Molecular detection of cosaviruses in a patient with acute flaccid paralysis and in sewage samples in Germany.

Cosaviruses (CoSV) were first identified in stool samples collected from non-polio acute flaccid paralysis (AFP) cases and their healthy contacts in Pakistan in 2003. The clinical importance of CoSV remains unclear as data on epidemiology are scarce and no routine diagnostic testing is done. In this study, we characterized human CoSV (HCoSV) in a child with non-polio AFP and in sewage samples collected in Berlin, Germany. Using unbiased high-throughput sequencing and specific PCR, we characterized a HCoSV-D in stool samples of a three-year-old child hospitalized in Germany with non-polio AFP and travel history to Pakistan. The shedding pattern and absence of other relevant pathogens suggests that HCoSV-D may have been involved in the genesis of AFP. The HCoSV-RNA concentration was high, with 2.57 × 106 copies per mL fecal/suspension, decreasing in follow-up samples. To investigate the possibility of local circulation of HCoSV, we screened Berlin sewage samples collected between 2013 and 2018. Molecular testing of sewage samples has shown the presence of CoSV in several parts of the world, but until now not in Germany. Of our sewage samples, 54.3 % were positive for CoSV, with up to three viral species identified in samples. Phylogenetically, the German sequences clustered intermixed with sequences obtained globally. Together, these findings emphasize the need for further clinical, epidemiological, environmental, pathogenicity and phylogenetic studies of HCoSV.

First-line treatment with R-CHOP or rituximab-bendamustine in patients with follicular lymphoma grade 3A-results of a retrospective analysis.

Based on centroblast frequency, follicular lymphoma (FL) is subdivided into grades 1-2, 3A, and 3B. Grade FL3A frequently coexists with FL1-2 (FL1-2-3A). Based on clinical trials, FL1-2 is treated with rituximab (R) or obinutuzumab plus bendamustine (B) or CHOP, while FL3B is treated with R-CHOP. In contrast, there are little data guiding therapy in FL3A. We present a retrospective, multicenter analysis of 95 FL3A or FL1-2-3A and 203 FL1-2 patients treated with R-CHOP or R-B first-line. R-CHOP facilitated a higher response rate (95% versus 76%) and longer overall survival (OS) (3-year OS 89% versus 73%, P = 0.008) in FL3A or FL1-2-3A, whereas the difference in progression-free survival (PFS) did not reach statistical significance. While transformation rates into aggressive lymphoma were similar between both groups, there were more additional malignancies after R-B compared with R-CHOP (6 versus 2 cases). In FL1-2, R-B achieved a higher 3-year PFS (79% versus 47%, P < 0.01), while there was no significant difference regarding OS or transformation. With the limitations of a retrospective analysis, these results suggest a benefit for R-CHOP over R-B in FL3A or FL1-2-3A. Confirmatory data from prospective clinical trials are needed.

[Mobile seizure monitoring in epilepsy patients]. / Mobiles Anfallsmonitoring bei Epilepsiepatienten.

Wearables are receiving much attention from both epilepsy patients and treating physicians, for monitoring of seizure frequency and warning of seizures. They are also of interest for the detection of seizure-associated risks of patients, for differential diagnosis of rare seizure types and prediction of seizure-prone periods. Accelerometry, electromyography (EMG), heart rate and further autonomic parameters are recorded to capture clinical seizure manifestations. Currently, a clinical use to document nocturnal motor seizures is feasible. In this review the available devices, data on the performance in the documentation of seizures, current options for clinical use and developments in data analysis are presented and critically discussed.

Comparison of clinical and laboratory characteristics during two major paediatric meningitis outbreaks of echovirus 30 and other non-polio enteroviruses in Germany in 2008 and 2013.

