The dissociation of (a+c) misfit dislocations at the InGaN/GaN interface.

In hexagonal materials, (a+c) dislocations are typically observed to dissociate into partial dislocations. Edge (a+c) dislocations are introduced into (0001) nitride semiconductor layers by the process of plastic relaxation. As there is an increasing interest in obtaining relaxed InGaN buffer layers for the deposition of high In content structures, the study of the dissociation mechanism of misfit (a+c) dislocations laying at the InGaN/GaN interface is then crucial for understanding their nucleation and glide mechanisms. In the case of the presented plastically relaxed InGaN layers deposited on GaN substrates, we observe a trigonal network of (a+c) dislocations extending at the interface with a rotation of 3° from <1 1 ¯ $\bar 1$ 00> directions. High-resolution microscopy studies show that these dislocations are dissociated into two Frank-Shockley 1/6<2 2 ¯ $\bar 2$ 03> partial dislocations with the I1 BSF spreading between them. Atomistic simulations of a dissociated edge (a+c) dislocation revealed a 3/5-atom ring structure for the cores of both partial dislocations. The observed separation between two partial dislocations must result from the climb of at least one of the dislocations during the dissociation process, possibly induced by the mismatch stress in the InGaN layer.

Primary laparoscopic fundoplication in selected patients with gastroesophageal reflux disease.

BACKGROUND: Despite proton pump inhibitors being a powerful therapeutic tool, laparoscopic fundoplication (LF) has proven successful in the treatment of gastroesophageal reflux disease (GERD), through mechanical augmentation of a weak antireflux barrier and the advantages of minimally invasive access. A critical patient selection for LF, based on thorough preoperative assessment, is important for the management of GERD-patients. The purpose of this study is to provide an overview on the management of GERD-patients treated by primary LF in a specialized center and to illustrate the possible outcome after several years. METHODS: Patients were selected after going through diagnostic workup consisting of patient's history and physical examination, upper gastrointestinal endoscopy, assessment of gastrointestinal Quality of Life Index, screening for somatoform disorders, functional assessment by esophageal manometry, (impedance)-24-hour-pH-monitoring, and selective radiographic studies. The indication for LF was based on EAES-guidelines. Either a floppy and short Nissen fundoplication was performed or a posterior Toupet-hemifundoplication was chosen. A long-term follow-up assessment was attempted after surgery. RESULTS: In total, n = 1131 patients were evaluated (603 males; 528 females; mean age; 48.3 years; and mean body mass index: 27). The mean duration between onset of symptoms and surgery was 8 years. Nissen: n = 873, Toupet: n = 258; conversion rateerativ: 0.5%; morbidity 4%, mortality: 1 (1131). Mean follow-up (n = 898; 79%): 5.6 years; pre/post-op results: esophagitis: 66%/12.1%; Gastrointestinal Quality of Life Index: median: 92/119; daily proton pump inhibitors-intake after surgery: 8%; and operative revisions 4.3%. CONCLUSIONS: In conclusion, our data show that careful patient selection for laparoscopic fundoplication and well-established technical concepts of mechanical sphincter augmentation can provide satisfying results in the majority of patients with severe GERD.

Human cytomegalovirus multiple-strain infections and viral population diversity in haematopoietic stem cell transplant recipients analysed by high-throughput sequencing.

Human cytomegalovirus (HCMV) is an important opportunistic pathogen in allogeneic haematopoietic stem cell transplant (HSCT) recipients. High-throughput sequencing of target-enriched libraries was performed to characterise the diversity of HCMV strains present in this high-risk group. Forty-four HCMV-DNA-positive plasma specimens (median viral input load 321 IU per library) collected at defined time points from 23 HSCT recipients within 80 days of transplantation were sequenced. The genotype distribution for 12 hypervariable HCMV genes and the number of HCMV strains present (i.e. single- vs. multiple-strain infection) were determined for 29 samples from 16 recipients. Multiple-strain infection was observed in seven of these 16 recipients, and five of these seven recipients had the donor (D)/recipient (R) HCMV-serostatus combination D + R + . A very broad range of genotypes was detected, with an intrahost composition that was generally stable over time. Multiple-strain infection was not associated with particular virological or clinical features, such as altered levels or duration of antigenaemia, development of acute graft-versus-host disease or increased mortality. In conclusion, despite relatively low viral plasma loads, a high frequency of multiple-strain HCMV infection and a high strain complexity were demonstrated in systematically collected clinical samples from this cohort early after HSCT. However, robust evaluation of the pathogenic role of intrahost viral diversity and multiple-strain infection will require studies enrolling larger numbers of recipients.

