionally, from the healthy animals, CTs immediately after and four hours post-BAL were obtained. Thorax CTs were evaluated for alterations in lung density, measured in Hounsfield units, and a visual semi-quantitative scoring system. An increase in the lung density was observed on the immediately post-BAL CT but resolved within 24 hours in the healthy animals. In the infected animals, a significant difference in both the lung density and CT score was still found 24 hours after BAL. Furthermore, the differences between timepoints in CT score were increased for the second BAL. These results indicate that the effect of BAL on infected lungs is not completed within the first 24 hours. Therefore, it is of importance to acknowledge the interference between BAL and CT in rhesus macaques.

Objective: To develop a method to define a multi-stakeholder perspective on health-service quality that enables the expression of differences in systematically identified stakeholders' perspectives, and to pilot the approach for cataract care. Design: Mixed-method study between 2014 and 2015. Setting: Cataract care in the Netherlands. Participants: Stakeholder representatives. Intervention(s): We first identified and classified stakeholders using stakeholder theory. Participants established a multi-stakeholder perspective on quality of cataract care using concept mapping, this yielded a cluster map based on multivariate statistical analyses. Consensus-based quality dimensions were subsequently defined in a plenary stakeholder session. Main outcome measure(s): Stakeholders and multi-stakeholder perspective on health-service quality. Results: Our analysis identified seven definitive stakeholders, as follows: the Dutch Ophthalmology Society, ophthalmologists, general practitioners, optometrists, health insurers, hospitals and private clinics. Patients, as dependent stakeholders, were considered to lack power by other stakeholders; hence, they were not classified as definitive stakeholders. Overall, 18 stakeholders representing ophthalmologists, general practitioners, optometrists, health insurers, hospitals, private clinics, patients, patient federations and the Dutch Healthcare Institute sorted 125 systematically collected indicators into the seven following clusters: patient centeredness and accessibility, interpersonal conduct and expectations, experienced outcome, clinical outcome, process and structure, medical technical acting and safety. Importance scores from stakeholders directly involved in the cataract service delivery process correlated strongly, as did scores from stakeholders not directly involved in this process. Conclusions: Using a case study on cataract care, the proposed methods enable different views among stakeholders concerning quality dimensions to be systematically revealed, and the stakeholders jointly agreed on these dimensions. The methods helped to unify different quality definitions and facilitated operationalisation of quality measurement in a way that was accepted by relevant stakeholders.

Housing primates in naturalistic groups provides social benefits relative to solitary housing. However, food intake may vary across individuals, possibly resulting in overweight and underweight individuals. Information on relative adiposity (the amount of fat tissue relative to body weight) is needed to monitor overweight and underweight of group‐housed individuals. However, the upper and lower relative adiposity boundaries are currently only known for macaques living solitarily in small cages. We determined the best measure of relative adiposity and explored the boundaries of overweight and underweight to investigate their incidence in group‐housed adult male and female rhesus macaques and long‐tailed macaques living in spacious enclosures at the Biomedical Primate Research Centre (BPRC), the Netherlands. During yearly health checks different relative adiposity measures were obtained. For long‐tailed macaques, comparable data on founder and wild animals were also available. Weight‐for‐height indices (WHI) with height to the power of 3.0 (WHI3.0) for rhesus macaques and 2.7 (WHI2.7) for long‐tailed macaques were optimally independent of height and were highly correlated with other relative adiposity measures. The boundary for overweight was similar in group‐housed and solitary‐housed macaques. A lower boundary for underweight, based on 2% body fat similar to wild primates, gave a better estimate for underweight in group‐housed macaques. We propose that for captive group‐housed rhesus macaques relative adiposity should range between 42 and 67 (WHI3.0) and for long‐tailed macaques between 39 and 62 (WHI2.7). The majority of group‐housed macaques in this facility have a normal relative adiposity, a considerable proportion (17–23%) is overweight, and a few (0–3%) are underweight., HIGHLIGHTS Weight‐for‐height indices WHI3.0 for group‐housed rhesus macaques and WHI2.7 for long‐tailed macaques were independent of height.The best boundary for underweight in group‐housed macaques was based on 2% body fat of wild primates, rather than 8% body fat of solitary‐housed macaques.

