Influence of the substitution position on spin communication in photoexcited perylene-nitroxide dyads.

By virtue of the modularity of their structures, their tunable optical and magnetic properties, and versatile applications, photogenerated triplet-radical systems provide an ideal platform for the study of the factors controlling spin communication in molecular frameworks. Typically, these compounds consist of an organic chromophore covalently attached to a stable radical. After formation of the chromophore triplet state by photoexcitation, two spin centres are present in the molecule that will interact. The nature of their interaction is governed by the magnitude of the exchange interaction between them and can be studied by making use of transient electron paramagnetic resonance (EPR) techniques. Here, we investigate three perylene-nitroxide dyads that only differ with respect to the position where the nitroxide radical is attached to the perylene core. The comparison of the results from transient UV-vis and EPR experiments reveals major differences in the excited state properties of the three dyads, notably their triplet state formation yield, excited state deactivation kinetics, and spin coherence times. Spectral simulations and quantum chemical calculations are used to rationalise these findings and demonstrate the importance of considering the structural flexibility and the contribution of rotational conformers for an accurate interpretation of the data.

PDI-trityl dyads as photogenerated molecular spin qubit candidates.

Owing to their potential applications in the field of quantum information science, photogenerated organic triplet-radical conjugates have attracted an increasing amount of attention recently. Typically, these compounds are composed of a chromophore appended to a stable radical. After initialisation of the system by photoexcitation, a highly spin-polarised quartet state may be generated, which serves as a molecular spin qubit candidate. Here, we investigate three perylene diimide (PDI)-based chromophore-radical systems with different phenylene linkers and radical counterparts by both optical spectroscopy and transient electron paramagnetic resonance (EPR) techniques. Femtosecond transient absorption measurements demonstrate chromophore triplet state formation on a picosecond time scale for PDI-trityl dyads, while excited state deactivation is found to be slowed down considerably in a PDI-nitroxide analogue. The subsequent investigation of the coherent spin properties by transient EPR confirms quartet state formation by triplet-doublet spin mixing for all investigated dyads and the suitability of the two studied PDI-trityl dyads as spin qubit candidates. In particular, we show that using tetrathiaryl trityl as the radical counterpart, an intense spin polarisation is observed even at room temperature and quartet state coherence times of 3.0 µs can be achieved at 80 K, which represents a considerable improvement compared to previously studied systems.

Amiodarone prevents wave front-tail interactions in patients with heart failure: an in silico study.

Amiodarone (AM) is an antiarrhythmic drug whose chronic use has proved effective in preventing ventricular arrhythmias in a variety of patient populations, including those with heart failure (HF). AM has both class III [i.e., it prolongs the action potential duration (APD) via blocking potassium channels) and class I (i.e., it affects the rapid sodium channel) properties; however, the specific mechanism(s) by which it prevents reentry formation in patients with HF remains unknown. We tested the hypothesis that AM prevents reentry induction in HF during programmed electrical stimulation (PES) via its ability to induce postrepolarization refractoriness (PRR) via its class I effects on sodium channels. Here we extend our previous human action potential model to represent the effects of both HF and AM separately by calibrating to human tissue and clinical PES data, respectively. We then combine these models (HF + AM) to test our hypothesis. Results from simulations in cells and cables suggest that AM acts to increase PRR and decrease the elevation of takeoff potential. The ability of AM to prevent reentry was studied in silico in two-dimensional sheets in which a variety of APD gradients (ΔAPD) were imposed. Reentrant activity was induced in all HF simulations but was prevented in 23 of 24 HF + AM models. Eliminating the AM-induced slowing of the recovery of inactivation of the sodium channel restored the ability to induce reentry. In conclusion, in silico testing suggests that chronic AM treatment prevents reentry induction in patients with HF during PES via its class I effect to induce PRR.NEW & NOTEWORTHY This work presents a new model of the action potential of the human, which reproduces the complex dynamics during premature stimulation in heart failure patients with and without amiodarone. A specific mechanism of the ability of amiodarone to prevent reentrant arrhythmias is presented.