Viral meningitis is mainly caused by non-polio enteroviruses (NPEV). Large-scale data on the clinical characteristics between different outbreaks within the same region are lacking. This study aimed to analyse a possible influence of the circulating NPEV genotype on the disease outcome of affected children. A retrospective cohort study analysing two major outbreaks of NPEV meningitis in Germany in 2008 and 2013 was conducted in cooperation with the National Reference Centre for Poliomyelitis and Enteroviruses (NRC PE) and five German children's hospitals. A total of 196 patients with laboratory-confirmed NPEV meningitis were enrolled. In 2008, children with NPEV meningitis had significantly higher fever and showed more behavioural changes and less back pain. To better define typical findings in echovirus 30 (E-30) meningitis, patients were split into the following three groups: E-30 positive patients, patients with "Non E-30" infection and patients with "Untyped" NPEV infection. E-30 positive patients were significantly older and their disease course was more acute, with early admission to but also early discharge from hospital. E-30 positive patients showed a significantly higher rate of headache and meningism, and a lower rate of diarrhoea and clinically defined septicaemia when compared to the others. Regarding laboratory testing, E-30 positive patients presented with significantly elevated peripheral blood neutrophil counts when compared to patients with "Non E-30" or "Untyped" NPEV infection. In conclusion, E-30 meningitis in children shows a characteristic pattern of clinical features. To further characterise NPEV strains worldwide, continuous surveillance and typing of NPEV strains causing central nervous system disease is warranted.

Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma.

Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of ⩾107 cells/sample, and novel software tools were constructed for automatic plasma cell gating. Multicenter evaluation of 110 follow-up BM from MM patients in very good partial response (VGPR) or CR showed a higher sensitivity for NGF-MRD vs conventional 8-color flow-MRD -MRD-positive rate of 47 vs 34% (P=0.003)-. Thus, 25% of patients classified as MRD-negative by conventional 8-color flow were MRD-positive by NGF, translating into a significantly longer progression-free survival for MRD-negative vs MRD-positive CR patients by NGF (75% progression-free survival not reached vs 7 months; P=0.02). This study establishes EuroFlow-based NGF as a highly sensitive, fully standardized approach for MRD detection in MM which overcomes the major limitations of conventional flow-MRD methods and is ready for implementation in routine diagnostics.

Allogeneic hematopoietic stem cell transplantation for poor-risk CLL: dissecting immune-modulating strategies for disease eradication and treatment of relapse.

To elucidate factors contributing to the effectiveness of allogeneic hematopoietic stem cell transplantation (alloHCT) in high-risk CLL, immune interventions, GvHD and clinical outcome of 77 consecutive patients allografted for CLL were analyzed. Immune modulation (immunosuppression tapering, rituximab-augmented donor lymphocyte infusions) was guided by minimal residual disease (MRD) monitoring and commenced at a median of 91 (22-273) days after alloHCT, resulting in a probability of being event free and MRD-negative 1 year after transplant of 57% (84% in those encountering chronic GvHD). Patients who were event free and MRD-negative at the 12-month landmark had a 4-year PFS of 77% and largely remained durably MRD-negative if MRD clearance had occurred subsequent to immune modulation. Three-year overall survival, PFS, relapse incidence and non-relapse mortality of all 77 patients were 69, 57, 26 and 24%, respectively. Survival was not affected by EBMT risk category but by active disease at alloHCT, which could not be overcome by intensification of conditioning. Twenty-three patients who experienced relapse post alloHCT had a survival of 56% at 2 years after CLL recurrence. In conclusion, MRD-guided immune modulation after alloHCT for high-risk CLL can provide durable MRD clearance in more than half of the patients.

Measurements of the neutron spectrum in transit to Mars on the Mars Science Laboratory.

The Mars Science Laboratory spacecraft, containing the Curiosity rover, was launched to Mars on 26 November 2011. Although designed for measuring the radiation on the surface of Mars, the Radiation Assessment Detector (RAD) measured the radiation environment inside the spacecraft during most of the 253-day, 560-million-kilometer cruise to Mars. An important factor for determining the biological impact of the radiation environment inside the spacecraft is the specific contribution of neutrons with their high biological effectiveness. We apply an inversion method (based on a maximum-likelihood estimation) to calculate the neutron and gamma spectra from the RAD neutral particle measurements. The measured neutron spectrum (12-436 MeV) translates into a radiation dose rate of 3.8±1.2 µGy/day and a dose equivalent of 19±5 µSv/day. Extrapolating the measured spectrum (0.1-1000 MeV), we find that the total neutron-induced dose rate is 6±2 µGy/day and the dose equivalent rate is 30±10 µSv/day. For a 360 day round-trip from Earth to Mars with comparable shielding, this translates into a neutron induced dose equivalent of about 11±4 mSv.