Bacterial taxa with significantly different relative abundances in the Dutch and Finnish cohorts. All FDR-corrected p values are

In this chapter, we present a theory on how organizational performance feedback influences individual decision-maker cognitions and thereby changes a team’s attention focus in terms of strategy. We argue that when performance compares unfavorably to aspiration levels, decision-makers reconsider current strategies in favor of unfamiliar, uncertain ones and become more risk tolerant. Furthermore, as decision-makers devote additional cognitive resources to do so, changes in attention focus in a decision-making team will be observed. Using data from a business simulation and repeated questionnaires, we capture the teams’ attention focus and the organizational performance feedback evaluation process of the individuals and teams.

Many controversies surround the usefulness of dual-task training in Parkinson's disease (PD). This study (1) compared the efficacy of two different dual-task training programs for improving dual-task gait and (2) assessed the possible fall risk of such training.Patients (N = 121) with a diagnosis of PD (aged 65.93 [±9.22] years, Hoehn and Yahr stage II-III on-medication) were randomized to (1) a consecutive group in which gait and cognitive tasks were trained separately or (2) an integrated group in which gait and cognitive tasks were trained simultaneously. Both interventions involved 6 weeks of at-home physiotherapist-led training. Two baseline tests were performed as a 6-week control period before training. Posttests were performed immediately after training and at 12-week follow-up. Dual-task gait was assessed during trained and untrained secondary tasks to assess consolidation of learning. Fall risk was determined by a weekly telephone call for 24 weeks.No significant time by group interactions were found, suggesting that both training modes had a similar effect on dual-task gait. Immediately after training, and not after the control period, significant improvements (P.001) in dual-task gait velocity were found in all trained and untrained dual tasks. Improvements ranged between 7.75% and 13.44% when compared with baseline values and were retained at 12-week follow-up. No significant change in fall risk occurred in both study arms (P = .84).Consecutive and integrated dual-task training led to similar and sustained improvements in dual-task gait velocity without increasing fall risk. These novel findings support adoption of dual-task training in clinical practice. © 2017 International Parkinson and Movement Disorder Society.

Telomeres, nucleoprotein complexes at chromosome ends, protect chromosomes against end-to-end fusion. Previous in vitro studies in human fibroblast models indicated that telomere dysfunction results in chromosome instability. Loss of telomere function can result either from critical shortening of telomeric DNA or from loss of distinct telomere-capping proteins. It is less clear whether telomere dysfunction has an important role in human cancer development in vivo. Acute myeloid leukemia (AML) is a good model to study mechanisms that generate chromosome instability in human cancer development because distinct groups of AML are characterized either by aberrations that theoretically could result from telomere dysfunction (terminal deletions, gains/losses of chromosome parts, nonreciprocal translocations), or aberrations that are unlikely to result from telomere dysfunction (e.g., reciprocal translocations or inversions). Here we demonstrate that AML with multiple chromosome aberrations that theoretically could result from telomere dysfunction is invariably characterized by critically short telomeres. Short telomeres in this group are not associated with low telomerase activity or decreased expression of essential telomeric capping proteins TRF2 and POT1. In contrast, telomerase activity levels are significantly higher in AML with short telomeres. Notably, short telomeres in the presence of high telomerase may relate to significantly higher expression of TRF1, a negative regulator of telomere length. Our observations suggest that, consistent with previous in vitro fibroblast models, age-related critical telomere shortening may have a role in generating chromosome instability in human AML development.

Background: Although movement disorders that occur following a stroke have long been recognised in short series of patients, their frequency and clinical and imaging features have not been reported in large series of patients with stroke. Methods: We reviewed consecutive patients with involuntary abnormal movements (IAMs) following a stroke who were included in the Eugenio Espejo Hospital Stroke Registry and they were followed up for at least one year after the onset of the IAM. We determined the clinical features, topographical correlations, and pathophysiological implications of the IAMs. Results: Of 1500 patients with stroke 56 developed movement disorders up to one year after the stroke. Patients with chorea were older and the patients with dystonia were younger than the patients with other IAMs. In patients with isolated vascular lesions without IAMs, surface lesions prevailed but patients with deep vascular lesions showed a higher probability of developing abnormal movements. One year after onset of the IAMs, 12 patients (21.4%) completely improved their abnormal movements, 38 patients (67.8%) partially improved, four did not improve (7.1%), and two patients with chorea died. In the nested case–control analysis, the patients with IAMs displayed a higher frequency of deep lesions (63% v 33%; OR 3.38, 95% CI 1.64 to 6.99, p

