Subcycle observation of lightwave-driven Dirac currents in a topological surface band.

Harnessing the carrier wave of light as an alternating-current bias may enable electronics at optical clock rates1. Lightwave-driven currents have been assumed to be essential for high-harmonic generation in solids2-6, charge transport in nanostructures7,8, attosecond-streaking experiments9-16 and atomic-resolution ultrafast microscopy17,18. However, in conventional semiconductors and dielectrics, the finite effective mass and ultrafast scattering of electrons limit their ballistic excursion and velocity. The Dirac-like, quasi-relativistic band structure of topological insulators19-29 may allow these constraints to be lifted and may thus open a new era of lightwave electronics. To understand the associated, complex motion of electrons, comprehensive experimental access to carrier-wave-driven currents is crucial. Here we report angle-resolved photoemission spectroscopy with subcycle time resolution that enables us to observe directly how the carrier wave of a terahertz light pulse accelerates Dirac fermions in the band structure of the topological surface state of Bi2Te3. While terahertz streaking of photoemitted electrons traces the electromagnetic field at the surface, the acceleration of Dirac states leads to a strong redistribution of electrons in momentum space. The inertia-free surface currents are protected by spin-momentum locking and reach peak densities as large as two amps per centimetre, with ballistic mean free paths of several hundreds of nanometres, opening up a realistic parameter space for all-coherent lightwave-driven electronic devices. Furthermore, our subcycle-resolution analysis of the band structure may greatly improve our understanding of electron dynamics and strong-field interaction in solids.

Lightwave valleytronics in a monolayer of tungsten diselenide.

As conventional electronics approaches its limits 1 , nanoscience has urgently sought methods of fast control of electrons at the fundamental quantum level 2 . Lightwave electronics 3 -the foundation of attosecond science 4 -uses the oscillating carrier wave of intense light pulses to control the translational motion of the electron's charge faster than a single cycle of light5-15. Despite being particularly promising information carriers, the internal quantum attributes of spin 16 and valley pseudospin17-21 have not been switchable on the subcycle scale. Here we demonstrate lightwave-driven changes of the valley pseudospin and introduce distinct signatures in the optical readout. Photogenerated electron-hole pairs in a monolayer of tungsten diselenide are accelerated and collided by a strong lightwave. The emergence of high-odd-order sidebands and anomalous changes in their polarization direction directly attest to the ultrafast pseudospin dynamics. Quantitative computations combining density functional theory with a non-perturbative quantum many-body approach assign the polarization of the sidebands to a lightwave-induced change of the valley pseudospin and confirm that the process is coherent and adiabatic. Our work opens the door to systematic valleytronic logic at optical clock rates.

Esophageal function and non-acid reflux evaluated by impedance-24 h-pH-metry, high-resolution manometry, and gastroscopy after one-anastomosis gastric bypass-outcomes of a prospective mid-term study.

BACKGROUND: One-Anastomosis Gastric Bypass (OAGB) is the third most common bariatric operation for patients with obesity worldwide. One concern about OAGB is the presence of acid and non-acid reflux in a mid- and long-term follow-up. The aim of this study was to objectively evaluate reflux and esophagus motility by comparing preoperative and postoperative mid-term outcomes. SETTING: Cross-sectional study; University-hospital based. METHODS: This study includes primary OAGB patients (preoperative gastroscopy, high-resolution manometry (HRM), and impedance-24 h-pH-metry) operated at Medical University of Vienna before 31st December 2017. After a mean follow-up of 5.1 ± 2.3 years, these examinations were repeated. In addition, history of weight, remission of associated medical problems (AMP), and quality of life (QOL) were evaluated. RESULTS: A total of 21 patients were included in this study and went through all examinations. Preoperative weight was 124.4 ± 17.3 kg with a BMI of 44.7 ± 5.6 kg/m2, total weight loss after 5.1 ± 2.3 years was 34.4 ± 8.3%. In addition, remission of AMP and QOL outcomes were very satisfactory in this study. In gastroscopy, anastomositis, esophagitis, Barrett´s esophagus, and bile in the pouch were found in: 38.1%, 28.3%, 9.5%, and 42.9%. Results of HRM of the lower esophageal sphincter pressure were 28.0 ± 15.6 mmHg, which are unchanged compared to preoperative values. Nevertheless, in the impedance-24 h-pH-metry, acid exposure time and DeMeester score decreased significantly to 1.2 ± 1.2% (p = 0.004) and 7.5 ± 8.9 (p = 0.017). Further, the total number of refluxes were equal to preoperative; however, the decreased acid refluxes were replaced by non-acid refluxes. CONCLUSION: This study has shown decreased rates of acid reflux and increased non-acid reflux after a mid-term outcome of primary OAGB patients. Gastroscopy showed signs of chronic irritation of the gastrojejunostomy, pouch, and distal esophagus, even in asymptomatic patients. Follow-up gastroscopies in OAGB patients after 5 years may be considered.