Double-Unit Superomedio-Central (DUS) Pedicle Inverted-T Reduction Mammaplasty in Gigantomastia: A 7-year Single-Center Retrospective Study.

INTRODUCTION: Reduction mammaplasty in patients with gigantomastia is challenging. The Double-Unit technique with a Superomedio-Central pedicle and inverted-T incision is the standard technique for reduction mammaplasty in our clinic. The aim of this study was to review our approach in cases with gigantomastia in comparison with the current literature. PATIENTS AND METHODS: From 01/2011 to 12/2017, we performed 831 reduction mammaplasties in 630 patients. The Double-Unit  Superomedio-Central  (DUS) pedicle and inverted-T incision was implemented as a standard procedure for gigantomastia. Patient demographics and the outcome parameters complication rate, patient satisfaction with the aesthetic result, nipple sensibility, and surgical revision rate were obtained and retrospectively analyzed. RESULTS: In 37 patients, 55 reduction mammaplasties were performed with more than 1000 g per breast. Mean resection weight was 1311 g on right side and 1289 g on left side. Mean age was 52.5 years, mean body mass index was 32.8 kg/m2, mean sternal-notch-to-nipple distance was 38.3 cm. A free NAC graft was necessary in four breasts. Overall complication rate was 14.5%; secondary surgical revision rate was 12.7%. 91% of the patients were "very satisfied" and "satisfied" with the aesthetic result. Nipple sensibility was rated "high" and "medium" in 83%. CONCLUSION: The Double-Unit technique with a Superomedio-Central pedicle and inverted-T incision is very effective to achieve volume reduction and aesthetically pleasing reproducible results with a low complication rate in cases with gigantomastia. LEVEL OF EVIDENCE: Level of Evidence This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

[The 8th edition of the TNM staging system-a curse or a blessing for oropharyngeal carcinoma?] / Die 8. Version der TNM-Klassifikation ­ Fluch oder Segen für das Oropharynxkarzinom?

At the beginning of 2017, the 8th edition of the TNM classification was presented. For oropharyngeal carcinoma, this was accompanied by a paradigm shift, as a separation of the classification depending on the association with human papillomavirus (HPV) status has been established. By considering the literature, this paper provides an overview of the characteristics of HPV-associated carcinomas, the new features of the TNM classification, and the existing points of discussion. The revision has improved the prognostic significance of the TNM classification; however, there are still tumor- and patient-dependent influencing factors that must be considered for future versions.

Diabetes self-management education exposure and glycated haemoglobin levels among Marshallese participants in a randomized controlled study.

AIMS: A randomized control trial (RCT) of diabetes self-management education (DSME), undertaken by a community-based participatory research (CBPR) partnership between the University of Arkansas for Medical Sciences (UAMS) and the Marshallese community in Arkansas. The RCT examined the effect of hours of intervention exposure, with the hypothesis that increased exposure is one reason the Adapted-Family DSME was found to be more effective than the Standard DSME. METHODS: Some 221 Marshallese with type 2 diabetes were randomized to an Adapted-Family DSME group (in-home setting) (n = 110) or a Standard DMSE group (community setting) (n = 111). The Adapted-Family DSME included 10 h of education that covered the core self-care elements recommended by the American Diabetes Association (ADA) and American Association of Diabetes Educators' (AADE) recommendations. The Standard DSME included 10 h of intervention with all ADA and AADE core elements. RESULTS: The number of hours of intervention exposure in the Adapted-Family DSME arm (mean = 8.0; median = 10.0) was significantly higher than the number of hours of intervention received in the Standard DSME arm (mean = 1.5; median = 0.0). As hypothesized, higher exposure was associated with a significant reduction in HbA1c in a model including only study arm and exposure (P = 0.01), and in a model including study arm, exposure, and all demographic variables (P = 0.046). CONCLUSIONS: This finding is consistent with previous reviews that showed increased exposure to DSME produced improved glycaemic control and ≥ 10 h of DSME produces clinically meaningful reductions in HbA1c .