The critical factors in the regulation of telomere length are not yet clearly defined. Telomerase is a key player in telomere elongation, although previous studies have shown that telomeres are differentially elongated after telomerase reconstitution. Moreover, a clear relation between the level of telomerase activity and telomere length was not observed. To investigate which factors are critical in telomere length regulation, we generated 24 telomerase-reconstituted primary human fibroblast clones. In these clones, in vitro telomerase activity level is clearly related to telomere length. High levels of telomerase activity are associated with longer telomeres and better telomere maintenance over time. The correlation coefficient, however, indicates that the level of telomerase activity is not the only factor in the regulation of telomere length. Clearly, factors that are not measured in an in vitro telomerase activity assay are involved in telomere length regulation in vivo. To investigate which telomerase components are critical in regulating telomerase activity levels, we studied expression levels of hTERT mRNA and hTR. Expression is highly variable between individual clones, but not related to the level of telomerase activity or telomere length. Our results indicate that expression levels of hTERT mRNA and hTR do not regulate the activity level of the telomerase complex, suggesting posttranscriptional modification of hTERT or the presence of additional proteins that modulate telomerase enzyme activity.

Recent research addressed the relationship between staff behaviour and challenging behaviour of individuals with an intellectual disability (ID). Consequently, research on interventions aimed at staff is warranted. The present study focused on the effectiveness of a staff training aimed at emotional intelligence and interactions between staff and clients. The effects of the training on emotional intelligence, coping style and emotions of support staff were investigated.Participants were 214 support staff working within residential settings for individuals with ID and challenging behaviour. The experimental group consisted of 76 staff members, 138 staff members participated in two different control groups. A pre-test, post-test, follow-up control group design was used. Effectiveness was assessed using questionnaires addressing emotional intelligence, coping and emotions.Emotional intelligence of the experimental group changed significantly more than that of the two control groups. The experimental group showed an increase in task-oriented coping, whereas one control group did not. The results with regard to emotions were mixed. Follow-up data revealed that effects within the experimental group were still present four months after the training ended.A staff training aimed at emotional intelligence and staff-client interactions is effective in improving emotional intelligence and coping styles of support staff. However, the need for more research aiming at the relationship between staff characteristics, organisational factors and their mediating role in the effectiveness of staff training is emphasised.

Human chromosomes terminate in a series of T2AG3 repeats, which, together with associated proteins, are essential for chromosome stability. In somatic cells, these sequences are known to be gradually lost through successive cells divisions; however, information about changes on specific chromosomes is not available. Individual telomeres could mediate important biological effects as was shown in yeast, in which loss of a single telomere results in cell-cycle arrest and chromosome loss. We now demonstrate by quantitative fluorescence in situ hybridization (Q-FISH; ref. 7) that the number of T2AG3 repeats on specific chromosome arms is very similar in different tissues from the same donor and varies only to some extent between donors. In all sixteen individuals studied, telomeres on chromosome 17p were shorter than the median telomere length--a finding confirmed by analysis of terminal restriction fragments from sorted chromosomes. These observations provide evidence of chromosome-specific factors regulating the number of T2AG3 repeats in individual telomeres and raise the possibility that the relatively short telomeres on chromosome 17p contribute to the frequent loss of 17p alleles in human cancers.

The ultra-long telomeres that have been observed in mice are not in accordance with the concept that critical telomere shortening is related to aging and immortalization. Here, we have used quantitative fluorescence in situ hybridization to estimate (T 2 AG 3 ) n lengths of individual telomeres in various mouse strains. Telomere lengths were very heterogeneous, but specific chromosomes of bone marrow cells and skin fibroblasts from individual mice had similar telomere lengths. We estimate that the shortest telomeres are around 10 kb in length, indicating that each mouse cell has a few telomeres with (T 2 AG 3 ) n lengths within the range of human telomeres. These short telomeres may be critical in limiting the replicative potential of murine cells.

