Looking at individual symptoms: the dynamic network structure of depressive symptoms in cancer survivors and their preferences for psychological care.

PURPOSE: The majority of depressed cancer survivors do not receive psychological care, possibly because offered care does not align with their experiences and preferences. We examined (1) which depressive symptoms cancer survivors would like to receive psychological care for; (2) how distinct depressive symptoms are related to each other in the contemporaneous and temporal network of depressive symptoms; and (3) whether survivors' care needs correspond to the interconnectedness of these specific symptoms. METHOD: Fifty-two cancer survivors suffering from at least mild depressive symptoms and were not receiving psychological care filled out a baseline questionnaire about their care needs for distinct depressive symptoms, followed by ecological momentary assessments (EMA) assessing depressive symptoms (14 days, five times a day). Multi-level vector autoregression analysis was used to estimate associations between distinct depressive symptoms as well as their centrality within the network. RESULTS: Cancer survivors most strongly preferred to receive care for fatigue, feeling down, little enjoyment, and sleep problems. Fatigue, together with worry and lack of concentration, most strongly predicted the onset of other symptoms. Little enjoyment and feeling down were two of the most central symptoms (i.e., strongly connected to other symptoms) in the contemporaneous network and were most strongly influenced by other symptoms in the temporal network. CONCLUSIONS: Clinicians can offer specific interventions that target fatigue, as these played an important role in the onset of symptoms and would align with survivors' needs. IMPLICATIONS FOR CANCER SURVIVORS: Offering such symptom-specific care may increase the uptake of psychological interventions in cancer survivors.

[RCT about mindfulness-based cognitive therapy for psychological distress in cancer patients]. / RCT naar mindfulness-based cognitieve therapie voor psychische klachten bij oncologische patiënten.

BACKGROUND: Cancer patients may experience psychological distress, like anxiety and depressive symptoms. Mindfulness-based cognitive therapy (MBCT) has been shown to alleviate this psychological distress. However, patients experience barriers in participating in face-to-face MBCT. Individual internet-based MBCT (eMBCT) could be an alternative.
AIM: To compare MBCT and eMBCT to treatment as usual (TAU) for psychological distress in cancer patients.
METHOD: 245 cancer patients with psychological distress were randomly allocated to MBCT (n = 77), eMBCT (n = 90) or TAU (n = 78). Patients completed baseline (T0) and post-intervention (T1) assessments. The primary outcome was psychological distress on the Hospital Anxiety and Depression Scale. Outcomes were analyzed using linear mixed modeling on the intention-to-treat sample. Since both interventions were compared to TAU, the type I error rate was set to p < 0.025.
RESULTS: Compared to TAU, patients reported significantly less psychological distress after both MBCT (Cohen's d = 0.43, p < 0.001) and eMBCT (Cohen's d = 0.63, p < 0.001).
CONCLUSION: Compared to TAU, MBCT and eMBCT were similarly effective in reducing psychological distress in a sample of distressed heterogeneous cancer patients.

Exploring the clinical outcome of Mindfulness-Based Cognitive Therapy for bipolar and unipolar depressive patients in routine clinical practice: a pilot study.

BACKGROUND: Mindfulness Based Cognitive Therapy (MBCT) has been adopted as an evidence-based treatment for unipolar depressive disorder (UDD). Although MBCT has not been included in the treatment guidelines for bipolar disorder (BD), MBCT is regularly being offered to patients with BD in routine clinical practice. In this pilot study we used routine outcome monitoring (ROM) data to explore whether there are indications that patients with BD might benefit less from MBCT than patients with UDD in terms of feasibility and effectiveness. METHODS: The study population consisted of patients with BD (n = 30) or UDD (n = 501) who received MBCT at the Radboudumc Centre for Mindfulness in Nijmegen, the Netherlands. Patients completed self-report measures of depressive symptom severity, worry, well-being, mindfulness skills and self-compassion pre- and post MBCT as part of the ROM. RESULTS: There were significant less patients with BD who decided to start MBCT after intake than patients with UDD. No differences in dropout between groups were found. Results showed significant moderate to large improvements in both groups after MBCT, while no differences between groups were found, on all outcome measures. CONCLUSIONS: This study demonstrates that there are no indications that MBCT, when delivered in heterogeneous patient groups in routine clinical practice, is less beneficial for patients with BD than patients with UDD in terms of feasibility and effectiveness. This lends support to conduct an adequately powered RCT to examine the (cost-)effectiveness of MBCT in BD as the next step before implementing MBCT on a larger scale in patients with BD.

