Voriconazole plus terbinafine combination antifungal therapy for invasive Lomentospora prolificans infections: analysis of 41 patients from the FungiScope® registry 2008-2019.

OBJECTIVES: Lomentospora prolificans is an emerging cause of serious invasive fungal infections. Optimal treatment of these infections is unknown, although voriconazole-containing treatment regimens are considered the treatment of choice. The objective of this study was to evaluate the role of combination antifungal therapy for L. prolificans infections. METHODS: We performed a retrospective review of medical records of patients with invasive L. prolificans infection diagnosed between 1 January 2008 and 9 September 2019 that were documented in the FungiScope® registry of rare invasive fungal infections. We compared clinical outcomes between antifungal treatment strategies. RESULTS: Over the study period, 41 individuals with invasive L. prolificans infection from eight different countries were documented in the FungiScope® registry. Overall, 17/40 (43%) had treatment response/stable disease and 21/40 (53%) had a fatal outcome attributed to invasive fungal infection. Combination antifungal therapy was associated with increased 28-day survival (15/24 survived versus 4/16 receiving monotherapy; p 0.027) and the combination voriconazole plus terbinafine trended to be associated with higher rates of treatment success (10/16, 63%, 95% CI 35%-85%) compared with other antifungal treatment regimens (7/24, 29%, 95% CI 13%-51%, p 0.053). In Kaplan-Meier survival analysis there was a higher survival probability in individuals receiving the voriconazole/terbinafine combination compared with other antifungal regimens (median survival 150 days versus 17 days). CONCLUSIONS: While overall mortality was high, combination antifungal treatment, and in particular combination therapy with voriconazole plus terbinafine may be associated with improved treatment outcomes compared with other antifungal regimens for the treatment of invasive L. prolificans infections.

Medication use in patients with chronic rhinosinusitis in Germany - a large retrospective patient-based study.

BACKGROUND: The aim of the present study was to provide an insight into medical treatment practices among patients with chronic rhinosinusitis (CRS) in Germany. An investigation of ICD codes and ATC classes of CRS patients in general and otolaryngology offices in Germany should reveal the prevalent treatment behaviors of German physicians. METHODS: The present study used data from the Disease Analyzer database (IQVIA). The study sample included patients from 940 general (GP) and 106 otolaryngology (ENT) practices who were coded as having chronic sinusitis (ICD-10: J32) or nasal polyps (ICD-10: J33) in 2015 (index date). The primary outcome measures were the number of patients with these diagnoses per practice as well as the proportion of patients with prescriptions for topical corticosteroids, systemic corticosteroids, antibiotics, antihistamines, and local decongestants within 365 days after the first diagnosis. RESULTS: This retrospective study included 26,768 patients with coding for chronic sinusitis (ICD-10: J32) and 516 patients for nasal polyps (ICD-10: J33) in 940 GP practices and 19,826 patients with coding for chronic sinusitis (ICD-10: J32) and 1,773 patients for nasal polyps (ICD-10: J33) in 106 ENT practices. In patients coded as having chronic sinusitis (ICD-10: J32), topical corticosteroids were prescribed at a low rate (GP: 12.3%, ENT: 34.3%). In patients coded as having nasal polyps (ICD-10: J33), topical corticosteroid usage was higher in GP practices (27.3%) and in ENT practices (71.2%). CONCLUSIONS: Topical corticosteroid usage in CRS patients in GP practices in Germany is as low as in other Western countries. Increased usage of topical corticosteroids in CRS patients with polyposis should be encouraged in GP and ENT practices.

Healthcare burden of probable and proven invasive mucormycosis: a multi-centre cost-of-illness analysis of patients treated in tertiary care hospitals between 2003 and 2016.

