Olfactory disorders in childhood: A comparative study of olfaction in children with adenoid hyperplasia versus a control group and the postoperative effects of adenoidectomy with respect to olfactory ability.

PURPOSE: Hyposmia in childhood is poorly characterized. The "U-Sniff Test", validated for children with anosmia, can be used to objectify olfactory impairment but has not been used to distinguish between hyposmia and normosmia. Therefore, we investigated children with enlarged adenoids with respect to hyposmia, its correlation with adenoid size, and the sensitivity of questionnaires to predict olfactory impairment. METHODS: In a prospective comparison, olfaction was assessed by "U-Sniff Test" (score 0-12; <8 hyposmia) in 41 children (5-18 years) with adenoid hyperplasia and compared with 196 children without any respiratory affection (control) after exclusion of previous SARS-Cov2-infection from December 2020 to December 2021. ENT-related complaints were collected using a self-designed questionnaire. We were able to include 13 children in a follow-up examination to compare preoperative performance in the "U-Sniff Test" with postoperative outcome after adenoidectomy. STATISTICS: chi-square-test (p < 0.05), odds-ratio, Spearman's rho, ROC-, cluster analysis. RESULTS: Severe hyposmia was present in 36.6% of children with adenoid-hyperplasia compared to 3.1% of the control-group. Adenoid-children scored significantly more often between 8 and 10 points (58.5%) than the control (31.6%; p < 0.01). Adenoid size and olfactory performance correlate significantly (r: 0.83; CI -0.89 … -0.72). Hyposmia in the adenoid group is characterized predominately by loss of the odors banana, butter and rose. None of children with hyposmia or parents reported impaired olfactory performance. Postoperatively, olfactory function improved significantly in 85% of cases (p 0.01, SD ± 1.71, Δ3.54points). CONCLUSION: Questionnaires are insufficient to detect hyposmia in this cohort. In contrast, the "U-Sniff Test" detects even reduced olfactory performance without reaching the cut-off value, which represents the majority of test results in the adenoid group. Therefore, we recommend the classification of moderate hyposmia (8-10 points) to be included for our study population.

The experience of D/deaf healthcare professionals during the coronavirus pandemic.

BACKGROUND: The coronavirus pandemic, in particular the introduction of masks, presented a huge challenge for the UK's D/deaf community, many of whom rely on visual cues in lipreading and sign language. This particularly affected D/deaf healthcare professionals (HCPs), who faced significant communication challenges at work due to the lack of transparent masks or other reasonable adjustments. AIMS: To determine the impact that a lack of transparent masks and reasonable adjustments had on communication, confidence at work and well-being among D/deaf HCPs during the coronavirus pandemic. METHODS: A survey was sent to all members of the 'UK Deaf Healthcare Professionals Group' on Facebook, the 'Healthcare Professionals with Hearing Loss' listserver and promoted on Social Media. RESULTS: Eighty-three responses were received. Nine (11%) individuals had access to transparent masks. Over three-quarters of respondents reported feeling anxious and fearful of making a mistake due to communication difficulties. Fourteen (17%) were removed from clinical roles due to a lack of reasonable adjustments. One-third felt they would need to consider an alternative career if improvements were not made. Seventy-eight per cent felt the communication needs of D/deaf HCPs had not been met during the pandemic. CONCLUSIONS: D/deaf HCPs felt left behind, isolated and frustrated by a lack of transparent masks and reasonable adjustments to meet their communication needs. Loss of experienced, qualified HCPs has a significant economic and workforce impact, particularly during a pandemic. Urgent action is needed to ensure D/deaf HCPs are provided with the workplace support required under the Equality Act (2010).

Matrix heater in the gravitational wave observatory GEO 600.

Large scale laser interferometric gravitational wave detectors (GWDs), such as GEO 600 require high quality optics to reach their design sensitivity. The inevitable surface imperfections, inhomogeneities, and light-absorption induced thermal lensing in the optics, can convert laser light from the fundamental mode to unwanted higher order modes, and pose challenges to the operation and sensitivity of the GWDs. Here we demonstrate the practical implementation of a thermal projection system which reduces those unwanted effects via targeted spatial heating of the optics. The thermal projector consists of 108 individually addressable heating elements which are imaged onto the beam splitter of GEO 600. We describe the optimization of the spatial heating profile and present the obtained results.

Alignment sensing and control for squeezed vacuum states of light.

