Hosing of a Long Relativistic Particle Bunch in Plasma.

Experimental results show that hosing of a long particle bunch in plasma can be induced by wakefields driven by a short, misaligned preceding bunch. Hosing develops in the plane of misalignment, self-modulation in the perpendicular plane, at frequencies close to the plasma electron frequency, and are reproducible. Development of hosing depends on misalignment direction, its growth on misalignment extent and on proton bunch charge. Results have the main characteristics of a theoretical model, are relevant to other plasma-based accelerators and represent the first characterization of hosing.

Acceleration of electrons in the plasma wakefield of a proton bunch.

High-energy particle accelerators have been crucial in providing a deeper understanding of fundamental particles and the forces that govern their interactions. To increase the energy of the particles or to reduce the size of the accelerator, new acceleration schemes need to be developed. Plasma wakefield acceleration1-5, in which the electrons in a plasma are excited, leading to strong electric fields (so called 'wakefields'), is one such promising acceleration technique. Experiments have shown that an intense laser pulse6-9 or electron bunch10,11 traversing a plasma can drive electric fields of tens of gigavolts per metre and above-well beyond those achieved in conventional radio-frequency accelerators (about 0.1 gigavolt per metre). However, the low stored energy of laser pulses and electron bunches means that multiple acceleration stages are needed to reach very high particle energies5,12. The use of proton bunches is compelling because they have the potential to drive wakefields and to accelerate electrons to high energy in a single acceleration stage13. Long, thin proton bunches can be used because they undergo a process called self-modulation14-16, a particle-plasma interaction that splits the bunch longitudinally into a series of high-density microbunches, which then act resonantly to create large wakefields. The Advanced Wakefield (AWAKE) experiment at CERN17-19 uses high-intensity proton bunches-in which each proton has an energy of 400 gigaelectronvolts, resulting in a total bunch energy of 19 kilojoules-to drive a wakefield in a ten-metre-long plasma. Electron bunches are then injected into this wakefield. Here we present measurements of electrons accelerated up to two gigaelectronvolts at the AWAKE experiment, in a demonstration of proton-driven plasma wakefield acceleration. Measurements were conducted under various plasma conditions and the acceleration was found to be consistent and reliable. The potential for this scheme to produce very high-energy electron bunches in a single accelerating stage20 means that our results are an important step towards the development of future high-energy particle accelerators21,22.

Transition between Instability and Seeded Self-Modulation of a Relativistic Particle Bunch in Plasma.

We use a relativistic ionization front to provide various initial transverse wakefield amplitudes for the self-modulation of a long proton bunch in plasma. We show experimentally that, with sufficient initial amplitude [≥(4.1±0.4) MV/m], the phase of the modulation along the bunch is reproducible from event to event, with 3%-7% (of 2π) rms variations all along the bunch. The phase is not reproducible for lower initial amplitudes. We observe the transition between these two regimes. Phase reproducibility is essential for deterministic external injection of particles to be accelerated.

Proton-driven plasma wakefield acceleration in AWAKE.

In this article, we briefly summarize the experiments performed during the first run of the Advanced Wakefield Experiment, AWAKE, at CERN (European Organization for Nuclear Research). The final goal of AWAKE Run 1 (2013-2018) was to demonstrate that 10-20 MeV electrons can be accelerated to GeV energies in a plasma wakefield driven by a highly relativistic self-modulated proton bunch. We describe the experiment, outline the measurement concept and present first results. Last, we outline our plans for the future. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

[Functional rehabilitation of severe laryngopharyngeal injuries after near-lethal suicide attempt by hanging]. / Funktionelle Rehabilitation schwerer laryngopharyngealer Verletzungen nach Suizidversuch durch Erhängen.

BACKGROUND: Hanging is a common method of suicide with an estimated mortality rate of about 70%. Survival of patients with severe laryngopharyngeal injuries after strangulation is not common. However, clinical findings of patients reaching the hospital alive may be minimal. A rapid onset of multidisciplinary diagnostic and therapeutic management is mandatory, followed by psychiatric treatment and functional rehabilitation. CASE PRESENTATION AND RESULTS: Two uncommon cases after severe laryngopharyngeal injury due to near-lethal suicide attempt by hanging demonstrate the emergency management and reconstructive surgery. Subsequent tracheal cannula management and swallowing therapy to full recovery are described. In addition, a proposal for an interdisciplinary treatment algorithm for those patients is presented. CONCLUSION: Minimal external clinical findings after near-lethal suicide attempts by hanging do not exclude severe internal injuries of the upper aerodigestive tract structures. After reconstructive surgery an appropriate tracheal cannula management and an early and intensive swallowing therapy parallel to the psychiatric treatment is mandatory to restore voice, airway and deglutition.

