Highly dynamic gamma-ray emissions are common in tropical thunderclouds.

Thunderstorms emit fluxes of gamma rays known as gamma-ray glows1,2, sporadically observed by aircraft1,3-7, balloons8-11 and from the ground12-18. Observations report increased gamma-ray emissions by tens of percent up to two orders of magnitude above the background, sometimes abruptly terminated by lightning discharges1,3-5. Glows are produced by the acceleration of energetic electrons in high-electric-field regions within thunderclouds8 and contribute to charge dissipation3. Glows had been considered as quasi-stationary phenomena3,5,12, with durations up to a few tens of seconds and spatial scales up to 10-20 km. However, no measurements of the full extension in space and time of a gamma-ray-glow region and their occurring frequency have been reported so far. Here we show that tropical thunderclouds over ocean and coastal regions commonly emit gamma rays for hours over areas up to a few thousand square kilometres. Emission is associated with deep convective cores; it is not uniform and continuous but shows characteristic timescales of 1-10 s and even subsecond for individual glows. The dynamics of gamma-glowing thunderclouds strongly contradicts the quasi-stationary picture of glows and instead resembles that of a huge gamma-glowing 'boiling pot' in both pattern and behaviour.

Flickering gamma-ray flashes, the missing link between gamma glows and TGFs.

Two different hard-radiation phenomena are known to originate from thunderclouds: terrestrial gamma-ray flashes (TGFs)1 and gamma-ray glows2. Both involve an avalanche of electrons accelerated to relativistic energies but are otherwise different. Glows are known to last for one to hundreds of seconds, have moderate intensities and originate from quasi-stationary thundercloud fields2-5. TGFs exhibit high intensities and have characteristic durations of tens to hundreds of microseconds6-9. TGFs often show a close association with an emission of strong radio signals10-17 and optical pulses18-21, which indicates the involvement of lightning leaders in their generation. Here we report unique observations of a different phenomenon, which we call flickering gamma-ray flashes (FGFs). FGFs resemble the usual multi-pulse TGFs22-24 but have more pulses and each pulse has a longer duration than ordinary TGFs. FGF durations span from 20 to 250 ms, which reaches the lower boundary of the gamma-ray glow duration. FGFs are radio and optically silent, which makes them distinct from normal TGFs. An FGF starts as an ordinary gamma-ray glow, then suddenly increases exponentially in intensity and turns into an unstable, 'flickering' mode with a sequence of pulses. FGFs could be the missing link between the gamma-ray glows and conventional TGFs, whose absence has been puzzling the atmospheric electricity community for two decades.

Reproductive factors and breast arterial calcification: a systematic review and meta-analysis.

BACKGROUND: Breast arterial calcification (BAC) is a common incidental finding on screening mammography. Recent evidence suggests that BAC is associated with cardiovascular disease (CVD). We systematically reviewed the associations between BAC and reproductive factors (menopausal status, hormone replacement therapy [HRT] use, oral contraceptive [OC] use and parity). METHODS: MEDLINE and EMBASE databases, references of relevant papers and Web of Science were searched up to February 2020 for English-language studies that evaluated these associations. Study quality were determined and a random effects model was used to assess these associations. RESULTS: Nineteen observational studies (n = 47,249; three cohort studies, seven case-control studies, nine cross-sectional studies) were included. BAC was associated with menopause (nine studies; n = 15,870; odds ratio [OR] 2.67; 95% confidence interval [CI] 1.50-4.77) and parity (seven studies; n = 27,728; OR 2.50; 95% CI 1.68-3.71) and inversely with HRT use (10 studies; n = 33,156; OR 0.57; 95% CI 0.40-0.80). No association was found with OC use. Eleven studies were considered good in quality. Marked heterogeneity existed across all analyses. CONCLUSIONS: BAC is associated with HRT use, menopause and parity. However, careful interpretation is required as marked heterogeneity existed across all analyses. Traditional cardiovascular risk factors may need to be taken into account in future investigations of associations between BAC and reproductive factors. PROSPERO: CRD42020141644.

Mindfulness-Based Cognitive Therapy as Migraine Intervention: a Randomized Waitlist Controlled Trial.