Beam alignment is an important practical aspect of the application of squeezed states of light. Misalignments in the detection of squeezed light result in a reduction of the observable squeezing level. In the case of squeezed vacuum fields that contain only very few photons, special measures must be taken in order to sense and control the alignment of the essentially dark beam. The GEO 600 gravitational wave detector employs a squeezed vacuum source to improve its detection sensitivity beyond the limits set by classical quantum shot noise. Here, we present our design and implementation of an alignment sensing and control scheme that ensures continuous optimal alignment of the squeezed vacuum field at GEO 600 on long time scales in the presence of free-swinging optics. This first demonstration of a squeezed light automatic alignment system will be of particular interest for future long-term applications of squeezed vacuum states of light.

Phase control of squeezed vacuum states of light in gravitational wave detectors.

Quantum noise will be the dominant noise source for the advanced laser interferometric gravitational wave detectors currently under construction. Squeezing-enhanced laser interferometers have been recently demonstrated as a viable technique to reduce quantum noise. We propose two new methods of generating an error signal for matching the longitudinal phase of squeezed vacuum states of light to the phase of the laser interferometer output field. Both provide a superior signal to the one used in previous demonstrations of squeezing applied to a gravitational-wave detector. We demonstrate that the new signals are less sensitive to misalignments and higher order modes, and result in an improved stability of the squeezing level. The new signals also offer the potential of reducing the overall rms phase noise and optical losses, each of which would contribute to achieving a higher level of squeezing. The new error signals are a pivotal development towards realizing the goal of 6 dB and more of squeezing in advanced detectors and beyond.

First long-term application of squeezed states of light in a gravitational-wave observatory.

We report on the first long-term application of squeezed vacuum states of light to improve the shot-noise-limited sensitivity of a gravitational-wave observatory. In particular, squeezed vacuum was applied to the German-British detector GEO 600 during a period of three months from June to August 2011, when GEO 600 was performing an observational run together with the French-Italian Virgo detector. In a second period, the squeezing application continued for about 11 months from November 2011 to October 2012. During this time, squeezed vacuum was applied for 90.2% (205.2 days total) of the time that science-quality data were acquired with GEO 600. A sensitivity increase from squeezed vacuum application was observed broadband above 400 Hz. The time average of gain in sensitivity was 26% (2.0 dB), determined in the frequency band from 3.7 to 4.0 kHz. This corresponds to a factor of 2 increase in the observed volume of the Universe for sources in the kHz region (e.g., supernovae, magnetars). We introduce three new techniques to enable the long-term application of squeezed light, and show that the glitch rate of the detector did not increase from squeezing application. Squeezed vacuum states of light have arrived as a permanent application, capable of increasing the astrophysical reach of gravitational-wave detectors.

Impact of graft size and commissural resuspension height on aortic valve competence in valve-sparing aortic replacement under physiological pressures.

BACKGROUND: Valve competence in valve-sparing aortic root replacement has been described as being influenced by commissural height as well as graft size. The aim of this study was to investigate the impact of a gradual reduction of commissural height and graft diameter on aortic insufficiency under physiological conditions in an IN VITRO model. METHODS: Porcine aortic valves were reimplanted into a tubular graft and a native commissural height was obtained. Subsequently the height was reduced by 10 % and 20 %, respectively. To investigate the impact of graft size, a 30 % reduction of the prosthesis diameter was carried out in valves with both native and reduced commissural heights. All conditions were investigated under pulsatile flow simulation and static pressure exposure. RESULTS: Reduction of commissural height caused regurgitation at both 10 % and 20 % lower heights, which was more pronounced in grafts with 20 % reduction. Graft undersizing resulted in significant reflux, with regurgitation even occurring with valves in a native commissural position. CONCLUSIONS: Valve competence is impaired both by the reduction of commissural height and by reduced graft size. In particular, reimplantation of aortic valves into undersized grafts promotes valve insufficiency even if commissural height is well adjusted.

[Quantitative methylation-specific PCR for the diagnosis of lung cancer]. / Quantitative methylierungsspezifische PCR zur Lungenkarzinomdiagnostik.

Efficient, preferably early diagnosis of lung cancer represents a major challenge. Under this aspect the sensitivity of conventional histomorphology and cytomorphology procedures is unsatisfactory. This review highlights technical aspects, possibilities and drawbacks of the application of aberrant promoter methylation as a biomarker for lung cancer diagnostics using specimens of pulmonary exfoliative cytology.

High power, low-noise, and multiply resonant photodetector for interferometric gravitational wave detectors.

We have developed a new photodetector circuit for use in interferometric gravitational wave detectors. The circuit can detect high laser power with low noise and provide multiple outputs for different signal frequencies. The dynamic range of this circuit is increased in comparison with the photodetector design used until the end of 2005.