BACKGROUND: Invasive mucormycosis (IM) is a rare invasive fungal infection with a high mortality rate. However, data concerning the clinical and economic burden of IM are scarce. AIM: To evaluate the direct treatment costs and additional expenditures of patients with IM. METHODS: A retrospective cost-of-illness analysis of cases with IM extracted from FungiScope - Global Registry for Emerging Fungal Infections, accessible through the epidemiological research platform www.ClinicalSurveys.net, was undertaken. Results of patients with IM were compared with those of matched patients with similar underlying conditions based on the German Diagnosis Related Group (G-DRG) coding. FINDINGS: Out of 46 patients with probable/proven IM, 31 (67%) patients were male and the median age was 53 years (range 11-88 years). Forty-two patients (92%) had haematological diseases as the most common risk factor. Analysis of cost factors identified antifungal treatment due to IM as the primary cost driver [€22,816, 95% confidence interval (CI) €15,036-32,346], with mean overall direct treatment costs of €53,261 (95% CI €39,660-68,825). Compared with matched patients, patients with IM were treated in hospital for 26.5 additional days (standard deviation 31.8 days; P < 0.001), resulting in mean additional costs of €32,991 (95% CI €21,558-46,613; P < 0.001). Probable IM, as well as absence of chemotherapy, surgical measures due to IM, and antifungal prophylaxis were associated with lower overall costs. Nineteen patients (41.3%) died during hospitalization. CONCLUSION: This study demonstrates the considerable healthcare burden of IM. The choice of antifungal agent for treatment of IM had no impact on overall cost.

[Diagnoses of thyroid disorders in ENT and general practices in Germany between 2008 and 2016]. / Diagnosen von Schilddrüsenerkrankungen in HNO-Praxen und Hausarztpraxen in Deutschland 2008­2016.

OBJECTIVE: The aim of this study was to investigate thyroid disorder diagnoses in otorhinolaryngologic (ENT) practices in Germany compared to general (GP) practices using data from a representative Germany-wide practice database. METHODS: The database was retrospectively searched for diagnoses of thyroid disorders made in ENT and GP practices between January 2008 and December 2016. Data were collected on the most common three-character disease classes (categories) from the "Disorders of thyroid gland" (E00-E07) group as well as the "Benign neoplasm of thyroid gland" (D34) and "Malignant neoplasm of thyroid gland" (C73) categories. The periods 2008-2010, 2011-2013, and 2014-2016 were evaluated. RESULTS: The database included 71 ENT and 506 GP practices with continuous participation from 2008 to 2016. The relative frequency (patients/practice) of diagnoses from the "Disorders of thyroid gland" group was 4.4-times higher in GP than in ENT practices. The relative frequency of benign neoplasms of the thyroid gland was 5­times higher in GP than in ENT practices. The relative frequency of malignant neoplasms of the thyroid gland was almost identical in GP and ENT practices. The most frequent diagnoses in both ENT and GP practices were found in the categories "Other nontoxic goiter" (E04) and "Other hypothyroidism" (E03). Diagnoses in the categories "Hyperthyroidism" (E05) and "Thyroiditis" (E06) were less frequent. Diagnoses of thyroid neoplasms were the least frequent, with benign neoplasms diagnosed more frequently in GP practices and malignant neoplasms diagnosed more frequently in ENT practices. During the study period, the diagnostic frequency of thyroid diseases decreased in ENT practices, whereas it increased in GP practices. CONCLUSION: Despite the increasing interest in establishing thyroid surgery in ENT clinics in Germany in recent years, thyroid diagnoses in ENT practices in Germany have been continuously declining, whereas they have considerably increased in GP practices. The reason for this may be health insurance provider-related differences in reimbursement practices for GPs and specialists.

Impact of TP53 mutation status on systemic treatment outcome in ALK-rearranged non-small-cell lung cancer.