Method for Using IMU-Based Experimental Motion Data in BVH Format for Musculoskeletal Simulations via OpenSim.

Biomechanical simulation allows for in silico estimations of biomechanical parameters such as muscle, joint and ligament forces. Experimental kinematic measurements are a prerequisite for musculoskeletal simulations using the inverse kinematics approach. Marker-based optical motion capture systems are frequently used to collect this motion data. As an alternative, IMU-based motion capture systems can be used. These systems allow flexible motion collection without nearly any restriction regarding the environment. However, one limitation with these systems is that there is no universal way to transfer IMU data from arbitrary full-body IMU measurement systems into musculoskeletal simulation software such as OpenSim. Thus, the objective of this study was to enable the transfer of collected motion data, stored as a BVH file, to OpenSim 4.4 to visualize and analyse the motion using musculoskeletal models. By using the concept of virtual markers, the motion saved in the BVH file is transferred to a musculoskeletal model. An experimental study with three participants was conducted to verify our method's performance. Results show that the present method is capable of (1) transferring body dimensions saved in the BVH file to a generic musculoskeletal model and (2) correctly transferring the motion data saved in the BVH file to a musculoskeletal model in OpenSim 4.4.

Distance dependence of enhanced intersystem crossing in BODIPY-nitroxide dyads.

Photogenerated organic triplet-doublet systems have attracted an increasing amount of attention in recent years due to their versatility and suitability for a range of technological applications in the emerging field of molecular spintronics. Such systems are typically generated by enhanced intersystem crossing (EISC) preceded by photoexcitation of an organic chromophore covalently linked to a stable radical. After formation of the chromophore triplet state by EISC, triplet state and stable radical may interact, whereby the nature of the interaction depends on the exchange interaction JTR between them. If JTR surpasses all other magnetic interactions in the system, molecular quartet states may be formed by spin mixing. For the design of new spintronic materials based on photogenerated triplet-doublet systems, it is crucial to gain further knowledge about the factors influencing the EISC process and the yield of the subsequent quartet state formation. Here we investigate a series of three BODIPY-nitroxide dyads characterised by different separation distances and different relative orientations of the two spin centres. Our combined results from optical spectroscopy, transient electron paramagnetic resonance, and quantum chemical calculations suggest that the chromophore triplet formation by EISC is mediated by dipolar interactions and depends primarily on the distance between the chromophore and radical electrons, while the yield of the subsequent quartet state formation by triplet-doublet spin mixing is influenced by the absolute magnitude of JTR.

Anonymization of whole slide images in histopathology for research and education.

Objective: The exchange of health-related data is subject to regional laws and regulations, such as the General Data Protection Regulation (GDPR) in the EU or the Health Insurance Portability and Accountability Act (HIPAA) in the United States, resulting in non-trivial challenges for researchers and educators when working with these data. In pathology, the digitization of diagnostic tissue samples inevitably generates identifying data that can consist of sensitive but also acquisition-related information stored in vendor-specific file formats. Distribution and off-clinical use of these Whole Slide Images (WSIs) are usually done in these formats, as an industry-wide standardization such as DICOM is yet only tentatively adopted and slide scanner vendors currently do not provide anonymization functionality. Methods: We developed a guideline for the proper handling of histopathological image data particularly for research and education with regard to the GDPR. In this context, we evaluated existing anonymization methods and examined proprietary format specifications to identify all sensitive information for the most common WSI formats. This work results in a software library that enables GDPR-compliant anonymization of WSIs while preserving the native formats. Results: Based on the analysis of proprietary formats, all occurrences of sensitive information were identified for file formats frequently used in clinical routine, and finally, an open-source programming library with an executable CLI tool and wrappers for different programming languages was developed. Conclusions: Our analysis showed that there is no straightforward software solution to anonymize WSIs in a GDPR-compliant way while maintaining the data format. We closed this gap with our extensible open-source library that works instantaneously and offline.