Hematopoietic reconsitution after transplantation requires the presence of cells with early and late repopulating ability. To determine the contribution of relatively immature and mature hematopoietic progenitor cells in engraftment, we used a modified rhodamine staining procedure to purify populations of rhodamine 123 (Rho)bright, Rhodull and Rho− cells from mouse steady-state bone marrow. Following transplantation of these subsets of stem cells in lethally irradiated mice, marrow repopulating cells were mainly present in the small fraction of Rho− cells, indicating that hematopoietic stem cells have a relatively high expression of P-glycoprotein. Similar cell populations could be purified from cytokine-mobilized blood following treatment with cyclophosphamide and G-CSF. The Rho−cell population contained the majority of hematopoietic stem cells with in vivo marrow repopulating ability. In methylcellulose colony assays, the majority of the committed progenitor cells were present in Rhodull and Rhobright fractions. These results indicate that relatively primitive populations of hematopoietic stem cells that lack colony-forming capacity in vitro mediate the early phase of engraftment following syngeneic stem cell transplantation. Stem Cells 1997; 15(suppl 1): 47–53

A novel cDNA encoding a putative secreted protein was isolated from murine bone marrow. The encoded protein named MCLP ( m urine c athelin- l ike p rotein) was found to be highly homologous to the pig cathelin, and to four neutrophil antimicrobial polypeptides: CAP 18, indolicidin, Bac 5 and FALL-39. Secondary structure prediction studies identified a highly cationic region in the C-terminal part of prepro-MCLP with a tendency to adopt an amphipathic α-helical conformation, as observed in many antimicrobial peptides. However, no antibacterial activity was observed with the synthetic peptide corresponding to this region of MCLP.

Thrombotic microangiopathy (TMA) can be a late complication of bone marrow transplantation (BMT). A patient is described in whom the haemolytic uraemic syndrome developed 10 months after BMT and who died of E. coli sepsis while on maintenance haemodialysis. The literature is reviewed, regarding clinical presentation, incidence, pathogenesis and therapy. TMA can be observed, after an interval of 3-12 months, in about 6-26% of patients following BMT. Reported cases vary considerably in clinical severity, from mild presentations to severe TMA with high mortality rates despite intensive therapy. Important pathogenetic roles are ascribed to the conditioning total body irradiation and the use of cyclosporin A, but other factors may be involved as well. Next to supportive therapy, plasma exchange and the use of ACE inhibitors may be of value in treating BMT-associated TMA.

To improve the cost-benefit ratio of our current screening program for retinopathy of prematurity (ROP), the records of 312 infants who had been screened for ROP were studied retrospectively. Using a safety-index containing three well known risk factors (birthweight, gestational age, oxygen use), infants were classified to be at high risk or low risk for the development of ROP. When all high risk infants would have been screened extensively from the 5 th postnatal week onwards and all low risk infants would have been screened once at the 7 th postnatal week, a 9.8% reduction of ophthalmological examinations would have been obtained at the expense of missing 2.9% of non vision threatening ROP.

Early detection of retinopathy of prematurity (ROP) in premature and very-low-birth-weight infants is crucial. In this retrospective study, 581 infants either with a birth weight below 1500 g or a gestational age of less than 32 weeks, or who did not fit these criteria but were judged to be at increased risk, were screened for ROP. ROP developed in 159 (27.4%). The incidence of ROP appeared to be inversely proportional to birth weight and gestational age. Infants with a birth weight below 750 g had a significantly higher risk of developing stage 3 and 4 ROP. The mean age at detection was 7.6 ± 1.6 weeks. Nearly all of the ROP cases and all of the stage 3 and 4 cases were detected between the 5th and 10th week. Because screening should be focused on these visionthreatening stages, ophthalmic examinations should be concentrated in, but not limited to, the period between the 5th and the 10th postnatal week.