Consolidation and prediction of long-term treatment effect of group and online mindfulness-based cognitive therapy for distressed cancer patients.

BACKGROUND: Group face-to-face and individual internet-based mindfulness-based cognitive therapy (MBCT and eMBCT) have been demonstrated to reduce psychological distress for distressed cancer patients in a randomized controlled trial (RCT). This study focused on the long-term effects of this RCT during the nine-month follow-up period, and on possible predictors, moderators and working mechanisms. METHODS: Distressed cancer patients (n = 245) were randomized to MBCT or eMBCT. Data were collected at baseline, post-treatment, three- and nine-month follow-up. Data were analyzed with linear mixed effect models and (hierarchical) linear regressions. RESULTS: Analyses revealed long-term reductions in psychological distress and rumination, and long-term increases in positive mental health and mental health-related quality of life (QoL) in both interventions over the course of the nine-month follow-up. Interestingly, patients reported less psychological distress in the follow-up period after eMBCT in comparison to MBCT. Less psychological distress, rumination and neuroticism, and more extraversion and agreeableness at baseline predicted less psychological distress at the nine-month follow-up after both interventions. Less mindful and conscientious patients at baseline benefited more from eMBCT than from MBCT. Regarding working mechanisms, changes in mindfulness skills, fear of cancer recurrence and rumination during both interventions predicted less psychological distress at follow-up. CONCLUSIONS: Our findings suggest most improvements in cancer patients' increase over time after both interventions. Furthermore, patients seemed to benefit more from eMBCT than MBCT based on psychological distress levels, especially those patients with low levels of mindfulness skills and conscientiousness.

Mindfulness-based stress reduction added to care as usual for lung cancer patients and/or their partners: A multicentre randomized controlled trial.

OBJECTIVE: Lung cancer patients report among the highest distress rates of all cancer patients. Partners report similar distress rates. The present study examined the effectiveness of additional mindfulness-based stress reduction (care as usual [CAU] + MBSR) versus solely CAU to reduce psychological distress in lung cancer patients and/or their partners. METHODS: We performed a multicentre, parallel-group, randomized controlled trial. Mindfulness-based stress reduction is an 8-week group-based intervention, including mindfulness practice and teachings on stress. Care as usual included anticancer treatment, medical consultations, and supportive care. The primary outcome was psychological distress. Secondary outcomes included quality of life, caregiver burden, relationship satisfaction, mindfulness skills, self-compassion, rumination, and posttraumatic stress symptoms. Outcomes were assessed at baseline, post-intervention, and 3-month follow-up. Linear mixed modeling was conducted on an intention-to-treat sample. Moderation (gender, disease stage, baseline distress, participation with/without partner) and mediation analyses were performed. RESULTS: A total of 31 patients and 21 partners were randomized to CAU + MBSR and 32 patients and 23 partners to CAU. After CAU + MBSR patients reported significantly less psychological distress (p = .008, d = .69) than after CAU. Baseline distress moderated outcome: those with more distress benefitted most from MBSR. Additionally, after CAU + MBSR patients showed more improvements in quality of life, mindfulness skills, self-compassion, and rumination than after CAU. In partners, no differences were found between groups. CONCLUSION: Our findings suggest that psychological distress in lung cancer patients can be effectively treated with MBSR. No effect was found in partners, possibly because they were more focused on patients' well-being rather than their own.

Unobtrusive ECG monitoring in the NICU using a capacitive sensing array.

The thin skin of preterm babies is easily damaged by adhesive electrodes, tapes, chest drains and needle-marks. The scars caused could be disfiguring or disabling to 10% of preterm newborns. Capacitive sensors present an attractive option for pervasively monitoring neonatal ECG, and can be embedded in a support system or even a garment worn by the neonate. This could improve comfort and reduce pain aiding better recovery as well as avoiding the scars caused by adhesive electrodes. In this work, we investigate the use of an array of capacitive sensors unobtrusively embedded in a mattress and used in a clinical environment for 15 preterm neonates. We also describe the analysis framework including the fusion of information from all sensors to provide a more accurate ECG signal. We propose a channel selection strategy as well as a method using physiological information to obtain a reliable ECG signal. When sensor coverage is well attained, results for both instantaneous heart rate and ECG signal shape analysis are very encouraging. The study also provides several insights on important factors affecting the results. These include the effect of textile type, number of layers, interferences (e.g. people walking by), motion severity and interventions. Incorporating this knowledge in the design of a capacitive sensing system would be crucial in ensuring that these sensors provide a reliable ECG signal when embedded in a neonatal support system.