[Aberrant promoter methylation as biomarker for molecular cytological diagnosis of lung cancer]. / Aberrante Promotor-Methylierungen als Tumormarker für die molekularzytologische Diagnostik des Lungenkarzinoms.

Aberrant promoter methylation represents a main mechanism of tumor suppressor gene inactivation and may serve as a new source for biomarker discovery. This study investigated its applicability as a molecular tool for lung cancer diagnostics on bronchial aspirates. A methylation assay was developed applying a quantitative methylation specific real-time PCR (QMSP). A total of 552 patients with the differential diagnosis of lung cancer were investigated. The QMSP findings on bronchial aspirates were compared with the methylation status of respective genes investigated in microdissected tumor tissues (QMSP, cloning and sequencing of promoter regions after bisulfite conversion). Among the genes tested a marker panel consisting of APC, p16(INK4a) and RASSF1A proved to be the best suited for lung cancer diagnostics. This panel allowed for a correct diagnosis of lung cancer in cases with an ambiguous or false negative conventional cytology. In a cohort study on 247 patients, the combination of histology (sensitivity 59 %), cytology (sensitivity 44 %) and QMSP-assay (sensitivity 53 %) raised the sensitivity of a single bronchoscopy for the diagnosis of lung cancer up to 81%. The methylation assay yielded its major diagnostic surplus with respect to peripheral tumors representing 59 % of all primaries detected. In patients without antecedent lung cancer its specificity considering malignancy was >99 %. Therefore, the QMSP-assay is a promising technique which could enhance the sensitivity and diagnostic impact of conventional cytology. The assay is applicable to residual material of regular diagnostic cytology even in retrospect.

Spontaneous malignant transformation of conventional giant cell tumor.

Spontaneous malignant transformation of conventional giant cell tumor (GCT) of bone is exceedingly rare. We report on a case of GCT of the iliac crest in a 35-year-old woman with malignant change into a high-grade osteosarcoma 10 years after the first appearance of GCT on a radiograph. Since the patient refused therapy for personal reasons the tumor remained untreated until sarcomatous transformation occurred. Image cytometry showed DNA aneuploidy and a suspiciously high 2c deviation index (2cDI) in the primary bone lesion. A thorough review of the world literature revealed only seven fully documented cases of secondary malignant GCT which matched the definition of a "sarcomatous growth that occurs at the site of a previously documented benign giant cell tumor" and not treated by radiotherapy. These cases as well as the current one suggest that a spontaneous secondary malignant GCT presents as a frankly sarcomatous tumor in the form of an osteosarcoma or malignant fibrous histiocytoma. It usually appears at sites of typical GCTs-often without any recurrent intermediate state-and is diagnosed 3 or more years after the primary bone lesion. The prognosis is poor.

[Molecular cytopathology of lung cancer--prevalence of genetic alterations and their role in the development of molecular biomarkers]. / Molekulare Zytopathologie bösartiger Lungentumoren--Prävalenz der genetischen Alterationen und ihre Bedeutung für die Entwicklung molekularer Biomarker.

Carcinogenesis of lung cancer proceeds via a complex process that involves multiple genetic abnormalities, which do not necessarily have a linear progression. Genetic alterations include aneuploidy, deletions and amplifications of chromosomal regions, loss of heterozygosity (LOH), microsatellite alterations, point mutations and aberrant promoter methylation. There is considerable effort to use these genetic alterations as molecular biomarkers for early cancer diagnosis applying different approaches. An ideal tumor marker should be highly sensitive, tumor specific, easily to handle and non-cost intensive. While previous studies used screening for mutations, LOH and microsatellite alterations, more recent strategies concentrate on multicolor fluorescence in situ hybridization (FISH) and aberrant promoter methylation. Since in general the genetic alterations are prone to be more extensive in tumor cells as compared to non-tumor cells, methods that provide quantitative data (e.g., methylation specific real-time PCR) are likely to improve specificity. Consequently, molecular biomarkers could constribute to a more accurate risk assessment in carcinogen exposed individuals and early molecular cytologic diagnosis of precancerous lesions and cancers of the lung.

Prognostic significance of DNA cytometry in carcinoma of the uterine cervix FIGO stage IB and II.