Chorea may occur as part of the symptomatology of acute stroke; it occasionally also may be delayed or progressive. Patients with vascular-related chorea typically present with an acute or subacute onset of chorea of one side of the body (hemichorea), contralateral to the lesion. Cerebrovascular disease is the most common cause of sporadic chorea. Lesions are most frequently found in the thalamus and lentiform nucleus, and less often in subthalamic nucleus. The differential diagnosis of choreic syndromes relies not so much on differences in the phenomenology of the hyperkinesia but the age at onset, mode of onset, time course, family history, drug use, distribution of chorea in the body, and presence of accompanying neurological findings. Magnetic resonance imaging is preferred to demonstrate the presence of strategic small lesions in regions that are difficult to image with computed tomography, such as the globus pallidus, thalamus, and subthalamic nucleus. Although the prognosis of hemichorea can be benign, the long-term prognosis is not specifically determined by the hemichorea but by the long-term prognosis of stroke patients. Symptomatic treatment with antichoreic drugs may be necessary in the acute phase. Surgery is rarely indicated to treat vascular chorea.

Staff working with clients with intellectual disabilities (ID) who display challenging behaviour may contribute to the continuation of this behaviour, because it causes emotional reactions such as anxiety, anger and annoyance, which may prohibit adequate response behaviour. To enhance staff behaviour and treatment skills a training that aimed at improving emotional intelligence (EQ) was developed.The goal of this study was to assess whether an EQ training in combination with a video-feedback training programme improves emotional intelligence of staff working with clients with ID and challenging behaviour.Participants were 60 staff members working with individuals with ID and challenging behaviour. Thirty-four staff members participated in a 4-month training programme and 26 constituted the control group. A pretest-posttest control group design was used. Effectiveness was assessed by using the Dutch version of the Bar-On EQ-i and the judgments of experts on emotional intelligence.Emotional intelligence of the experimental group changed significantly more than that of the control group. Judgments of experts on emotional intelligence indicated that the change of emotional intelligence of the experimental group improved positively.The positive effect of the training programme on emotional intelligence is consistent with previous research on emotional intelligence and suggests that emotional intelligence of staff working with clients with ID and challenging behaviour can be influenced by training.

Chorea may occur as part of the symptomatology of acute stroke; it occasionally also may be delayed or progressive. Patients with vascular-related chorea typically present with an acute or subacute onset of chorea of one side of the body (hemichorea), contralateral to the lesion. Cerebrovascular disease is the most common cause of sporadic chorea. Lesions are most frequently found in the thalamus and lentiform nucleus, and less often in subthalamic nucleus. The differential diagnosis of choreic syndromes relies not so much on differences in the phenomenology of the hyperkinesia but the age at onset, mode of onset, time course, family history, drug use, distribution of chorea in the body, and presence of accompanying neurological findings. Magnetic resonance imaging is preferred to demonstrate the presence of strategic small lesions in regions that are difficult to image with computed tomography, such as the globus pallidus, thalamus, and subthalamic nucleus. Although the prognosis of hemichorea can be benign, the long-term prognosis is not specifically determined by the hemichorea but by the long-term prognosis of stroke patients. Symptomatic treatment with antichoreic drugs may be necessary in the acute phase. Surgery is rarely indicated to treat vascular chorea.

Human umbilical cord blood (UCB) may be used as an alternative source of bone marrow repopulating cells in allogeneic bone marrow transplantation in children. It has been reported that high numbers of hematopoietic progenitor cells (HPC) from umbilical cord blood may be lost during simple cell-separation techniques. This may seriously hamper the use of UCB as an alternative source of bone marrow repopulating cells. In this study we demonstrate that UCB can be separated into various cell fractions using several cell-separation methods including red blood cell lysis, methylcellulose sedimentation, and density gradients without significant loss of HPC, when cell separations are initiated within 8 h. We demonstrate that UCB contains a high concentration of immature HPC as compared with bone marrow grafts. Using FACS analysis of cells harvested from single colonies derived from single cell- single well-sorted CD34++ CD33- UCB cells, the high frequency of multipotential HPC was illustrated. These results suggest that UCB may contain sufficient HPC for hematopoietic stem cell transplantation in adults.

A well-known way of using tendency survey data is the construction of Composite Leading Indicators (CLIs). It is rather peculiar that CLIs pretend to predict macroeconomic aggregates, while their construction is not consistent with the way actual macroeconomic statistics are compiled. This paper contains preliminary results of an attempt to integrate tendency survey indicators into the framework of the Dutch Quarterly Accounts. We conclude that tendency survey indicators can contribute to an explanation of trends in “real” economic variables. Many of these indicators lead the Quarterly Accounts indicators. They can, therefore, contribute to a timely estimation of National Accounts aggregates.

