High-responsivity operation of quantum cascade detectors at 9 µm.

Quantum cascade detectors (QCDs) are devices operating at zero external bias with a low dark-current. They show linear detection and high saturation intensities, making them suitable candidates for heterodyne detection in long-wave infrared (LWIR) free space optical communication systems. We present an approach to mitigate the performance limitation at long wavelengths, by a comparison of similar single and multi-period QCDs for optimizing their responsivity and noise behaviour. Our InGaAs/InAlAs/InP ridge QCDs are designed for operation at λ = 9.124 µm. Optical waveguide simulations support the accurate optical characterization. A detailed device analysis reveals room-temperature responsivities of 111 mA/W for the 15-period and 411 mA/W for the single-period device.

High-speed interband cascade infrared photodetectors: photo-response saturation by a femtosecond oscillator.

Interband cascade infrared photodetectors (ICIPs) combine interband optical transitions with fast intraband transport to achieve high-frequency and broad-wavelength operation at room temperature. Here we study the bias-dependent electronic impulse response of ICIPs with a mid-infrared synchronously pumped optical parametric oscillator (OPO). Since the OPO produces ultrashort 104-fs pulses, it is possible to probe the impulse response of the ICIP. From this impulse response, we identify two characteristic decay times, indicating the contribution of electron as well as hole carriers. A reverse bias voltage applied to the ICIP reduces both time scales and leads to an increased electrical cut-off frequency. The OPO emits up to 500 mW average power, of which up to 10 mW is directed to the ICIP in order to test its saturation characteristics under short-pulse illumination. The peak of the impulse response profile as well as the average photocurrent experience a gradual saturation behavior, and we determine the corresponding saturation powers by measuring the photo-response as a function of average power directed to the ICIP. We demonstrate that an increasing reverse bias increases the saturation power as well as the responsivity of the ICIP.

Unifying Frequency Combs in Active and Passive Cavities: Temporal Solitons in Externally Driven Ring Lasers.

Frequency combs have become a prominent research area in optics. Of particular interest as integrated comb technology are chip-scale sources, such as semiconductor lasers and microresonators, which consist of resonators embedding a nonlinear medium either with or without population inversion. Such active and passive cavities were so far treated distinctly. Here we propose a formal unification by introducing a general equation that describes both types of cavities. The equation also captures the physics of a hybrid device-a semiconductor ring laser with an external optical drive-in which we show the existence of temporal solitons, previously identified only in microresonators, thanks to symmetry breaking and self-localization phenomena typical of spatially extended dissipative systems.

Baseline characteristics, disease severity and treatment history of patients with atopic dermatitis included in the German AD Registry TREATgermany.

BACKGROUND: The Atopic Dermatitis (AD) TREATgermany registry was initiated by the German Society for Dermatology (DDG) in 2011 to evaluate the 'real-life' situation of health care for patients with AD. OBJECTIVES: Interim data analysis on baseline characteristics as well as current and prescribed systemic treatments of the TREATgermany registry patients. METHODS: Patients (≥18 years) with moderate-to-severe AD [objective (o)SCORAD > 20], or with current or previous anti-inflammatory systemic treatment for AD within 24 months, were included and are followed up over at least 24 months. To assess clinical signs, the eczema area severity index (EASI, 0-72), the oSCORAD (0-83) and the Investigator Global Assessment (IGA; 6-point scale) were used. The disease severity was globally scored by the patients [Patient Global Assessment (PGA); six-step Likert scale]. Disease symptoms were assessed by the patient-oriented eczema measure (POEM, 0-28) and numeric rating scales (NRS, 0-10). Health-related quality of life was measured using the dermatological life quality index (DLQI, 0-30). RESULTS: A total of 612 patients were recruited across 32 sites between 06/2016 and 01/2019 (mean age: 42.6 ± 14.2 years; mean oSCORAD: 40.8 ± 16.3). The mean POEM score was 16.3 ± 7.5. Pruritus was rated highest among subjective symptoms (NRS: 5.4 ± 2.7). The mean DLQI value was 11.3 ± 7.5. The frequency of arterial hypertension was lower (20.8%) compared with the general population, whilst this was higher for depression (10%). More than 60% of the patients had received systemic glucocorticosteroids, and 36.8% had received cyclosporine A prior to inclusion. Dupilumab was the leading substance documented as either 'current' (12.1%) or 'prescribed' (31.4%) at baseline. CONCLUSIONS: These 'real-life' data clearly demonstrate the substantial disease burden. Most of TREATgermany patients were already treated with or prescribed dupilumab at baseline. Moreover, current findings indicate the urgent need for further alternative agents in order to achieve a perceptible improvement of quality of life of patients with moderate-to-severe AD.

