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Purpose: eHealth-based exercise therapies were developed to increase stroke patients' adherence to home-based motor rehabilitation. However, these eHealth tools face a rapid decrease in use after a couple of weeks. This study investigates stroke patients' motivation for home-based upper extremity rehabilitation with eHealth tools and their relation with Basic Psychological Needs. Materials and methods: This is a qualitative study using thematic analysis. We conducted semi-structured interviews with stroke patients with upper extremity motor impairments, who were discharged home from a rehabilitation centre, after they interacted with a novel eHealth coach demonstrator in their homes for five consecutive days. Results: We included ten stroke patients. Thematic analysis resulted in eight themes for home-based rehabilitation motivation: Curiosity, Rationale, Choice, Optimal challenge, Reference, Encouragement, Social Support and Trustworthiness. Those themes are embedded into three Basic Psychological Needs: "Autonomy", "Competence", and "Relatedness". Conclusion: Eight motivational themes related to the three Basic Psychological Needs describe stroke patients' motivation for home-based upper extremity rehabilitation. We recommend considering those themes when developing a home-based eHealth intervention for stroke patients to increase the alignment of eHealth tools to the patient's needs and reduce motivational decreases in home-based rehabilitation. IMPLICATIONS FOR REHABILITATION: Stroke patients show motivational decreases and decreased use of eHealth tools in home-based rehabilitation after a couple of weeks. Eight motivational themes describe home-based rehabilitation motivation in stroke patients: Curiosity, Rationale, Choice, Optimal challenge, Reference, Encouragement, Social Support and Trustworthiness. Those themes are embedded into three Basic Psychological Needs: "Autonomy", "Competence", and "Relatedness". Those themes should be considered when developing a home-based eHealth intervention for stroke patients to increase the alignment of eHealth tools to the patient's needs and reduce motivational decreases in home-based rehabilitation. [ABSTRACT FROM AUTHOR]

Socioeconomic status (SES) tends to influence an individual's access to health care. It is commonly assumed that a poorer SES is associated with a weaker physical health status, especially in disadvantaged populations such as people with cerebral palsy (CP). However, to our knowledge, no study has looked at this assumption. Therefore, the aim of this study was to describe and compare the physical health status of ambulant adults with bilateral CP with different SES backgrounds. In addition, the physical health status of the ambulatory adults with CP was compared to well‐matched, typically developing adults. Twenty‐eight ambulatory adults with CP (gross motor functional classification system Level I/II/III: n = 11/12/5; SES low/middle/high: n = 10/9/9), and 28 matched typically developing adults were recruited for this study. No differences were observed between adults with CP from different SES backgrounds. Differences in physical health status between typically developing adults and ambulatory adults with CP in all SES backgrounds were found in passive range of motion (p < 0.05), muscle strength (p < 0.001), selectivity (p < 0.001), and muscle tone (p < 0.001) and balance (p < 0.05). The main finding of this study is that physical health status did not differ between ambulatory adults with CP from different SES backgrounds. This finding shows that SES does not always directly impact physical health status in ambulatory adults with CP and highlights the importance of an individual approach. Future research should determine the impact of SES on nonambulatory adults with CP. [ABSTRACT FROM AUTHOR]

AbstracteHealth solutions at home are gaining interest and relevance in healthcare; however, they face challenges in sustaining motivation for therapy due to difficulties in creating meaningful connections between technology and people receiving care. In this article, we explore how embodied agents in eHealth interventions could be designed to establish a motivating relationship with people in the context of home-based stroke rehabilitation. We studied this potential by referring to the need for social relatedness in Self-Determination-Theory (SDT) and how this translates to the design of embodied agents’ characters, the collaborations they afford and the partnerships they establish over time. In co-creative ideation sessions with stroke survivors, this potential was explored, resulting in an interactive prototype of ‘Edo the Coach’, i.e. an embodied agent for home-based upper extremity stroke rehabilitation that was evaluated by stroke survivors in their home contexts. Based on the insights gained, we reflect on the potential of using SDT for designing embodied agents that foster motivational relationships between patient and agent as an answer to the growing demand for eHealth-supported self-care within an increasingly digitized healthcare context. [ABSTRACT FROM AUTHOR]

Introduction: Cochlear implantation is the standard treatment for severe to profound hearing loss. While cochlear implant (CI) users can communicate effectively in quiet environments, speech understanding in noise remains challenging. Bimodal hearing, combining a CI in one ear and a hearing aid (HA) in the other, has shown advantages over unilateral electrical hearing, especially for speech understanding in noisy conditions. Beamforming is a technique used to improve speech understanding in noise by detecting sound direction and enhancing frontal (speech) sounds while attenuating background noise. One specific beamformer, Stereozoom, combines signals from microphones in both ears to create a focused beam toward the front resulting in a binaural beamformer (BB), in order to improve speech intelligibility in noise for bilateral and bimodal CI users. Methods: A prospective crossover study involving 17 bimodal CI users was conducted, and participants were tested with various device configurations (CI, HA, CI + HA) with and without BB. Speech recognition testing with the Dutch/Flemish matrix test was performed in a sound-attenuated booth with diffuse noise to simulate realistic listening conditions. Results: The results showed a statistically significant benefit of bimodal hearing over the CI configuration and showed a statistical significant benefit of BB for the CI and CI + HA configuration. The benefit of BB in the HA configuration was not statistically significant probably due to the higher variance. The benefit of BB in the three configurations did not differ statistically significant. Conclusion: In conclusion, bimodal hearing offers advantages for speech understanding in noise for CI users. BB provides a benefit in various device configurations, leading to improved speech intelligibility when speech comes from the front in challenging listening environments. Plain Language Summary: Cochlear implantation is the standard treatment for severe to profound hearing loss. While cochlear implant (CI) users can communicate effectively in quiet environments, speech understanding in noise remains challenging. Bimodal hearing, combining a CI in one ear and a hearing aid (HA) in the other, has shown advantages over unilateral electrical hearing, especially for speech understanding in noisy conditions. We analyzed the effect of the addition of the HA to the CI in this paper. There are also other processing techniques available to improve speech understanding in noise for this population. In this paper, one of these techniques, beamforming, is studied in different configurations. Therefore, 17 participants with a CI in one ear and a HA in the other ear are included. They performed a speech test for different configurations with and without beamforming to be able to analyze the effect of beamforming. [ABSTRACT FROM AUTHOR]

Telerehabilitation systems have the potential to enable therapists to monitor and assist stroke patients in achieving high-intensity upper extremity exercise in the home environment. We adopted an iterative user-centred approach, including multiple data sources and meetings with end-users and stakeholders to define the user requirements for home-based upper extremity rehabilitation using wearable motion sensors for subacute stroke patients. We performed a requirement analysis consisting of the following steps: 1) context & groundwork; 2) eliciting requirements; 3) modelling & analysis; 4) agreeing requirements. During these steps, a pragmatic literature search, interviews and focus groups with stroke patients, physiotherapists and occupational therapists were performed. The results were systematically analysed and prioritised into "must-haves", "should-haves", and "could-haves". We formulated 33 functional requirements: eighteen must-have requirements related to blended care (2), exercise principles (7), exercise delivery (3), exercise evaluation (4), and usability (2); ten should-haves; and five could-haves. Six movement components, including twelve exercises and five combination exercises, are required. For each exercise, appropriate exercise measures were defined. This study provides an overview of functional requirements, required exercises, and required exercise measures for home-based upper extremity rehabilitation using wearable motion sensors for stroke patients, which can be used to develop home-based upper extremity rehabilitation interventions. Moreover, the comprehensive and systematic requirement analysis used in this study can be applied by other researchers and developers when extracting requirements for designing a system or intervention in a medical context. This study provides an extensive overview of user requirements for home-based upper extremity rehabilitation using wearable motion sensors in stroke patients. These requirements can be used as a basis for developing home-based UE telerehabilitation interventions. Including these requirements may facilitate the clinical implementation of such telerehabilitation systems. The comprehensive and systematic approach used in this sudy can be applied by other researchers and developers when extracting requirements for designing a system or intervention in a medical context. [ABSTRACT FROM AUTHOR]