Lightwave-driven quasiparticle collisions on a subcycle timescale.

Ever since Ernest Rutherford scattered α-particles from gold foils, collision experiments have revealed insights into atoms, nuclei and elementary particles. In solids, many-body correlations lead to characteristic resonances--called quasiparticles--such as excitons, dropletons, polarons and Cooper pairs. The structure and dynamics of quasiparticles are important because they define macroscopic phenomena such as Mott insulating states, spontaneous spin- and charge-order, and high-temperature superconductivity. However, the extremely short lifetimes of these entities make practical implementations of a suitable collider challenging. Here we exploit lightwave-driven charge transport, the foundation of attosecond science, to explore ultrafast quasiparticle collisions directly in the time domain: a femtosecond optical pulse creates excitonic electron-hole pairs in the layered dichalcogenide tungsten diselenide while a strong terahertz field accelerates and collides the electrons with the holes. The underlying dynamics of the wave packets, including collision, pair annihilation, quantum interference and dephasing, are detected as light emission in high-order spectral sidebands of the optical excitation. A full quantum theory explains our observations microscopically. This approach enables collision experiments with various complex quasiparticles and suggests a promising new way of generating sub-femtosecond pulses.

Real-time observation of interfering crystal electrons in high-harmonic generation.

Acceleration and collision of particles has been a key strategy for exploring the texture of matter. Strong light waves can control and recollide electronic wavepackets, generating high-harmonic radiation that encodes the structure and dynamics of atoms and molecules and lays the foundations of attosecond science. The recent discovery of high-harmonic generation in bulk solids combines the idea of ultrafast acceleration with complex condensed matter systems, and provides hope for compact solid-state attosecond sources and electronics at optical frequencies. Yet the underlying quantum motion has not so far been observable in real time. Here we study high-harmonic generation in a bulk solid directly in the time domain, and reveal a new kind of strong-field excitation in the crystal. Unlike established atomic sources, our solid emits high-harmonic radiation as a sequence of subcycle bursts that coincide temporally with the field crests of one polarity of the driving terahertz waveform. We show that these features are characteristic of a non-perturbative quantum interference process that involves electrons from multiple valence bands. These results identify key mechanisms for future solid-state attosecond sources and next-generation light-wave electronics. The new quantum interference process justifies the hope for all-optical band-structure reconstruction and lays the foundation for possible quantum logic operations at optical clock rates.

Recommendations for treatment of critically ill patients with COVID-19 : Version 3 S1 guideline.

Since December 2019 a novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has rapidly spread around the world resulting in an acute respiratory illness pandemic. The immense challenges for clinicians and hospitals as well as the strain on many healthcare systems has been unprecedented.The majority of patients present with mild symptoms of coronavirus disease 2019 (COVID-19); however, 5-8% become critically ill and require intensive care treatment. Acute hypoxemic respiratory failure with severe dyspnea and an increased respiratory rate (>30/min) usually leads to intensive care unit (ICU) admission. At this point bilateral pulmonary infiltrates are typically seen. Patients often develop a severe acute respiratory distress syndrome (ARDS).So far, remdesivir and dexamethasone have shown clinical effectiveness in severe COVID-19 in hospitalized patients. The main goal of supportive treatment is to ascertain adequate oxygenation. Invasive mechanical ventilation and repeated prone positioning are key elements in treating severely hypoxemic COVID-19 patients.Strict adherence to basic infection control measures (including hand hygiene) and correct use of personal protection equipment (PPE) are essential in the care of patients. Procedures that lead to formation of aerosols should be carried out with utmost precaution and preparation.