4.3 µm quantum cascade detector in pixel configuration.

We present the design simulation and characterization of a quantum cascade detector operating at 4.3µm wavelength. Array integration and packaging processes were investigated. The device operates in the 4.3µm CO2 absorption region and consists of 64 pixels. The detector is designed fully compatible to standard processing and material growth methods for scalability to large pixel counts. The detector design is optimized for a high device resistance at elevated temperatures. A QCD simulation model was enhanced for resistance and responsivity optimization. The substrate illuminated pixels utilize a two dimensional Au diffraction grating to couple the light to the active region. A single pixel responsivity of 16mA/W at room temperature with a specific detectivity D* of 5⋅107 cmHz/W was measured.

New X-Ray Tomography Method Based on the 3D Radon Transform Compatible with Anisotropic Sources.

In this work, we propose a novel computed tomography (CT) approach for three-dimensional (3D) object reconstruction, based on a generalized tomographic geometry with two-dimensional angular sampling (two angular degrees of freedom). The reconstruction is based on the 3D Radon transform and is compatible with anisotropic beam conditions. This allows isotropic 3D imaging with a source, which can be extended along one direction for increased flux, while high resolution is achieved by a small source size only in the orthogonal direction. This novel scheme for analytical CT is demonstrated by numerical simulations and proof-of-concept experiments. In this way high resolution and coherence along a single direction determines the reconstruction quality of the entire 3D data set, opening up, for example, new opportunities to achieve nanoscale resolution and/or phase contrast with low brilliance sources such as laboratory x-ray or neutron sources.

Quantum cascade detector utilizing the diagonal-transition scheme for high quality cavities.

A diagonal optically active transition in a quantum cascade detector is introduced as optimization parameter to obtain quality factor matching between a photodetector and a cavity. A more diagonal transition yields both higher extraction efficiency and lower noise, while the reduction of the absorption strength is compensated by the resonant cavity. The theoretical limits of such a scheme are obtained, and the impact of losses and cavity processing variations are evaluated. By optimizing the quantum design for a high quality cavity, a specific detectivity of 10(9) Jones can be calculated for λ = 8µm and T = 300K.

[Exploration of Problem Patterns in Orthopedic Medical Rehabilitation on Behalf of the German Pension Insurance to Improve Access Management and Treatment Adequacy]. / Exploration von Problemlagen in der orthopädischen Rehabilitation der gesetzlichen Rentenversicherung zur Optimierung der Zuweisungs- und Behandlungsadäquanz.

OBJECTIVE: To explore problem patterns of patients with musculoskeletal disorders assigned to and treated with a conventional (CR), behavioural-medical (BMR) or work-related (WR) rehabilitation concept. METHODS: We conducted interviews with 8 patients per concept, focus groups with 2 rehabilitation teams and 1 focus group with socio-medical assessors. For the interviews patients with chronic back pain were included, receiving inpatient rehabilitation. Data was examined by qualitative content analysis. RESULTS: We identified 7 problem patterns (one typical for patients in CR, 3 typical for specified subgroups in BMR resp. WR), differing in psychological co-morbidity, limitations of work-related activities and participation, psychosocial stress and pain. On the basis of detailed characterizations of these patterns, we developed recommendations for access and treatment management. CONCLUSION: The study specifies and demarcates different problem patterns in orthopedic rehabilitation and, therefore helps to further improve access management and treatment adequacy. Future studies should verify the generated findings on representative samples.