Observation of atom pairs in spontaneous four-wave mixing of two colliding Bose-Einstein condensates.

We study atom scattering from two colliding Bose-Einstein condensates using a position sensitive, time resolved, single atom detector. In analogy to quantum optics, the process can also be thought of as spontaneous, degenerate four-wave mixing of de Broglie waves. We find a clear correlation between atoms with opposite momenta, demonstrating pair production in the scattering process. We also observe a Hanbury Brown-Twiss correlation for collinear momenta, which permits an independent measurement of the size of the pair production source and thus the size of the spatial mode. The back-to-back pairs occupy very nearly two oppositely directed spatial modes, a promising feature for future quantum optics experiments.

Comparison of the Hanbury Brown-Twiss effect for bosons and fermions.

Fifty years ago, Hanbury Brown and Twiss (HBT) discovered photon bunching in light emitted by a chaotic source, highlighting the importance of two-photon correlations and stimulating the development of modern quantum optics. The quantum interpretation of bunching relies on the constructive interference between amplitudes involving two indistinguishable photons, and its additive character is intimately linked to the Bose nature of photons. Advances in atom cooling and detection have led to the observation and full characterization of the atomic analogue of the HBT effect with bosonic atoms. By contrast, fermions should reveal an antibunching effect (a tendency to avoid each other). Antibunching of fermions is associated with destructive two-particle interference, and is related to the Pauli principle forbidding more than one identical fermion to occupy the same quantum state. Here we report an experimental comparison of the fermionic and bosonic HBT effects in the same apparatus, using two different isotopes of helium: (3)He (a fermion) and 4He (a boson). Ordinary attractive or repulsive interactions between atoms are negligible; therefore, the contrasting bunching and antibunching behaviour that we observe can be fully attributed to the different quantum statistics of each atomic species. Our results show how atom-atom correlation measurements can be used to reveal details in the spatial density or momentum correlations in an atomic ensemble. They also enable the direct observation of phase effects linked to the quantum statistics of a many-body system, which may facilitate the study of more exotic situations.

Hanbury Brown Twiss effect for ultracold quantum gases.

We have studied two-body correlations of atoms in an expanding cloud above and below the Bose-Einstein condensation threshold. The observed correlation function for a thermal cloud shows a bunching behavior, whereas the correlation is flat for a coherent sample. These quantum correlations are the atomic analog of the Hanbury Brown Twiss effect. We observed the effect in three dimensions and studied its dependence on cloud size.

Prevention of experimental autoimmune encephalomyelitis in the common marmoset (Callithrix jacchus) using a chimeric antagonist monoclonal antibody against human CD40 is associated with altered B cell responses.

Inhibition of CD40-CD40 ligand interaction is a potentially effective approach for treatment of autoimmune diseases, such as multiple sclerosis. We have investigated this concept with a chimeric antagonist anti-human CD40 mAb (ch5D12) in the marmoset monkey experimental autoimmune encephalomyelitis (EAE) model. Marmosets were immunized with recombinant human myelin oligodendrocyte glycoprotein (rMOG) and treated from the day before immunization (day -1) until day 50 with either ch5D12 (5 mg/kg every 2-4 days) or placebo. On day 41 after the induction of EAE, four of four placebo-treated monkeys had developed severe clinical EAE, whereas all animals from the ch5D12-treated group were completely free of disease symptoms. High serum levels of ch5D12 associated with complete coating of CD40 on circulating B cells were found. At necropsy placebo- and ch5D12-treated animals showed similar MOG-specific lymphoproliferative responses in vitro, but ch5D12 treatment resulted in strongly reduced anti-MOG IgM Ab responses and delayed anti-MOG IgG responses. Most importantly, treatment with ch5D12 prevented intramolecular spreading of epitope recognition. Postmortem magnetic resonance imaging and immunohistologic analysis of the CNS showed a markedly reduced lesion load after ch5D12 treatment. In conclusion, the strong reduction of clinical, pathological, and radiological aspects of EAE by ch5D12 treatment in this preclinical model points to a therapeutic potential of this engineered antagonist anti-CD40 mAb for multiple sclerosis.

Novel monoclonal antibodies against proteolipid protein peptide 139-151 demonstrate demyelination and myelin uptake by macrophages in MS and marmoset EAE lesions.