BACKGROUND: Based on promising effects seen in a pilot study evaluating a generic mindfulness-based program for migraine, we developed a migraine-specific adaptation of the Mindfulness-Based Cognitive Therapy (MBCT) program. The aim of this study was to evaluate this program for feasibility and effectiveness in a randomized controlled trial. METHOD: Fifty-four patients suffering from migraine were randomly allocated to either waitlist or the adapted MBCT. Outcomes were migraine-related parameters as well as variables of psychological functioning and coping. Assessment took place at baseline and post-intervention, for the intervention group also at follow-up (7 months). The effects of the intervention were analyzed by the use of ANCOVAs and linear mixed models. RESULTS: With respect to migraine parameters we did not find a significant group difference in the primary outcome (headache-related impairment), but the intervention resulted in a significant reduction of headache frequency (p = .04). In the analysis of secondary outcomes, MBCT showed superiority in four out of eight psychological parameters (perceived stress, anxiety, rumination, catastrophizing) with small to medium effect sizes. The intervention proved to be feasible and participants reported high degrees of contentment and achievement of personal goals. CONCLUSIONS: The migraine-specific MBCT program did not result in improvements with regard to headache-related impairment but showed a reduction in headache frequency as well as improved psychological functioning in secondary outcomes. TRIAL REGISTRATION: This trial was registered in the German Trial Registry "Deutsches Register Klinischer Studien" (ID: DRKS00007477), which is a WHO-listed primary trial register.

A closer look at 30 day hospital readmissions after head and neck cancer surgery.

PURPOSE: 30-day hospital readmissions after head and neck cancer surgery continue to be a significant source of patient harm and healthcare expenditure. While there is substantial data in the literature assessing predictive factors for readmissions after head and neck cancer surgery, there are a paucity of studies which attempt to understand if such readmissions are preventable. The goal of this paper is to determine factors associated with 30-day hospital readmissions after head and neck cancer surgery and to understand if these readmissions were preventable. MATERIALS AND METHODS: Retrospective review from a single academic tertiary care center. Patients readmitted within 30 days after undergoing surgery for cancers of the head and neck between 2015 and 2018 were identified. RESULTS: Over a 3-year period, 26 patients undergoing resection with or without reconstruction of head and neck cancers were readmitted to the hospital within 30 days of discharge. There were 15 (58%) men and 11 (42%) women with a mean age of 68 years (SD 14 years). Twenty-one (81%) patients had squamous cell carcinoma and 13 (50%) had a primary site in the oral cavity. Thirteen (50%) had undergone free or regional flap reconstruction. The indication for readmission was related to the surgical wound in 19 (73%) and to medical complications in 7 (27%). Each case was categorized as "possibly preventable" versus "uncertain if preventable" based on whether a reasonable and feasible change in management may have prevented readmission. Six (23%) readmissions were deemed possibly preventable. Four were related to the surgical wound where initial free or regional flaps may have prevented complication. Two were medical complications that may have benefited from longer inpatient observation. CONCLUSIONS: For a subset of patients readmitted within 30 days of head and neck cancer surgery, a reasonable and feasible change in management may have prevented their hospital readmission. The significance of better understanding this patient population is underscored by the high mortality rate.

Resilience and cortical thickness: a MRI study.

Resilience is defined as the psychological resistance which enables the processing of stress and adverse life events and thus constitutes a key factor for the genesis of psychiatric illness. However, little is known about the morphological correlates of resilience in the human brain. Hence, the aim of this study is to examine the neuroanatomical expression of resilience in healthy individuals. 151 healthy subjects were recruited and had to complete a resilience-specific questionnaire (RS-11). All of them underwent a high-resolution T1-weighted MRI in a 3T scanner. Fine-grained cortical thickness was analyzed using FreeSurfer. We found a significant positive correlation between the individual extent of resilience and cortical thickness in a right hemispherical cluster incorporating the lateral occipital cortex, the fusiform gyrus, the inferior parietal cortex as well as the middle and inferior temporal cortex, i.e., a reduced resilience is associated with a decreased cortical thickness in these areas. We lend novel evidence for a direct linkage between psychometric resilience and local cortical thickness. Our findings in a sample of healthy individuals show that a lower resilience is associated with a lower cortical thickness in anatomical areas are known to be involved in the processing of emotional visual input. These regions have been demonstrated to play a role in the pathogenesis of stress and trauma-associated disorders. It can thus be assumed that neuroanatomical variations in these cortical regions might modulate the susceptibility for the development of stress-related disorders.

Evidence for alterations of cortical folding in anorexia nervosa.

