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Just over a century ago, Dr. Gertrud Hurler described what is now commonly called Hurler syndrome. This rare inherited condition became known by terms describing its cardinal physical signs; the eponymous name was not proposed. In 1936, Ellis et al. coined the term "gargoylism" to name the syndrome. We propose that the film The Hunchback of Notre Dame played a key role in the original association of Hurler syndrome with the architectural figures known as gargoyles and with the persistence of the term. Over time, due in large part to its extremely negative connotations and lack of accuracy, "gargoylism" was abandoned. It has been supplanted by a sophisticated clinical understanding of mucopolysaccharidosis type 1 (MPS1), the underlying enzymatic defect, and dramatic advances in early diagnosis and treatment.

Objective. Three different breast positron emission tomography (PET) insert geometries are proposed for integration into an existing magnetic resonance imaging (MRI) breast coil (Breast Biopsy Coil, NORAS MRI products) to be used inside a whole-body PET/MRI scanner (Biograph mMR, Siemens Healthineers) to enhance the sensitivity and spatial resolution of imaging inside the breast. Approach. Monte Carlo simulations were performed to predict and compare the performance characteristics of the three geometries in terms of the sensitivity, spatial resolution, scatter fraction, and noise equivalent count rate (NECR). In addition, the background single count rate due to organ uptake in a clinical scan scenario was predicted using a realistic anthropomorphic phantom. Main results. In the center of the field of view (cFOV), absolute sensitivities of 3.1%, 2.7%, and 2.2% were found for Geometry A (detectors arranged in two cylinders), Geometry B (detectors arranged in two partial cylinders), and Geometry C (detectors arranged in two half cylinders combined with two plates), respectively. The full width at half maximum spatial resolution was determined to be 1.7 mm (Geometry A), 1.8 mm (Geometry B) and 2.0 mm (Geometry C) at 5 mm from the cFOV. Designs with multiple scintillation-crystal layers capable of determining the depth of interaction (DOI) strongly improved the spatial resolution at larger distances from the transaxial cFOV. The system scatter fractions were 33.1% (Geometries A and B) and 32.3% (Geometry C). The peak NECRs occurred at source activities of 300 MBq (Geometry A), 310 MBq (Geometry B) and 340 MBq (Geometry C). The background single-event count rates were 17.1 × 106 cps (Geometry A), 15.3 × 106 cps (Geometry B) and 14.8 × 106 cps (Geometry C). Geometry A in the three-layer DOI variant exhibited the best PET performance characteristics but could be challenging to manufacture. Geometry C had the lowest impact on the spatial resolution and the lowest sensitivity among the investigated geometries. Significance. Geometry B in the two-layer DOI variant represented an effective compromise between the PET performance and manufacturing difficulty and was found to be a promising candidate for the future breast PET insert.

Precise measurement of temperature is important in studies of chemical and biological systems as reaction kinetics are almost universally sensitive to temperature. However, the use of conventional temperature probes can introduce an exogenous temperature disturbance resulting in measurement artifacts. Infrared pyrometry is a noninvasive technique for temperature measurement, however, the challenge for current infrared pyrometry is low sensitivity to small temperature variations, which in many cases precludes determination of key diagnostic information. Here, we report a sensitive differential infrared pyrometer based on spatial modulation using a resonant oscillating mirror, which enables a sensitivity to temperature variations on the microkelvin scale. The instrument is employed to monitor minuscule heat evolution in an acid-base reaction and the decomposition of H