Background: We analyzed whether co-occurring mutations influence the outcome of systemic therapy in ALK-rearranged non-small-cell lung cancer (NSCLC). Patients and methods: ALK-rearranged stage IIIB/IV NSCLC patients were analyzed with next-generation sequencing and fluorescence in situ hybridization analyses on a centralized diagnostic platform. Median progression-free survival (PFS) and overall survival (OS) were determined in the total cohort and in treatment-related sub-cohorts. Cox regression analyses were carried out to exclude confounders. Results: Among 216 patients with ALK-rearranged NSCLC, the frequency of pathogenic TP53 mutations was 23.8%, while other co-occurring mutations were rare events. In ALK/TP53 co-mutated patients, median PFS and OS were significantly lower compared with TP53 wildtype patients [PFS 3.9 months (95% CI: 2.4-5.6) versus 10.3 months (95% CI: 8.6-12.0), P < 0.001; OS 15.0 months (95% CI: 5.0-24.9) versus 50.0 months (95% CI: 22.9-77.1), P = 0.002]. This difference was confirmed in all treatment-related subgroups including chemotherapy only [PFS first-line chemotherapy 2.6 months (95% CI: 1.3-4.1) versus 6.2 months (95% CI: 1.8-10.5), P = 0.021; OS 2.0 months (95% CI: 0.0-4.6) versus 9.0 months (95% CI: 6.1-11.9), P = 0.035], crizotinib plus chemotherapy [PFS crizotinib 5.0 months (95% CI: 2.9-7.2) versus 14.0 months (95% CI: 8.0-20.1), P < 0.001; OS 17.0 months (95% CI: 6.7-27.3) versus not reached, P = 0.049] and crizotinib followed by next-generation ALK-inhibitor [PFS next-generation inhibitor 5.4 months (95% CI: 0.1-10.7) versus 9.9 months (95% CI: 6.4-13.5), P = 0.039; OS 7.0 months versus 50.0 months (95% CI: not reached), P = 0.001). Conclusions: In ALK-rearranged NSCLC co-occurring TP53 mutations predict an unfavorable outcome of systemic therapy. Our observations encourage future research to understand the underlying molecular mechanisms and to improve treatment outcome of the ALK/TP53 co-mutated subgroup.

[Evaluation of the infrastructure for clinical surgical studies in Germany : A nationwide survey of the surgical study network CHIR-Net]. / Evaluation zur Infrastruktur für klinisch chirurgische Studien in Deutschland : Eine bundesweite Umfrage des chirurgischen Studiennetzwerks (CHIR-Net).

BACKGROUND: In order to improve the quality and quantity of clinical trials in Germany a surgical study network called CHIR-Net funded by the Federal Ministry of Education and Research (BMBF) was established. The focus was on building an infrastructure for the performance of surgical multicenter, randomized controlled clinical trials with the inclusion of university and non-university hospitals. The education of clinicians with an interest in clinical research and the transfer of research ideas (as investigator initiated trials, IIT) were clear goals for this grant. The aim of this article is to evaluate the incentive measures by comparison of clinics with and without participation in CHIR-Net structures. MATERIAL AND METHODS: A nationwide online survey included a total of 475 heads of surgical departments of whom 268 worked in hospitals with participation in CHIR-Net structures and 207 at hospitals without. They were asked to answer 20 questions in the following categories: education and activities in clinical trials, number of publications and participation in grant applications at the BMBF and/or German Research Foundation (DFG). The evaluation of the survey was performed according to a priori defined criteria. RESULTS: The response rate was 23.4% and 68 CHIR-Net hospitals and 43 non-CHIR-Net hospitals participated in the survey. The comparison of the results between the hospitals showed that the network significantly contributed to improvement of the study culture, especially in the areas of education in clinical research, infrastructure for clinical trials, study activity, grant applications and publication rates. CONCLUSION: The hospitals that participate in CHIR-Net structures were superior to hospitals that do not participate in CHIR-Net structures regarding study activity, infrastructure for clinical trials, study-specific education of clinicians, grant applications and publication rates. The goal of the grant was achieved and the funding led to manifold, long-term cooperation and a clear improvement of the study culture in surgery.

[What is new in symptomatic MS treatment: Part 3-bladder dysfunction]. / Neues zur symptomatischen MS-Therapie: Teil 3 ­ Blasenfunktionsstörungen.

The symptomatic treatment of multiple sclerosis (MS) nowadays is of similar importance as immunotherapy within a comprehensive concept of therapy of this chronic disease, since it contributes considerably to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Klinisches Kompetenznetz Multiple Sklerose (KKNMS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation took place. These new findings together with further aspects of disease measures and overall treatment strategies of the respective symptoms, as well as treatment goals are introduced in a series of six individual contributions. Here, the symptoms of bladder dysfunction will be discussed.

