Wide-area transepithelial sampling with computer-assisted 3-dimensional analysis (WATS) markedly improves detection of esophageal dysplasia and Barrett's esophagus: analysis from a prospective multicenter community-based study.

The 4-quadrant forceps biopsy (FB) protocol for identifying Barrett's esophagus (BE) and esophageal dysplasia (ED) suffers from poor sensitivity due to significant sampling error. We investigated the benefit of wide-area transepithelial sampling with 3-dimensional computer-assisted analysis (WATS) used adjunctively to the combination of random and targeted FB in the detection of ED, and as a secondary outcome, BE. In this multicenter prospective trial, community endoscopists at 21 sites utilized WATS as an adjunct to both targeted and random FB in patients undergoing BE screening and surveillance. Investigators alternated taking FB and WATS samples first. WATS specimens were analyzed at CDx Diagnostics (Suffern, NY) while FB samples were analyzed by each site's regular pathologists. Data were de-identified and then aggregated for analysis. Of 12,899 patients enrolled, FB identified 88 cases of ED, and WATS detected an additional 213 cases missed by FB. These 213 cases represented an absolute increase of 1.65%, raising the yield from 0.68% to 2.33%. Adding WATS to FB increased the overall detection of ED by 242% (95% CI: 191%-315%). Fewer than 61 patients needed to be tested with WATS to identify an additional case of ED. The combination of random and targeted FB identified 1,684 cases of BE, and WATS detected an additional 2,570 BE cases. The absolute incremental yield of adding WATS to FB is 19.9%, increasing the rate of detection from 13.1% to 33%. Adding WATS to FB increased the overall detection of BE by 153% (95% CI: 144-162%). The number needed to test with WATS in order to detect an additional case of BE was 5. Whether FB or WATS was done first did not impact the results. In this study, comprised of the largest series of patients evaluated with WATS, adjunctive use of the technique with targeted and random FB markedly improved the detection of both ED and BE. These results underscore the shortcomings of FB in detecting BE-associated neoplasia, which can potentially impact the management and clinical outcomes of these patients.

Femtosecond laser written arrayed waveguide gratings with integrated photonic lanterns.

We demonstrate for the first time functional arrayed waveguide gratings (AWGs) fabricated using the femtosecond laser direct-write technique. This fabrication technique is a mask-less alternative to lithography enabling design flexibility and rapid prototyping. It is ideal for customized small scale production for new applications. The devices were demonstrated in the visible region at 632.8 nm with a measured free spectral range (FSR) of 22.2 nm, and 1.35 nm resolution. To highlight the advantages of using a 3-dimensional fabrication technique, a 3-port photonic lantern was integrated with an AWG in a single monolithic chip. Integration of this type is not feasible with lithography-based AWG fabrication and can increase the functionality of AWGs for sensing applications.

Novel concept for visible and near infrared spectro-interferometry: laser-written layered arrayed waveguide gratings.

With the growing complexity of astronomical instruments devoted to interferometry, such as MATISSE (a 4 telescope beam combiner) or FIRST (a 9 sub-apertures beam combiner), and the rebirth of space projects such as LIFE (a mid-infrared interferometer), integrated optics devices can be an interesting and complementary approach for beam combination of a large number of apertures. Moreover, one of the approaches for beam combination is pairwise combination of the inputs (either from individual telescopes or from aperture masking on a single telescope), which scales as N(N-1)/2 for an N input system. Astrophotonics devices are attractive to reduce mass and system complexity, while achieving all the beam combination in a single chip, even for a high number of inputs. The aim of this work is to develop a compact photonic device for astronomical applications and demonstrate a proof-of-concept of a spectro-interferometer. In this paper ultrafast laser inscription is used to fabricate three arrayed waveguide gratings (AWGs) stacked vertically. This arrangement enables spectral dispersion and interferometry to be measured simultaneously. Individual AWGs were designed for operation at 633 nm, and demonstrated at 633nm and 830nm. A scan between 790 and 830nm was also achieved to study the wavelength behavior of the AWG. Using a segmented mirror, light at 633nm or 830nm was injected simultaneously into three AWGs layered 40 µm apart, showing analogous behavior for all three layers and no unexpected crosstalk. Finally the three outputs were vertically combined to obtain interference fringes, showing the feasibility of spectro-interferometry and opening the way for compact astrophotonic devices devoted to phase closure studies, used in astronomy to reduce the effect of atmospheric turbulence.