Introduction/Background* Endometrial carcinoma patient care was based on histopathologic examination for many years. However, conventional pathologic features are known to suffer from high inter-observer variability and may be irreproducible in many cases. TCGA-derived molecular classification was shown to provide clinically meaningful data and was recently introduced to ESGO/ESTRO/ESP endometrial carcinoma consensus guidelines. It was the aim of this study to quantify alterations in risk-assessment if molecular classification is added to conventional prognosticators. Methodology Consecutive primary endometrial carcinoma patients diagnosed in 2016 were identified in participating centres. Original risk classification (‘ORC16’, ESGO/ESMO guidelines 2016) was compared to current molecular-based risk assessment (‘MBR21’, ESGO/ESMO guidelines 2021). Clinical and histopathological data were collected and tumor specimens were retrospectively submitted to PMS2, MSH6 and p53 immunohistochemistry and POLE mutation testing. Result(s)* 226 patients were identified across five major European gynecologic oncology centres. Complete molecular and clinical data were available from 198 cases with a median follow-up time of 52.1 months. Median age was 64.9 years (30.9-90.9), 165 cases (83,3%) were endometrioid histotype. Grade distribution included 85(42.9%) G1, 63(31.8%) G2, and 46(23.3%) G3 tumors. 98(49.5%) patients had stage IA disease, with the remaining stage IB (n=51;25.8%), stage II (n=16;8.0%), and stage III/IV (n=33;16.7%). Molecular classification yielded 43(21.7%) MMR-D, 18(9.1%) POLE, 43(21.7%) p53abn, and 94(47.5%) p53wt tumors. If ORC16 was compared to MBR21, risk was found to be higher in 15(7.6%) cases, whereas 27(13.6%) cases were assigned to a lower risk group. No survival events were observed in the 9 patients where risk was changed from high-intermediate or high to low-risk. Conclusion* We were able to demonstrate clinically relevant alterations of endometrial carcinoma risk assessment in a significant number of patients after adding TCGA-derived molecular data to conventional risk classification. Potential molecular-guided changes in patient management may help to avoid over- and undertreatment and will ultimately give rise to precision medicine strategies in endometrial carcinoma patient care.

A Laser-Driven Plasma X-ray Source (LPXS) can provide intense, hard X-rays in femtosecond pulses emitted from a micrometer-size spot on a recirculating liquid-metal target. Unlike X-ray tubes based on electron beams, which are subject to constraints of the electron optics and space-charge effects, there is no fundamental limit to the amount of laser power that can be concentrated into the micrometer focus. With the increasing availability of industrial picosecond and femtosecond laser systems it now is practical to offer high average X-ray flux, combined with far higher brilliance and far shorter pulses than possible with X-ray tubes. Because the laser target in an LPXS is a liquid-metal, each laser shot encounters a fresh surface. Metal vapor and droplets are collected and recirculated to the target metal pump for maintenance-free operation. Hard X-rays are generated at tens of keV photon energies consisting of continuum radiation and, depending on the target material composition, of Ga-K, Bi-K or In-K emission lines.

The horizonal transfer of plasmid-encoded genes allows bacteria to adapt to constantly shifting environmental pressures, bestowing functional advantages to their bacterial hosts such as antibiotic resistance, metal resistance, virulence factors, and polysaccharide utilization. However, common molecular methods such as short- and long-read sequencing of microbiomes cannot associate extrachromosomal plasmids with the genome of the host bacterium. Alternative methods to link plasmids to host bacteria are either laborious, expensive, or prone to contamination. Here we present the One-step Isolation and Lysis PCR (OIL-PCR) method, which molecularly links plasmid-encoded genes with the bacterial 16S rRNA gene via fusion PCR performed within an emulsion. After validating this method, we apply it to identify the bacterial hosts of three clinically relevant beta-lactamases within the gut microbiomes of neutropenic patients, as they are particularly vulnerable multidrug-resistant infections. We successfully detect the known association of a multi-drug resistant plasmid with Klebsiella pneumoniae, as well as the novel associations of two low-abundance genera, Romboutsia and Agathobacter. Further investigation with OIL-PCR confirmed that our detection of Romboutsia is due to its physical association with Klebsiella as opposed to directly harboring the beta-lactamase genes. Here we put forth a robust, accessible, and high-throughput platform for sensitively surveying the bacterial hosts of mobile genes, as well as detecting physical bacterial associations such as those occurring within biofilms and complex microbial communities.