[Patient Satisfaction after Pitch Elevation and Development of a Therapy Algorithm]. / Zufriedenheit nach Stimmerhöhung bei Transsexualität ­ Entwicklung eines Therapiealgorithmus.

Objective: Voice feminization is an important step in the therapy of male-to-female transsexualism. Approaches are conservative voice therapy and surgical interventions. The most powerful parameter of gender perception is the fundamental frequency. Besides the vocal pitch, there are other parameters influencing gender perception of a voice, e. g. intonation, prosody or formant frequencies. Material and methods: In 21 male to female transgender persons after surgical elevation of the vocal pitch the Voice Handicap Index (VHI), the Life Satisfaction Questionnaire (FLZ) and a new addendum were used. A new algorithm for voice feminization in male-to-female transsexualism was deduced. Results: After elevation of the vocal pitch, the self-confidence of the male-to-female transgender persons has increased. Despite of an elevated pitch some persons were not satisfied with their voice. Conclusion: Surgical intervention changes only the pitch of a voice. To change other parameters, conservative voice therapy is necessary. If the transgender persons are able to reach a satisfying female voice with conservative voice therapy alone, surgical intervention is not indicated.

[Direct Drive Simulation - Sound-Simulation of the Vibrant Soundbridge®]. / Direct Drive Simulation - Klangsimulation des Vibrant Soundbridge®-Hörens.

BACKGROUND: The Direct-Drive-Simulation (DDS) tends to simulate the sound quality of hearing with the active middle ear implant Vibrant Soundbridge(®) (VSB). Up to now a scientific evaluation of the validity is missing. Furthermore, the test procedure has not been described yet. Aim of this study was to evaluate the test validity and to describe the test realization in detail. MATERIAL AND METHODS: 10 patients evaluated their sound impression on scales from 1 to 10 concerning sound quality during DDS, postoperative free field testing at least 3 month after the first fitting of the VSB and in the everyday life situation. 3 patients were implanted bilaterally. Together, 36 data sets could be analyzed. RESULTS: Coupling of the Floating Mass Transducer (FMT), which was placed inside of a silicone probe during DDS was successful in all cases. In 11 out of 13 cases the coupling quality was judged as "good" an only in 2 cases as "medium". None of the patients needed local anesthesia. Comparing the evaluation of the sound impression during DDS preoperatively, and with the implanted VSB in free field testing and in everyday life no significant differences were found. CONCLUSION: The DDS offers the possibility of a realistic preoperative sound simulation of the "VSB-hearing" in case of sensorineural hearing loss. Thus, the test is supposed to facilitate the patient's decision towards possible treatment options. The specialist gets additional information regarding the indication especially when audiologic indication criteria are critical. The DDS should be a basic part of the preoperative diagnostic prior to VSB-implantation.

DFNB16 is a frequent cause of congenital hearing impairment: implementation of STRC mutation analysis in routine diagnostics.

Increasing attention has been directed toward assessing mutational fallout of stereocilin (STRC), the gene underlying DFNB16. A major challenge is due to a closely linked pseudogene with 99.6% coding sequence identity. In 94 GJB2/GJB6-mutation negative individuals with non-syndromic sensorineural hearing loss (NSHL), we identified two homozygous and six heterozygous deletions, encompassing the STRC region by microarray and/or quantitative polymerase chain reaction (qPCR) analysis. To detect smaller mutations, we developed a Sanger sequencing method for pseudogene exclusion. Three heterozygous deletion carriers exhibited hemizygous mutations predicted as negatively impacting the protein. In 30 NSHL individuals without deletion, we detected one with compound heterozygous and two with heterozygous pathogenic mutations. Of 36 total patients undergoing STRC sequencing, two showed the c.3893A>G variant in conjunction with a heterozygous deletion or mutation and three exhibited the variant in a heterozygous state. Although this variant affects a highly conserved amino acid and is predicted as deleterious, comparable minor allele frequencies (MAFs) (around 10%) in NSHL individuals and controls and homozygous variant carriers without NSHL argue against its pathogenicity. Collectively, six (6%) of 94 NSHL individuals were diagnosed with homozygous or compound heterozygous mutations causing DFNB16 and five (5%) as heterozygous mutation carriers. Besides GJB2/GJB6 (DFNB1), STRC is a major contributor to congenital hearing impairment.