Experimental autoimmune encephalomyelitis (EAE) induced by immunization of mice with epitopes of the proteolipid protein (PLP), a major myelin constituent, forms a useful model for the study of multiple sclerosis (MS). In addition, MS patients display PLP-specific T- and B-cell responses, suggesting that PLP reactivity is relevant to pathogenesis.Here, the generation and characterization of a panel of mouse monoclonal antibodies (Mab) against PLP139-151, the prominent encephalitogenic sequence in SJL/J mice is described. Five Mab were generated by conventional immunization of an SJL/J mouse and hybridoma generation. These Mab reacted well with the PLP139-151 peptide in ELISA and belonged to the IgG2a and IgG2b subclasses, consistent with CD4+ T helper 1-cell-supported antibody formation. The Mab also efficiently detected PLP peptide-BSA conjugates in Western blot, confirming their multi-assay applicability. The Mab were subsequently used to determine the occurrence of demyelination in brains of MS patients and marmoset monkeys with EAE. Immunohistochemistry on both paraffin and frozen sections demonstrated a homogeneous expression of PLP139-151 in normal myelin, and a complete absence in lesions containing demyelinated areas, confirming that the Mab can be used as a general myelin marker. In active demyelinating MS lesions, the Mab visualized the peptide in the cytoplasm of macrophages containing phagocytosed myelin. In conclusion, this panel of Mab against the encephalitogenic PLP139-151 epitope forms a useful tool for further study of autoantigen expression, demyelination/remyelination and the staging of lesional activity in MS patients, as well as in EAE models in distinct animal species.

Recognition properties of V3-specific antibodies to V3 loop peptides derived from HIV-1 gp120 presented in multiple conformations.

To identify structural constraints and amino acid sequences important for antibody recognition of the third variable domain (V3) of HIV-1 gp120, we have studied the solution conformation of three 35-mer circular V3 loop peptides derived from HIV-1 strains which differ in syncytium- (SI) and non-syncytium-inducing (NSI) capacity. In addition to 2D NMR and CD analyses, fluid- and solid-phase immunoassays were performed using V3-specific antibodies to V3 peptides and gp120 derived from different strains of HIV-1. NMR and CD spectroscopy indicated that circular and linear V3 loops exist in water as a dynamic ensemble of multiple conformations. Amino acid substitutions and biochemical modifications of the V3 loop were found to affect antibody binding depending on the presentation of the antigens. From NMR observations and immunological experiments, we provide evidence for a V3 loop specific monoclonal antibody interaction which is directed predominantly against linear epitopes rather than against discontinuous epitopes. The absence of a single defined solution conformation of 35-mer circular V3 peptides should be taken into account when using V3-related peptides to investigate structural elements in the V3 domain of the gp120 envelope protein of HIV-1 involved in biological processes of the virus.

Therapy with antibodies against CD40L (CD154) and CD44-variant isoforms reduces experimental autoimmune encephalomyelitis induced by a proteolipid protein peptide.

Interactions between mononuclear cells are required for the formation of inflammatory infiltrates in the CNS and the activation of cellular effector functions provoking demyelination in MS. Membrane-expressed costimulatory molecules are crucial to such interactions. We therefore investigated whether two costimulatory molecules, CD40L (CD154, expressed on activated CD4-possible T cells) and selected CD44-variant isoforms (expressed on activated CD4-positive T cells), are targets for immunotherapy in MS. The model of experimental autoimmune encephalomyelitis (EAE) induced in SJL-mice by immunization with a peptide derived from the proteolipid protein (PLP139-151) was optimized to address these questions. A previous observation that anti-CD40L (CD154) monoclonal antibodies can effectively prevent EAE in this model was confirmed, and extended by demonstrating that CD40 is expressed by cells of the monocytic lineage infiltrating the spinal cord. In vivo treatment with antibody against the standard isoform of CD44 (CD44s or CD44H) did not affect disease burden. In contrast, combined treatment with antibodies against the isoforms CD44v6, v7 and v10, which are thought to be involved in inflammatory processes, reduced the disease burden considerably. In addition, CD44v10-expressing cells were detected in the spinal cord. These data support the idea that CD40-CD40L interactions form a target for immunotherapy of MS, and indicate that cells expressing CD44v6, v7 and/or v10-containing isoforms have such potential as well.

Expression of accessory molecules and cytokines in acute EAE in marmoset monkeys (Callithrix jacchus).