Synthesis and turnover of the bacterial cell wall must be tightly coordinated to avoid structural integrity failure and cell death. Details of this coordination are poorly understood, particularly if and how cell wall turnover enzymes are required for the activity of the different cell wall synthesis machines, the aPBPs and the Rod system., The bacterial cell wall is composed primarily of peptidoglycan (PG), a poly-aminosugar that is essential to sustain cell shape, growth, and structural integrity. PG is synthesized by class A/B penicillin-binding proteins (a/bPBPs) and shape, elongation, division, and sporulation (SEDS) proteins like RodA (as part of the Rod system cell elongation machinery) and degraded by “autolytic” enzymes to accommodate growth processes. It is thought that autolysins (particularly endopeptidases [EPs]) are required for PG synthesis and incorporation by creating gaps that are patched and paved by PG synthases, but the exact relationship between autolysins and PG synthesis remains incompletely understood. Here, we have probed the consequences of EP depletion for PG synthesis in the diarrheal pathogen Vibrio cholerae. We found that EP depletion resulted in severe morphological and division defects, but these cells continued to increase in mass and aberrantly incorporated new cell wall material. Mass increase proceeded in the presence of Rod system inhibitors, but cells lysed upon inhibition of aPBPs, suggesting that aPBPs are required for structural integrity under these conditions. The Rod system, although not essential for the observed mass increase, remained functional even after prolonged EP depletion. Last, heterologous expression of an EP from Neisseria gonorrhoeae fully complemented growth and morphology of an EP-insufficient V. cholerae, highlighting the possibility that the PG synthases may not necessarily function via direct interaction with EPs. Overall, our findings suggest that during EP insufficiency in V. cholerae, aPBPs become essential for structural integrity while the Rod system is unable to promote proper cell expansion.

The period of the early Middle Ages has the potential to do fairly well by the global turn in the humanities, including art history. Early medievalists have long been skeptical of the European nati...

The bacterial cell wall is composed primarily of peptidoglycan (PG), a poly-aminosugar that is essential to sustain cell shape, growth and structural integrity. PG is synthesized by two different types of synthase complexes (class A Penicillin-binding Proteins [PBP]s/Lpos and Shape, Elongation, Division, Sporulation [SEDS]/class B PBP pairs) and degraded by ‘autolytic’ enzymes to accommodate growth processes. It is thought that autolsyin activity (and particulary the activity of endopeptidases, EPs) is required for PG synthesis and incorporation by creating gaps that are patched and paved by PG synthases, but the exact relationship between autolysins and the separate synthesis machineries remains incompletely understood. Here, we have probed the consequences of EP depletion for PG synthesis in the diarrheal pathogen Vibrio cholerae. We found that EP depletion resulted in severe morphological defects, increased cell mass, a decline in viability, and continuing (yet aberrant) incorporation of cell wall material. Mass increase and cell wall incorporation proceeded in the presence of Rod system inhibitors, but was abolished upon inhibition of aPBPs. However, the Rod system remained functional (i.e., exhibited sustained directed motion) even after prolonged EP depletion, without effectively promoting cell elongation. Lastly, heterologous expression of an EP from Neisseria gonorrhoeae could fully complement growth and morphology of an EP-insufficient V. cholerae. Overall, our findings suggest that in V. cholerae, the Rod system requires endopeptidase activity (but not necessarily direct interaction with EPs) to promote cell expansion and substantial PG incorporation, whereas aPBPs are able to engage in sacculus construction even during severe EP insufficiency.ImportanceSynthesis and turnover of the bacterial cell wall must be tightly co-ordinated to avoid structural integrity failure and cell death. Details of this coordination are poorly understood, particularly if and how cell wall turnover enzymes are required for the activity of the different cell wall synthesis machines. Our results suggest that in Vibrio cholerae, one class of turnover enzymes, the endopeptidases, are required only for substantial PG incorporation mediated by the Rod system, while the aPBPs maintain structural integrity during endopeptidase insufficiency. Our results suggest that aPBPs are more versatile than the Rod system in their ability to recognize cell wall gaps formed by autolysins other than the major endopeptidases, adding to our understanding of the co-ordination between autolysins and cell wall synthases. A detailed understanding of autolysin biology may promote the development of antibiotics that target these essential turnover processes.