State of illness-dependent associations of neuro-cognition and psychopathological syndromes in a large transdiagnostic cohort.

BACKGROUND: There is a lack of knowledge regarding the relationship between dimensional psychopathological syndromes and neurocognitive functions, particularly across the major psychiatric disorders (i.e., Major Depressive Disorder (MDD), Bipolar Disorder (BD), and Schizophrenia (SZ)). METHOD: SANS, SAPS, HAMA, HAM-D, and YMRS were assessed in 1064 patients meeting DSM-IV-TR criteria for MDD, BD, SZ or schizoaffective disorder (SZA). In addition, a comprehensive neuropsychological test battery was administered. Psychopathological syndromes derived from factor analysis and present state of illness were used to explore psychopathology-cognition relationships. Correlational analyses were corrected for age, sex, verbal IQ, years of education, and DSM-IV-TR diagnosis. Age of onset and total duration of hospitalizations as proxies for illness severity were tested as moderators on the cognition - psychopathology relationship. RESULTS: The negative syndrome, positive formal thought disorder as well as the paranoid-hallucinatory syndrome exhibited associations with neuro-cognition in an illness state-dependent manner, while the psychopathological factors depression and increased appetite only showed weak associations. Illness severity showed moderating effects on the neurocognitive-psychopathology relationship only for the negative syndrome and positive formal thought disorder. LIMITATIONS: No healthy control subjects were entered into the analyses because of lack of variance in psychopathological symptoms, which prevents from drawing conclusions regarding the relative level of potential cognitive impairments. CONCLUSIONS: This study suggests the relationship of neuro-cognition and psychopathology to be highly state of illness-dependent across affective and psychotic disorders. Results hint at the moderating effects of illness severity on psychopathological factors that might be more treatment resistant.

Calculation of exchange couplings in the electronically excited state of molecular three-spin systems.

Photogenerated molecular three-spin systems, composed of a chromophore and a covalently bound stable radical, are promising candidates for applications in the field of molecular spintronics. Through excitation with light, an excited doublet state and a quartet state are generated, whereby their energy difference depends on the exchange interaction J TR between the chromophore triplet state (T) and the stable radical (R). In order to establish design rules for new materials to be used in molecular spintronics devices, it is of great importance to gain knowledge on the magnitude of J TR as well as the factors influencing J TR on a molecular level. Here, we present a robust and reliable computational method to determine excited state exchange couplings in three-electron-three-centre systems based on a CASSCF/QD-NEVPT2 approach. The methodology is benchmarked and then applied to a series of molecules composed of a perylene chromophore covalently linked to various stable radicals. We calculate the phenomenological exchange interaction J TR between chromophore and radical, which can be compared directly to the experiment, but also illustrate how the individual exchange interactions J ij can be extracted using an effective Hamiltonian that corresponds to the Heisenberg-Dirac-Van-Vleck Hamiltonian. The latter procedure enables a more detailed analysis of the contributions to the exchange interaction J TR and yields additional insight that will be invaluable for future design optimisation.

Surgical Resection of Metastatic Malignant Small Bowel Obstruction.

Small bowel cancer is a rare cause of small bowel obstruction (SBO) that is often discovered too late, leading to a poor prognosis at diagnosis. This case describes an African American patient with a previous history of abdominal surgery who presented to the emergency department with a partial small bowel obstruction (PSBO) that failed to resolve with conservative measures, therefore requiring surgical intervention. An exploratory laparoscopy revealed a firm apple core mass obstructing the lumen of the proximal jejunum 20 cm from the ligament of Treitz. The involved portion of the small bowel was resected with wide margins and sent to pathology. The small bowel was reconstructed by a functional end-to-end anastomosis, and the patient was admitted for observation until the return of bowel function. The pathology report, returned four weeks after the patient's discharge, reported metastatic adenocarcinoma originating from the small intestine. The patient was referred to oncology for further management of his metastatic cancer. Small bowel cancer, although rare, should always be part of the differential diagnosis in the case of small bowel obstruction. If cancer is suspected during exploratory surgery, the entire peritoneal cavity should be explored, and oncologic bowel resection should be performed with adequate margins. Final staging then occurs in the postoperative period.