[Barriers for Migrants Regarding the Access to Medical Rehabilitation on Behalf of the German Pension Insurance]. / Barrieren für Migranten beim Zugang in die medizinische Rehabilitation der gesetzlichen Rentenversicherung.

OBJECTIVE: To identify barriers for migrants regarding the access to medical rehabilitation on behalf of the German Pension Insurance. METHODS: Focus groups with migrants (n=5, 42 participants) and experts (n=1, 14 participants) were conducted and examined by qualitative content analysis. RESULTS: We identified 4 categories of access barriers: 1. system-related, migrant-specific, 2. person-related, migrant-specific, 3. system-related, primarily not migrant-specific, and 4. person-related, primarily not migrant-specific barriers. Barriers in categories 3 and 4 are mostly class- or gender-specific. Due to associations between migration background, social status and gender roles, these barriers are often of specific importance to migrants as well. Taking such intersections of single categories of inequality (migration background, social status, gender) into account, access barriers can interact and form complexes of barriers. CONCLUSION: In order to explain and overcome the low utilization of medical rehabilitation by migrants, the interaction of migrant-, class- and gender-specific barriers in the system and in persons have to be considered.

[Significance of Mesenchymal Stem Cells in Gastrointestinal Disorders]. / Bedeutung mesenchymaler Stammzellen in der Viszeralmedizin.

In this review we summarise the recent developments regarding the experimental and clinical use of mesenchymal stem cells (MSCs), focusing mainly on the treatment of gastrointestinal disorders. Next to their relevance in the field of regenerative medicine and immunology, this population of cells has also raised great expectations for possible applications in cancer therapy. While clinical trials were able to demonstrate the efficacy of MSCs in cases of inflammatory bowel disease and degenerative conditions of the liver, controversial results have been presented regarding their antineoplastic potential in gastrointestinal tumours. MSCs can differentiate into a large variety of specialised cells. They are capable of regulating both wound healing and immune responses through paracrine and endocrine signalling. Moreover, MSCs can be transfected with a great number of different therapeutic genes - considering their ability to selectively migrate towards neoplastic tissues, this feature allows for targeted therapy of solid tumours. Transfected genes can be designed so that they are expressed exclusively in the vicinity of the tumour, eventually triggering apoptosis in cancer cells. In this review, we demonstrate the natural distribution of exogenously applied MSCs in the host. Furthermore, we mention various methods of tracking MSCs in vivo and different parameters of administration that tend to influence therapeutic outcome (e.g., origin of MSCs, mode of application, or the potency of transfected genes). Finally, this review points out the hazards of MSC therapy, emphasising the risks related to their widespread clinical use.

[Specific work-related problems: do they matter in access to work-related medical rehabilitation?]. / Besondere berufliche Problemlagen: Spielen sie eine Rolle beim Zugang in die medizinisch-beruflich orientierte Rehabilitation?

BACKGROUND: The study determined if need for rehabilitation in work-related medical rehabilitation (WMR) is more frequently characterised by specific work-related problems than in conventional medical rehabilitation (MR). METHODS: In 6 rehabilitation centres, persons with back pain (M50, M51, M53, M54) were surveyed about work-related restrictions of work ability at begin of their rehabilitation. RESULTS: Differences in work ability of WMR and MR patients confirmed need-related access. However, these differences were exclusively explained by screening-based access decisions. If access was not supported by a screening, WMR and MR patients did not differ. Decisions by rehabilitation centres compared with decisions by insurance agencies resulted in similar differences between WMR and MR patients. CONCLUSION: Screening-based decisions about access enable a more need-related access to WMR. As there were no differences between access decisions by rehabilitation centres and insurance agencies, access decisions can be realised already by the insurance agency.

[Is the guideline for work-related medical rehabilitation successfully implemented?]. / Gelingt die Umsetzung des Anforderungsprofils zur Durchführung der medizinisch-beruflich orientierten Rehabilitation?