[The Traumatic Tympanic Membrane Perforation - Aetiology and Therapy]. / Ätiologie und Therapie der traumatischen Trommelfellperforation.

BACKGROUND: The use of cotton swabs is well known as a cause of a traumatic membrane perforation. More reasons are known. A detailed description of the aetiology and therapy in Germany does not exist. The treatment consist of a readaptation of the perforation an splinting of the tympanic membrane with paper sheets or silicon foils. MATERIALS AND METHODS: 238 patients with an acute tympanic membrane perforation were included in this retrospective study. They were treated between 2005 and 2010. RESULTS: The mean causes of a traumatic tympanic membrane perforation were slaps with the open hand (37.4%), the use of a cotton swab (19.3%) and high diving (13.0%). The perforations have been splinted with paper sheets or silicon foils. The rate of complete wound closure after splinting with different materials are comparable (71.9% and 81.8%). The side effects are low. CONCLUSION: This is the first study about the aetiology of traumatic tympanic membrane perforations in Germany. There is no statistic difference between the 2 materials for tympanic membrane splinting. A traumatic tympanic membrane perforation should be treatet at least to improve the air conduction threshold.

[Speech perception in noise with the "wuerzburg speech test for children"]. / Sprachverstehen im Störlärm mit dem Würzburger Kindersprachtest.

BACKGROUND: Patients with hearing loss complain of a reduced speech perception in noise. For school children and adults there are several standardized audiometric tests available to measure the outcome in background noise like the HSM-Test, OlSa or OlKiSa. However, for kindergarden and preschool children a comparable speech perception test in noise does not exist. The aim of this study was to evaluate and standardize the recently developed "wuerzburg speech test for children" in noise. MATERIALS AND METHODS: 24 children aged 5-9 years with bilateral normal hearing were included. They have been tested with the test IV of the "wuerzburg speech test for children" in noise. This test consists of 3 lists, each with 20 two-syllable words. For the background noise, a 32 time delayed interference of the speech items were used. RESULTS: The speech perception threshold (SRT) at 60 dB (SPL) depending on the signal to noise ratio (SNR) was measured for each child. The overall averaged SNR was -8.3 dB. Furthermore a small, non-significant influence by the age of the children to the test results was seen. CONCLUSION: The "wuerzburg speech test for children" is suitable to measure the individual speech perception in noise. It is appropriate for kindergarden, preschool and school children. The test material consists of the uptodate vocabulary of children. The average SRT was -8.3 dB SNR, which is comparable with the published literature.

Smoking is associated with increased eryptosis, suicidal erythrocyte death, in a large population-based cohort.

Smoking has multiple detrimental effects on health, and is a major preventable cause of premature death and chronic disease. Despite the well-described effect of inhaled substances from tobacco smoke on cell toxicity, the association between smoking and suicidal erythrocyte death, termed eryptosis, is virtually unknown. Therefore, the blood samples of 2023 participants of the German National Cohort Study (NAKO) were analyzed using flow cytometry analysis to determine eryptosis from fluorescent annexin V-FITC-binding to phosphatidylserine-exposing erythrocytes. Blood analyses were complemented by the measurement of hematologic parameters including red blood cell count, hematocrit, hemoglobin, mean corpuscular cell volume (MCV) and mean corpuscular hemoglobin (MCH). Eryptosis was higher in smokers than in non- and ex-smokers, and positively associated with the number of cigarettes smoked daily (r = 0.08, 95% CI [0.03, 0.12]). Interestingly, despite increased eryptosis, smokers had higher red blood cell indices than non-smokers. To conclude, smokers were characterized by higher eryptosis than non-smokers, without showing any obvious detrimental effect on classic hematological parameters.

Filamentation of a relativistic proton bunch in plasma.

We show in experiments that a long, underdense, relativistic proton bunch propagating in plasma undergoes the oblique instability, which we observe as filamentation. We determine a threshold value for the ratio between the bunch transverse size and plasma skin depth for the instability to occur. At the threshold, the outcome of the experiment alternates between filamentation and self-modulation instability (evidenced by longitudinal modulation into microbunches). Time-resolved images of the bunch density distribution reveal that filamentation grows to an observable level late along the bunch, confirming the spatiotemporal nature of the instability. We provide a rough estimate of the amplitude of the magnetic field generated in the plasma by the instability and show that the associated magnetic energy increases with plasma density.