Accessing the triplet state of perylenediimide by radical-enhanced intersystem crossing.

Owing to their exceptional photophysical properties and high photostability, perylene diimide (PDI) chromophores have found various applications as building blocks of materials for organic electronics. In many light-induced processes in PDI derivatives, chromophore excited states with high spin multiplicities, such as triplet or quintet states, have been revealed as key intermediates. The exploration of their properties and formation conditions is thus expected to provide invaluable insight into their underlying photophysics and promises to reveal strategies for increasing the performance of optoelectronic devices. However, accessing these high-multiplicity excited states of PDI to increase our mechanistic understanding remains a difficult task, due to the fact that the lowest excited singlet state of PDI decays with near-unity quantum yield to its ground state. Here we make use of radical-enhanced intersystem crossing (EISC) to generate the PDI triplet state in high yield. One or two 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO) stable radicals were covalently attached to the imide position of PDI chromophores with and without p-tert-butylphenoxy core substituents. By combining femtosecond UV-vis transient absorption and transient electron paramagnetic resonance spectroscopies, we demonstrate strong magnetic exchange coupling between the PDI triplet state and TEMPO, resulting in the formation of excited quartet or quintet states. Important differences in the S1 state deactivation rate constants and triplet yields are observed for compounds bearing PDI moieties with different core substitution patterns. We show that these differences can be rationalized by considering the varying importance of competitive excited state decay processes, such as electron and excitation energy transfer. The comparison of the results obtained for different PDI-TEMPO derivatives leads us to propose design guidelines for optimizing the efficiency of triplet sensitization in molecular assemblies by EISC.

QRS micro-fragmentation as a mortality predictor.

AIMS: Fragmented QRS complex with visible notching on standard 12-lead electrocardiogram (ECG) is understood to represent depolarization abnormalities and to signify risk of cardiac events. Depolarization abnormalities with similar prognostic implications likely exist beyond visual recognition but no technology is presently suitable for quantification of such invisible ECG abnormalities. We present such a technology. METHODS AND RESULTS: A signal processing method projects all ECG leads of the QRS complex into optimized three perpendicular dimensions, reconstructs the ECG back from this three-dimensional projection, and quantifies the difference (QRS 'micro'-fragmentation, QRS-µf) between the original and reconstructed signals. QRS 'micro'-fragmentation was assessed in three different populations: cardiac patients with automatic implantable cardioverter-defibrillators, cardiac patients with severe abnormalities, and general public. The predictive value of QRS-µf for mortality was investigated both univariably and in multivariable comparisons with other risk factors including visible QRS 'macro'-fragmentation, QRS-Mf. The analysis was made in a total of 7779 subjects of whom 504 have not survived the first 5 years of follow-up. In all three populations, QRS-µf was strongly predictive of survival (P < 0.001 univariably, and P < 0.001 to P = 0.024 in multivariable regression analyses). A similar strong association with outcome was found when dichotomizing QRS-µf prospectively at 3.5%. When QRS-µf was used in multivariable analyses, QRS-Mf and QRS duration lost their predictive value. CONCLUSION: In three populations with different clinical characteristics, QRS-µf was a powerful mortality risk factor independent of several previously established risk indices. Electrophysiologic abnormalities that contribute to increased QRS-µf values are likely responsible for the predictive power of visible QRS-Mf.

[Quality of treatment outcomes in alcohol- and substance-related disorders: an evaluation of inpatients from ten psychiatric hospitals]. / Ergebnisqualität bei alkohol- und substanzbezogenen Störungen: eine Auswertung stationär behandelter Patienten aus 10 psychiatrischen Kliniken.