• Our understanding of lymphoma predisposition has evolved rapidly over the last decades, accelerated by novel technologies. • Lymphoma-predisposing conditions include inborn errors of immunity, autoimmune disease and immunosuppressive treatment. • Shared characteristic features across clinically unique conditions reveal underlying mechanisms for lymphoma predisposition. • New insights in lymphomagenesis provide opportunities for early detection, prevention and tailored treatment of lymphoma. Lymphoma is a heterogeneous group of malignancies arising from lymphocytes, which poses a significant challenge in terms of diagnosis and treatment due to its diverse subtypes and underlying mechanisms. This review aims to explore the shared and distinct features of various forms of lymphoma predisposing conditions, with a focus on genetic, immunological and molecular aspects. While diseases such as autoimmune disorders, inborn errors of immunity and iatrogenic immunodeficiencies are biologically and immunologically distinct, each of these diseases results in profound immune dysregulation and a predisposition to lymphoma development. Interestingly, the increased risk is often skewed towards a particular subtype of lymphoma. Patients with inborn errors of immunity in particular present with extreme forms of lymphoma predisposition, providing a unique opportunity to study the underlying mechanisms. External factors such as chronic infections and environmental exposures further modulate the risk of lymphoma development. Common features of conditions predisposing to lymphoma include: persistent inflammation, recurrent DNA damage or malfunctioning DNA repair, impaired tumor surveillance and viral clearance, and dysregulation of fundamental cellular processes such as activation, proliferation and apoptosis. Our growing understanding of the underlying mechanisms of lymphomagenesis provides opportunities for early detection, prevention and tailored treatment of lymphoma development. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the feasibility and explore the efficacy of the Arm Activity Tracker (AAT). The AAT is a device based on wrist-worn accelerometers that provides visual and tactile feedback to stimulate daily life upper extremity (UE) activity in stroke patients. Methods: A randomised, crossover within-subject study was conducted in sub-acute stroke patients admitted to a rehabilitation centre. Feasibility encompassed (1) adherence: the dropout rate and the number of participants with insufficient AAT data collection; (2) acceptance: the technology acceptance model (range: 7–112) and (3) usability: the system usability scale (range: 0–100). A two-way ANOVA was used to estimate the difference between the baseline, intervention and control conditions for (1) paretic UE activity and (2) UE activity ratio. Results: Seventeen stroke patients were included. A 29% dropout rate was observed, and two participants had insufficient data collection. Participants who adhered to the study reported good acceptance (median (IQR): 94 (77–111)) and usability (median (IQR): 77.5 (75–78.5)-). We found small to medium effect sizes favouring the intervention condition for paretic UE activity (η2G = 0.07, p = 0.04) and ratio (η2G = 0.11, p = 0.22). Conclusion: Participants who adhered to the study showed good acceptance and usability of the AAT and increased paretic UE activity. Dropouts should be further evaluated, and a sufficiently powered trial should be performed to analyse efficacy. [ABSTRACT FROM AUTHOR]

During the 2015–2016 outbreak of Zika virus (ZIKV) in the Americas, a previously unknown severe complication of ZIKV infection during pregnancy resulting in birth defects was reported. Since the ZIKV outbreak occurred in regions that were highly endemic for the related dengue virus (DENV), it was speculated that antibody-dependent enhancement (ADE) of a ZIKV infection, caused by the presence of cross-reactive DENV antibodies, could contribute to ZIKV disease severity. Emerging evidence indicates that, while in vitro models can show ADE of ZIKV infection, ADE does not seem to contribute to congenital ZIKV disease severity in humans. However, the role of ADE of ZIKV infection during pregnancy and in vertical ZIKV transmission is not well studied. In this study, we hypothesized that pregnancy may affect the ability of myeloid cells to become infected with ZIKV, potentially through ADE. We first systematically assessed which cell lines and primary cells can be used to study ZIKV ADE in vitro, and we compared the difference in outcomes of (ADE) infection experiments between these cells. Subsequently, we tested the hypothesis that pregnancy may affect the ability of myeloid cells to become infected through ADE, by performing ZIKV ADE assays with primary cells isolated from blood of pregnant women from different trimesters and from age-matched non-pregnant women. We found that ADE of ZIKV infection can be induced in myeloid cell lines U937, THP-1, and K562 as well as in monocyte-derived macrophages from healthy donors. There was no difference in permissiveness for ZIKV infection or ADE potential of ZIKV infection in primary cells of pregnant women compared to non-pregnant women. In conclusion, no increased permissiveness for ZIKV infection and ADE of ZIKV infection was found using in vitro models of primary myeloid cells from pregnant women compared to age-matched non-pregnant women. [ABSTRACT FROM AUTHOR]

This article relates and compares some important features of Western religious and secular morality by way of surveying the debate over different answers to the question whether morality depends on religion in some significant way. The three main ways examined are whether morality depends on religion for an objective foundation, whether morality depends on religion for its content, and whether morality depends on religion for motivation. What emerges is that while religion can provide an objective foundation, a worthy content, and an admirable motivation for those who accept its distinctive theological claims, secularists can provide plausible, if debatable, alternatives to a theological foundation, as well as a moral content and motivation that can have interesting overlaps with those of religious ethics. [ABSTRACT FROM AUTHOR]

Whereas it is well documented how parents experience the diagnostic process of their child with autism spectrum disorder (ASD), less is known about parental experiences with the course of the early identification process and first steps in receiving care for their child with ASD symptoms. This mixed-method study investigated these experiences as well as barriers and improvement strategies regarding early detection in the Netherlands. A parental survey (N = 45) showed that, on average, initial concerns started at 22 months. A focus group (N = 10) revealed multiple barriers and proposed strategies of improvement in three domains: "Knowledge and Expertise", "Attention to Parental Needs" and "System and Organization". Strategies to improve early identification will be discussed based on parental perspectives and professional perspectives. [ABSTRACT FROM AUTHOR]