[Oncologic aspects in treatment of pathologic fractures]. / Onkologische Aspekte der Behandlung pathologischer Frakturen.

BACKGROUND: Pathological fractures are not only incisive events for tumor patients often with the need of surgical treatment but also often represent a relevant challenge in the overall concept of oncological treatment. OBJECTIVE: The aim of this article is to illustrate the necessity of a pre-interventional interdisciplinary consideration of disease-specific and patient-specific characteristics. MATERIAL AND METHODS: A literature search and evaluation of existing guidelines were carried out including the keywords "bone metastases" and "pathological fractures" with respect to the oncological and radiotherapeutic treatment. RESULTS: An essential classification of the surgical and other needs for treatment is carried out by the identification of the underlying disease and dissemination situation. For tumor-related pathological fractures a palliative treatment situation is present in most cases. Nevertheless, a possible oligometastasis and an increasing number of effective systemic treatment methods must be taken into consideration when planning the surgical treatment. In addition to the therapeutic emergency indications in spinal compression or symptomatic hypercalcemia, both additive radiotherapy and supplementary pharmaceutical osteoprotection have to be addressed in this context. Radiotherapy in particular represents an effective alternative option for symptom and tumor control. CONCLUSION: The work-up of the multifaceted oncological treatment concept represents an interdisciplinary challenge, which ideally defines the further treatment procedure, including fracture treatment, in an interdisciplinary tumor board within an overall oncological concept.

[S2k Guideline - Recommendations for Inpatient Therapy of Patients with COVID-19]. / S2k-Leitlinie ­ Empfehlungen zur stationären Therapie von Patienten mit COVID-19.

Since December 2019, the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome - Corona Virus-2) has been spreading rapidly in the sense of a global pandemic. This poses significant challenges for clinicians and hospitals and is placing unprecedented strain on the healthcare systems of many countries. The majority of patients with Coronavirus Disease 2019 (COVID-19) present with only mild symptoms such as cough and fever. However, about 6 % require hospitalization. Early clarification of whether inpatient and, if necessary, intensive care treatment is medically appropriate and desired by the patient is of particular importance in the pandemic. Acute hypoxemic respiratory insufficiency with dyspnea and high respiratory rate (> 30/min) usually leads to admission to the intensive care unit. Often, bilateral pulmonary infiltrates/consolidations or even pulmonary emboli are already found on imaging. As the disease progresses, some of these patients develop acute respiratory distress syndrome (ARDS). Mortality reduction of available drug therapy in severe COVID-19 disease has only been demonstrated for dexamethasone in randomized controlled trials. The main goal of supportive therapy is to ensure adequate oxygenation. In this regard, invasive ventilation and repeated prone positioning are important elements in the treatment of severely hypoxemic COVID-19 patients. Strict adherence to basic hygiene, including hand hygiene, and the correct wearing of adequate personal protective equipment are essential when handling patients. Medically necessary actions on patients that could result in aerosol formation should be performed with extreme care and preparation.

[Injury patterns in interstitial lung diseases]. / Schädigungsmuster interstitieller Lungenerkrankungen.