Anorexia nervosa (AN) is highly heritable, and the perspective on the etiology of AN has changed from a behavioral to a neurobiological and neurodevelopmental view. However, cortical folding as an important marker for deviations in brain development has yet rarely been explored in AN. Hence, in order to determine potential cortical folding alterations, we investigated fine-grained cortical folding in a cohort of 26 patients with AN, of whom 6 patients were recovered regarding their weight at the time point of MRI measurement. MRI-derived cortical folding was computed and compared between patients and healthy controls at about 150,000 points per hemisphere using a surface-based technique (FreeSurfer). Patients with AN exhibited highly significant increased cortical folding in a right dorsolateral prefrontal cortex region (DLPFC). Furthermore, a statistical trend in the same direction was found in the right visual cortex. We did not find a correlation of local cortical folding and current symptoms of the disease. In conclusion, our analyses provide first evidence that altered DLPFC cortical folding plays a role in the etiology of AN. The absence of correlations with clinical parameters implicates a relatively independence of cortical folding alterations from the current symptomatology and might thus be regarded as a trait characteristic of the disease potentially related to other neurobiological features of AN.

High levels of neuroticism are associated with decreased cortical folding of the dorsolateral prefrontal cortex.

The personality trait neuroticism has been identified as a vulnerability factor for common psychiatric diseases and defining potential neuroanatomical markers for early recognition and prevention strategies is mandatory. Because both personality traits and cortical folding patterns are early imprinted and timely stable there is reason to hypothesize an association between neuroticism and cortical folding. Thus, to identify a putative linkage, we tested whether the degree of neuroticism is associated with local cortical folding in a sample of 109 healthy individuals using a surface-based MRI approach. Based on previous findings we additionally tested for a potential association with cortical thickness. We found a highly significant negative correlation between the degree of neuroticism and local cortical folding of the left dorsolateral prefrontal cortex (DLPFC), i.e., high levels of neuroticism were associated with low cortical folding of the left DLPFC. No association was found with cortical thickness. The present study is the first to describe a linkage between the extent of local cortical folding and the individual degree of neuroticism in healthy subjects. Because neuroticism is a vulnerability factor for common psychiatric diseases such as depression our finding indicates that alterations of DLPFC might constitute a neurobiological marker elevating risk for psychiatric burden.

ZNF804A genetic variation (rs1344706) affects brain grey but not white matter in schizophrenia and healthy subjects.

BACKGROUND: Genetic variation in the gene encoding ZNF804A, a risk gene for schizophrenia, has been shown to affect brain functional endophenotypes of the disorder, while studies of white matter structure have been inconclusive. METHOD: We analysed effects of ZNF804A single nucleotide polymorphism rs1344706 on grey and white matter using voxel-based morphometry (VBM) in high-resolution T1-weighted magnetic resonance imaging scans of 62 schizophrenia patients and 54 matched healthy controls. RESULTS: We found a significant (p < 0.05, family-wise error corrected for multiple comparisons) interaction effect of diagnostic group x genotype for local grey matter in the left orbitofrontal and right and left lateral temporal cortices, where patients and controls showed diverging effects of genotype. Analysing the groups separately (at p < 0.001, uncorrected), variation in rs1344706 showed effects on brain structure within the schizophrenia patients in several areas including the left and right inferior temporal, right supramarginal/superior temporal, right and left inferior frontal, left frontopolar, right and left dorsolateral/ventrolateral prefrontal cortices, and the right thalamus, as well as effects within the healthy controls in left lateral temporal, right anterior insula and left orbitofrontal cortical areas. We did not find effects of genotype of regional white matter in either of the two cohorts. CONCLUSIONS: Our findings demonstrate effects of ZNF804A genetic variation on brain structure, with diverging regional effects in schizophrenia patients and healthy controls in frontal and temporal brain areas. These effects, however, might be dependent on the impact of other (genetic or non-genetic) disease factors.

Perceptions of low-income mothers about the causes and ways to prevent overweight in children.