[New aspects of symptomatic MS treatment: Part 4-sexual dysfunction and eye movement disorders]. / Neues zur symptomatischen MS-Therapie: Teil 4 ­ Störungen der Sexualfunktion und der Augenbewegungen.

The symptomatic treatment of multiple sclerosis (MS) is nowadays of similar importance as immunotherapy within a comprehensive treatment concept of this chronic disease. It makes a considerable contribution to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of the quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Clinical Competence Network Multiple Sclerosis (Klinisches Kompetenznetz Multiple Sklerose, KKNMS) in 2014, several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation have taken place. These new findings together with further aspects of disease measurement methods and overall treatment strategies of the respective symptoms as well as treatment goals are introduced in several individual contributions. In this article the symptoms of sexual dysfunction and eye movement disorders are discussed.

[New aspects of symptomatic MS treatment: Part 6 - cognitive dysfunction and rehabilitation]. / Neues zur symptomatischen MS-Therapie: Teil 6 ­ kognitive Störungen und Rehabilitation.

The symptomatic treatment of multiple sclerosis (MS) is nowadays of similar importance as immunotherapy within a comprehensive treatment concept of this chronic disease. It makes a considerable contribution to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of the quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Clinical Competence Network Multiple Sclerosis ("Klinisches Kompetenznetz Multiple Sklerose", KKN-MS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation have taken place. These new findings together with further aspects of disease measurement methods and overall treatment strategies of the respective symptoms, as well as treatment goals are introduced in several individual contributions. In this article the symptoms of cognitive disorders and the growing impact of rehabilitation are discussed.

[New aspects of symptomatic MS treatment: Part 5 - fatigue]. / Neues zur symptomatischen MS-Therapie: Teil 5 ­ Fatigue.

The symptomatic treatment of multiple sclerosis (MS) is nowadays of similar importance as immunotherapy within a comprehensive treatment concept of this chronic disease. It makes a considerable contribution to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of the quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Clinical Competence Network Multiple Sclerosis (Klinisches Kompetenznetz Multiple Sklerose, KKN-MS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation have taken place. These new findings together with further aspects of disease measurement methods and overall treatment strategies of the respective symptoms as well as treatment goals are introduced in a series of 6 individual contributions. In this article the symptom of fatigue is discussed.

[What is new in symptomatic MS treatment: Part 2-gait disorder and spasticity]. / Neues zur symptomatischen MS­Therapie: Teil 2 ­ Gangstörung und Spastik.

The symptomatic treatment of multiple sclerosis (MS) nowadays is of similar importance as immunotherapy within a comprehensive concept of therapy of this chronic disease, since it contributes considerably to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Klinisches Kompetenznetz Multiple Sklerose (KKN­MS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation took place. These new findings together with further aspects of disease measures and overall treatment strategies of the respective symptoms, as well as treatment goals are introduced in a series of six individual contributions. Here, the symptoms of gait disorders and spasticity will be discussed.

[What is new in symptomatic MS treatment: Part 1-introduction and methodical approach, ataxia and tremor]. / Neues zur symptomatischen MS­Therapie: Teil 1 ­ Einleitung und methodisches Vorgehen, Ataxie und Tremor.

The symptomatic treatment of multiple sclerosis (MS) nowadays is of similar importance as immunotherapy within a comprehensive concept of therapy of this chronic disease, since it contributes considerably to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Klinisches Kompetenznetz Multiple Sklerose (KKN­MS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation took place. These new findings together with further aspects of disease measures and overall treatment strategies of the respective symptoms, as well as treatment goals are introduced in a series of six individual contributions. Here, the topic will be introduced, the methodical approach will be explained, and the treatment of ataxia and tremor will be discussed.

Risk factors for epistaxis in patients followed in general practices in Germany.