A Zika virus (ZIKV) infection during pregnancy can result in severe birth defects such as microcephaly. To date, it is incompletely understood how ZIKV can cross the human placenta. Furthermore, results from studies in pregnant mice and non-human primates are conflicting regarding the role of cross-reactive dengue virus (DENV) antibodies on transplacental ZIKV transmission. Elucidating how ZIKV can cross the placenta and which risk factors contribute to this is important for risk assessment and for potential intervention strategies for transplacental ZIKV transmission. In this study we use an ex vivo human placental perfusion model to study transplacental ZIKV transmission and the effect that cross-reactive DENV antibodies have on this transmission. By using this model, we demonstrate that DENV antibodies significantly increase ZIKV uptake in perfused human placentas and that this increased uptake is neonatal Fc-receptor-dependent. Furthermore, we show that cross-reactive DENV antibodies enhance ZIKV infection in term human placental explants and in primary fetal macrophages but not in primary trophoblasts. Our data supports the hypothesis that presence of cross-reactive DENV antibodies could be an important risk factor for transplacental ZIKV transmission. Furthermore, we demonstrate that the ex vivo placental perfusion model is a relevant and animal friendly model to study transplacental pathogen transmission. Author summary: Zika virus is a mosquito-transmitted virus that can cause severe birth defects such as microcephaly when the infection occurs during pregnancy. Understanding how Zika virus crosses the placenta during pregnancy is important for future prevention strategies for vertical Zika virus transmission. Despite significant efforts to study this, to date it remains incompletely understood how Zika virus can cross the placenta and which risk factors contribute to this form of transmission. In this study we use an ex vivo placental perfusion model to study transplacental Zika virus transmission. The ex vivo placental perfusion model is a highly physiological and animal friendly model that mimics the in vivo conditions during pregnancy. We found that antibodies against the closely related dengue virus can significantly enhance placental uptake of Zika virus and Zika virus infection of human placental explants and fetal macrophages. These findings indicate that presence of cross-reactive dengue virus antibodies could contribute to transplacental Zika virus transmission. [ABSTRACT FROM AUTHOR]

Background: Although the short-term outcomes of selective dorsal rhizotomy (SDR) in children with cerebral palsy (CP) have been well documented, less is known about the long-term benefits of SDR, especially while aging.Research Question: Does the gait of adults with CP, who underwent SDR in childhood, change during a nine-year aging follow-up period? Do associations exists between the gait deviation index (GDI) and contextual factors at follow-up?Methods: Three-dimensional motion data was captured (Vicon system) of 26 adults (10 female) with CP and spastic diplegia at baseline (17-to-26 years post-SDR) and at nine-year follow-up (26-to-35 years post-SDR), as well as 41 matched typically developed (TD) adults used for reference data. Kinematic, non-dimensional temporal distance and GDI parameters were determined, and associations with contextual factors were studied.Results: At follow-up the adults with CP had a (median [interquartile ranges]) age of 35.8 [34.2-41.2] years and classified as Gross Motor Function Classification System (GMFCS) level I (n = 13), level II (n = 10) and level III (n = 3). Overall no clinically relevant change in gait quality (GDI) was detected over the nine-year follow-up period. However, small changes were found in hip and knee range of motion, peak knee flexion and walking speed. In line with the baseline study, a number of gait parameters were different to TD adults. The only association found was between GDI and GMFCS at follow-up (r = 0.64, p < 0.01).Significance: The overall walking pattern of the adults with CP who underwent SDR in childhood was characterised by mild crouch gait with minimal signs of spasticity, confirming former physical examination findings. Some small changes in certain gait parameters were determined, though clinically the gait quality remained stable during the nine-year aging period. This finding supports the stability of the gait pattern during mid-life in adults with CP, who met the strict SDR selection criteria. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine the incidence of spinal deformities in ambulant adults with cerebral palsy (CP) and spastic diplegia, more than 15 years after orthopaedic interval surgery approach (ISA) treatment, and its relationship to contextual factors, level of pain and physical status.Methods: Spinal X-rays, pain (Oswestry Disability Index (ODI) and location/frequency) questionnaires and physical examination assessing lower extremity muscle strength (Medical Research Council scale), motor control (selectivity scale) and muscle tone (Ashworth score) were conducted in 30 adults with spastic diplegic CP.Results: Mild scoliosis (curve 12-22°) was determined in eight (28%) participants. Hyperkyphosis (> 50°) was reported in two (7%) and lumbar hyperlordosis (> 60°) in five (17%) participants. Pain was most commonly reported at cervical (n = 19, 63%) and lumbosacral (n = 18, 60%) area, resulting in 'moderate disability' for six (20%) and 'severe disability' for one (3%) participant. Most apparent physical abnormalities determined were hip abduction weakness and increased rectus femoris muscle tone. Regarding correlations, no relations were found for scoliosis curvature, but kyphosis curvature was related to females, ODI scores (lifting and sitting) and increased muscle tone of ankle plantar flexor muscles, lordosis curvature to passive hip extension mobility, and hip flexors and ankle plantar flexors muscle tone.Conclusion: Adults with spastic diplegic CP who received their first orthopaedic intervention more than 15 years ago (based on ISA) showed similar incidence of spinal deformities as reported in the younger CP population, suggesting stability of spinal curvature into adulthood. These slides can be retrieved under Electronic Supplementary Material. [ABSTRACT FROM AUTHOR]

Background: End-stage renal disease is associated with premature ageing of the T cell immune system but inter-individual variation is substantial. The hypothesis was tested that advanced immunological T cell ageing assessed by peripheral T cell differentiation increases the long-term mortality risk after renal transplantation. Results: Circulating T cells of 211 recipients of a kidney from a living donor were analyzed before and in the first year after transplantation. The number of CD31-positive naive T cells (as a marker for recent thymic emigrants) and the differentiation status of the memory T cells was assessed. Thirty recipients died during follow-up of at least 5 years. Absolute numbers of naive CD4+ (living:258 cells/μl vs. deceased:101 cells/μl, p < 0.001) and naive CD8+ T cells (living:97 cells/μl vs. deceased:37 cells/μl, p < 0.001) were significantly lower in the deceased group prior to transplantation. In a multivariate proportional hazard analysis the number of naive CD4+ T cells remained associated with all-cause mortality (HR 0.98, CI 0.98–0.99, p < 0.001). The low number of naive T cells in the deceased patient group was primarily caused by a decrease in recent thymic emigrants (i.e. less CD31+ naive T cells) indicating a lowered thymus function. In addition, the physiological age-related compensatory increase in CD31− naïve T cells was not observed. Within the first year after transplantation, the number and characteristics of naive T cells remained stable. Conclusions: A severe reduction in circulating naïve T cells because of a decrease in recent thymic emigrants is highly associated with all-cause mortality after renal transplantation. [ABSTRACT FROM AUTHOR]

Background: Single-event multilevel surgery (SEMLS) approach is regarded as the golden standard in developed countries to improve gait and functional mobility in children with cerebral palsy (CP). However, this approach is not always feasible in developing countries. Therefore, orthopedic surgery based on an interval surgery approach (ISA) is still commonly used in developing countries, although little is known about the long term outcomes of an ISA. Therefore, the aim of this study was to describe the gait patterns of adults with CP, who have been treated with ISA, which started more than 15 years ago. Materials and Methods: Thirty adults with CP and spastic diplegia, who received ISA treatment 21.6–33.7 years ago, were recruited for this study and participated in three-dimensional gait analysis. Twenty kinematic and nondimensional temporal-distance parameters were captured, while the overall gait deviation index (GDI) was also calculated. Data of the adults with CP were compared to normative data of typically developing (TD) adults. Results: Although all adults with CP were still ambulant, their gait parameters significantly differed from TD adults, with a lower GDI in the adults with CP. The CP gait patterns were characterized by excessive hip flexion and hip internal rotation as well as a stiff-knee gait. Conclusion: Although different to TD adults, the gait patterns observed in the adult with CP treated with ISA is in line with other studies. Gait patterns suggest that derotation osteotomies potentially could have improved the long term gait patterns. Although SEMLS might be the preferred treatment method, potentially resulting in better outcomes, ISA can also be used to treat children with CP in developing countries as India and South Africa, where a SEMLS approach is not always feasible. [ABSTRACT FROM AUTHOR]