Outbreak investigation identifies a single Listeria monocytogenes strain in sheep with different clinical manifestations, soil and water.

Listeria (L.) monocytogenes causes orally acquired infections and is of major importance in ruminants. Little is known about L. monocytogenes transmission between farm environment and ruminants. In order to determine potential sources of infection, we investigated the distribution of L. monocytogenes genetic subtypes in a sheep farm during a listeriosis outbreak by applying four subtyping methods (MALDI-TOF-MS, MLST, MLVA and PFGE). L. monocytogenes was isolated from a lamb with septicemia and from the brainstem of three sheep with encephalitis. Samples from the farm environment were screened for the presence of L. monocytogenes during the listeriosis outbreak, four weeks and eight months after. L. monocytogenes was found only in soil and water tank swabs during the outbreak. Four weeks later, following thorough cleaning of the barn, as well as eight months later, L. monocytogenes was absent in environmental samples. All environmental and clinical L. monocytogenes isolates were found to be the same strain. Our results show that the outbreak involving two different clinical syndromes was caused by a single L. monocytogenes strain and that soil and water tanks were potential infection sources during this outbreak. However, silage cannot be completely ruled out as the bales fed prior to the outbreak were not available for analysis. Faeces samples were negative, suggesting that sheep did not act as amplification hosts contributing to environmental contamination. In conclusion, farm management appears to be a crucial factor for the limitation of a listeriosis outbreak.

[Prevention of Obesity and Promotion of Healthy Nutrition in Children by a Kindergarten-Based Intervention: An Evaluation Study]. / Übergewichtsprävention und Förderung gesunder Ernährung bei Kindern: Evaluation eines institutionellen Verpflegungskonzeptes.

This outcome evaluation study has investigated different diet concepts in day-care centres and their effects on health-related dietary behaviour of children and their families. No advantage of a certain approach to manage food and diet-related activities in day-care centres could be shown.

Off-flavour masking of secondary lipid oxidation products by pea dextrin.

The aim of the present study was to evaluate the off-flavour masking potential of pea dextrin (PD) in emulsions rich in ω-3 and ω-6-fatty acids in comparison with maltodextrin (MD) and 2-hydroxypropyl-ß-cyclodextrin (HPBCD). After optimisation of the homogenisation procedure, stable emulsions were prepared and stored for up to eight weeks. The development of six secondary lipid oxidation products: propanal, 1-penten-3-one, 1-penten-3-ol, hexanal, (E,E)-2,4-heptadienal and (E,Z)-2,6-nonadienal, was monitored via headspace gas chromatography after solid-phase microextraction. Sensory evaluation of the emulsions was performed by a trained panel. PD already showed masking properties for propanal, 1-penten-3-one, hexanal and (E,E)-2,4-heptadienal during validation of the gas chromatographic analysis, but not for 1-penten-3-ol or (E,Z)-2,6-nonadienal. During storage, the course of lipid oxidation was similar in all emulsions as concluded from the hydroperoxide value. Results from the sensory evaluation confirmed a masking of rancid off-flavour. In conclusion, pea dextrin is suitable for masking off-flavour resulting from early stages of lipid oxidation.

[How do Prevention Projects Reach their Target Groups? Results of a Survey with Prevention Projects]. / Wie erreichen Präventionsprojekte ihre Zielgruppen? Auswertung einer Befragung der im Rahmen des BMBF-Förderschwerpunkts Präventionsforschung geförderten Projekte.

AIM: The aim of this study was to assess methods used to access target groups in prevention projects funded within the prevention research framework by the German Federal Ministry of Education and Research. METHODS: A survey with prevention projects was conducted. Access strategies, communication channels, incentives, programme reach, and successful practical recruitment strategies were explored. RESULTS: 38 out of 60 projects took part in the survey. Most projects accessed their target group within structured settings (e. g., child day-care centers, schools, workplaces). Multiple communication channels and incentives were used, with written information and monetary incentives being used most frequently. Only few projects were able to report their programme reach adequately; programme reach was highest for programmes accessing the target groups in structured settings. The respondents viewed active recruitment via personal communication with the target group and key persons in the settings as the most successful strategy. CONCLUSION: The paper provides an overview on recruitment strategies used in current preven-tion projects. More systematic research on programme reach is necessary.