BACKGROUND: The goal of the present study was to analyze the risk factors for epistaxis in patients followed in general practices in Germany. METHODS: The current study sample included patients aged 18 years or older who received a first epistaxis diagnosis between January 2012 and December 2016 (index date). Epistaxis patients and controls without epistaxis were matched (1:1) on the basis of age, gender, insurance status and physician. RESULTS: A total of 16,801 patients with epistaxis and 16,801 control subjects were included in this study. Of the subjects, 53.2% were men, and the mean age was 59.6 years (SD=21.2 years). Epistaxis was found to be positively associated with hypertension, obesity, chronic sinusitis, other disorders of the nose and nasal sinuses, anxiety disorder, and adjustment disorder (ORs ranging from 1.13 to 1.44). Epistaxis was also associated with the prescription of vitamin K antagonists, preparations from the heparin group, platelet aggregation inhibitors excluding heparin, direct thrombin inhibitors, direct factor Xa inhibitors, other antithrombotic agents, selective serotonin reuptake inhibitors and nasal steroids (ORs ranging from 1.15 to 3.55). CONCLUSIONS: Overall, epistaxis risk is increased by multiple medical and psychiatric disorders. Several antithrombotic and nasal steroid therapies are also associated with this risk.

[Postoperative wound infections : Diagnosis, classification and treatment]. / Der postoperative Wundinfekt : Diagnose, Klassifikation und Behandlung.

BACKGROUND: Surgical site infections are a frequent complication of surgery and a severe burden for the patient as well as for the healthcare system. Sound knowledge of the disease pattern is an essential prerequisite for effective therapy. OBJECTIVE: This article presents an overview of the diagnosis, classification and treatment options for surgical site infections. MATERIAL AND METHODS: Based on the existing experience, the currently available evidence and pathophysiological considerations, an overview of the diagnostic possibilities, the existing classification systems and the treatment options is presented. RESULTS: The diagnosis of surgical site infections is based on the clinical symptoms and can particularly be supported by the microbiological analysis of wound samples. There is no validated classification system but the definition of the Centers for Disease Control and Prevention is most commonly used. After initial bedside processing, debridement and wound cleansing are the basis for the further treatment, which is supplemented by the rational use of antiseptics and antibiotics. The use of modern dressings with the aim of maintaining a physiological moist wound environment promotes wound healing. The negative pressure wound therapy is an available treatment option. Rare diseases need to be considered. CONCLUSION: The low level of evidence and critical consideration of the treatment options have been discussed in many guidelines, consensus documents and systematic reviews on the basis of which this article was written. Strengthening the evidence situation through intensive, targeted research should be the goal.

A multicentre, randomized, single-blind, parallel-group study comparing the efficacy and tolerability of benzoyl peroxide 3%/clindamycin 1% with azelaic acid 20% in the topical treatment of mild-to-moderate acne vulgaris.

BACKGROUND: Mild-to-moderate acne vulgaris is treated with a range of mono- and combination therapies; however, clinical evidence is still required to optimize treatment recommendations. OBJECTIVE: To compare the efficacy, tolerability and safety of a combination of benzoyl peroxide 3% and clindamycin 1% (BPO + CLN) with azelaic acid 20% (AzA) for the topical treatment of mild-to-moderate acne vulgaris. METHOD: This was a randomized, assessor-blinded, parallel-group, multicentre study conducted in Germany. Patients with a confirmed diagnosis of acne vulgaris, aged 12-45 years, were randomized 1 : 1 to once-daily BPO + CLN gel or twice-daily AzA cream for up to 12 weeks. The primary endpoint was the percentage change in inflammatory lesions from baseline at Week 4. Secondary endpoints included total and inflammatory lesion counts and tolerability assessments. For selected secondary endpoints, inductive statistical analysis was performed post hoc. Patient safety was assessed by adverse event (AE) monitoring. RESULTS: Efficacy was assessed in the modified intent-to-treat (mITT) population [patients using ≥1 dose of study medication (ITT), plus baseline and ≥1 post-baseline lesion count (n = 215)]. There was a statistically significant difference in the primary endpoint, with a median decrease of -52.6% for BPO + CLN (n = 107) vs.-38.8% for AzA (n = 108; P = 0.0004). There was also a greater difference in secondary lesion endpoints at Week 12, with a median decrease in inflammatory lesions of -78.8% and -65.3% and total lesions of -69.0% and -53.9% with BPO + CLN and AzA, respectively (both P < 0.0001). Tolerability was acceptable for both treatments. Overall, 55.6% (BPO + CLN) and 69.7% (AzA) of patients reported treatment-emergent AEs, and 15.7% and 35.8% of patients experienced application site reactions with BPO + CLN (24 events; 17 patients) and AzA (60 events; 39 patients) treatment, respectively (ITT population). CONCLUSION: BPO + CLN demonstrated greater efficacy than AzA in the treatment of mild-to-moderate acne vulgaris and has a positive tolerability and safety profile.