BACKGROUND: The guideline for work-related medical rehabilitation (WMR) in responsibility of the German Pension Insurance describes standards of work-related measures in medical rehabilitation. We investigated if contents and recommended amount of treatment were successfully implemented and which improvements were associated with the implementation. METHODS: Implementation of the WMR guideline was evaluated at 7 inpatient orthopaedic rehabilitation centres. Patients completed questionnaires at beginning of rehabilitation, at dis-charge and 3 months after discharge. Details -regarding the treatments provided were extracted from the standardised discharge report. RESULTS: The recommended amount of social counselling and work-related psychosocial therapy measures were appropriate. However, there were discrepancies regarding the recommended amount of functional capacity training. The standardised mean difference (SMD) between baseline and 3-month follow-up sick leave duration indicated an almost medium-sized effect (SMD=0.47; 95% CI: 0.28-0.66). An additional 5 h of work-related therapy was associated with a 1.2-week decrease in sick leave duration (95% CI: -2.38 to -0.03). CONCLUSION: The guideline was for the most part successfully implemented and sets important standards for the roll-out of WMR. The nationwide implementation of the WMR guideline requires a continuous quality assurance that -enables promptly feedback about the achieved implementation level.

Targeting the vasculature of visceral tumors: novel insights and treatment perspectives.

BACKGROUND: Angiogenesis, the formation of new blood vessels from the endothelium of the existing vasculature, describes a crucial process in tumor growth, disease progression, and metastasis. Therefore, the upcoming strategy of inhibiting tumor angiogenesis has generated different treatment modalities, which have been transferred into clinical practice in recent years. Currently, this concept is applied to target the vasculature of different visceral tumors and intensive clinical research has just started. MATERIALS AND METHODS: This review summarizes the modifications of systemic treatment of visceral tumors by targeting the vasculature in the past years. Moreover, novel targets and treatment strategies will be discussed to evaluate future directions. RESULTS: Leading antiangiogenic drugs combined with systemic chemotherapy have been applied with increasing success during the last years. Therefore, the concept of combining vascular targeting agents with established chemotherapeutic regimens has been increasingly adopted into the therapies of different visceral tumors. CONCLUSION: Targeting the vasculature of visceral tumors in combination with established standard tumor therapies includes major clinical potential for future therapy concepts.

Nonsuppurative encephalitis in a dog.

A 4-year-old male German Hunting Terrier presented with tremor, dyspnea, trismus, spasms of the musculature of the larynx and pharynx, and hypothermia and subsequently died despite intensive clinical care. Prior clinical signs included vomitus and diarrhea. Microscopic examination of the brain revealed a multifocal nonsuppurative brain stem encephalitis; a few intralesional neurons contained intranuclear inclusions. By immunohistochemistry, Aujeszky disease virus (Suid herpesvirus 1) antigen was detected in neurons in the brain and in ganglion cells of the trigeminal ganglia. Viral culture of brain tissue confirmed the presence of Aujeszky disease virus. Histopathologic findings in the brain with the identification of Aujeszky disease virus by immunohistochemistry and polymerase chain reaction are consistent with Aujeszky disease virus-induced encephalitis. Sequencing revealed a 100% homology of the isolated Aujeszky disease virus with Aujeszky disease virus isolates of wild boar from Eastern Germany.

Dosimetry of heavy ion exposure to human cells using nanoscopic imaging of double strand break repair protein clusters.

The human body is constantly exposed to ionizing radiation of different qualities. Especially the exposure to high-LET (linear energy transfer) particles increases due to new tumor therapy methods using e.g. carbon ions. Furthermore, upon radiation accidents, a mixture of radiation of different quality is adding up to human radiation exposure. Finally, long-term space missions such as the mission to mars pose great challenges to the dose assessment an astronaut was exposed to. Currently, DSB counting using γH2AX foci is used as an exact dosimetric measure for individuals. Due to the size of the γH2AX IRIF of ~ 0.6 µm, it is only possible to count DSB when they are separated by this distance. For high-LET particle exposure, the distance of the DSB is too small to be separated and the dose will be underestimated. In this study, we developed a method where it is possible to count DSB which are separated by a distance of ~ 140 nm. We counted the number of ionizing radiation-induced pDNA-PKcs (DNA-PKcs phosphorylated at T2609) foci (size = 140 nm ± 20 nm) in human HeLa cells using STED super-resolution microscopy that has an intrinsic resolution of 100 nm. Irradiation was performed at the ion microprobe SNAKE using high-LET 20 MeV lithium (LET = 116 keV/µm) and 27 MeV carbon ions (LET = 500 keV/µm). pDNA-PKcs foci label all DSB as proven by counterstaining with 53BP1 after low-LET γ-irradiation where separation of individual DSB is in most cases larger than the 53BP1 gross size of about 0.6 µm. Lithium ions produce (1.5 ± 0.1) IRIF/µm track length, for carbon ions (2.2 ± 0.2) IRIF/µm are counted. These values are enhanced by a factor of 2-3 compared to conventional foci counting of high-LET tracks. Comparison of the measurements to PARTRAC simulation data proof the consistency of results. We used these data to develop a measure for dosimetry of high-LET or mixed particle radiation exposure directly in the biological sample. We show that proper dosimetry for radiation up to a LET of 240 keV/µm is possible.