BACKGROUND: Childhood overweight and obesity remain major health conditions, affecting nearly one-third of children in the USA. Multiple factors have been identified that contribute to children becoming overweight; however, little is known regarding what low-income mothers perceive to be the causes of and the ways to prevent children from becoming overweight. METHODS: Low-income mothers (n = 286) with children aged 4-8 years participated in semi-structured interviews, during which they were asked for their opinions about the causes of and ways to prevent children from becoming overweight. After themes were identified, interviews were coded for the presence or absence of each theme. RESULTS: The majority of mothers were non-Hispanic White (69.2%) and overweight or obese (77.3%). Additionally, many of the children (41.9%) were overweight or obese. Six causes of children becoming overweight were identified by mothers: types or quantities of food eaten (90.9%); parenting behaviours (44.9%); lack of activity (42.3%); genetics, slow metabolism or medical issues (24.5%); stress or emotion (5.2%); and limited access to resources (3.5%). Five ways to prevent children from becoming overweight identified by mothers included the following: healthy eating (84.9%), more activity (54.8%), limiting screen time (19.9%), limiting sugar-sweetened beverages (12.2%) and drinking more water (6.6%). The majority of mothers (77.1%) reported that they carried out their suggestions to prevent their children from becoming overweight. CONCLUSION: Within this cohort with a high prevalence of maternal and child overweight, most mothers identified many of the evidence-based strategies for childhood obesity prevention. Future intervention development may benefit from focusing on content areas that were less commonly identified by mothers as well as helping mothers translate knowledge to implementation.

Association between white matter fiber structure and reward-related reactivity of the ventral striatum.

Individual responsiveness to rewards or rewarding stimuli may affect various domains of normal as well as pathological behavior. The ventral striatum/nucleus accumbens (NAcc) constitutes a key brain structure in the regulation of reward-appetitive behavior. It remains unclear, however, to which extent individual reward-related BOLD response in the NAcc is dependent on individual characteristics of connecting white matter fiber tracts. Using tract-based spatial statistics (TBSS) and statistical parametric mapping (SPM) this combined DTI - fMRI study investigated this question by correlating NAcc BOLD signal upon receipt of a monetary reward with different white matter characteristics (FA, axial diffusivity, radial diffusivity). The results show that increased integrity of white matter as assessed by FA in the cingulate and corpus callosum, the inferior fronto-occipital fasciculus, the anterior thalamic radiation and the anterior limb of the internal capsule was positively correlated with reward-related activation in the NAcc. There were no negative correlations as well as no significant results regarding axial and radial diffusivity. These findings indicate that microstructural properties of fiber tracts connecting, amongst others, the cortex with the striatum may influence intensity of reward-related responsiveness of the ventral striatum by constraining or increasing efficiency in information transfer within relevant circuitries involved in processing of reward.

Functional connectivity and grey matter volume of the striatum in schizophrenia.

BACKGROUND: Alterations in the dopaminergic reward system, predominantly the striatum, constitute core characteristics of schizophrenia. AIMS: Functional connectivity of the dorsal striatum during reward-related trial-and-error learning was investigated in 17 people with schizophrenia and 18 healthy volunteers and related to striatal grey matter volume and psychopathology. METHOD: We used voxel-based morphometry and psychophysiological interaction to examine striatal volume and connectivity. RESULTS: A reduced functional connectivity between left striatum and temporo-occipital areas, precuneus and insula could be detected in the schizophrenia group. The positive correlation between grey matter volume and functional connectivity of the left striatum yielded significant results in a very similar network. Connectivity of the left striatum was negatively correlated with negative symptoms. CONCLUSIONS: Present results suggest a disruption in striatal functional connectivity that is closely linked to grey matter morphometry of the striatum. Decreased connectivity between the striatum and psychopathologically relevant networks may explain the emergence of negative symptoms.

Common variation in NCAN, a risk factor for bipolar disorder and schizophrenia, influences local cortical folding in schizophrenia.

BACKGROUND: Recent studies have provided strong evidence that variation in the gene neurocan (NCAN, rs1064395) is a common risk factor for bipolar disorder (BD) and schizophrenia. However, the possible relevance of NCAN variation to disease mechanisms in the human brain has not yet been explored. Thus, to identify a putative pathomechanism, we tested whether the risk allele has an influence on cortical thickness and folding in a well-characterized sample of patients with schizophrenia and healthy controls. METHOD: Sixty-three patients and 65 controls underwent T1-weighted magnetic resonance imaging (MRI) and were genotyped for the single nucleotide polymorphism (SNP) rs1064395. Folding and thickness were analysed on a node-by-node basis using a surface-based approach (FreeSurfer). RESULTS: In patients, NCAN risk status (defined by AA and AG carriers) was found to be associated with higher folding in the right lateral occipital region and at a trend level for the left dorsolateral prefrontal cortex. Controls did not show any association (p > 0.05). For cortical thickness, there was no significant effect in either patients or controls. CONCLUSIONS: This study is the first to describe an effect of the NCAN risk variant on brain structure. Our data show that the NCAN risk allele influences cortical folding in the occipital and prefrontal cortex, which may establish disease susceptibility during neurodevelopment. The findings suggest that NCAN is involved in visual processing and top-down cognitive functioning. Both major cognitive processes are known to be disturbed in schizophrenia. Moreover, our study reveals new evidence for a specific genetic influence on local cortical folding in schizophrenia.