Interstitial lung diseases (ILD) consist of a complex group of hundreds of non-neoplastic pulmonary diseases with divergent clinical presentation, morphology and progression tendency. This great number of clinical entities contrasts with a limited number of injury patterns. By definition, an adequate classification requires a synopsis of the clinical, radiological and morphological findings. The ATS/ERS (American Thoracic Society/ European Respiratory Society) guidelines recommend an open lung biopsy if high-resolution computed tomography does not provide conclusive results. Due to the focal nature and overlapping features of injury patterns, microscopic categorization is not always possible. In order to broaden the diagnostic criteria by using molecular patterns the Lung Research Working Group of the Institute of Pathology of Hannover Medical School, Europe's leading transplant center, is working up fresh explanted human lungs in a standardized manner. These fresh specimens are used for translational research by means of functional, morphological and molecular techniques in order to identify disease-specific regulatory processes and to make them usable diagnostically and therapeutically.

[Possibilities and limitations of molecular pathology in dermatohistology]. / Möglichkeiten und Grenzen der Molekularpathologie in der Dermatohistologie.

Malignant tumours, infections caused by microorganisms or genodermatoses are diagnosed with additional help of molecular pathology methods. Polymerase chain reaction (PCR), sequencing and in situ hybridisations play an important role. It remains to be seen if methods such as "liquid biopsies" or "single cell genomics" can be developed as routine diagnostics. High technical efforts, high costs and no possibility for resistency testing is accompanied by fast verification, high sensitivity and high specificity. Overall, molecular pathology results have to be combined with the clinical picture, histology or immunohistochemistry and culturing results to achieve a correct diagnosis for the patient.

[Bridging anticoagulation in patients receiving vitamin K antagonists : Current status]. / Überbrückende Antikoagulation bei Patienten unter Vitamin-K-Antagonisten : Eine Bestandsaufnahme.

Approximately 30% of patients receiving oral anticoagulation using vitamin K antagonists (VKA) require surgery within 2 years. In this context, a clinical decision on the need and the mode of a peri-interventional bridging with heparin is needed. While a few years ago, bridging was almost considered a standard of care, recent study results triggered a discussion on which patients will need bridging at all. Revisiting the currently available recommendations and study results the conclusion can be drawn that the indications for bridging with heparin must nowadays be taken more narrowly and considering the individual patient risk of bleeding and thromboembolism. Bridging with heparin is only needed in patients with a very high risk of thromboembolism. This overview aims to give guidance for a risk-adapted peri-interventional approach to management of patients with a need for long-term anticoagulation using VKA.

[Bridging anticoagulation in patients receiving vitamin K antagonists : Current status]. / Überbrückende Antikoagulation bei Patienten unter Vitamin-K-Antagonisten : Eine Bestandsaufnahme.

Approximately 30% of patients receiving oral anticoagulation using vitamin K antagonists (VKA) require surgery within 2 years. In this context, a clinical decision on the need and the mode of a peri-interventional bridging with heparin is needed. While a few years ago, bridging was almost considered a standard of care, recent study results triggered a discussion on which patients will need bridging at all. Revisiting the currently available recommendations and study results the conclusion can be drawn that the indications for bridging with heparin must nowadays be taken more narrowly and considering the individual patient risk of bleeding and thromboembolism. Bridging with heparin is only needed in patients with a very high risk of thromboembolism. This overview aims to give guidance for a risk-adapted peri-interventional approach to management of patients with a need for long-term anticoagulation using VKA.

Co-morbidities and bleeding in elderly patients with haemophilia-A survey of the German, Austrian and Swiss Society of Thrombosis and Haemostasis Research (GTH).

BACKGROUND: Nowadays patients with haemophilia survive longer due to improvements in haemophilia care. It has been hypothesized that the bleeding type and frequency may vary with age and are influenced by co-morbidities and co-medication in elderly patients. OBJECTIVES: To investigate a large group of patients older than 60 years of age with haemophilia concerning haemophilia treatment, bleeding pattern changes, co-morbidities, co-medication, bleeding sites and patient mortality. METHODS: A retrospective multi-centre data collection study was initiated on behalf of the German, Austrian and Swiss Society of Thrombosis and Haemostasis Research (GTH). Parameters of interest were investigated over the 5 years prior to study entry. RESULTS: A total of 185 haemophilia patients (mean age, 69.0±7.0 years, 29% with severe haemophilia) were included in the study. Regular prophylaxis was performed in 30% of the patients with severe haemophilia. In total, the annual bleeding rate was 2.49 and in patients with severe haemophilia 5.61, mostly caused by joint bleeds. Hypertension was the most common co-morbidity, but it occurred significantly less frequently than in an age-matched general population older than 70 years; 12% of the patients suffered from ischaemic heart disease, and 13% of the patients received anticoagulant or antiplatelet therapy. Within the observation period, 17% of the patients with severe haemophilia developed a higher frequency of bleeding symptoms, which was significantly associated with the use of antiplatelet or anticoagulant drugs. CONCLUSIONS: The most common co-morbidity of the patient population was hypertension, a considerable part had ischemic heart disease and antiplatelet or anticoagulant drugs.