Modification of Dzyaloshinskii-Moriya-Interaction-Stabilized Domain Wall Chirality by Driving Currents.

We measure and analyze the chirality of Dzyaloshinskii-Moriya-interaction (DMI) stabilized spin textures in multilayers of Ta|Co_{20}F_{60}B_{20}|MgO. The effective DMI is measured experimentally using domain wall motion measurements, both in the presence (using spin-orbit torques) and absence of driving currents (using magnetic fields). We observe that the current-induced domain wall motion yields a change in effective DMI magnitude and opposite domain wall chirality when compared to field-induced domain wall motion (without current). We explore this effect, which we refer to as current-induced DMI, by providing possible explanations for its emergence, and explore the possibility of its manifestation in the framework of recent theoretical predictions of DMI modifications due to spin currents.

Regional challenges: evaluation of a hepatitis outreach programme using transient elastography (FibroScan) in Victoria.

BACKGROUND: Evaluation of an outreach programme using a mobile transient elastography (TE) device (FibroScan) to improve liver disease assessment in different clinical settings. AIMS: To evaluate a programme of liver fibrosis assessment by TE and to compare fibrosis scores between different sites and patient groups. METHODS: Prospective cohort study. TE was conducted at a tertiary hospital and during outreach clinics in three different settings: community clinics, clinics for people who use drugs (PWUD) and regional clinics in rural Victoria. All patients referred for TE at the participating locations were eligible during the study period. RESULTS: A total of 200 of 623 patients was assessed and evaluated during outreach sessions (regional 100; PWUD 18; community 82). While the majority of patients in community centres were infected with hepatitis B (68%), most patients in regional clinics and in PWUD settings had hepatitis C virus (HCV) (81 and 100%, respectively). Significantly more patients assessed at regional clinics and PWUD settings presented with severe fibrosis (F3-F4, F4): regional clinics 39%; PWUD 31%; tertiary 11%; community 7%, (P <0.001). Multivariable logistic regression analysis revealed that older age, alcohol consumption, male sex, increased alanine transferase levels, HCV infection and importantly, evaluation at regional sites were independently associated with severe fibrosis. CONCLUSIONS: A TE-based outreach programme allows for assessment of liver fibrosis in varied and regional populations. The finding that patients in regional settings and PWUD presented with more advanced fibrosis should prompt improvements in healthcare to improve access for these populations.

Neuropsychiatric disease relevance of circulating anti-NMDA receptor autoantibodies depends on blood-brain barrier integrity.

In 2007, a multifaceted syndrome, associated with anti-NMDA receptor autoantibodies (NMDAR-AB) of immunoglobulin-G isotype, has been described, which variably consists of psychosis, epilepsy, cognitive decline and extrapyramidal symptoms. Prevalence and significance of NMDAR-AB in complex neuropsychiatric disease versus health, however, have remained unclear. We tested sera of 2817 subjects (1325 healthy, 1081 schizophrenic, 263 Parkinson and 148 affective-disorder subjects) for presence of NMDAR-AB, conducted a genome-wide genetic association study, comparing AB carriers versus non-carriers, and assessed their influenza AB status. For mechanistic insight and documentation of AB functionality, in vivo experiments involving mice with deficient blood-brain barrier (ApoE(-/-)) and in vitro endocytosis assays in primary cortical neurons were performed. In 10.5% of subjects, NMDAR-AB (NR1 subunit) of any immunoglobulin isotype were detected, with no difference in seroprevalence, titer or in vitro functionality between patients and healthy controls. Administration of extracted human serum to mice influenced basal and MK-801-induced activity in the open field only in ApoE(-/-) mice injected with NMDAR-AB-positive serum but not in respective controls. Seropositive schizophrenic patients with a history of neurotrauma or birth complications, indicating an at least temporarily compromised blood-brain barrier, had more neurological abnormalities than seronegative patients with comparable history. A common genetic variant (rs524991, P=6.15E-08) as well as past influenza A (P=0.024) or B (P=0.006) infection were identified as predisposing factors for NMDAR-AB seropositivity. The >10% overall seroprevalence of NMDAR-AB of both healthy individuals and patients is unexpectedly high. Clinical significance, however, apparently depends on association with past or present perturbations of blood-brain barrier function.