Training and assessing convolutional neural network performance in automatic vascular segmentation using Ga-68 DOTATATE PET/CT.

To evaluate a convolutional neural network's performance (nnU-Net) in the assessment of vascular contours, calcification and PET tracer activity using Ga-68 DOTATATE PET/CT. Patients who underwent Ga-68 DOTATATE PET/CT imaging over a 12-month period for neuroendocrine investigation were included. Manual cardiac and aortic segmentations were performed by an experienced observer. Scans were randomly allocated in ratio 64:16:20 for training, validation and testing of the nnU-Net model. PET tracer uptake and calcium scoring were compared between segmentation methods and different observers. 116 patients (53.5% female) with a median age of 64.5 years (range 23-79) were included. There were strong, positive correlations between all segmentations (mostly r > 0.98). There were no significant differences between manual and AI segmentation of SUVmean for global cardiac (mean ± SD 0.71 ± 0.22 vs. 0.71 ± 0.22; mean diff 0.001 ± 0.008, p > 0.05), ascending aorta (mean ± SD 0.44 ± 0.14 vs. 0.44 ± 0.14; mean diff 0.002 ± 0.01, p > 0.05), aortic arch (mean ± SD 0.44 ± 0.10 vs. 0.43 ± 0.10; mean diff 0.008 ± 0.16, p > 0.05) and descending aorta (mean ± SD < 0.001; 0.58 ± 0.12 vs. 0.57 ± 0.12; mean diff 0.01 ± 0.03, p > 0.05) contours. There was excellent agreement between the majority of manual and AI segmentation measures (r ≥ 0.80) and in all vascular contour calcium scores. Compared with the manual segmentation approach, the CNN required a significantly lower workflow time. AI segmentation of vascular contours using nnU-Net resulted in very similar measures of PET tracer uptake and vascular calcification when compared to an experienced observer and significantly reduced workflow time.

Moderate-intensity continuous training reduces triglyceridemia and improves oxygen consumption in dyslipidemic apoCIII transgenic mice.

This study aimed to investigate metabolism modulation and dyslipidemia in genetic dyslipidemic mice through physical exercise. Thirty-four male C57Bl/6 mice aged 15 months were divided into non-transgenic (NTG) and transgenic overexpressing apoCIII (CIII) groups. After treadmill adaptation, the trained groups (NTG Ex and CIII Ex) underwent an effort test to determine running performance and assess oxygen consumption (V̇O2), before and after the training protocol. The exercised groups went through an 8-week moderate-intensity continuous training (MICT) program, consisting of 40 min of treadmill running at 60% of the peak velocity achieved in the test, three times per week. At the end of the training, animals were euthanized, and tissue samples were collected for ex vivo analysis. ApoCIII overexpression led to hypertriglyceridemia (P<0.0001) and higher concentrations of total plasma cholesterol (P<0.05), low-density lipoprotein (LDL) cholesterol (P<0.01), and very low-density lipoprotein (VLDL) cholesterol (P<0.0001) in the animals. Furthermore, the transgenic mice exhibited increased adipose mass (P<0.05) and higher V̇O2peak compared to their NTG controls (P<0.0001). Following the exercise protocol, MICT decreased triglyceridemia and cholesterol levels in dyslipidemic animals (P<0.05), and reduced adipocyte size (P<0.05), increased muscular glycogen (P<0.001), and improved V̇O2 in all trained animals (P<0.0001). These findings contribute to our understanding of the effects of moderate and continuous exercise training, a feasible non-pharmacological intervention, on the metabolic profile of genetically dyslipidemic subjects.

Clinical phenotype and functional analysis of a rare XIAP/BIRC4 mutation.