OBJECTIVE: To assess the prognostic value of DNA-image cytometry in cervical carcinoma of the uterus and its relation to other established prognostic factors. STUDY DESIGN: The study included 116 cases of cervical carcinoma FIGO stages IB and II which were treated with radical abdominal hysterectomy. The median follow-up was 55 months (range 1-162 months). DNA image cytometry was performed on cytologic specimens prepared by enzymatic cell separation from formalin-fixed, paraffin-embedded tissues. DNA stemline ploidy, DNA stemline aneuploidy, 5c exceeding rate, 9c exceeding rate, 2c deviation index, and DNA malignancy grade were computed. DNA-variables as well as various clinical and histological variables were related to survival rates. RESULTS: In multivariate statistical analysis DNA stemline ploidy using 2.2c as a cut-off value and FIGO stage showed to be statistically significant available presurgery predictors of survival, whereas the postsurgical parameters lymphonodal status, tumor size and parametrial involvement were significantly correlated with survival. The synopsis of all parameters in a multivariate Cox model indicated that - with declining relevance - the number of positive pelvic lymph nodes, DNA stemline ploidy using a cut-off level at a modal value of 2.2c, largest pelvic lymph node, 5c exceeding rate, and ratio of carcinoma area to cervix area, were of predictive value for survival. CONCLUSIONS: Our results suggest that prognostic information deducted from classical staging parameters is successfully complemented by DNA image cytometry which can be applied pretherapeutically.

Overexpression of cathepsin B and urokinase plasminogen activator is associated with increased risk of recurrence and metastasis in patients with chondrosarcoma.

BACKGROUND: Deregulation of the cellular protease network has been shown to be responsible for aggressive clinical behavior in several common human malignancies. In the current study, the authors evaluated the expression patterns of proteases in patients with chondrosarcoma of bone and correlated these patterns with clinical outcome. METHODS: The expression levels of urokinase plasminogen activator; matrix metalloproteinase types-1, -2, and -9; and cathepsins B and L were determined immunohistochemically in 114 cases of chondrosarcomas of bone and were correlated with their clinicopathologic parameters as well as with long term follow-up data. RESULTS: Overexpression of cathepsin B was associated with a high rate of local recurrence (P = 0.006) and a decreased recurrence free survival (P = 0.005). Overexpression of urokinase plasminogen activator was associated with an increased rate of metastasis (P = 0. 013), a decreased metastasis free survival (P = 0.016), and a decreased 5-year overall survival rate (P = 0.048). The univariate Cox model showed that tumor extension into soft tissue, high histologic grade, and overexpression of cathepsin B were predictors of adverse outcome. Multivariate analysis showed only overexpression of cathepsin B and tumor extension into soft tissue to be independent predictors of local recurrence. CONCLUSIONS: Overexpression of cathepsin B and urokinase plasminogen activator can be used to identify those patients with chondrosarcoma of bone who have an increased risk of local recurrence and distant metastases.

Mutation of p53 with loss of heterozygosity in the osteosarcomatous component of a dedifferentiated chondrosarcoma.

We investigated a dedifferentiated chondrosarcoma of a 61-year-old woman with an osteosarcomatous high-grade component for p53 alteration. The low-grade cartilaginous and the high-grade osteosarcomatous components of the tumor were macrodissected and evaluated separately by immunohistochemistry and molecular biology. We used PCR-SSCP analysis and direct sequencing to screen exons 4-8 for p53 mutations. The p53 intron 1-polymorphism was investigated for loss of heterozygosity. A functionally relevant p53 missense mutation in codon 193 of exon 6 (A-to-T transversion) with loss of wild-type allele was detected only in the dedifferentiated component. Using the monoclonal antibody DO-1, immunohistochemistry failed to show p53 overexpression. This evidence of p53 mutation may be regarded as at least a co-factor that "switched" the preexisting low-grade conventional chondrosarcoma to a highly malignant dedifferentiated tumor.

Rosai-Dorfman disease and generalized AA amyloidosis: a case report.

We report on a patient who, at 31 years of age, was found to suffer from sinus histiocytosis with massive lymphadenopathy (SHML; Rosai-Dorfman disease) with nodal and extranodal involvement as described previously. Five years later the patient presented with nephrotic syndrome caused by a generalized AA amyloidosis, and he subsequently died from pulmonary thromboembolism owing to renal vein thrombosis. Retrospective analysis of serum levels of C-reactive protein (CRP) showed that during the last 3 years before his death, he had a persistently elevated CRP level ranging from 73 to 161 mg/L, despite antiinflammatory treatment with prednisolone, methotrexate, or 6-mercaptopurine. These figures indicate that the patient was probably suffering from a permanent acute phase response which, in the absence of any other evidence of a chronic inflammatory disease which commonly causes AA amyloidosis, was most likely owing to SHML.