The potential and perspective of peroral endoscopic esophageal myotomy for achalasia.

The therapeutic spectrum of this disorder consists of medical therapy, endoscopic balloon dilatation, endoscopic Botox injection, open or laparoscopic cardia myotomy, and most recently transesophageal endoscopic myotomy (POEM peroral endoscopic myotomy). The most important requirement is a well-experienced team in interventional flexible endoscopy. The endoscopist as well as the assisting staff should have experience in advanced therapeutic endoscopic techniques and hemostasis to handle all necessary endoscopic instruments such as injection needles, needle knife, triangle knife, coagulation graspers, and endoscopic clip handling and closures. In addition, advanced surgical and especially laparoscopic skills and experience as well as surgical knowledge about esophageal disease must be available in case of conversion and/or consultation. Prior to this procedure, the patient undergoes a detailed diagnostic work-up to confirm the diagnosis of achalasia. The procedures are performed in general anesthesia. The patient is brought in a supine position, and the abdomen is free for inspection and palpation during the procedure. The myotomy can be performed in different locations around the esophageal circumference. In Europe, several centers with large experience in esophageal disease, laparoscopy, and especially advanced interventional endoscopy have started to introduce this POEM-technique in their clinical practice. Initial success and low complication rates are quite promising and show a great future perspective for this technique. In the USA, POEM is a procedure with a substantial increase in numbers performed in the past years with a low complication rate. The largest series are performed in Asia with a great clinical success. The perspective of POEM may be the lesser access trauma. Its potential can be also realized in Redo cases, where experienced centers have initial experience with POEM after POEM and POEM after LHMD.

[Chronic otitis mediaChronic Otitis Media]. / Die chronische Otitis media.

There are 2 different kinds of chronic otitis media: Otitis media chronica mesotympanalis and otitis media chronica epitympanalis (cholesteatoma). The incidence of chronic otitis media as reported in literature differs in a wide range. The incidence rates vary between 0.45 and 46%. Both, otitis media chronica mesotympanalis and cholesteatoma, lead to eardrum perforation due to lengthy and recurring inflammations. Furthermore, chronic otitis media is characterized by frequently recurring otorrhea and conductive hearing loss.

[Differential Treatment Strategy of Pleural Empyema in a Post-Pneumonectomy Cavity]. / Differenzierte Behandlungsstrategie des Pleuraempyems in der Postpneumonektomiehöhle.