Conserving genetic diversity in the honeybee: comments on Harpur et al. (2012).

The article by Harpur et al. (2012) 'Management increases genetic diversity of honey bees via admixture' concludes that '…honey bees do not suffer from reduced genetic diversity caused by management and, consequently, that reduced genetic diversity is probably not contributing to declines of managed Apis mellifera populations'. In the light of current honeybee and beekeeping declines and their consequences for honeybee conservation and the pollination services they provide, we would like to express our concern about the conclusions drawn from the results of Harpur et al. (2012). While many honeybee management practices do not imply admixture, we are convinced that the large-scale genetic homogenization of admixed populations could drive the loss of valuable local adaptations. We also point out that the authors did not account for the extensive gene flow that occurs between managed and wild/feral honeybee populations and raise concerns about the data set used. Finally, we caution against underestimating the importance of genetic diversity for honeybee colonies and highlight the importance of promoting the use of endemic honeybee subspecies in apiculture.

Immediate effects of individualized heparin and protamine management on hemostatic activation and platelet function in adult patients undergoing cardiac surgery with tranexamic acid antifibrinolytic therapy.

OBJECTIVE: This randomized prospective study was initiated to clarify whether individualized heparin and protamine dosing has immediate effects on hemostatic activation and platelet function in adult cardiac surgery. METHODS: Sixty adults undergoing elective coronary artery bypass grafting (CABG) were assigned to receive individualized heparin and protamine (HMS group, n= 29) or a standard dose (ACT group, n=24). Measures of thrombin generation and Multiplate (Verum Diagnostica, Munich, Germany) platelet function tests were performed before and after cardiopulmonary bypass (CPB). RESULTS: HMS patients received higher heparin (p = 0.006) and lower protamine (p<0.001) doses. Post-CPB, HMS managed patients showed significantly lower thrombin generation (thrombin-antithrombin (TAT) p<0.02) than the ACT group. Moreover, HMS managed patients had a better preservation of platelet function (COL p = 0.013; ADP p = 0.04; TRAP p = 0.04). CONCLUSION: An individualized and stable heparin concentration and appropriate dosing of protamine can reduce thrombin generation and preserve platelet function, even in short-time CPB.

Characterization and prognostic impact of ACTBL2-positive tumor-infiltrating leukocytes in epithelial ovarian cancer.

Actin beta-like 2 (ACTBL2) was recently identified as a new mediator of migration in ovarian cancer cells. Yet, its impact on tumor-infiltrating and thus migrating leukocytes (TILs) remains to date unknown. This study characterizes the subset of ACTBL2-expressing TILs in epithelial ovarian cancer (EOC) and elucidates their prognostic influence on the overall survival of EOC patients with special regard to different histological subtypes. Comprehensive immunohistochemical analyses of Tissue-Microarrays of 156 ovarian cancer patients revealed, that a tumor infiltration by ACTBL2-positive leukocytes was significantly associated with an improved overall survival (OS) (61.2 vs. 34.4 months; p = 0.006) and was identified as an independent prognostic factor (HR = 0.556; p = 0.038). This significant survival benefit was particularly evident in patients with low-grade serous carcinoma (OS: median not reached vs. 15.6 months, p < 0.001; HR = 0.058, p = 0.018). In the present cohort, ACTBL2-positive TILs were mainly composed of CD44-positive cytotoxic T-cells (CD8+) and macrophages (CD68+), as depicted by double-immunofluorescence and various immunohistochemical serial staining. Our results provide significant evidence of the prognostic impact and cellular composition of ACTBL2-expressing TILs in EOC. Complementary studies are required to analyze the underlying molecular mechanisms of ACTBL2 as a marker for activated migrating leukocytes and to further characterize its immunological impact on ovarian carcinogenesis.

Factors influencing Nosema bombi infections in natural populations of Bombus terrestris (Hymenoptera: Apidae).