In 2015-2016, a Zika virus (ZIKV) outbreak occurred in the Americas. In 2017, we conducted a ZIKV serosurvey in Suriname in which 770 participants were recruited from 1 urban area and 2 rural villages in the tropical rainforest. All collected samples were tested for presence of ZIKV antibodies using a ZIKV immunoglobulin G enzyme-linked immunosorbent assay and a virus neutralization assay. We found that 35.1% of the participants had neutralizing antibodies against ZIKV. In 1 remote village in the rainforest, 24.5% of the participants had neutralizing antibodies against ZIKV, suggesting that ZIKV was widely spread across Suriname. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) has been known for decades to circulate in Africa and Asia. However, major complications of a ZIKV infection have recently become apparent for reasons that are still not fully elucidated. One of the hypotheses for the seemingly increased pathogenicity of ZIKV is that cross-reactive dengue antibodies can enhance a ZIKV infection through the principle of antibody-dependent enhancement (ADE). Recently, ADE in ZIKV infection has been studied, but conclusive evidence for the clinical importance of this principle in a ZIKV infection is lacking. Conversely, the widespread circulation of ZIKV in dengue virus (DENV)-endemic regions raises new questions about the potential contribution of ZIKV antibodies to DENV ADE. In this review, we summarize the results of the evidence to date and elaborate on other possible detrimental effects of cross-reactive flavivirus antibodies, both for ZIKV infection and the risk of ZIKV-related congenital anomalies, DENV infection, and dengue hemorrhagic fever. [ABSTRACT FROM AUTHOR]

Analysis and interpretation of Ig and TCR gene rearrangements in the conventional, low-throughput way have their limitations in terms of resolution, coverage, and biases. With the advent of high-throughput, nextgeneration sequencing (NGS) technologies, a deeper analysis of Ig and/or TCR (IG/TR) gene rearrangements is now within reach, which impacts on all main applications of IG/TR immunogenetic analysis. To bridge the generation gap from low- to high-throughput analysis, the EuroClonality-NGS Consortium has been formed, with the main objectives to develop, standardize, and validate the entire workflow of IG/TR NGS assays for 1) clonality assessment, 2) minimal residual disease detection, and 3) repertoire analysis. This concerns the preanalytical (sample preparation, target choice), analytical (amplification, NGS), and postanalytical (immunoinformatics) phases. Here we critically discuss pitfalls and challenges of IG/TR NGS methodology and its applications in hemato-oncology and immunology. [ABSTRACT FROM AUTHOR]

The number of elderly patients with end-stage renal disease (ESRD) has increased significantly during the last decade. Elderly ESRD patients are vulnerable to infectious complications because of an aged immune system. Additional immunological ageing effects may be derived from the uraemic environment and cytomegalovirus (CMV) latency. Elderly patients may be affected by these factors in particular, but data in this age group are limited. To assess the degree of immunological ageing and proliferative capacity of T lymphocytes, 49 elderly ESRD patients (defined as aged ≥ 65 years) on the renal transplantation waiting list were recruited and compared to 44 elderly healthy individuals (HI), matched for age and CMV serostatus. CMV latency was associated with more highly differentiated CD4+ and CD8+ T cells in both elderly HI and patients. Elderly CMV seropositive ESRD patients showed a substantial reduction in the number of naive CD4+ and CD8+ T cells compared with age- and CMV serostatus-matched HI. Elderly ESRD patients also showed significantly decreased numbers of central memory CD4+ and CD8+ T cells compared with HI, independently of CMV serostatus. In addition, thymic output and relative telomere length of both CD4+ and CD8+ T cells were decreased in CMV seropositive ESRD patients compared with HI. The proliferative capacity of T cells was similar for patients and HI. Elderly ESRD patients have an advanced aged T cell compartment when compared to age-matched healthy controls, which is driven mainly by CMV latency. [ABSTRACT FROM AUTHOR]

People with spinal cord injury (SCI) often experience secondary health conditions (SHCs), which are addressed during interdisciplinary follow-up clinics. We adapted the design of our clinic, by introducing a questionnaire concerning functioning and SHCs, additional measurements of blood pressure and saturation, and participants were seen by either a specialized nurse or rehabilitation physician. In this study, we investigated the effects of these adaptations and the experienced satisfaction of the participants. The results showed an increased number of recommendations in the adapted design, compared to the initial design. Further, the nature of the recommendations shifted from somatic issues to recommendations regarding psychosocial functioning and regarding (the use of) devices. The added measurements revealed an average high systolic blood pressure, which led to more referrals to the general practitioner. The clinical weight and pulmonary functions stayed stable over time. The current adaptations in design expanded and optimized the number and nature of recommendations regarding SHCs to participants. The questionnaire helps the participant to prepare for the clinic and the professionals to tailor their recommendations, resulting in highly satisfied participants. [ABSTRACT FROM AUTHOR]

In the context of CO 2 removal from biogas, a series of binderless zeolite LTA adsorbents with a macroscopic bead format (0.5–1.0 mm) and with hierarchical porosity (i.e. with the zeolitic micropores being accessible through meso- and macropores mainly in the 10–100 nm range) was synthesized with a variety of Si/Al ratios (1.2–3.9) using Amberlite IRA-900 anion-exchange resin beads as a hard template. The CO 2 and CH 4 adsorption capacity of the beads in Na-form with different Si/Al ratios were measured, reaching higher CO 2 /CH 4 selectivity and similar, yet slightly higher CO 2 adsorption compared to commercial zeolite LTA pellets containing a binder. Subsequently, one the zeolitic beads was subjected to different degrees of ion-exchange (0–96%) with KCl and then tested in the adsorption of CO 2 and CH 4. The best performance among all the ion-exchanged beads was achieved with Na 58 K 42 -LTA beads, which gave very high CO 2 /CH 4 selectivity (1540). Although essentially no CH 4 was adsorbed on these beads, the CO 2 adsorption capacity was still substantial (1.9 mmol g−1 at 0.4 bar CO 2 , i.e. the partial pressure of CO 2 in biogas). [Display omitted] • Binderless zeolite LTA beads with hierarchical porosity were synthesized. • Our zeolite beads displayed higher CO 2 /CH 4 selectivity than commercial LTA beads. • By partial ion-exchange with KCl, a CO 2 /CH 4 selectivity of 1540 was achieved. [ABSTRACT FROM AUTHOR]

Background: End stage renal disease (ESRD) is associated with defective T-cell mediated immunity. A diverse T-cell receptor (TCR) Vβ repertoire is central to effective T-cell mediated immune responses to foreign antigens. In this study, the effect of ESRD on TCR Vβ repertoire was assessed. Results: A higher proportion of ESRD patients (68.9%) had a skewed TCR Vβ repertoire compared to age and cytomegalovirus (CMV) - IgG serostatus matched healthy individuals (31.4%, P < 0.001). Age, CMV serostatus and ESRD were independently associated with an increase in shifting of the TCR Vβ repertoire. More differentiated CD8+ T cells were observed in young ESRD patients with a shifted TCR Vβ repertoire. CD31-expressing naive T cells and relative telomere length of T cells were not significantly related to TCR Vβ skewing. Conclusions: ESRD significantly skewed the TCR Vβ repertoire particularly in the elderly population, which may contribute to the uremia-associated defect in T-cell mediated immunity. [ABSTRACT FROM AUTHOR]