Pitfalls in accelerometer-based measurement of physical activity: The presence of reactivity in an adult population.

When a behavior is monitored, it is likely to change, even if no change may be intended. This phenomenon is known as measurement reactivity. We investigated systematic changes in accelerometer-based measures over the days of monitoring as an indicator of measurement reactivity in an adult population. One hundred seventy-one participants from the general population (65% women; mean age = 55 years, range: 42-65 years) wore accelerometers for 7 consecutive days to measure sedentary behavior and physical activity (PA). Latent growth models were used (a) to investigate changes in accelerometer wear time over the measurement days and (b) to identify measurement reactivity indicated by systematic changes in sedentary time (ST), light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA). Over the measurement days, participants reduced accelerometer wear time by trend (rate of change [b] = -4.7 min/d, P = .051, Cohen's d = .38), increased ST (b = 2.4 min/d, P = .018, d = .39), and reduced LPA (b = -2.4 min/d, P = .015, d = .38). Participants did not significantly reduce MVPA (P = .537). Our data indicated that accelerometry might generate reactivity. Small effects on ST and LPA were found. Thus, the validity of accelerometer-based data on ST and LPA may be compromised. Systematic changes observed in accelerometer wear time may further bias accelerometer-based measures. MVPA seems to be less altered due to the presence of an accelerometer.

Cardiopulmonary fitness is strongly associated with body cell mass and fat-free mass: The Study of Health in Pomerania (SHIP).

Peak oxygen uptake (VO2peak) is commonly indexed by total body weight (TBW) to determine cardiopulmonary fitness (CPF). This approach may lead to misinterpretation, particularly in obese subjects. We investigated the normalization of VO2peak by different body composition markers. We analyzed combined data of 3848 subjects (1914 women; 49.7%), aged 20-90, from two independent cohorts of the population-based Study of Health in Pomerania (SHIP-2 and SHIP-TREND). VO2peak was assessed by cardiopulmonary exercise testing. Body cell mass (BCM), fat-free mass (FFM), and fat mass (FM) were determined by bioelectrical impedance analysis. The suitability of the different markers as a normalization variable was evaluated by taking into account correlation coefficients (r) and intercept (α-coefficient) values from linear regression models. A combination of high r and low α values was considered as preferable for normalization purposes. BCM was the best normalization variable for VO2peak (r = .72; P ≤ .001; α-coefficient = 63.3 mL/min; 95% confidence interval [CI]: 3.48-123) followed by FFM (r = .63; P ≤ .001; α-coefficient = 19.6 mL/min; 95% CI: -57.9-97.0). On the other hand, a much weaker correlation and a markedly higher intercept were found for TBW (r = .42; P ≤ .001; α-coefficient = 579 mL/min; 95% CI: 483 to 675). Likewise, FM was also identified as a poor normalization variable (r = .10; P ≤ .001; α-coefficient = 2133; 95% CI: 2074-2191). Sex-stratified analyses confirmed the above order for the different normalization variables. Our results suggest that BCM, followed by FFM, might be the most appropriate marker for the normalization of VO2peak when comparing CPF between subjects with different body shape.

Demonstration of an efficient, photonic-based astronomical spectrograph on an 8-m telescope.

We demonstrate for the first time an efficient, photonic-based astronomical spectrograph on the 8-m Subaru Telescope. An extreme adaptive optics system is combined with pupil apodiziation optics to efficiently inject light directly into a single-mode fiber, which feeds a compact cross-dispersed spectrograph based on array waveguide grating technology. The instrument currently offers a throughput of 5% from sky-to-detector which we outline could easily be upgraded to ∼ 13% (assuming a coupling efficiency of 50%). The isolated spectrograph throughput from the single-mode fiber to detector was 42% at 1550 nm. The coupling efficiency into the single-mode fiber was limited by the achievable Strehl ratio on a given night. A coupling efficiency of 47% has been achieved with ∼ 60% Strehl ratio on-sky to date. Improvements to the adaptive optics system will enable 90% Strehl ratio and a coupling of up to 67% eventually. This work demonstrates that the unique combination of advanced technologies enables the realization of a compact and highly efficient spectrograph, setting a precedent for future instrument design on very-large and extremely-large telescopes.

Modal noise in an integrated photonic lantern fed diffraction-limited spectrograph.