When a modulated light beam is absorbed by an incompressible particle, the photoacoustic effect can take place through heat diffusion into the surrounding fluid followed by thermal expansion and the generation of sound. When two laser beams modulated at different frequencies irradiate a particle in aqueous solution, the effect of one laser is to modulate the thermal expansion coefficient of the solution in the proximity of the particle at its modulation frequency. Heat diffusion into the same region of fluid from absorption of radiation from the second laser takes place in fluid where the thermal expansion coefficient is modulated so that the photoacoustic effect is produced at the sum and difference frequencies of the two lasers. Here, a theory for the photoacoustic effect at the heterodyne frequency for a single particle and the corresponding experiments with carbon particles of different sizes are reported.

The Ludwig-Soret effect, also known as thermal diffusion, refers to the separation of gas, liquid, or solid mixtures in a temperature gradient. The motion of the components of the mixture is governed by a nonlinear, partial differential equation for the density fractions. Here solutions to the nonlinear differential equation for a binary mixture are discussed for an externally imposed, exponential temperature field. The equation of motion for the separation without the effects of mass diffusion is reduced to a Hamiltonian pair from which spatial distributions of the components of the mixture are found. Analytical calculations with boundary effects included show shock formation. The results of numerical calculations of the equation of motion that include both thermal and mass diffusion are given.

This chapter examines the twentieth- and twenty-first-century display in Germany of the thirteenth-century equestrian statue known as the Magdeburg Rider; it concentrates on the sculpture’s presence in museum exhibitions. In the modern history of German Gothic sculpture, the Magdeburg Rider has almost always been part of a triumvirate with the Bamberg Rider and the donor figures from Naumburg. Like modern cultural–historical exhibitions, Deutsche Grose (DG) displayed a range of objects from the past: works of art, documents, other kinds of artifacts. DG put great emphasis on the Magdeburg Rider. It was the centerpiece of the gallery in which it stood and one of only sixteen objects illustrated in the exhibition’s catalogue. The effect of the Magdeburg Rider in DG was significantly affected by two museological innovations of the exhibition. Each gallery of DG was designed to echo, but not to copy fully, an architectural monument from the era displayed in that room.

The photoacoustic (PA) effect combing with the piezoelectric effect has been designed for trace gas detection, which has been expected to be operational over a wide temperature range. In this paper, the lead-free piezoelectric crystals LiNbO3 (LN), NdCa 4 O(BO 3 ) 3 (NdCOB) and $\alpha-$BiB 3 O 6 (BIBO) are studied and compared for potential PA trace gas detection. The piezoelectric voltage coefficients of LN $(g21)$, NdCOB $(g12)$ and BIBO $(g21)$ were characterized and found to be on the order of 0.026 Vm/N, 0.047 Vm/N and 0.225 Vm/N at room temperature, respectively. Among the three kinds of piezoelectric crystals, the BIBO crystal possesses the highest longitudinal piezoelectric coefficient $d_{22}$ and the largest piezoelectric voltage coefficient $g_{22}$, being on the order of 40 pC/N and 0.538 Vm$\bullet$/N, respectively. The piezoelectric voltage coefficients for NdCOB and BIBO crystal were obtained to show good temperature stability and maintained the similar values over the temperature range, while the value of $g_{21}$ for LN crystal showed a decrease with increasing temperature. Taking advantage of the strong piezoelectric activity and high mechanical quality factor Q of BIBO crystal, piezoelectric transducer with central resonance frequency of $\sim$443 kHz was fabricated for PA trace gas detection. The final detection limit for trace sulfur hexafluoride (SF 6 ) gas was extended to the parts-per-quadrillion level.

ispartof: JOURNAL OF APPLIED PHYSICS vol:128 issue:24 status: published

The King-Devick test appears to be a promising tool in screening for concussions. However, limited evidence exists on the baseline associations between the K-D test and age and baseline screening tools used after concussion. Additionally, there are no published reference values for the K-D test in high school football players. The K-D test, the Balance Error Scoring System, and the Limits of Stability (LOS) test were administered to 157 high school football players. Additionally, a subsample of 62 participants completed the test twice to examine the reliability of K-D test. There was no relationship between the K-D test and the BESS, or the reaction time and directional control of LOS test. Students aged between 16 and 18 years demonstrated faster K-D test performance compared to students between 13 and 15 years of age. However, there was no association between K-D test and history of concussion. The reliability of the K-D test was (ICC2,1 = 0.89), and the minimal detectable change was 6.10 s. Normative reference values for high school football players are presented in this study.