[The new TNM classification for lung tumors : Changes and the assessment of multiple tumor foci]. / Die neue TNM-Klassifikation für Lungentumoren : Änderungen und Bewertung multipler Tumorherde.

Recently a new TNM classification for tumors of the lung was published, encompassing some relevant changes, for example how to deal with multiple lung tumors. This article comprehensively describes respective changes. Furthermore, background information on how the new TNM classification was built and what should be done in the future to further improve prognosis and outcome prediction is reviewed.

Augmentation of Transient Donor Cell Chimerism and Alloantigen-Specific Regulation of Lung Transplants in Miniature Swine.

Donor alloantigen infusion induces T cell regulation and transplant tolerance in small animals. Here, we study donor splenocyte infusion in a large animal model of pulmonary transplantation. Major histocompatibility complex-mismatched single lung transplantation was performed in 28 minipigs followed by a 28-day course of methylprednisolone and tacrolimus. Some animals received a perioperative donor or third party splenocyte infusion, with or without low-dose irradiation (IRR) before surgery. Graft survival was significantly prolonged in animals receiving both donor splenocytes and IRR compared with controls with either donor splenocytes or IRR only. In animals with donor splenocytes and IRR, increased donor cell chimerism and CD4(+) CD25(high+) T cell frequencies were detected in peripheral blood associated with decreased interferon-γ production of leukocytes. Secondary third-party kidney transplants more than 2 years after pulmonary transplantation were acutely rejected despite maintained tolerance of the lung allografts. As a cellular control, additional animals received third-party splenocytes or donor splenocyte protein extracts. While animals treated with third-party splenocytes showed significant graft survival prolongation, the subcellular antigen infusion showed no such effect. In conclusion, minipigs conditioned with preoperative IRR and donor, or third-party, splenocyte infusions may develop long-term donor-specific pulmonary allograft survival in the presence of high levels of circulating regulatory T cells.

The impact of social factors on outcomes in patients with bleeding disorders.

INTRODUCTION: In haemophilia, clinical outcomes are mainly determined by the severity of clotting factor deficiency, treatment regimen, availability of clotting factor concentrate and age. Information about the relevance of patient-related factors such as education, social status or impact of the disease on the patient's life is scarce. AIM: To assess the impact of social status and disease-related impairment of certain aspects of the patient's life on clinical and psychosocial outcomes in patients with inherited bleeding disorders (PWBD). METHODS: Consecutive patients of a single centre were assessed by questionnaires on social status and quality of life (SF-36). Social status was defined by school and professional education, employment and financial income of patients as well as school education of their parents. RESULTS: Fifty-seven PWBD (mean age, 38 ± 16 years) were enrolled, 60% were treated on-demand; PWBD had a median number of 2.5 (0-34) annual bleeds and a median orthopaedic joint score of 6 (0-38). No significant differences were found for clinical and psychosocial outcomes across social status groups. More than half of the patients reported that haemophilia had an impact on their school education, childhood and leisure activities. Patients with a high impact of haemophilia on their lives were less satisfied with their lives (P < 0.002), reported worse quality of life in all domains of the SF-36, had a worse joint score (P < 0.024) and reported more pain (P < 0.013). CONCLUSION: The perceived impact of haemophilia on patients' lives seems to have a stronger impact on clinical and psychosocial outcomes than patients' actual social status.