In an attempt to develop a streamlined astrophotonic instrument, we demonstrate the realization of an all-photonic device capable of both multimode to single mode conversion and spectral dispersion on an 8-m class telescope with efficient coupling. The device was a monolithic photonic spectrograph which combined an integrated photonic lantern and an efficient arrayed waveguide grating device. During on-sky testing, we discovered a previously unreported type of noise that made spectral extraction and calibration extremely difficult. The source of the noise was traced to a wavelength-dependent loss mechanism between the feed fiber's multimode near-field pattern and the modal acceptance profile of the integrated photonic lantern. Extensive modeling of the photonic components replicates the wavelength-dependent loss, and demonstrates an identical effect on the final spectral output. We outline that this could be mitigated by directly injecting into the integrated photonic lantern.

Clinical experience with single-nucleotide polymorphism-based non-invasive prenatal screening for 22q11.2 deletion syndrome.

OBJECTIVES: To evaluate the performance of a single-nucleotide polymorphism (SNP)-based non-invasive prenatal test (NIPT) for the detection of fetal 22q11.2 deletion syndrome in clinical practice, assess clinical follow-up and review patient choices for women with high-risk results. METHODS: In this study, 21 948 samples were submitted for screening for 22q11.2 deletion syndrome using a SNP-based NIPT and subsequently evaluated. Follow-up was conducted for all cases with a high-risk result. RESULTS: Ninety-five cases were reported as high risk for fetal 22q11.2 deletion. Diagnostic testing results were available for 61 (64.2%) cases, which confirmed 11 (18.0%) true positives and identified 50 (82.0%) false positives, resulting in a positive predictive value (PPV) of 18.0%. Information regarding invasive testing was available for 84 (88.4%) high-risk cases: 57.1% (48/84) had invasive testing and 42.9% (36/84) did not. Ultrasound anomalies were present in 81.8% of true-positive and 18.0% of false-positive cases. Two additional cases were high risk for a maternal 22q11.2 deletion; one was confirmed by diagnostic testing and one had a positive family history. There were three pregnancy terminations related to screening results of 22q11.2 deletion, two of which were confirmed as true positive by invasive testing. CONCLUSIONS: Clinical experience with this SNP-based non-invasive screening test for 22q11.2 deletion syndrome indicates that these deletions have a frequency of approximately 1 in 1000 in the referral population with most identifiable through this test. Use of this screening method requires the availability of counseling and other management resources for high-risk pregnancies.

Towards femtosecond laser written arrayed waveguide gratings.

The fabrication of arrayed waveguide gratings (AWGs) using the femtosecond laser direct-write technique is investigated. We successfully demonstrate the fabrication of large planar waveguides that act as 2D free propagation zones. These slabs were found to have a highly uniform refractive index with a standard deviation of 1.97% relative to the total index contrast. The incorporation of low loss linear adiabatic tapers resulted in an increase of transmission by 90%. Strategies for manufacturing integrated laser written AWGs using continuous contouring to avoid lossy defects are discussed and demonstrated.

Holmium-doped 2.1 µm waveguide chip laser with an output power > 1 W.

We demonstrate the increasing applicability of compact ultra-fast laser inscribed glass guided-wave lasers and report the highest-power glass waveguide laser with over 1.1 W of output power in monolithic operation in the short-infrared near 2070 nm achieved (51% incident slope efficiency). The holmium doped ZBLAN chip laser is in-band pumped by a 1945 nm thulium fiber laser. When operated in an extended-cavity configuration, over 1 W of output power is realized in a linearly polarized beam. Broad and continuous tunability of the extended-cavity laser is demonstrated from 2004 nm to 2099 nm. Considering its excellent beam quality of M² = 1.08, this laser shows potential as a flexible master oscillator for single frequency and mode-locking applications.

Spectral narrowing of Yb:YAG waveguide lasers through hybrid integration with ultrafast laser written Bragg gratings.

Laser written waveguides in crystalline materials can be used to make highly efficient, high gain lasers. The bi-directional emission from such lasers however is typically broadband with poor spectral control. Hybridizing a tapered, mode matched laser written Bragg grating with a broadband Yb:YAG crystalline waveguide laser, we demonstrate single longitudinal mode output from one end of the device. Careful control of the grating characteristics led to laser thresholds below 90 mW, slope efficiencies greater than 42% and output powers greater than 20 mW.

[Turnover of Non-medical Staff in Outpatient Oncology Practices: Is Building Social Capital a Solution?]. / Fluktuation bei nicht-ärztlichem Personal in onkologischen Schwerpunktpraxen: Sozialkapitalaufbau als Lösungsansatz?