Bumblebees are of profound ecological importance because of the pollination services they provide in natural and agricultural ecosystems. Any decline of these pollinators is therefore of great concern for ecosystem functioning. Increased parasite pressures have been discussed as a major factor for the loss of pollinators. One of the main parasites of bumblebees is Nosema bombi, an intracellular microsporidian parasite with considerable impact on the vitality of the host. Here we study the effect of host colony density and host genetic variability on N. bombi infections in natural populations of the bumblebee Bombus terrestris. We sampled males and workers from six B. terrestris populations located in an agricultural landscape in Middle Sweden to determine the prevalence and degree of N. bombi infections. All individuals were genotyped with five microsatellite markers to infer the colony densities in the sampled populations and the genetic variability of the host population. We confirmed that genetic variability and sex significantly correlate with the degree of infection with N. bombi. Males and workers with lower genetic variability had significantly higher infection levels than average. Also colony density had a significant impact on the degree of infection, with high density populations having higher infected individuals.

Middle-ear effusion in children with cleft palate: congenital or acquired?

OBJECTIVE: Cleft palates are one of the most common congenital malformations. Because of the loss of Eustachian tube function, middle-ear ventilation is reduced. The aim of this study was to determine if middle-ear effusions were present at birth or at the three-month audiological evaluation. METHOD: A total of 53 children with a cleft palate were included. Data review included the results of newborn hearing screening, microscopic findings, a tympanometry, a free field audiometry and intra-operative findings. RESULTS: A total of 58.4 per cent of patients had a median, 26.4 per cent had a bilateral, 11.3 per cent had a unilateral and 3.8 per cent had a limited soft palate cleft. Newborn hearing screening showed a pass in 83.1 per cent of newborns bilaterally. The first ear microscopy showed a bilateral middle-ear effusion in 90.6 per cent of cases. During cleft surgery, bilateral paracentesis was performed in all cases, and in 90.6 per cent middle-ear effusion was sucked out. CONCLUSION: The majority of children with a cleft palate do not present with middle-ear effusion at birth. It develops within several days or weeks of life.

Shift work has a genetic basis in honeybee pollen foragers (Apis mellifera L.).

Division of labour is a fundamental property of any social system. The specialization of different individuals in different tasks increases the overall work performance and efficiency. Specialization is thought to be the very foundation of the success of human societies but also in complex colonies of social insects. In human societies an advanced form of division of labour, especially since the industrialisation, is shift work, where individuals perform the same task but in subsequent cohorts in time. Although social insects can measure and are aware of time, shift work has not been documented in colonies of social insects so far. We observed foragers of two honeybee (Apis mellifera) colonies (approximately 140 workers each) and genotyped them with microsatellite DNA markers. We determined paternity and assigned them to the various subfamilies in the colony to test whether there is genetic variance for shift work in foraging honeybees. We could show that the patriline identity of the foragers had a significant effect on foraging either in the morning or evening. Individual foragers differed in their preference for the "early" or "late" shift, and shift work indeed existed in the colony.

Workers dominate male production in the neotropical bumblebee Bombus wilmattae (Hymenoptera: Apidae).

BACKGROUND: Cooperation and conflict in social insects are closely linked to the genetic structure of the colony. Kin selection theory predicts conflict over the production of males between the workers and the queen and between the workers themselves, depending on intra-colonial relatedness but also on other factors like colony efficiency, sex ratios, cost of worker reproduction and worker dominance behaviour. In most bumblebee (Bombus) species the queen wins this conflict and often dominates male production. However, most studies in bumblebees have been conducted with only a few selected, mostly single mated species from temperate climate regions. Here we study the genetic colony composition of the facultative polyandrous neotropical bumblebee Bombus wilmattae, to assess the outcome of the queen-worker conflict over male production and to detect potential worker policing. RESULTS: A total of 120 males from five colonies were genotyped with up to nine microsatellite markers to infer their parentage. Four of the five colonies were queen right at point of time of male sampling, while one had an uncertain queen status. The workers clearly dominated production of males with an average of 84.9% +/- 14.3% of males being worker sons. In the two doubly mated colonies 62.5% and 96.7% of the male offspring originated from workers and both patrilines participated in male production. Inferring the mother genotypes from the male offspring, between four to eight workers participated in the production of males. CONCLUSIONS: In this study we show that the workers clearly win the queen-worker conflict over male production in B. wilmattae, which sets them apart from the temperate bumblebee species studied so far. Workers clearly dominated male production in the singly as well the doubly mated colonies, with up to eight workers producing male offspring in a single colony. Moreover no monopolization of reproduction by single workers occurred.