A 20-year-old woman was admitted to the hospital because of fever and mediastinal lymphadenopathy. Six years before admission Raynaud's phenomenon was diagnosed. Two years later she developed symmetrical polyarthritis with morning stiffness. Latex agglutination and antinuclear antibodies (ANA) were positive. She was treated with indomethacin, gold and chloroquine

Item does not contain fulltext Recent literature suggests that after non-myeloablative allogeneic (NMA) stem cell transplantation (SCT), the incidence of extramedullary (EM) relapse in multiple myeloma (MM) patients is increased and that these relapses have a poor prognosis. However, numbers on incidence and treatment outcome are scarce. We collected data from 54 relapsed MM patients from a total group of 172 treated with sequential autologous and allogeneic NMA SCT at seven transplantation centres. There were 43 (79.6%) systemic relapses, including 6 with concurrent EM localisation. Five patients had a local EM relapse only. Six patients relapsed with only bone involvement. Patients with deletion of chromosome 13 had a higher incidence of EM relapse (30.8 versus 5.6%, P=0.06). EM relapses were treated with donor lymphocyte infusion, radiotherapy, or chemotherapy, especially with novel agents. The response rate was 45.5%, which was not different when compared to patients without EM disease (54.1%). Overall survival and progression-free survival were not significantly different in patients with EM disease, when compared to those without EM disease. In conclusion, the incidence of relapse with EM disease following allogeneic NMA SCT was 20.4%. There was no negative impact of EM relapse on response rate, overall survival and progression-free survival.

In EEG correlated fMRI interictal spikes as identified in the EEG during scanning of an epilepsy patient are used as events in an event related fMRI design. Spike identification, whether automatic or by a human observer, is accompanied by uncertainty and inevitably leads to false detections and missed events. This situation is not common in event related fMRI, where events are usually controlled by the experimental paradigm. In a simulation study based on a well controlled fMRI motor task we evaluated the effect on the significance of the expected fMRI activation of missed and false events. It is found that the impact of missed events is larger, suggesting that uncertain spikes should be included in the analysis.

An 82-year-old man was brought into the emergency department after an epileptic seizure. Although the seizure took place in his bed and was not followed by a fall, his right hip was broken. No underlying bone abnormalities were found. The patient received a femoral headneck prosthesis and recovered fully. Fractures are more common in patients with epilepsy than in the general population, due to both seizure-related trauma and a relatively high prevalence of osteoporosis, which is due partly to the use of anti-epileptic drugs. However, even after a seizure without trauma in a patient without underlying abnormalities of bone structure, a fracture may arise as a result of the force of the muscle contractions during the seizure.

textabstractTelomeric proteins have an essential role in the regulation of the length of the telomeric DNA tract and in protection against end-to-end chromosome fusion. Telomere organization and how individual proteins are involved in different telomere functions in living cells is largely unknown. By using green fluorescent protein tagging and photobleaching, we investigated in vivo interactions of human telomeric DNA-binding proteins with telomeric DNA. Our results show that telomeric proteins interact with telomeres in a complex dynamic fashion: TRF2, which has a dual role in chromosome end protection and telomere length homeostasis, resides at telomeres in two distinct pools. One fraction ( approximately 73%) has binding dynamics similar to TRF1 (residence time of approximately 44 s). Interestingly, the other fraction of TRF2 binds with similar dynamics as the putative end-protecting factor hPOT1 (residence time of approximately 11 min). Our data support a dynamic model of telomeres in which chromosome end-protection and telomere length homeostasis are governed by differential binding of telomeric proteins to telomeric DNA.

This chapter is based in part on bachelor thesis work by the second author. Data used in this study were collected as part of the first author’s doctoral work funded by the Center for Innovation Research at Tilburg University.