Background and purpose With the introduction of Intensity Modulated Radiotherapy (IMRT) and image-guided plan-of-the-day strategies, the treatment of cervical cancer has become more sensitive to intra-fraction uncertainties. In this study we quantified intra-fraction changes in cervix-uterus shape, bladder and rectum filling, and patient setup using pre- and post-fraction CBCT scans. Materials and methods A total of 632 CBCT scans were analyzed for 16 patients with large tip-of-uterus displacement (>2.5 cm) measured in an empty and full bladder CT scan. In all scans, the bladder, cervix-uterus, and rectum were delineated. For rectum and bladder, intra-fraction volume changes were assessed. Systematic cervix-uterus intra-fraction displacements were obtained by non-rigidly aligning the pre-fraction cervix-uterus to that in the post-fraction CBCT. Intra-fraction patient setup changes were obtained by rigidly aligning pre- and post-CBCTs using the bony anatomy. Results The mean time between pre- and post-fraction CBCT scan was 20.8 min. The group-mean intra-fraction displacements averaged over the cervix-uterus were 0.1 ± 1.4/1.8 ± 1.5/−2.8 ± 1.8 (LR/CC/AP) mm. The group-mean 5th and 95th percentile intra-fraction displacements were −2.3,2.1/−0.8,4.9/−5.8,0.5 (LR/CC/AP) mm. There was a significant correlation between bladder inflow rate and cervix-uterus motion ( r = 0.6 and p < 0.01). Intra-fraction changes in patient setup were 1.3/0.4/0.6 and 1.4/1.0/1.1 mm (LR/CC/AP), for systematic and random changes, respectively. Conclusion Intra-fraction cervix-uterus motion can be considerable and should be taken into account using appropriate PTV margins. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate a new type of marker and a new method of marker implantation and to assess interfraction cervix motion for a large population of patients with locally advanced cervical cancer by daily cone beam computed tomographic (CBCT) imaging.Methods and Materials: We investigated the position of markers in 50 patients treated in prone position during at least 23 fractions. To reduce streaking artifacts in the planning CT scan, a new type of polymeric marker was used and compared with conventional gold markers. In addition, a new method of implantation was used in an attempt to reduce marker loss. In each fraction, a CT scan was acquired before dose delivery and aligned to the bony anatomy of the planning CT scan, simulating the clinical setup protocol. First, sufficient visibility of the markers was verified. Then, systematic and random displacement of the marker centroids was recorded and analyzed in 3 directions with regard to the planning CT and the first CBCT (to evaluate the presence of a vaginal catheter in the planning CT). Streaking artifacts were quantified with the standard deviation of the mean squared intensity difference in a radius around the marker.Results: Marker loss was minimal during treatment: in only 3 of the 50 patients 1 marker was lost. Streaking artifacts for the new markers were reduced compared with conventional gold markers. For the planning CT, M/Σ/σ were 0.4/3.4/2.2 mm, 1.0/5.5/4.5 mm, and -3.9/5.1/3.6 mm for the left-right, anterior-posterior, and cranial-caudal directions, respectively. With regard to the first CBCT scan, M/Σ/σ were 0.8/2.8/2.1, 0.6/4.4/4.4, and -1.3/4.5/3.6 mm.Conclusions: A new type of marker and implantation method was shown to have significantly reduced marker loss and streaking artifacts compared with gold fiducial markers. The recorded marker displacement confirms results reported in the existing literature but for a larger dataset. [ABSTRACT FROM AUTHOR]

Background: The intelligence of individuals with Autism Spectrum Disorder (ASD) varies considerably. The pattern of cognitive deficits associated with ASD may differ depending on intelligence. We aimed to study the absolute and relative severity of cognitive deficits in participants with ASD in relation to IQ. Methods: A total of 274 children (M age = 12.1, 68.6% boys) participated: 30 ASD and 22 controls in the below average Intelligence Quotient (IQ) group (IQ<85), 57 ASD and 54 controls in the average IQ group (85115). Matching for age, sex, Full Scale IQ (FSIQ), Verbal IQ (VIQ), Performance IQ (PIQ) and VIQ-PIQ difference was performed. Speed and accuracy of social cognition, executive functioning, visual pattern recognition and basic processing speed were examined per domain and as a composite score. Results: The composite score revealed a trend significant IQ by ASD interaction (significant when excluding the average IQ group). In absolute terms, participants with below average IQs performed poorest (regardless of diagnosis). However, in relative terms, above average intelligent participants with ASD showed the most substantial cognitive problems (particularly for social cognition, visual pattern recognition and verbal working memory) since this group differed significantly from the IQ-matched control group (p < .001), whereas this was not the case for below-average intelligence participants with ASD (p = .57). Conclusions: In relative terms, cognitive deficits appear somewhat more severe in individuals with ASD and above average IQs compared to the below average IQ patients with ASD. Even though high IQ ASD individuals enjoy a certain protection from their higher IQ, they clearly demonstrate cognitive impairments that may be targeted in clinical assessment and treatment. Conversely, even though in absolute terms ASD patients with below average IQs were clearly more impaired than ASD patients with average to above average IQs, the differences in cognitive functioning between participants with and without ASD on the lower end of the IQ spectrum were less pronounced. Clinically this may imply that cognitive assessment and training of cognitive skills in below average intelligent children with ASD may be a less fruitful endeavour. These findings tentatively suggest that intelligence may act as a moderator in the cognitive presentation of ASD, with qualitatively different cognitive processes affected in patients at the high and low end of the IQ spectrum. [ABSTRACT FROM AUTHOR]

Objective Patients infected with the human immunodeficiency virus ( HIV) have an increased risk of metabolic complications such as dyslipidaemia, insulin resistance and hypertension; symptoms that are also associated with an excess of the hormone cortisol. We studied the relationship between long-term cortisol levels and metabolic syndrome (MetS) in HIV-infected patients. Design Cross-sectional study performed at the outpatient clinic of infectious diseases of the Erasmus MC, University Medical Center Rotterdam, the Netherlands. Methods Fasting blood samples and anthropometric data were collected in 126 HIV-infected patients. An ELISA-based technique was used to determine long-term cortisol levels in scalp hair. Cortisol levels were compared to 191 healthy controls. Results A higher risk of MetS was observed in HIV patients with a low hair cortisol (odds ratio lower vs upper tertile 4·23, P = 0·04). Hair cortisol levels were not significantly different between HIV patients and healthy controls (16·4 pg/mg vs 13·5 pg/mg; P = 0·14). Conclusion The risk of MetS was significantly higher in HIV-infected patients in the lowest hair cortisol group compared with patients in the highest hair cortisol group. This finding contrasts with results from studies in uninfected individuals where a high cortisol level in hair is associated with metabolic syndrome. The results of this study suggest that these metabolic complications might be related to relative cortisol hypersensitivity in HIV patients. [ABSTRACT FROM AUTHOR]