INTRODUCTION: Pleural empyema in a post-pneumonectomy cavity (PEC) occurs with a frequency of 2% -15% and a mortality of more than 10%. It can occur with or without bronchopleural fistula (BPF). The treatment of empyema in the PEC requires a strict algorithm: drainage, bronchoscopy, closure of the fistula, thorough cleaning of the PEC, filling the cavity, thoracoplasty. METHODS: 39 cases with an empyema in the PEC were analysed retrospectively (men: n = 38; women: n = 1; mean age: 60.3 ±â€Š7.6 years). In 32 (82.1%) of the patients, a BPF was detected (right: n = 26, left: n = 6). The average length of stay in hospital was 125 days (22 - 293 days). Cleaning of the PEC was achieved in all surviving patients (n = 23, 65.1%). All patients (n = 39) underwent bronchoscopy with placement of a chest tube for drainage. The BPF was closed in three cases (7.7%) with a stent while in 12 cases (30.8%) a vascularized flap was used. In 14 patients (35.9%) the bronchial stump was either reclosed with sutures or resected. In three cases (7.7%) a re-anastomosis was performed. RESULTS: The PEC became sterile by regular flushing with antibiotic solution in three patients (7.7%). In 35.9% of the patients (n = 14), aggressive surgical debridement (Weder procedure) was necessary. A thoracic window was applied in 22 patients (56.4%), followed by negative pressure wound therapy (NPWT) and change of dressing every three to four days or a tamponade of the thoracic cavity with simple dressings. In 19 patients (48.7%) the thoracic cavity was sealed with an antibiotic solution. In 5 cases an Alexander thoracoplasty took place. CONCLUSIONS: Pleural empyema after pneumonectomy still poses a serious postoperative complication. A bronchopleural fistula is often detected. Thus, two problems arise at the same time ­ fistula and infection in the pleural cavity. Through a strict algorithm, both problems can be dealt with in stages. After sealing the fistula, the thoracic cavity is thoroughly cleaned and finally the thorax is closed. Only in a small number of patients (1.3%) in whom these measures remain ineffective (persistent MRSA, aspergillus colonization) should the cavity be obliterated by thoracoplasty.

Telehealth: experience of the first 120 consultations delivered from a new refugee telehealth clinic.

BACKGROUND: In 2011, the Australian Government introduced Medicare item numbers for telehealth consultations. This is a rapidly expanding method of healthcare provision. AIMS: We assessed the demographic and disease profile of refugee patients attending a new telehealth clinic, and calculated the patient travel avoided. We examined technical challenges and assessed the performance of two videoconferencing solutions using different bandwidth and latencies. METHODS: We audited the first 120 patients attending the telehealth clinic. During consultations, the patient was with the general practitioner (GP) and linked by internet videoconference using VIDYO, GoToMeeting or Skype, to the specialist at a tertiary referral hospital. Travel avoided was calculated and technical problems were assessed by the participating specialist. Bandwidth and latency variations were examined within a university broadband testing facility. RESULTS: The two most frequently managed conditions were hepatitis C and latent tuberculosis. Twenty-nine different GP were included and 42 consultations required an interpreter. Nearly 500 km of travel and 127 kg of CO(2) production was avoided per consultation. Technical issues were faced in 25% of consultations, most frequently sound problems and connections dropping out. A bandwidth of at least 512 kbps and latency of no more than 300 ms was necessary to conduct an adequate multipoint videoconference. CONCLUSIONS: Telehealth using videoconferencing adds a new component to care of refugee and immigrant patients settling in regional areas. Telehealth will be improved by changes to improve simplicity and standardisation of videoconferencing, but requires ongoing Medicare funding to allow sufficient administrative support.

[Differential diagnosis of nasal obstruction]. / Differenzialdiagnosen bei Nasenatmungsbehinderung.

Nasal obstruction can have a variety of different causes. The following text describes important diseases of the nose and paranasal sinuses, which are associated with the symptom of nasal obstruction and discusses specifics of diagnosis and therapy.

Avapritinib-based SAR studies unveil a binding pocket in KIT and PDGFRA.

Avapritinib is the only potent and selective inhibitor approved for the treatment of D842V-mutant gastrointestinal stromal tumors (GIST), the most common primary mutation of the platelet-derived growth factor receptor α (PDGFRA). The approval was based on the NAVIGATOR trial, which revealed overall response rates of more than 90%. Despite this transformational activity, patients eventually progress, mostly due to acquired resistance mutations or following discontinuation due to neuro-cognitive side effects. These patients have no therapeutic alternative and face a dismal prognosis. Notable, little is known about this drug's binding mode and its medicinal chemistry development, which is instrumental for the development of the next generation of drugs. Against this background, we solve the crystal structures of avapritinib in complex with wild-type and mutant PDGFRA and stem cell factor receptor (KIT), which provide evidence and understanding of inhibitor binding and lead to the identification of a sub-pocket (Gα-pocket). We utilize this information to design, synthesize and characterize avapritinib derivatives for the determination of key pharmacophoric features to overcome drug resistance and limit potential blood-brain barrier penetration.