STUDY AIM: While a lot is known about potential and actual turnover of non-medical hospital staff, only few data exist for the outpatient setting. In addition, little is known about actual instruments which leaders can use to influence staff turnover in physician practices. In the literature, the social capital of an organisation, which means the amount of trust, common values and reciprocal behaviour in the organisation, has been discussed as a possible field of action. In the present study, staff turnover as perceived by outpatient haematologists and oncologists is presented and analysed as to whether social capital is associated with that staff turnover. In conclusion, measures to increase the social capital of a practice are presented. METHODS: The present study is based on data gathered in a questionnaire-based survey with members of the Professional Organisation of -Office-Based Haematologists and Oncologists (N=551). The social capital of the practice was captured from the haematologists and oncologists using an existing and validated scale. To analyse the impact of the practice's social capital on staff turnover, as perceived by the physicians, bivariate correlations and linear regression analyses were calculated. RESULTS: In total, 152 haematologists and oncologists participated in the study which represents a response rate of 28%. In the regression analyses, social capital appears as a significant and strong predictor of staff turnover (beta=-0.34; p<0.001). CONCLUSIONS: Building social capital within the practice may be an important contribution to reducing staff turnover although the underlying study design does not allow for drawing causal conclusions regarding this relationship. To create social capital in their practice, outpatient physicians may apply measures that facilitate social interaction among staff, foster trust and facilitate cooperation. Such measures may already be applied when hiring and training new staff, but also continuously when leading employees and when organising work tasks, e.g., by establishing regular team meetings.

[ADHD in adulthood: Diagnostics and therapy]. / ADHS im Erwachsenenalter : Diagnostik und Therapie.

Traditionally, attention deficit hyperactivity disorder (ADHD) was assumed to be a childhood disorder. In the meantime a persistence of symptoms into adulthood has been shown in 60% of those affected. Besides the core symptoms of inattentiveness, hyperactivity and impulsivity, adults with ADHD often suffer from comorbid disorders and functional impairment in multiple domains. In recent years diagnostic guidelines and standardized questionnaires have been developed, which facilitate the diagnostics of ADHD. In addition various therapeutic approaches have emerged and randomized controlled studies have demonstrated the efficacy. The aim of the article is to present the current standard of knowledge with respect to the diagnostics and treatment of ADHD.

Widely tunable short-infrared thulium and holmium doped fluorozirconate waveguide chip lasers.

We report widely tunable (≈ 260 nm) Tm(3+) and Ho(3+) doped fluorozirconate (ZBLAN) glass waveguide extended cavity lasers with close to diffraction limited beam quality (M(2) ≈ 1.3). The waveguides are based on ultrafast laser inscribed depressed claddings. A Ti:sapphire laser pumped Tm(3+)-doped chip laser continuously tunes from 1725 nm to 1975 nm, and a Tm(3+)-sensitized Tm(3+):Ho(3+) chip laser displays tuning across both ions evidenced by a red enhanced tuning range of 1810 to 2053 nm. We also demonstrate a compact 790 nm diode laser pumped Tm(3+)-doped chip laser which tunes from 1750 nm to 1998 nm at a 14% incident slope efficiency, and a beam quality of M(2) ≈ 1.2 for a large mode-area waveguide with 70 µm core diameter.

Competition of Faraday rotation and birefringence in femtosecond laser direct written waveguides in magneto-optical glass.

We consider the process of Faraday rotation in femtosecond laser direct-write waveguides. The birefringence commonly associated with such waveguides may be expected to impact the observable Faraday rotation. Here, we theoretically calculate and experimentally verify the competition between Faraday rotation and birefringence in two waveguides created by laser writing in a commercial magneto-optic glass. The magnetic field applied to induce Faraday rotation is nonuniform, and as a result, we find that the two effects can be clearly separated and used to accurately determine even weak birefringence. The birefringence in the waveguides was determined to be on the scale of Δn = 10(-6) to 10(-5). The reduction in Faraday rotation caused by birefringence of order Δn = 10(-6) was moderate and we obtained approximately 9° rotation in an 11 mm waveguide. In contrast, for birefringence of order 10(-5), a significant reduction in the polarization azimuth change was found and only 6° rotation was observed.

Effects of grazer presence on genetic structure of a phenotypically diverse diatom population.