AIM OF THE STUDY: Alcohol and substance-related disorders (ICD 10 F1x.x) are among the most frequent diagnoses made in hospitalized patients requiring somatic and psychiatric care. In order to assess the success of treatment, it is important to establish and implement outcome indicators in practice. METHOD: In 2016, global treatment indicators for admission and at discharge were collected at 10 Vitos clinics in Hesse (CGI and GAF). More than 10,000 patients with ICD10 F1x diagnoses were included in the evaluation. RESULTS: The evaluations show significant improvements of the clinical status as well as differences in treatment duration, remissions and gender differences. CONCLUSION: The study suggests that global indicators of outcome quality are useful in the assessment of treatment success of alcohol and substance-related disorders. Limitations of the study design, instruments and sample are critically reviewed.

Postoperative Work and Activity Restrictions After Abdominal Surgery: A Systematic Review.

OBJECTIVE: This systematic review aims to assess what is known about convalescence following abdominal surgery. Through a review of the basic science and clinical literature, we explored the effect of physical activity on the healing fascia and the optimal timing for postoperative activity. BACKGROUND: Abdominal surgery confers a 30% risk of incisional hernia development. To mitigate this, surgeons often impose postoperative activity restrictions. However, it is unclear whether this is effective or potentially harmful in preventing hernias. METHODS: We conducted 2 separate systematic reviews using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The first assessed available basic science literature on fascial healing. The second assessed available clinical literature on activity after abdominal surgery. RESULTS: Seven articles met inclusion criteria for the basic science review and 22 for the clinical studies review. The basic science data demonstrated variability in maximal tensile strength and time for fascial healing, in part due to differences in layer of abdominal wall measured. Some animal studies indicated a positive effect of physical activity on the healing wound. Most clinical studies were qualitative, with only 3 randomized controlled trials on this topic. Variability was reported on clinician recommendations, time to return to activity, and factors that influence return to activity. Interventions designed to shorten convalescence demonstrated improvements only in patient-reported symptoms. None reported an association between activity and complications, such as incisional hernia. CONCLUSIONS: This systematic review identified gaps in our understanding of what is best for patients recovering from abdominal surgery. Randomized controlled trials are crucial in safely optimizing the recovery period.

Diabetes distress sources among Filipinos with type 2 diabetes mellitus in the outpatient department of a tertiary government hospital

@#<p style="text-align: justify;"><strong>Objective:</strong> The sources of diabetes distress, defined as hidden negative emotions from the demands of daily self-management, are unknown to Filipinos with type 2 diabetes mellitus in the outpatient department. Therefore, we aimed to 1) explore the sources of distress in the perspective of Filipinos with type 2 diabetes mellitus and 2) create a conceptual framework of diabetes distress for Filipinos with T2DM.</p><p style="text-align: justify;"><strong>Methods:</strong> Focus group discussions were done and audiotaped among Filipinos with type 2 diabetes (n=17). The transcript underwent content analysis to generate themes and subthemes. Relationships were determined between codes, categories, and themes elicited in the study to create a conceptual framework unique to Filipinos.</p><p style="text-align: justify;"><strong>Results:</strong> The content analysis revealed five themes of diabetes distress: caregiver factor, socio-economic factor, psycho-emotional factor, medication-related factor, and health care service delivery factor. The socio-economic factor was a distinct theme missing in the prevailing validated questionnaires. Therefore, an adapted conceptual framework was created, as approved by the expert panel.</p><p style="text-align: justify;"><strong>Conclusion:</strong> In conclusion, Filipinos with type 2 diabetes mellitus in the outpatient department have multiple sources of diabetes distress, namely, caregiver factor, socio-economic factor, psycho-emotional factor, medication-related factor, and health care service delivery factor. The socio-economic factor is a unique theme identified among Filipinos. Recognizing the sources of diabetes distress is vital to accurately screen Filipinos with type 2 diabetes mellitus and optimize management outcomes. The study findings will help develop and validate the questionnaire to screen diabetes distress unique to Filipinos.</p>

[Burden of Children of Patients with Mental Illness - A High Risk Population that Needs Selective and Indicated Prevention?] / Belastung von Kindern psychisch erkrankter Eltern im Normgruppenvergleich ­ eine Hochrisikogruppe für selektive und indizierte Prävention?