X-linked lymphoproliferative syndromes (XLP) are rare primary immunodeficiencies. Mutations within the XIAP/BIRC4 gene characterize XLP type 2 and cause XIAP deficiency. We present the case of a 5-year-old boy with a novel mutation of the XIAP/BIRC4 gene and describe the immunological phenotype for the first time. We characterized the distinct immunological phenotype and evaluated the family history accordingly.

Long-acting injectable progesterone treatment prior to puberty induction in gilts.

Progesterone (P4) has a pivotal role on female puberty attainment in most farm animals. However, there are no studies evaluating the effect of P4 treatment previously to boar exposure for puberty induction in gilts. Therefore, serum P4 concentration, estrus expression and reproductive performance after boar stimuli were evaluated in gilts intramuscularly treated with long-acting P4 before boar exposure. In Experiment I, prepubertal gilts received either 1 mL of saline (control) or intramuscular (I.M.) P4 treatment (150 mg, 300 mg or 600 mg; n = 6 per treatment). Serum P4 concentration for P4-treated gilts was greater than for control gilts for at least 8 d for P4300 and P4600 groups (P < 0.05), but greater until after 16 d only for those treated with 600 mg (P < 0.05). In Experiments II (prepubertal) and III (peripubertal), gilts received either saline (control) or 300 mg P4 I.M. and those showing estrus signs were artificially inseminated (AI), whereas gilts without estrus expression were culled. In prepubertal gilts (Exp. II), estrus expression rate did not differ (P < 0.05) for control (79.1%; n = 110) and P4-treated gilts (81.5%; n = 108). In peripubertal gilts (Exp. III), although estrus expression did not differ between control (77.6%; n = 106) and P4-treated (69.6%; n = 102) gilts (P > 0.05), P4-treated gilts presented longer (23.1 ± 1.4 days) interval from treatment to estrus expression than control gilts (17.1 ± 1.3 days; P < 0.05). In Experiments II and III, the proportion of culled gilts with ovarian structures consistent with normal estrous cycles, farrowing rate, and litter size did not differ between treatments (P > 0.05). In conclusion, I.M. treatment with 300 or 600 mg of long-acting P4 was efficient in maintaining high P4 concentrations in prepubertal gilts for at least 8 days. However, P4 treatment over this time interval did not benefit the reproductive performance of prepubertal and peripubertal gilts.

Multimodal functional and structural imaging investigations in psychosis research.

Substantial pathophysiological questions about the relationship of brain pathologies in psychosis can only be answered by multimodal neuroimaging approaches combining different imaging modalities such as structural MRI (sMRI), functional MRI (fMRI), diffusion tensor imaging (DTI), positron emission tomography (PET) and magnetic-resonance spectroscopy. In particular, the multimodal imaging approach has the potential to shed light on the neuronal mechanisms underlying the major brain structural and functional pathophysiological features of schizophrenia and high-risk states such as prefronto-temporal gray matter reduction, altered higher-order cognitive processing, or disturbed dopaminergic and glutamatergic neurotransmission. In recent years, valuable new findings have been revealed in these fields by multimodal imaging studies mostly reflecting a direct and aligned correlation of brain pathologies in psychosis. However, the amount of multimodal studies is still limited, and further efforts have to be made to consolidate previous findings and to extend the scope to other pathophysiological parameters contributing to the pathogenesis of psychosis. Here, investigating the genetic foundations of brain pathology relationships is a major challenge for future multimodal imaging applications in psychosis research.

[Challenges of interdisciplinary collaboration in the management of rare diseases]. / Herausforderungen in der interdisziplinären Zusammenarbeit bei der Versorgung seltener Erkrankungen.

The care of patients with rare diseases is associated with many challenges, in particular those associated with high coordination complexity. In an explorative case study in a health-care network for patients with respiratory insufficiency, we have investigated the types and causes of coordination problems.We conducted semi-structured, qualitative interviews with 3 patients and their health-care providers. The evaluation of the views expressed in these interviews was worked up by applying qualitative content analysis.The network examined exhibits parallel structures. While the patient-centred interactions are ensuring patient care, learning processes among the health-care professionals take place and ideas for improved treatment are developed. Depending on the purpose, context-specific interaction patterns are evolving. Causes for coordination problems have been identified at the micro-, meso-, macro- and the indication-based levels, e. g., the low prevalence of the diseases and the lacking qualifications of the health-care professionals.Our results demonstrate the need for creating innovative health-care structures. Potential solutions range from the initiation of interdisciplinary working groups and cross-sectoral disease management guidelines tjhrough to the implementation of qualification measures.