Postoperative Heparin-Mediated Extracorporeal Low-Density Lipoprotein Fibrinogen Precipitation Aphaeresis Prevents Early Graft Occlusion after Coronary Artery Bypass Grafting.

Background Early graft occlusion due to thromboembolic events is a well-known complication after coronary artery bypass grafting (CABG). Fibrinogen, the coagulation factor I, is a glycoprotein that is transformed by thrombin into fibrin. It plays a major role in thrombus formation and is highly elevated after CABG. Our aim was to determine if postoperative lowering of fibrinogen levels by H.E.L.P. (heparin-mediated extracorporeal low-density lipoprotein [LDL] fibrinogen precipitation) aphaeresis could reduce the rate of early graft occlusion in patients with hypercholesterolemia undergoing CABG. Methods Between December 2004 and September 2009, 36 male patients with hypercholesterolemia (mean LDL cholesterol 128 ± 12 mg/dL), mean age 58 ± 9 years, underwent CABG. Mean preoperative fibrinogen level was 387 ± 17 mg/dL. H.E.L.P. aphaeresis was postoperatively performed when fibrinogen levels exceeded 350 mg/dL on day 1 and 250 mg/dL every consecutive day up to day 8. Pre- and postaphaeresis blood samples were obtained and plasma fibrinogen level reduction was calculated. Early graft occlusion was evaluated by means of coronary angiography or multislice computed tomography before discharge. Results A total of 128 distal anastomoses were performed in 36 patients (mean 3.6/patient). Postoperatively, 191 H.E.L.P. aphaeresis sessions were performed (mean 5.3/patient). Fibrinogen levels were lowered from 391 ± 10 mg/dL (preaphaeresis) to 171 ± 5 mg/dL (postaphaeresis; p < 0.001). Coronary angiography (multislice computed tomography in 7 patients) revealed graft patency in 125 of 128 grafts (98% patency) with three occluded venous grafts to target vessels of 1.5 mm. H.E.L.P. aphaeresis-related complications were limited to hypotensive episodes in two patients and bacteremia in one patient. Conclusions H.E.L.P. apheresis offers an easy, save, and efficient method to decrease fibrinogen postoperatively in patients having CABG. Showing excellent graft patency rates in comparison to the literature, this method is a promising tool to reduce early graft occlusion after CABG.

High spectral purity Kerr frequency comb radio frequency photonic oscillator.

Femtosecond laser-based generation of radio frequency signals has produced astonishing improvements in achievable spectral purity, one of the basic features characterizing the performance of an radio frequency oscillator. Kerr frequency combs hold promise for transforming these lab-scale oscillators to chip-scale level. In this work we demonstrate a miniature 10 GHz radio frequency photonic oscillator characterized with phase noise better than -60 dBc Hz(-1) at 10 Hz, -90 dBc Hz(-1) at 100 Hz and -170 dBc Hz(-1) at 10 MHz. The frequency stability of this device, as represented by Allan deviation measurements, is at the level of 10(-10) at 1-100 s integration time-orders of magnitude better than existing radio frequency photonic devices of similar size, weight and power consumption.

Ultralow noise miniature external cavity semiconductor laser.

Advanced applications in optical metrology demand improved lasers with high spectral purity, in form factors that are small and insensitive to environmental perturbations. While laboratory-scale lasers with extraordinarily high stability and low noise have been reported, all-integrated chip-scale devices with sub-100 Hz linewidth have not been previously demonstrated. Lasers integrated with optical microresonators as external cavities have the potential for substantial reduction of noise. However, stability and spectral purity improvements of these lasers have only been validated with rack-mounted support equipment, assembled with fibre lasers to marginally improve their noise performance. In this work we report on a realization of a heterogeneously integrated, chip-scale semiconductor laser featuring 30-Hz integral linewidth as well as sub-Hz instantaneous linewidth.