OBJECTIVE: To determinate behavioral problems of children of parents with mental illness. Conclusions for prevention. METHODS: Inpatients from a psychiatric hospital (N = 399) with children (4-18 yrs.) evaluated their children's behavior with the Child Behavior Checklist (CBCL). RESULTS: Children of mentally ill parents showed significantly more behavioral problems than children of healthy parents. They had overall fewer behavioral problems compared to children with mental illness, however, behavioral problems were similar with respect to "social problems" (4-11 year-old boys, 12-18 year-old girls) and "somatic complaints" (12-18 year-old boys and girls). CONCLUSION: Results indicate a selective, partly indicated, need for prevention. The data point towards certain areas of behavioral problems that should be particularly targeted when planning such programs.

[Implementation of a Multi-Professional, 'Operating System' Across Different Diseases for the Psychiatry: The Perspective of the User]. / Der Einsatz eines störungsübergreifenden, multiprofessionellen 'Betriebssystems' für die Psychiatrie: die Perspektive der Nutzer.

OBJECTIVE: Assessment of the practicability and acceptance of a guide, which was created based on the Dialectic Behavioral Therapy (DBT) regarding interactions, attitudes and basically overarching therapeutic interventions (GiMa-Therapy-Basics, GMTB) METHODS: Written survey of clinic staff (n = 83) from different professions as experts based on training and experienced in using the guide. RESULTS: Experts reported a high user acceptance. The applicability in psychiatry was estimated as high across psychiatric disorders. CONCLUSION: Guides based on mindfulness such as the GMTB constitute a promising basis to improve the work with seriously ill patients in psychiatry.

Factor analyses of multidimensional symptoms in a large group of patients with major depressive disorder, bipolar disorder, schizoaffective disorder and schizophrenia.

BACKGROUND: There is an ongoing discussion about which neurobiological correlates or symptoms separate the major psychoses (i.e. Major Depressive Disorder MDD, Bipolar Disorder BD, and Schizophrenia SZ). Psychopathological factor analyses within one of these disorders have resulted in models including one to five factors. Factor analyses across the major psychoses using a comprehensive set of psychopathological scales in the same patients are lacking. It is further unclear, whether hierarchical or unitarian models better summarize phenomena. METHOD: Patients (n = 1182) who met DSM-IV criteria for MDD, BD, SZ or schizoaffective disorder were assessed with the SANS, SAPS, HAMA, HAM-D, and YMRS. The sample was split into two and analyzed using explorative and confirmatory factor analyses to extract psychopathological factors independent of diagnosis. RESULTS: In the exploratory analysis of sample 1 (n = 593) we found 5 factors. The confirmatory analysis using sample 2 (n = 589) confirmed the 5-factor model (χ2 = 1287.842, df = 571, p < .0001: CFI = 0.932; RMSEA = 0.033). The 5-factors were depression, negative syndrome, positive formal thought disorder, paranoid-hallucinatory syndrome, and increased appetite. Increased appetite was not related to medication. None of the factors was specific for one diagnosis. Second order factor analysis revealed two higher order factors: negative/affective (I) and positive symptoms (II). CONCLUSION: This is the first study delineating psychopathological factors in a large group of patients across the spectrum of affective and psychotic disorders. In future neurobiological studies, we should consider transdiagnostic syndromes besides the traditional diagnoses.

[Disorder-related case groups for needs-based hospital care]. / Störungsbezogene Fallgruppen für eine bedarfsgerechte Krankenhausversorgung.