Accessory molecules and cytokines are involved in the immunopathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) in rodent models, and are potential targets for immunotherapy. Evaluation of such experimental therapies requires appropriate animal models. Therefore, we analysed the expression of selected accessory molecules and cytokines in the brain of marmoset monkeys (Callithrix jacchus) with acute EAE, a newly described non-human primate model for MS. All animals experienced active disease clinically and histopathologically with strong resemblance to MS. Perivascular infiltrates of mononuclear cells showed abundant expression of CD40. CD40 was expressed on macrophages, indicating that T cell priming and macrophage effector functions may result from local CD40-CD40L interactions. CD40 ligand (CD40L) and B7-2 (CD86) were also expressed, but to a lower extent, while B7-1 (CD80) expression was limited. Both pro-inflammatory and anti-inflammatory cytokines were produced within individual lesions during active disease (IFN-alpha, IFN-gamma, TNF-alpha, IL-1alpha, IL-1beta, IL-2, IL-4, IL-10 and IL-12). This suggests that relative levels rather than sequential expression of Th1- and Th2-type cytokines determine disease activity. These findings demonstrate the value of EAE in marmoset monkeys as a model to assess the role of accessory molecules and cytokines in multiple sclerosis, and to evaluate targeted intervention.

Predictive microbiology in a dynamic environment: a system theory approach.

The main factors influencing the microbial stability of chilled prepared food products for which there is an increased consumer interest-are temperature, pH, and water activity. Unlike the pH and the water activity, the temperature may vary extensively throughout the complete production and distribution chain. The shelf life of this kind of foods is usually limited due to spoilage by common microorganisms, and the increased risk for food pathogens. In predicting the shelf life, mathematical models are a powerful tool to increase the insight in the different subprocesses and their interactions. However, the predictive value of the sigmoidal functions reported in the literature to describe a bacterial growth curve as an explicit function of time is only guaranteed at a constant temperature within the temperature range of microbial growth. As a result, they are less appropriate in optimization studies of a whole production and distribution chain. In this paper a more general modeling approach, inspired by system theory concepts, is presented if for instance time varying temperature profiles are to be taken into account. As a case study, we discuss a recently proposed dynamic model to predict microbial growth and inactivation under time varying temperature conditions from a system theory point of view. Further, the validity of this methodology is illustrated with experimental data of Brochothrix thermosphacta and Lactobacillus plantarum. Finally, we propose some possible refinements of this model inspired by experimental results.

Computer aided microbial safety design of food processes.

To reduce the time required for product development, to avoid expensive experimental tests, and to quantify safety risks for fresh products and the consequence of processing there is a growing interest in computer aided food process design. This paper discusses the application of hybrid object-oriented and rule-based expert system technology to represent the data and knowledge of microbial experts and food engineers. Finite element models for heat transfer calculation routines, microbial growth and inactivation models and texture kinetics are combined with food composition data, thermophysical properties, process steps and expert knowledge on type and quantity of microbial contamination. A prototype system has been developed to evaluate changes in food composition, process steps and process parameters on microbiological safety and textual quality of foods.

A hidden region in the third variable domain of HIV-1 IIIB gp120 identified by a monoclonal antibody.

The third variable domain (V3 domain) of HIV-1 gp120 is involved in virus neutralization by antibody, in determination of cell tropism, and in syncytium-inducing/non-syncytium-inducing capacity. Antibodies are highly specific tools to delineate the role of different V3 amino acid sequences in these processes, and to dissect events occurring during synthesis of gp120/160, gp120-CD4 interaction, cellular infection, and syncytium formation. We describe here an IgG1 murine monoclonal antibody (MAb), coded IIIB-V3-01, that was raised with a synthetic peptide (FVTIGKIGNMRQAHC) derived from the carboxy-terminal flank of the HIV-1 IIIB V3 domain. The binding site of this antibody was mapped to the sequence IGKIGNMRQ, using Pepscan analysis. In ELISA, this antibody binds to E. coli-derived gp120 from HIV-1 IIIB, which is denatured and not glycosylated. The antibody showed no neutralizing activity against HIV-1 IIIB, MN, SF2, or RF in a virus neutralization assay and in a syncytium formation inhibition assay. In addition, this antibody did not react with gp120 expressed on the surface of IIIB-infected MOLT-3 cells in FACS analysis. To assess whether the epitope defined by MAb IIIB-V3-01 is hidden on native gp120, reactivity of the antibody with SDS-DTT-denatured or DTT-denatured glycosylated gp120 (CHO cell produced) was tested. Both these treatments exposed the epitope for binding. From these data we conclude that the epitope defined by MAB IIIB-V3-01 is hidden on glycosylated recombinant gp120, and is not accessible on gp120 expressed on the membrane of HIV-1, IIIB-infected cells.(ABSTRACT TRUNCATED AT 250 WORDS)