Superselective microcoil embolization in severe intractable epistaxis: an analysis of 12 consecutive cases from an otorhinolaryngologic and an interventional neuroradiologic point of view.

From 2006 to 2013, 12 patients with severe epistaxis refractory to prior conservative and surgical therapy were treated by superselective embolization of nasal arteries. Supersoft platinum microcoils with smallest diameters were used as the sole embolic agent in all cases. Coils were applied far distally in a stretched position for obtaining ideal target vessel superselectivity. The objective of this study is to evaluate efficacy and complications of superselective coil embolization for treatment of severe intractable epistaxis and to discuss results from an otorhinolaryngologic and an interventional neuroradiologic point of view. Retrospectively, all epistaxis inpatients between 2006 and 2013 were identified and subdivided by form of treatment: conservative, surgical and interventional therapy. Medical records of interventionally treated patients were reviewed for demographics, medical history, risk factors, clinical data, complications and short-term success, and patients were followed up for long-term success. Mean follow-up was 37 months. In 12 patients, 14 embolizations were carried out, with short-term success in 9 patients (75%), while early post-interventional rebleeding occurred in 3 patients (25%). Of 9 patients with short-term success, 1 died during stay, 1 was lost to follow-up and 1 had minor re-bleeding after 30 months. Six patients had short-term and long-term success. Before the first embolization, 3 ± 1 conservative and/or surgical procedures had been undertaken. Length of stay was 12.8 ± 3.6 days. 8 patients (67%) received red cell concentrates. Most frequent complications were mucosal damage and nasal pain, but these were related to repeated packing and surgery. Typical embolic complications as neurological or visual impairment or soft tissue necrosis were not observed in any patient. From the otorhinolaryngologic point of view, surgery is the treatment of choice in severe refractory epistaxis, but in case of repeated failure, superselective microcoil embolization is a valuable addition to the therapeutic spectrum. From the interventional neuroradiologic point of view, superselective microcoil embolization is an effective, well tolerable and safe procedure and complications may be reduced in comparison to microparticle embolization. Modern supersoft microcoils with smallest diameters enable ideal superselectivity of the target vessels.

What attracts elk onto cattle pasture? Implications for inter-species disease transmission.

In Southwest Alberta, beef cattle and wild elk (Cervus elaphus) have similar habitat preferences. Understanding their inter-species contact structure is important for assessing the risk of pathogen transmission between them. These spatio-temporal patterns of interactions are shaped, in part, by range management and environmental factors affecting elk distribution. In this study, resource selection modeling was used to identify factors influencing elk presence on cattle pasture and elk selection of foraging patches; furthermore, consequences for inter-species disease transmission were discussed. Data on pasture management practices and observations of elk were collected from 15 ranchers during interviews. Pasture use by elk was defined based on telemetry data (from GPS collars deployed on 168 elk in 7 herds) and rancher observations. At the patch scale, foraging patches used by elk were identified by spatio-temporal cluster analysis of telemetry data, whereas available patches were randomly generated outside the area delimited by used patches. For pastures and patches, landscape and human-managed features were characterized using remote sensing data and interviews, respectively. Attributes of available and used pastures (or patches) were compared using resource selection functions, on annual and seasonal (or annual and monthly) time scales. Additionally, intensity of pasture use was modeled using negative binomial regression. Cultivated hay land and mineral supplements were associated with elk presence on cattle pastures, whereas pastures with manure fertilization and higher traffic-weighted road densities were less likely to be used by elk. The effects of landscape (elevation, aspect, water access) and vegetation (forest cover, Normalized Difference Vegetation Index) characteristics on patch selection were consistent with typical elk habitat requirements. The presence of cattle and the traffic-weighted road density were negatively associated with patch selection. The apparent avoidance of cattle by elk reduced the risk of direct transmission of pathogens, except during winter months. However, human-managed features attracting elk to cattle pastures (e.g. hay land and mineral supplements) may increase inter-species pathogen transmission through indirect contacts.