It is widely believed that threatening stimuli in our environment capture attention. Much of the core evidence for attentional capture by threatening stimuli comes from the Emotional Stroop task. Yet recent evidence suggests that the Emotional Stroop task does not measure attentional capture (e.g., Algom et al., 2004). The present paper assesses whether threat words can capture attention using a modified Stroop Dilution procedure (e.g., Kahneman & Chajczyk, 1983), where attentional capture by a threat word is inferred from a reduction in color-word interference for threat words compared to non-threat words (emotional Stroop Dilution). The outcome of the present experiments indicates that threat words can capture attention, but only when task demands do not require that a word be attended. It is suggested that threat words produce (1) cognitive slowing, and influence two processes of selective attention (2) attentional capture and (3) the ability to filter irrelevant dimensions of an attended stimulus. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the clinical implementation of an online adaptive plan-of-the-day protocol for nonrigid target motion management in locally advanced cervical cancer intensity modulated radiation therapy (IMRT). Methods and Materials Each of the 64 patients had four markers implanted in the vaginal fornix to verify the position of the cervix during treatment. Full and empty bladder computed tomography (CT) scans were acquired prior to treatment to build a bladder volume-dependent cervix-uterus motion model for establishment of the plan library. In the first phase of clinical implementation, the library consisted of one IMRT plan based on a single model-predicted internal target volume (mpITV), covering the target for the whole pretreatment observed bladder volume range, and a 3D conformal radiation therapy (3DCRT) motion-robust backup plan based on the same mpITV. The planning target volume (PTV) combined the ITV and nodal clinical target volume (CTV), expanded with a 1-cm margin. In the second phase, for patients showing >2.5-cm bladder-induced cervix-uterus motion during planning, two IMRT plans were constructed, based on mpITVs for empty-to-half-full and half-full-to-full bladder. In both phases, a daily cone beam CT (CBCT) scan was acquired to first position the patient based on bony anatomy and nodal targets and then select the appropriate plan. Daily post-treatment CBCT was used to verify plan selection. Results Twenty-four and 40 patients were included in the first and second phase, respectively. In the second phase, 11 patients had two IMRT plans. Overall, an IMRT plan was used in 82.4% of fractions. The main reasons for selecting the motion-robust backup plan were uterus outside the PTV (27.5%) and markers outside their margin (21.3%). In patients with two IMRT plans, the half-full-to-full bladder plan was selected on average in 45% of the first 12 fractions, which was reduced to 35% in the last treatment fractions. Conclusions The implemented online adaptive plan-of-the-day protocol for locally advanced cervical cancer enables (almost) daily tissue-sparing IMRT. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to explore the physical status and gait patterns of children with spastic diplegia secondary to human immunodeficiency virus encephalopathy ( HIVE). Method A cross-sectional study was conducted on children diagnosed with HIVE and spastic diplegia. Sociodemographic and clinical background information was obtained, followed by three-dimensional gait analysis (3 DGA) and a physical examination including assessments of muscle tone, strength, motor control, contractures, and bony deformities of the lower extremities. Results Fourteen children (eight males, six females; mean age 5y 8mo [ SD 9mo], range 4y 4mo-6y 10mo) were studied. The cohort was divided into two groups based on distinctive gait patterns. Nine participants in group I showed only limited abnormalities. Group II displayed a more pathological gait pattern including stiff knee and equinus ankle abnormalities. Results of 3 DGA, as with the physical examination outcomes, showed increased impairments from proximal to distal (except for hip extension). Interpretation This study provides a first description of distinctive gait patterns and related physical characteristics of children with HIVE and spastic diplegia. Further research is necessary. [ABSTRACT FROM AUTHOR]

Summary: Polycomb group (PcG) proteins dynamically define cellular identities through epigenetic repression of key developmental genes. PcG target gene repression can be stabilized through the interaction in the nucleus at PcG foci. Here, we report the results of a high-resolution microscopy genome-wide RNAi screen that identifies 129 genes that regulate the nuclear organization of Pc foci. Candidate genes include PcG components and chromatin factors, as well as many protein-modifying enzymes, including components of the SUMOylation pathway. In the absence of SUMO, Pc foci coagulate into larger aggregates. Conversely, loss of function of the SUMO peptidase Velo disperses Pc foci. Moreover, SUMO and Velo colocalize with PcG proteins at PREs, and Pc SUMOylation affects its chromatin targeting, suggesting that the dynamic regulation of Pc SUMOylation regulates PcG-mediated silencing by modulating the kinetics of Pc binding to chromatin as well as its ability to form Polycomb foci. [ABSTRACT FROM AUTHOR]

Purpose: Automatic, atlas-based segmentation of medical images benefits from using multiple atlases, mainly in terms of robustness. However, a large disadvantage of using multiple atlases is the large computation time that is involved in registering atlas images to the target image. This paper aims to reduce the computation load of multiatlas-based segmentation by heuristically selecting atlases before registration. Methods: To be able to select atlases, pairwise registrations are performed for all atlas combinations. Based on the results of these registrations, atlases are clustered, such that each cluster contains atlas that registers well to each other. This can all be done in a preprocessing step. Then, the representatives of each cluster are registered to the target image. The quality of the result of this registration is estimated for each of the representatives and used to decide which clusters to fully register to the target image. Finally, the segmentations of the registered images are combined into a single segmentation in a label fusion procedure. Results: The authors perform multiatlas segmentation once with postregistration atlas selection and once with the proposed preregistration method, using a set of 182 segmented atlases of prostate cancer patients. The authors performed the full set of 182 leave-one-out experiments and in each experiment compared the result of the atlas-based segmentation procedure to the known segmentation of the atlas that was chosen as a target image. The results show that preregistration atlas selection is slightly less accurate than postregistration atlas selection, but this is not statistically significant. Conclusions: Based on the results the authors conclude that the proposed method is able to reduce the number of atlases that have to be registered to the target image with 80% on average, without compromising segmentation accuracy. [ABSTRACT FROM AUTHOR]

PCR-based immunoglobulin (Ig)/T-cell receptor (TCR) clonality testing in suspected lymphoproliferations has largely been standardized and has consequently become technically feasible in a routine diagnostic setting. Standardization of the pre-analytical and post-analytical phases is now essential to prevent misinterpretation and incorrect conclusions derived from clonality data. As clonality testing is not a quantitative assay, but rather concerns recognition of molecular patterns, guidelines for reliable interpretation and reporting are mandatory. Here, the EuroClonality (BIOMED-2) consortium summarizes important pre- and post-analytical aspects of clonality testing, provides guidelines for interpretation of clonality testing results, and presents a uniform way to report the results of the Ig/TCR assays. Starting from an immunobiological concept, two levels to report Ig/TCR profiles are discerned: the technical description of individual (multiplex) PCR reactions and the overall molecular conclusion for B and T cells. Collectively, the EuroClonality (BIOMED-2) guidelines and consensus reporting system should help to improve the general performance level of clonality assessment and interpretation, which will directly impact on routine clinical management (standardized best-practice) in patients with suspected lymphoproliferations. [ABSTRACT FROM AUTHOR]

PCR-based immunoglobulin (Ig)/T-cell receptor (TCR) clonality testing in suspected lymphoproliferations has largely been standardized and has consequently become technically feasible in a routine diagnostic setting. Standardization of the pre-analytical and post-analytical phases is now essential to prevent misinterpretation and incorrect conclusions derived from clonality data. As clonality testing is not a quantitative assay, but rather concerns recognition of molecular patterns, guidelines for reliable interpretation and reporting are mandatory. Here, the EuroClonality (BIOMED-2) consortium summarizes important pre- and post-analytical aspects of clonality testing, provides guidelines for interpretation of clonality testing results, and presents a uniform way to report the results of the Ig/TCR assays. Starting from an immunobiological concept, two levels to report Ig/TCR profiles are discerned: the technical description of individual (multiplex) PCR reactions and the overall molecular conclusion for B and T cells. Collectively, the EuroClonality (BIOMED-2) guidelines and consensus reporting system should help to improve the general performance level of clonality assessment and interpretation, which will directly impact on routine clinical management (standardized best-practice) in patients with suspected lymphoproliferations. [ABSTRACT FROM AUTHOR]

Abstract: This paper presents a decision algorithm for the analysis of the stability of a class of planar switched linear systems, modeled by hybrid automata. The dynamics in each location of the hybrid automaton is assumed to be linear and asymptotically stable; the guards on the transitions are hyperplanes in the state space. We show that for every pair of an ingoing and an outgoing transition related to a location, the exact gain in the norm of the vector induced by the dynamics in that location can be computed. These exact gains are used in defining a gain automaton which forms the basis of an algorithmic criterion to determine if a planar hybrid automaton is stable or not. [Copyright &y& Elsevier]