Expression and release of platelet protein disulphide isomerase in patients with haemophilia A.

INTRODUCTION: Despite similar residual factor VIII activity, patients with haemophilia A (HA) show significant interindividual variability with regard to bleeding frequency and severity, suggesting that additional factors modulate thrombin generation and fibrin deposition. Protein disulphide isomerase (PDI) is an abundant oxidoreductase that exerts pleiotropic effects in primary and secondary haemostasis and contributes to thrombosis and vascular inflammation. AIM: We conducted a pilot study to explore a potential role of platelet PDI in patients with HA. METHODS: Expression and release of platelet PDI were studied by flow cytometry and enzyme-linked immunosorbent assay, respectively. RESULTS: Compared to healthy male controls (n = 12), patients with HA (n = 24) showed significantly increased expression of PDI antigen on ADP- or TRAP-6-, but not on buffer-treated platelets, a finding that could not be explained by enhanced platelet activation, as indicated by expression of the α-granule protein, CD62P (P-selectin). While platelet agonists did not affect PDI secretion in healthy male controls, increased levels of PDI antigen were found in supernatants of TRAP-6-treated platelets from patients with HA. Importantly, in two patients with exceedingly high TRAP-6-induced PDI release over baseline, findings were consistent when platelets were isolated and stimulated on a separate occasion. No obvious association was found between platelet PDI and bleeding phenotype in this patient cohort. CONCLUSION: Agonist-induced expression and release of platelet PDI were increased in patients with HA. Larger studies are needed to clarify if variations in this platelet response contribute to the diversity in bleeding frequency and severity among patients with congenital factor VIII deficiency.

[Histological grading of breast cancer]. / Histologisches Grading beim Mammakarzinom.

From a historical perspective, histological grading was the earliest cell-based method for assessing tumor biology and the prognosis of breast cancer. This review article provides detailed and practical instructions for grading of breast cancer in routine diagnostics. Furthermore, the increasing relevance of precise histological grading in the era of molecular pathology is discussed.

SPECT/CT for SLN dissection in vulvar cancer: Improved SLN detection and dissection by preoperative three-dimensional anatomical localisation.

OBJECTIVE: In this study, we assessed the feasibility and clinical advantages of single photon emission computed tomography with CT (SPECT/CT) for sentinel lymph node (SLN) detection in vulvar cancer. METHODS: This is a unicentric prospective trial. Vulvar cancer patients underwent preoperative SLN marking (10MBq Technetium (TC)-99m-nanocolloid) and subsequent planar lymphoscintigraphy (LSG) and SPECT/CT for SLN visualization. Directly before surgery, a patent blue dye was injected. We assessed detection rates of SPECT/CT and those of planar LSG and intraoperative detection. We analyzed the sensitivity, negative predictive value and false negative rate. RESULTS: At Hannover Medical School, 40 vulvar cancer patients underwent SLN dissection after preoperative LSG and SPECT/CT. The mean diameter of all tumors in final histology was 2.23 (0.1-10.5) cm with a mean tissue infiltration of 3.93 (0.25-11) mm. In preoperative imaging, SPECT/CT identified significantly more SLNs (mean 8.7 (1-35) LNs per patient) compared to LSG (mean 5.9 (0-22) LNs, p<0.01). In addition, SPECT/CT led to a high spatial resolution and anatomical localization of SLNs. Thus, SPECT/CT identified aberrant lymphatic drainage in 7/40 (17.5%) patients. There were no significant differences, but significant correlation was found between SPECT/CT and intraoperative SLN identification. Regarding inguino-femoral LNs, for all patients who underwent complete groin dissection, sensitivity was 100%, NPV was 100% and false negative rate was 0%. CONCLUSION: SPECT/CT leads to higher SLN identification compared to LSG in vulvar cancer. Due to its higher spatial resolution and three-dimensional anatomical localisation of SLNs, SPECT/CT provides the surgeon with important additional information, facilitates intraoperative SLN detection and predicts aberrant lymphatic drainage.