Osseous manifestation of Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy). A case report and review of the literature.

Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) is an unusual form of histiocytic disorder. Bone lesions are infrequent. We describe a 33-year-old man with involvement of multiple bones but without lymphadenopathy at the time of presentation. The literature on osseous manifestation in this condition is reviewed.

[Pathology of Ewing sarcoma]. / Pathologie des Ewing-Sarkoms.

Ewing's sarcoma is a very rare tumor which has, however, attracted much oncological interest since the dramatic improvement of its prognosis under chemotherapy. Its histogenesis has been discussed controversially for a long time, including a possible origin in immature reticulum, myogenous, endothelial and undifferentiated mesenchymal cells. Repeated reports have also suggested a possible neuroectodermal genesis. Convincing arguments, however, have only been brought forward during recent years, since it was found that Ewing's sarcoma and malignant peripheral neuroectodermal tumor share a common chromosome translocation 11;22. In the meantime this hypothesis has been strengthened by numerous cell biological analyses. There seems to be no clear border between Ewing's sarcoma and malignant peripheral neuroectodermal tumors with definite neural differentiation. Histological differential diagnosis of Ewing's sarcoma has been improved by immunohistological methods. In most cases, they can be distinguished from lymphoma (leucocyte common antigen, B and T markers) and embryonal rhabdomyosarcoma (muscle specific actin, desmin) without problems. Apart from that, it is possible nowadays to obtain antibodies against the MIC 2-protein, which is preferably expressed in Ewing sarcoma. The diagnostics of Ewing's sarcoma and the malignant peripheral neuroectodermal tumor have considerably been enriched by the fact that the specific chromosome translocation t(11;22) can be proved molecular biologically. In contrast to the cytogenetic evidence, it is not necessary to establish cell cultures.

Intervertebral variation in trabecular microarchitecture throughout the normal spine in relation to age.

The vertebral bodies of the complete spine (C-3-L-5) were removed in 26 autopsy cases without evidence for primary or secondary bone disease (13 males aged 19-79 years and 13 females aged 17-90 years). A sagittal segment through the center of all vertebral bodies was embedded undecalcified in hydroxyethylmethacrylate and processed to so-called surface stained block grindings. Histomorphometric analysis of the complete segment was performed using a computer-assisted image analysis system (IBAS 2000). The structural parameters investigated were bone volume (BV/TV) and trabecular interconnection quantificated by trabecular bone pattern factor (TBPf). A close correlation of BV/TV and TBPf was found in all vertebral bodies irrespective of vertebral region (r = 0.8, p < 0.001). This indicates that the age-related decrease of trabecular bone mass is primarily the consequence of the transformation from plates to rods and the loss of whole trabecular structures. This basic principle is valid throughout the complete spine. However, the systematic analysis of vertebral trabecular bone from C-3 to L-5 revealed a significant intervertebral variation of trabecular microarchitecture. The density of trabecular structure of cervical vertebrae is much higher than that of thoracic and lumbar vertebrae (p < 0.001). The extent of age-related loss of trabecular bone mass and structure showed a decrease within the spine from the caudal to the cranial region (p < 0.05). The loss of bone volume in individuals between the ages of 30 and 80 years in the lumbar spine was 53%, whereas in the thoracic spine the decrease was 41%, and in the cervical spine only 24%.(ABSTRACT TRUNCATED AT 250 WORDS)

Polyostotic heterogeneity of the spine in osteoporosis. Quantitative analysis and three-dimensional morphology.

It was the aim of this study to record quantitatively and qualitatively the distribution of the three-dimensional microarchitecture throughout the human spine in osteoporosis. Bone biopsies of the iliac crest and the complete spine of 26 autopsy cases without skeletal disease and 11 female patients with proven osteoporosis were removed. Grindings of all vertebrae by a technique which we developed allowed two- and three-dimensional measurements simultaneously. The analysis included an evaluation of trabecular bone volume, trabecular interconnection, and trabecular thickness, as well as a qualitative investigation of the structure of cancellous bone. The bone loss in osteoporosis is a loss of structure. The relative loss of the trabecular microarchitecture is greater in the iliac crest than in the lumbar spine. It is a gradual change from normal bone to osteoporosis. Transformation from plates to rods and the loss of whole trabeculae are caused by perforations. The polyostotic heterogeneity in osteoporosis is remarkable. Adjacent vertebrae may show differences of up to 100% in bone structure and bone volume. This explains the difficulties in early diagnosis of osteoporosis. Due to the polyostotic heterogeneity it is impossible to define a threshold mineral content for osteoporotic fractures.