Abstract: The purpose of this study was to use three-dimensional gait analysis to describe the gait status of adults with spastic diplegia who underwent selective dorsal rhizotomy (SDR) in childhood. Outcome measures were the gait deviation index (GDI), non-dimensional temporal-distance parameters, and kinematics of the lower limbs. A total of 31 adults with spastic diplegia who had previously undergone SDR were eligible and participated in current study (SDR group). These participants had a median age of 26.8 years (range 21–44 years) with a mean time between surgery and assessment of 21.2±2.9 years (range 17–26 years). For comparison purposes, 43 typically developed adults also participated (CONTROL group), with a median age of 28.3 years (range 21–45 years). More than 17 years after SDR 58% of the SDR group showed improved GMFCS levels, while none of them deteriorated. The participants in the SDR group walked with a mild crouch gait, although there was a loading response, adequate swing-phase knee flexion, adequate swing-phase plantarflexion, reasonable speed and cadence. The gait status of the SDR group more than 17 years after SDR was similar to what has been reported in short-term follow-up studies, as well as our earlier 20 year follow-up study that did not include 3D gait analysis. Appropriate orthopaedic intervention was required in 61% of the study cohort. Whether the types and numbers of orthopaedic interventions are positively affected by SDR remains an open question. Further studies examining this question are warranted. In addition, long-term follow-up studies focused on other interventions would also be of clinical relevance. [Copyright &y& Elsevier]

Double-strand breaks (DSBs), arising from exposure to exogenous clastogens or as a by-product of endogenous cellular metabolism, pose grave threats to genome integrity. DSBs can sever whole chromosomes, leading to chromosomal instability, a hallmark of cancer. Healing broken DNA takes time, and it is therefore essential to temporarily halt cell division while DSB repair is underway. The seminal discovery of cyclin-dependent kinases as master regulators of the cell cycle unleashed a series of studies aimed at defining how the DNA damage response network delays cell division. These efforts culminated with the identification of Cdc25, the protein phosphatase that activates Cdc2/Cdk1, as a critical target of the checkpoint kinase Chk1. However, regulation works both ways, as recent studies have revealed that Cdc2 activity and cell cycle position determine whether DSBs are repaired by non-homologous end-joining or homologous recombination (HR). Central to this regulation are the proteins that initiate the processing of DNA ends for HR repair, Mre11-Rad50-Nbs1 protein complex and Ctp1/Sae2/CtIP, and the checkpoint kinases Tel1/ATM and Rad3/ATR. Here, we review recent findings and provide insight on how proteins that regulate cell cycle progression affect DSB repair, and, conversely how proteins that repair DSBs affect cell cycle progression. [ABSTRACT FROM AUTHOR]

On the basis of my own familiarity with the IRM as one of its former editors, I celebrate the journal's importance to me personally and to mission studies in the ecumenical family by selecting a few significant contributions for comment: 'The Kingdom of God as Strategy for Mission' by Raymond Fung; 'The Liturgy after the Liturgy,' by Professor Ion Bria; 'Gospel, Cultures and Filipina Migrant Workers,' by Jane Corpuz-Brock; 'Section III: The Earth is the Lord's', from San Antonio; and 'Towards a New Christian Sexual Ethics in the Light of HIV/ AIDS', by Armin Zimmermann. [ABSTRACT FROM AUTHOR]

The multifunctional Mre11-Rad50-Nbs1 (MRN) protein complex recruits ATM/Tel1 checkpoint kinase and CtIP/Ctp1 homologous recombination (HR) repair factor to double-strand breaks (DSBs). HR repair commences with the 59-to-39 resection of DNA ends, generating 39 single-strand DNA (ssDNA) overhangs that bind Replication Protein A (RPA) complex, followed by Rad51 recombinase. In Saccharomyces cerevisiae, the Mre11-Rad50-Xrs2 (MRX) complex is critical for DSB resection, although the enigmatic ssDNA endonuclease activity of Mre11 and the DNA-end processing factor Sae2 (CtIP/ Ctp1 ortholog) are largely unnecessary unless the resection activities of Exo1 and Sgs1-Dna2 are also eliminated. Mre11 nuclease activity and Ctp1/CtIP are essential for DSB repair in Schizosaccharomyces pombe and mammals. To investigate DNA end resection in Schizo. pombe, we adapted an assay that directly measures ssDNA formation at a defined DSB. We found that Mre11 and Ctp1 are essential for the efficient initiation of resection, consistent with their equally crucial roles in DSB repair. Exo1 is largely responsible for extended resection up to 3.1 kb from a DSB, with an activity dependent on Rqh1 (Sgs1) DNA helicase having a minor role. Despite its critical function in DSB repair, Mre11 nuclease activity is not required for resection in fission yeast. However, Mre11 nuclease and Ctp1 are required to disassociate the MRN complex and the Ku70- Ku80 nonhomologous end-joining (NHEJ) complex from DSBs, which is required for efficient RPA localization. Eliminating Ku makes Mre11 nuclease activity dispensable for MRN disassociation and RPA localization, while improving repair of a one- ended DSB formed by replication fork collapse. From these data we propose that release of the MRN complex and Ku from DNA ends by Mre11 nuclease activity and Ctp1 is a critical step required to expose ssDNA for RPA localization and ensuing HR repair. [ABSTRACT FROM AUTHOR]

Progressive loss of renal function is associated with a dysregulation of circulating T cells that may underlie their impaired T-cell immunity. Here we tested whether end-stage renal disease (ESRD)-related T-cell alterations are compatible with the concept of premature immunological aging. Younger patients (25-45 years old) with ESRD were found to resemble older healthy controls (60-80 years old) as they had a significant loss of naive T cells and a relative increase of memory T cells showing progressive terminal differentiation. A significant decrease in the content of T-cell receptor excision circles and telomere length in patients with ESRD confirmed these phenotypic data. The loss of naive T cells in patients with ESRD was associated with an excessive age-related decrease of recent thymic emigrants, indicating a premature decline in thymic function. Additionally, increased homeostatic proliferation of naive T cells was found in patients with ESRD, similar to that of older healthy individuals, with an increased susceptibility for activation-induced apoptosis. Therefore, both decreased thymic output and increased susceptibility of naive T cells for apoptosis may play a role in the loss of naive T cells in ESRD patients. Thus, our results are compatible with premature aging of the T-cell system of patients with ESRD comparable with that of healthy individuals 20-30 years older. [ABSTRACT FROM AUTHOR]

Immunoglobulin gene sequence analysis is widely utilized for prognostication in chronic lymphocytic leukemia (CLL) and the definition of standardized procedures has allowed reliable and reproducible results. Occasionally, a straightforward interpretation of the sequences is not possible because of the so-called 'problematic sequences' that do not fit the 'classic' interpretation and pose scientific questions at the cross-road between hematology and immunology. Thanks to a dedicated effort within the European Research Initiative on CLL (ERIC), we have now the possibility to present such cases, offer a scientific explanation and propose recommendations in terms of prognostication. [ABSTRACT FROM AUTHOR]