Monte Carlo simulations and phantom validation of low-dose radiotherapy to the lungs using an interventional radiology C-arm fluoroscope.

PURPOSE: To use MC simulations and phantom measurements to investigate the dosimetry of a kilovoltage x-ray beam from an IR fluoroscope to deliver low-dose (0.3-1.0 Gy) radiotherapy to the lungs. MATERIALS AND METHODS: PENELOPE was used to model a 125 kV, 5.94 mm Al HVL x-ray beam produced by a fluoroscope. The model was validated through depth-dose, in-plane/cross-plane profiles and absorbed dose at 2.5-, 5.1-, 10.2- and 15.2-cm depths against the measured beam in an acrylic phantom. CT images of an anthropomorphic phantom thorax/lungs were used to simulate 0.5 Gy dose distributions for PA, AP/PA, 3-field and 4-field treatments. DVHs were generated to assess the dose to the lungs and nearby organs. Gafchromic film was used to measure doses in the phantom exposed to PA and 4-field treatments, and compared to the MC simulations. RESULTS: Depth-dose and profile results were within 3.2% and 7.8% of the MC data uncertainty, respectively, while dose gamma analysis ranged from 0.7 to 1.0. Mean dose to the lungs were 1.1-, 0.8-, 0.9-, and 0.8- Gy for the PA, AP/PA, 3-field, and 4-field after isodose normalization to cover âˆ¼ 95% of each lung volume. Skin dose toxicity was highest for the PA and lowest for the 4-field, and both arrangements successfully delivered the treatment on the phantom. However, the dose distribution for the PA was highly non-uniform and produced skin doses up to 4 Gy. The dose distribution for the 4-field produced a uniform 0.6 Gy dose throughout the lungs, with a maximum dose of 0.73 Gy. The average percent difference between experimental and Monte Carlo values were -0.1% (range -3% to +4%) for the PA treatment and 0.3% (range -10.3% to +15.2%) for the 4-field treatment. CONCLUSION: A 125 kV x-ray beam from an IR fluoroscope delivered through two or more fields can deliver an effective low-dose radiotherapy treatment to the lungs. The 4-field arrangement not only provides an effective treatment, but also significant dose sparing to healthy organs, including skin, compared to the PA treatment. Use of fluoroscopy appears to be a viable alternative to megavoltage radiation therapy equipment for delivering low-dose radiotherapy to the lungs.

Low-dose radiotherapy to the lungs using an interventional radiology C-arm fluoroscope: Monte Carlo treatment planning and dose measurements in a postmortem subject.