BACKGROUND: The individual needs of patients are central to hospital care. Due to the resulting complexity grouping of patients with similar therapeutic needs seems to facilitate an efficient organization of processes and the required treatment resources in hospital care. OBJECTIVE: The aim of this study was to develop a system of disorder-related, treatment-oriented case groups as a possible tool for the efficient and needs-based organization of hospital care. MATERIAL AND METHODS: The disorder-related groups were developed in a multistage, mixed-methods design. The technical content and quantitative description of the case groups and the extent of treatment included all consecutive inpatient treatment cases discharged between 1 January 2017 and 31 December 2017 from 9 psychiatric hospitals in Hesse, Germany. RESULTS: All diagnoses in chapter F of the German modification of the International Statistical Classification of Diseases 10 (ICD-10-GM) were grouped into a total of 10 disorder-related groups. Analyses included 20,252 inpatient hospital treatment cases. Substantial management-relevant differences between the case groups could be identified and the various case group-specific configurations of clinically relevant comorbidities could be demonstrated. DISCUSSION: The presented disorder-related grouping system and configuration of comorbidities suggest a modular organization of therapeutic measures and constitute a promising basis for needs-based management of patient care. Future work will show to what degree the disorder-related groups can facilitate a needs-specific treatment and align economic and therapeutic interests of psychiatric care.

A model for human action potential dynamics in vivo.

Computational modeling based on experimental data remains an important component in cardiac electrophysiological research, especially because clinical data such as human action potential (AP) dynamics are scarce or limited by practical or ethical concerns. Such modeling has been used to develop and test a variety of mechanistic hypotheses, with the majority of these studies involving the rate dependence of AP duration (APD) including APD restitution and conduction velocity (CV). However, there is very little information regarding the complex dynamics at the boundary of repolarization (or refractoriness) and reexcitability. Here, we developed a "minimal" ionic model of the human AP, based on in vivo human monophasic AP (MAP) recordings obtained during clinical programmed electrical stimulation (PES) to address the progressive decrease in AP take-off potential (TOP) and associated CV slowing seen during three tightly spaced extrastimuli. Recent voltage-clamp data demonstrating the effect of intracellular calcium on sodium current availability were incorporated and were required to reproduce large (>15 mV) elevations in take-off potential and progressive encroachment. Introducing clinically observed APD gradients into the model enabled us to replicate the dynamic response to PES in patients leading to conduction block and reentry formation for the positive, but not the negative, APD gradient. Finally, we modeled the dynamics of reentry and show that spiral waves follow a meandering trajectory with a period of ~180 ms. We conclude that our model reproduces a variety of electrophysiological behavior including the response to sequential premature stimuli and provides a basis for studies of the initiation of reentry in human ventricular tissue.NEW & NOTEWORTHY This work presents a new model of the action potential of the human which reproduces the complex dynamics during premature stimulation in patients.

Infectious rain? Evaluation of human pathogen concentrations in stormwater in separate sewer systems.

Separate sewer systems collect and discharge rainwater directly into surface water bodies. In residential areas covering moderate traffic load these are alternative drainage routes to avoid combined sewer overflow discharge and to keep rivers clean as required by the EU Water Framework Directive. This overflow's microbial quality, however, needs to be evaluated, since stormwater run-offs are potential pathways for pathogens into river systems. Between 2010 and 2016, two separate sewer systems in North Rhine-Westphalia (Germany) were investigated. The stormwater outflow was sampled during discharge events and microbiologically analysed. The results showed high concentrations of Escherichia coli (1,100-1,100,000 CFU/100 mL) and Clostridium perfringens (20-13,000 CFU/100 mL). Campylobacter and Salmonella were detected in 97% and 43% of the samples. Giardia cysts were more often detected (31.6%) than Cryptosporidium oocysts (10.5%). The sources of human pathogens in rainwater run-off are heterogeneous. While roads have already been declared as chemical polluters via rainwater run-off, our study detected supplementary pollution of mainly faecal microorganisms. Presumably, failed connections in the sewer system itself are important sources of human pathogens. We suggest treatment of stormwater run-offs before being discharged into the river system.