Understanding the origin of band gap formation in graphene on metals: graphene on Cu/Ir(111).

Understanding the nature of the interaction at the graphene/metal interfaces is the basis for graphene-based electron- and spin-transport devices. Here we investigate the hybridization between graphene- and metal-derived electronic states by studying the changes induced through intercalation of a pseudomorphic monolayer of Cu in between graphene and Ir(111), using scanning tunnelling microscopy and photoelectron spectroscopy in combination with density functional theory calculations. We observe the modifications in the band structure by the intercalation process and its concomitant changes in the charge distribution at the interface. Through a state-selective analysis of band hybridization, we are able to determine their contributions to the valence band of graphene giving rise to the gap opening. Our methodology reveals the mechanisms that are responsible for the modification of the electronic structure of graphene at the Dirac point, and permits to predict the electronic structure of other graphene-metal interfaces.

Genetic analysis of poliovirus strains isolated from sewage in Poland.

The study describes genetic characterization of poliovirus (PV) strains isolated from sewage samples in Poland. The analyses were performed for the detection of any putative polio revertants and recombinants in three genomic regions by sequencing analysis. Thirty-six strains were analyzed. The analyzed strains were identified by neutralization assay as 7 strains of serotype P1, 10 strains of serotype P2, and 19 strains of serotype P3. Sewage isolates were sequenced in 5'UTR, VP1, and 3D genomic regions. All detected PVs were classified as vaccine strains on the basis of VP1 sequence. Mutational differences in the VP1 sequences of isolated viruses ranged from 0.0% to 0.4%, indicating a limited replication period. The genetic analysis of the 3D region showed that some strains have recombinant genomes. Nine strains were found as dipartite recombinants (seven strains--S3/S2, one strain--S2/S1, one strain--S3/S1), while one strain was found as tripartite recombinant (S3/S2/S1). No recombinants with non-PV enteroviruses were identified. None of wild-type PVs or vaccine-derived polioviruses (VDPVs) were detected. This study showed the absence of wild or VDPV circulation in the country and demonstrated the usefulness of environmental surveillance in addition to acute flaccid paralysis (AFP) surveillance in support of polio eradication initiatives.

[T1 bladder cancer: role of documentation for bladder tumor findings and targeted second resection]. / Das T1-Blasenkarzinom : Bedeutung der Dokumentation des Tumorbefundes und der gezielten Nachresektion.

BACKGROUND: For control resection of T1 bladder tumors an exact relocalization of the previously infiltrating tumor spread can be complicated by postreactive alterations, multiple scar tissue or change of surgeons. In this study the results of control transurethral resection of the bladder (TURB) after T1 high grade bladder tumors with the focus on localization and importance of standardized exact documentation were analyzed. PATIENTS AND METHODS: From July to February 2012 a control resection was performed in 167 patients due to a T1 high grade bladder cancer. The rates of residual tumor tissue and localization were investigated with standardized tumor documentation. RESULTS: Out of 167 patients with T1 bladder cancer who underwent a control resection tumor tissue was found in 58.1 % (97 out of 167) and in 85.6 % (83 out of 97) the primary site was affected (41.2 % only at primary site and 44.3 % additionally at other locations). In 11 patients (11.3 %) residual tumor tissue at the initial site was only detected histologically. CONCLUSIONS: Our results indicate that T1 high grade bladder cancers show a relevant rate of residual tumor tissue at control resection which confirms the clinical guidelines of the European Association of Urology (EAU) on mandatory resection. In most cases the primary tumor site is affected. The standardized bladder tumor documetation allows well-directed control resection also in patients with multiple scars and post-TUR alterations, even when performed by a different surgeon.

Measurements of energetic particle radiation in transit to Mars on the Mars Science Laboratory.

The Mars Science Laboratory spacecraft, containing the Curiosity rover, was launched to Mars on 26 November 2011, and for most of the 253-day, 560-million-kilometer cruise to Mars, the Radiation Assessment Detector made detailed measurements of the energetic particle radiation environment inside the spacecraft. These data provide insights into the radiation hazards that would be associated with a human mission to Mars. We report measurements of the radiation dose, dose equivalent, and linear energy transfer spectra. The dose equivalent for even the shortest round-trip with current propulsion systems and comparable shielding is found to be 0.66 ± 0.12 sievert.