Objective.The goal of this study was to use Monte Carlo (MC) simulations and measurements to investigate the dosimetric suitability of an interventional radiology (IR) c-arm fluoroscope to deliver low-dose radiotherapy to the lungs.Approach.A previously-validated MC model of an IR fluoroscope was used to calculate the dose distributions in a COVID-19-infected patient, 20 non-infected patients of varying sizes, and a postmortem subject. Dose distributions for PA, AP/PA, 3-field and 4-field treatments irradiating 95% of the lungs to a 0.5 Gy dose were calculated. An algorithm was created to calculate skin entrance dose as a function of patient thickness for treatment planning purposes. Treatments were experimentally validated in a postmortem subject by using implanted dosimeters to capture organ doses.Main results.Mean doses to the left/right lungs for the COVID-19 CT data were 1.2/1.3 Gy, 0.8/0.9 Gy, 0.8/0.8 Gy and 0.6/0.6 Gy for the PA, AP/PA, 3-field, and 4-field configurations, respectively. Skin dose toxicity was the highest probability for the PA and lowest for the 4-field configuration. Dose to the heart slightly exceeded the ICRP tolerance; all other organ doses were below published tolerances. The AP/PA configuration provided the best fit for entrance skin dose as a function of patient thickness (R2 = 0.8). The average dose difference between simulation and measurement in the postmortem subject was 5%.Significance.An IR fluoroscope should be capable of delivering low-dose radiotherapy to the lungs with tolerable collateral dose to nearby organs.

Comparison of image quality and lens dose in helical and sequentially acquired head CT.

AIM: To prospectively compare helical and traditional sequential acquisition of computed tomography (CT) images of the head with respect to lens dose, thyroid dose, and image quality. MATERIALS AND METHODS: Patients undergoing non-emergency unenhanced CT examinations of the head were prospectively randomized to sequential or helical multidetector CT (MDCT) acquisition. Lens dose and thyroid dose were measured directly using a MOSFET (metal oxide field effect transistor) system. The quality of images at the level of the basal ganglia and the posterior fossa were assessed by two neuroradiologists on a scale of 1 (poor) to 5 (very good), with respect to grey-white matter conspicuity and posterior fossa artefact respectively. RESULTS: The lens dose was significantly higher for the sequential technique than the helical technique (61.5±12.9 mGy versus 43.5±4.3 mGy; p<0.0001). The thyroid dose was not significantly different (1.6±0. 6 mGy versus 2.1±0.6 mGy; p=0.8). The sequential technique was ranked higher than the helical technique with respect to the basal ganglia image for overall quality and grey-white matter conspicuity, but the majority of images in both groups were rated good or excellent. Posterior fossa images showed more artefacts on the sequential images than the helical technique images. Signal-to-noise ratios for grey and white matter were better using the sequential technique. CONCLUSIONS: Helically acquired head CT images using 16 and 64 section MDCT are of comparable quality to sequential acquisition, have reduced posterior fossa artefacts and approximately two-thirds of the lens dose.

Effects of phenylephrine on the sublingual microcirculation during cardiopulmonary bypass.

BACKGROUND: The objective of the present study was to investigate sublingual microvascular blood flow and microcirculatory haemoglobin oxygen saturation (Smc(O(2))) during cardiopulmonary bypass (CPB) using constant systemic blood flow but different perfusion pressures achieved by phenylephrine administration. METHODS: Fifteen patients undergoing coronary artery bypass grafting were enrolled in this pilot study. Systemic haemodynamics, oxygen transport variables, arterial and mixed venous blood gas analysis, and microcirculatory variables were determined after initiation of general anaesthesia, during CPB (systemic blood flow=2.4 litre m(-2)), after increasing perfusion pressure by 20 mm Hg with a continuous infusion of phenylephrine, and after termination of phenylephrine infusion. RESULTS: CPB immediately resulted in a significant (P<0.05) decrease in systemic oxygen transport without alterations in sublingual microcirculatory blood flow and Smc(O(2)). Increasing perfusion pressure from 47 (SD 9) to 68 (7) mm Hg using phenylephrine=1.4 (1.0) microg kg(-1) min(-1) resulted in a significant decrease in sublingual small vessel blood flow (from median 2.5 to 1.8 arbitrary units) representing mostly capillary blood flow, but not in medium-sized vessels (median 3 to 2.8 arbitrary units). Concurrently, global tissue blood flow from 110 (54) to 197 (100) perfusion units and Smc(O(2)) increased from 72 (11)% to 84 (7)%, suggesting significant microcirculatory blood flow shunting in vessels with diameters >25 microm. CONCLUSIONS: Our data demonstrate that an increased perfusion pressure produced by phenylephrine at constant CPB flow may decrease microcirculatory blood flow in the sublingual mucosal microcirculation due to microvascular blood flow shunting.