In a multi-atlas based segmentation procedure, propagated atlas segmentations must be combined in a label fusion process. Some current methods deal with this problem by using atlas selection to construct an atlas set either prior to or after registration. Other methods estimate the performance of propagated segmentations and use this performance as a weight in the label fusion process. This paper proposes a selective and iterative method for performance level estimation (SIMPLE), which combines both strategies in an iterative procedure. In subsequent iterations the method refines both the estimated performance and the set of selected atlases. For a dataset of 100 MR images of prostate cancer patients, we show that the results of SIMPLE are significantly better than those of several existing methods, including the STAPLE method and variants of weighted majority voting. [ABSTRACT FROM PUBLISHER]

Abstract: Form feature modeling is a much used shape modeling technique that offers high-level control over a shape. When a feature-based interpretation of shape data is not available, e.g. when a shape is obtained by a laser range scanner or from a database of shapes, then the features must be reconstructed through feature recognition. Many methods for the recognition of machining features exist, but these methods cannot be used for freeform feature recognition, of which the complexity is much larger. In this paper, a new freeform feature recognition method is presented that is based on a new definition of the freeform feature concept. The method uses a three-step approach to feature recognition, in which first the global shape of a feature is matched to the target shape model. In a second step, this global shape is locally adapted to the target shape by adapting the definition of the feature. Finally, if the desired configuration of the feature has been determined, it can be used to reconstruct the target’s shape. In the first two steps, an evolutionary approach is taken to maximizing the similarity between the feature and the target shape. Finally, the target shape is reconstructed to incorporate the recognized feature. An extensive application example is given and the method is validated by applying it to a large number of artificially created test cases. [Copyright &y& Elsevier]

The aim of this study was to evaluate the mechanical status of the spine in patients with spastic diplegia 17–26 years after selective dorsal rhizotomy (SDR). We compared original radiographic reports from our earlier short-term follow-up study with current X-rays. In addition, we obtained magnetic resonance images (MRI) of the spine and additional information regarding back pain and clinical assessments. Thirty patients (17 males and 13 females; median age 26.8 years) participated in the current study, with median follow-up times of 4.0 and 21.4 years. Comparison of the X-ray results showed respectively: scoliosis 0% and 57%; kyphosis 0% and 7%; lordosis 21% and 40%; spondylolysis 18% and 37%; and spondylolisthesis grade I occurred in one patient. The only statistically significant difference was found for scoliosis ( p < 0.01). The majority had Cobb angles <30° with only two patients with curves of 35°. MRI scans showed spinal stenosis in 27%, black discs in 10%, and disc protrusion in 3%. Daily back pain was reported in 17%, while 23% reported “moderate disability” as a result of back and leg pain. No patient to date has required any surgical intervention on the spine. Except for spondylolisthesis, spinal deformities did appear to progress with time. However, this increase was not marked, and the development of relatively mild scoliosis was the only statistically significant increase. This group of patients requires continued follow-up. Further studies are required to ascertain the natural history of spinal deformity in adults with spastic diplegia who have not had SDR. [ABSTRACT FROM AUTHOR]

Proliferating cell nuclear antigen (PCNA) encircles DNA as a ring-shaped homotrimer and, by tethering DNA polymerases to their template, PCNA serves as a critical replication factor. In contrast to high-fidelity DNA polymerases, the activation of low-fidelity translesion synthesis (TLS) DNA polymerases seems to require damage-inducible monoubiquitylation (Ub) of PCNA at lysine residue 164 (PCNA-Ub). TLS polymerases can tolerate DNA damage, i.e. they can replicate across DNA lesions. The lack of proofreading activity, however, renders TLS highly mutagenic. The advantage is that B cells use mutagenic TLS to introduce somatic mutations in immunoglobulin (Ig) genes to generate high-affinity antibodies. Given the critical role of PCNA-Ub in activating TLS and the role of TLS in establishing somatic mutations in immunoglobulin genes, we analysed the mutation spectrum of somatically mutated immunoglobulin genes in B cells from PCNAK164R knock-in mice. A 10-fold reduction in A/T mutations is associated with a compensatory increase in G/C mutations—a phenotype similar to Polη and mismatch repair-deficient B cells. Mismatch recognition, PCNA-Ub and Polη probably act within one pathway to establish the majority of mutations at template A/T. Equally relevant, the G/C mutator(s) seems largely independent of PCNAK164 modification. [ABSTRACT FROM AUTHOR]

Genome function in higher. eukaryotes involves major changes in the spatial organization of the chromatin fiber. Nevertheless, our understanding of chromatin folding is remarkably limited. Polymer models have been used to describe chromatin folding. However, none of the proposed models gives a satisfactory explanation of experimental data. In particularly, they ignore that each chromosome occupies a confined space, i.e., the chromosome territory. Here, we present a polymer model that is able to describe key properties of chromatin over length scales ranging from 0.5 to 75 Mb. This random loop (RL) model assumes a self-avoiding random walk folding of the polymer backbone and defines a probability P for 2 monomers to interact, creating loops of a broad size range. Model predictions are compared with systematic measurements of chromatin folding of the q-arms of chromosomes 1 and 11. The RL model can explain our observed data and suggests that on the tens-of-megabases length scale P is small, i.e., 10-30 loops per 100 Mb. This is sufficient to enforce folding inside the confined space of a chromosome territory. On the 0.5- to 3-Mb length scale chromatin compaction differs in different subchromosomal domains. This aspect of chromatin structure is incorporated in the RL model by introducing heterogeneity along the fiber contour length due to different local looping probabilities. The RL model creates a quantitative and predictive framework for the identification of nuclear components that are responsible for chromatin-chromatin interactions and determine the 3-dimensional organization of the chromatin fiber. [ABSTRACT FROM AUTHOR]

(Very) severe acquired aplastic anemia ((v)SAA) and myelodysplastic syndrome (MDS) are rare diseases in childhood. (V)SAA is a bone marrow (BM) failure syndrome characterized by immune-mediated destruction of hematopoietic progenitors. MDS is a malignant clonal stem cell disorder, of which the hypoplastic variant is, in case of absence of a cytogenetic clone, difficult to separate from (v)SAA. Recently, studies provided a molecular signature of autoimmunity in adult (v)SAA, by showing oligoclonality based on the length of the TCR Vβ CDR3 region. We investigated retrospectively the frequency and the discriminative value of TCR Vβ CDR3 oligoclonality in pediatric (v)SAA and MDS patients. Peripheral blood (PB) and/or BM mononuclear cell samples of pediatric patients with (v)SAA (n=38), refractory cytopenia (MDS-RC) (n=28) and 18 controls were analysed via TCR Vβ heteroduplex PCR analysis of extracted RNA. A skewed TCR Vβ CDR3 repertoire was found in 21/38 (v)SAA and in 17/28 RC patients in contrast to 2/18 in the control group. These data suggest an overlapping group of RC and SAA patients that may share a common immune-mediated pathogenesis. Prospective studies are required to establish the clinical value of TCR Vβ CDR3 repertoire analysis to predict the clinical response in these patients.Leukemia (2008) 22, 1170–1174; doi:10.1038/leu.2008.23; published online 6 March 2008 [ABSTRACT FROM AUTHOR]

Feature recognition techniques have been developed in the past that dealt with parameterizing regular features. In response to the availability of free form shape, researchers have turned to free form features. Some of the methods developed for features can be re-used in the free form domain, but many methods have to be developed anew. In this paper it is argued that there is a need for a general framework to provide a common point of reference for new methods and to increase the cohesion between such methods. An initial framework is proposed for the definition of features and for one of the possible applications of features, feature recognition. Two existing free form feature recognition methods are analysed with regard to the framework, in order to critically review the proposed framework as well as the two methods. [ABSTRACT FROM AUTHOR]