Blocking growth by an electrically active subsurface layer: the effect of Si as an antisurfactant in the growth of GaN.

Combining aberration corrected high resolution transmission electron microscopy and density functional theory calculations we propose an explanation of the antisurfactant effect of Si in GaN growth. We identify the atomic structure of a Si delta-doped layer (commonly called SiN(x) mask) as a SiGaN(3) monolayer that resembles a √3×√3 R30° surface reconstruction containing one Si atom, one Ga atom, and a Ga vacancy (V(Ga)) in its unit cell. Our density functional theory calculations show that GaN growth on top of this SiGaN(3) layer is inhibited by forming an energetically unfavorable electrical dipole moment that increases with layer thickness and that is caused by charge transfer between cation dangling bonds at the surface to V(Ga) bound at subsurface sites.

[Diagnosis and therapy of bleeding in ENT]. / Blutungen im HNO-Bereich.

Bleeding in the oral cavity, nose or ear are common events in the daily routine of ENT specialists. Apart from trivial cases that often get outpatient treatment, there are numerous cases of serious bleeding that require stationary treatment and if necessary, an operative or interventional therapy. In the following section the most frequent types of bleeding, their diagnosis and therapy will be explained.

Kaposi's sarcoma-associated herpesvirus infection of endothelial cells inhibits neutrophil recruitment through an interleukin-6-dependent mechanism: a new paradigm for viral immune evasion.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), an endothelial cell (EC) neoplasm characterized by dysregulated angiogenesis and inflammation. KSHV infection of EC causes production of proinflammatory mediators, regarded as possible initiators of the substantial mononuclear leukocyte recruitment seen in KS. Conversely, KSHV immune evasion strategies exist, such as degradation of EC leukocyte adhesion receptors by viral proteins. Here, we report the effects of KSHV infection of primary EC on recruitment of flowing leukocytes. Infection did not initiate adhesion of any leukocyte subset per se. However, on cytokine-stimulated EC, KSHV specifically inhibited neutrophil, but not PBL or monocyte, transmigration, an observation consistent with the inflammatory cell profile found in KS lesions in vivo. This inhibition could be recapitulated on uninfected EC using supernatant from infected cultures. These supernatants contained elevated levels of human interleukin 6 (hIL-6), and both the KSHV- and the supernatant-induced inhibitions of neutrophil transmigration were abrogated in the presence of a hIL-6 neutralizing antibody. Furthermore, preconditioning of EC with hIL-6 mimicked the effect of KSHV. Using RNA interference (RNAi), we show that upregulation of suppressor of cytokine signaling 3 (SOCS3) was necessary for this effect of hIL-6. These studies reveal a novel paracrine mode of KSHV immune evasion, resulting in reduced recruitment of neutrophils, a cell type whose antiviral and antitumor roles are becoming increasingly appreciated. Moreover, the findings have implications for our understanding of the contribution of hIL-6 to the pathogenesis of other inflammatory disorders and tumors in which this cytokine is abundant.

Chronic hepatitis E in hematopoietic stem cell transplant patients in a low-endemic country?

Cases of chronic hepatitis E have been described in patients after kidney and liver transplantation. In addition, hepatitis E virus (HEV) reactivation was reported after hematopoietic stem cell transplantation (HSCT). We here evaluated if HEV infection might explain elevated liver enzymes in a well selected cohort of allogeneic HSCT patients with biochemical evidence of hepatitis (n = 52). Of note, none of the subjects tested positive for HEV RNA, including 2 HSCT patients who had been infected with HEV already before transplantation. Thus, both chronic courses of HEV infections and HEV reactivations seem to be rather rare events in HSCT patients in a non-endemic country.