We investigated whether [(123)I]-beta-CIT and single-photon emission computed tomography (SPECT) imaging distinguishes patients with clinically suspected vascular parkinsonism (VP) from patients with idiopathic Parkinson's disease (PD). [(123)I]beta-CIT SPECT is a sensitive marker of dopaminergic degeneration, and the degree of striatal binding reduction in PD correlates with disease severity. Thirteen patients who fulfilled rigid clinical criteria for VP (mean +/- S.D.: age, 76.5 +/- 5.3 years; disease duration, 3.6 +/- 2.8 years), 20 PD patients (age, 66.2 +/- 9.5 years; disease duration, 4.3 +/- 2.7 years), and 30 healthy persons (age, 44.6 +/- 19.2 years) underwent [(123)I]beta-CIT SPECT imaging. Age-corrected striatal beta-CIT binding was reduced on average by 40.8% in PD but was near normal in the VP group (mean reduction, 1.2%). This difference was statistically significant (Z = 4.68; P0.001). The left-right asymmetry of striatal beta-CIT binding was significantly increased in the PD group compared with normal controls and the VP group (F(2) = 17.4, P0.001). Moreover, putamen-caudate nucleus ratios were significantly reduced in PD compared with both VP patients and healthy controls (F(2) = 65.5, P0.001). Whole striatal beta-CIT binding was more than one standard deviation above the mean PD values in all but one of the individual VP patients. Our findings suggest that the presynaptic dopaminergic deficits seen in PD are absent in most patients with VP. [(123)I]beta-CIT SPECT imaging may be useful to help distinguish between PD and VP patients during life.

The anti-CD33 monoclonal antibody linked to NAc-gamma calicheamicin gemtuzumab ozogamicin (CMA-676) was used to treat a patient with Philadelphia/bcr-abl-positive acute myeloid leukaemia. We report a morphological and cytogenetic complete remission after treatment with two doses of gemtuzumab ozogamicin as a single agent. Using real-time polymerase chain reaction (PCR), gemtuzumab ozogamicin treatment resulted in a 3-log tumour mass reduction in bone marrow.

Blood cell transplantation is largely replacing bone marrow transplantation because engraftment is more rapid. This accelerated engraftment is thought to be mediated by relatively mature committed hematopoietic progenitor cells. Herein, we have used a modified rhodamine (Rho) staining procedure to identify and purify Rho+/++(dull/bright) and Rho−(negative) subpopulations of hematopoietic progenitor cells in murine cytokine-mobilized blood. The Rho+/++cell population contained >99% of committed progenitor cells within vitrocolony-forming ability. The Rho−cell population contained the majority of hematopoietic stem cells within vivomarrow repopulating ability. The rate of hematopoietic reconstitution was identical in recipients of grafts containing only purified Rho−stem cells or purified Rho−stem cells in combination with large numbers of Rho+/++committed progenitor cells. In contrast, transplantation of 3-fold more hematopoietic stem cells resulted in accelerated reconstitution, indicating that the reconstitution rate was determined by the absolute numbers of Rho−stem cells in the graft. In addition, we observed a 5- to 8-fold reduced frequency of the subset of hematopoietic stem cells with long-term repopulating ability in cytokine-mobilized blood in comparison to steady-state bone marrow. Our results indicate that hematopoietic stem cells and not committed progenitor cells mediate early hematopoietic reconstitution after blood cell transplantation and that relative to bone marrow, the frequency of stem cells with long-term repopulating ability is reduced in mobilized blood.

The limited life span of most blood cells requires the continuous production of cells, which in adults exceeds 10(12) cells/day. This impressive production of cells (approximately 4 x 10(16) cells over a lifetime) is achieved by the proliferation and differentiation of committed progenitor cells, which themselves are derived from a population of pluripotent stem cells with self-renewal potential. Paradoxically, the large majority of stem cells in adult bone marrow are quiescent cells. One possibility is that stem cells, like other somatic cells, have only a limited replicative potential (100 divisions). This hypothesis is supported by two key observations and the consideration that, in theory, 55 divisions can yield 4 x 10(16) cells. First, it was shown that 'candidate' stem cells purified from fetal and adult tissue showed dramatic functional differences in turn-over time and the ability to produce cells with stem cell properties, Second, these functional differences were found to correlate with a measurable loss of telomere repeats despite the presence of low but readily detectable levels of telomerase in all purified cell fractions. In order to address questions about the role of telomeres in normal and malignant haemopoiesis, we developed a quantitative fluorescence in situ hybridization technique. Here we review the characteristics of this novel tool to assess the number of telomere repeats at the end of individual chromosomes and provide an overview of recent observations.