Studies of predator-prey systems in both aquatic and terrestrial environments have shown that grazers structure the intraspecific diversity of prey species, given that the prey populations are phenotypically variable. Populations of phytoplankton have traditionally considered comprising only low intraspecific variation, hence selective grazing as a potentially structuring factor of both genetic and phenotypic diversity has not been comprehensively studied. In this study, we compared strain specific growth rates, production of polyunsaturated aldehydes, and chain length of the marine diatom Skeletonema marinoi in both grazer and non-grazer conditions by conducting monoclonal experiments. Additionally, a mesocosm experiment was performed with multiclonal experimental S. marinoi populations exposed to grazers at different levels of copepod concentration to test effects of grazer presence on diatom diversity in close to natural conditions. Our results show that distinct genotypes of a geographically restricted population exhibit variable phenotypic traits relevant to grazing interactions such as chain length and growth rates. Grazer presence affected clonal richness and evenness of multiclonal Skeletonema populations in the mesocosms, likely in conjunction with intrinsic interactions among the diatom strains. Only the production of polyunsaturated aldehydes was not affected by grazer presence. Our findings suggest that grazing can be an important factor structuring diatom population diversity in the sea and emphasize the importance of considering clonal differences when characterizing species and their role in nature.

Can a stressed oncologist be good in a consultation? A qualitative study on the oncologists' perception.

The aim of this exploratory study was to examine how the working conditions and job stress of private practice oncologists (PPOs) affect their interaction with patients. Data for the study were collected through semi-structured interviews with PPOs selected based on purposeful sampling criteria. The data were evaluated using content analysis. Factors perceived by PPOs to influence their level of stress and patient care were some of their own personal characteristics as well as working conditions both within and outside their practices. Apart from being able to name specific stressors (e.g., dysfunctional organisational workflow and interruptions during medical encounters), the oncologists also mentioned individual and organisational resources (e.g., professional experience, well-educated nurses and good work organisation) for coping with job stress and improving interaction with patients. Within this study, we identified some obstacles on the individual and organisational level for good patient care, as working conditions which might lead to time pressure and stress, which subsequently have an impact on quality in patient care (e.g., less time for personal issues during patient consultations). Future stress research should conduct a more in-depth investigation of these and other interventions at both the individual and organisational levels in order to improve patient care.

Analysis of risk factors for long-term glaucomatous damage development.

PURPOSE: The aim of this study was to analyze predictors of long-term glaucoma progression. PATIENTS AND METHODS: We followed 17 primary open angle glaucoma patients (POAG) and 25 ocular hypertensives (OHT) over three years, with regular follow-up examinations of both eyes every 6 months. Glaucoma damage was quantified by optical coherence tomography (retinal nerve fiber layer - OCT RNFL) and by perimetry. Corneal and hand temperature (infrared thermometer), corneal hysteresis, pachymetry and ocular pulse amplitude (OPA) readings were taken at baseline, and applanatory intraocular pressure and retinal vessel analysis recordings were made at baseline and follow-up visits. Forward-stepwise multiple regression analysis was performed. RESULTS: With OCT-RNFL progression as the dependent variable, the model selected initial diagnosis (OHT less probable of progressing), baseline RNFL thickness, retinal arterial and venous diameter and arterial flicker response as significant damage predictors. For visual field damage progression, these were: corneal temperature, OPA, initial diagnosis and venous flicker response (all p<0.05). CONCLUSION: Initial damage and vascular factors are strong predictors of future glaucoma progression.

[Complications in children and adults with cochlear implant]. / Postoperative Früh- und Spätkomplikationen bei Kindern und Erwachsenen nach CI-Implantation.

BACKGROUND: Complications in Children and Adults with Cochlear Implant Background: Cochlear Implants (CI) are developed in the last 20 years to a regular therapy in congenital deaf children/newborns and deafened teens and adults. The success of speech understanding with the CI in adults is so extraordinary that meanwhile also unilateral deaf, contralateral normal hearing persons are implanted. In case of early implanted children a nearly normal speech development is possible in most of the cases. MATERIAL UND METHODS: Nevertheless the surgical procedures is a challenge concerning the potential complications combined with a foreign body, the CI, in a non-steril part of the ear. RESULTS: This paper reports on the complications in a patients collective, implanted within 21 years. Separated within the severity of the complications and their therapeutic consequences (conservative and surgical) it could be shown that the incidence of severe perioperative complications within the second decade could be reduced from 3.92% (first decade) to 1.8%. Also the companies have learned to construct the products more save. CONCLUSION: In summary the reliable and complete postoperative control and the modification of therapy concepts leads to a constant reduction of complications.