Background. Mycosis Fungoides (MF) is the most common cutaneous T-cell lymphoma, and large cell trasformation (tMF) is an adverse prognostic event. Extra-cutaneous dissemination can occur in the course of the disease, but dissemination to the central nervous system (CNS) is uncommon. Moreover, CNS lymphomas are overall rare and most often of B-cell phenotype. We report a case of CNS large T-cell lymphoma presenting as multiple cerebral lesions in a patient with a history of MF. Methods. We report a case of a 33-year-old woman, known since the age of 16 for erythematous plaques thought to be atopic dermatitis, who developed, end 2012, multiple nodular skin lesions and peripheral adenopathies. Two skin lesions were biopsied simultaneously, and diagnosed as MF and tMF. A lymph node biopsy showed dermatopathic changes without lymphoma (Stage IIB). She received local treatment (UVB, PUVA and radiation therapy) and interferon therapy, and experienced almost complete remission. In 2015 neurological symptoms lead to evidence multiple cerebral lesions, suspicious for lymphoma, evaluated by stereotaxic biopsies. We compared histopathological and molecular features of these with previous skin specimens. After negative bone marrow staging biopsy, she was recently started on chemotherapy (MATRIX). Short follow-up shows rapidly worsening clinical conditions. Results. One of the initial skin biopsies showed atypical lymphoid cells with epidermotropism, Pautrier abcesses and CD4+ CD30- phenotype; the other revealed diffuse dermal infiltration by predominantly large cerebriform tumor cells with high proliferative fraction, and CD2−CD3 −CD4+/−CD7−CD30+ALK- EMA- non-cytotoxic immunophenotype. Altogether, these results led us to diagnose MF and tMF, respectively. The brain was infiltrated by large atypical lymphoid cells with cerebriform nuclei, somewhat anaplastic features and perivascular distribution. By immunohistochemistry, tumor cells were highly proliferative, with a CD2−CD3+CD5−CD7+CD30+ activated cytotoxic immunophenotype. A diagnosis of CD30+ cytotoxic peripheral T-cell lymphoma was retained. TRG and TRB clonality analyses revealed clonal rearrangements in skin and CNS biopsies, with identical patterns in both skin specimens but only minimally overlapping profiles when compared to the CNS sample. Der Pathologe 6 ? 2015 | 633 Conclusions. The reported case illustrates an uncommon finding of a CNS T-cell lymphoma in a patient with previous MF, questioning the clonal relationship between the two diseases and challenging the adequate classification of this CNS lymphoma as either a progression or a de novo lymphoma. Despite differences in immunophenotype and clonality patterns, this CNS lymphoma could possibly represent an aggressive divergent evolution of a primary cutaneous T-cell lymphoma. Additional sequencing is ongoing to try to solve the question.

The photoacoustic effect is usually studied in an isotropic medium on a laboratory scale. However, it is possible to use optical sources to launch pressure perturbations in the atmosphere consisting of both acoustic and gravity waves. Here photoacoustic theory is extended to incorporate the effects of a stratified atmosphere and a gravitational field on launching and propagation of pressure waves in the atmosphere. Properties of pressure waves corresponding to several optical excitation schemes are investigated. The acoustic component of the optically launched pressure waves is explored separately to delineate its properties from those found without the effects of a gravitational field.

A method for directional emissivity determination by measurement of absorption through a photothermal effect is described. The experimental results found for Au, Al, and graphite show good agreement with the theoretical prediction of the electromagnetic theory. It is shown as well that complex refractive indices can be determined by fitting angular absorption data with theory.

We show that emissivities in the near infrared can be determined relative to a reference surface employing the photoacoustic effect. The photoacoustic cell is equipped with two windows and a pair of synchronously moving chopping wheels so that the cell alternately views the test and the reference surface. The acoustic signals produced in the cell are detected with a microphone and that output is fed to a lock-in amplifier. The temperature of the test surface is varied to produce a null in the lock-in amplifier, which permits determination of a relative emissivity. Results of measurements for several plastic and metal surfaces are reported.

Although the photoacoustic effect is typically generated by amplitude-modulated continuous or pulsed radiation, the form of the wave equation for pressure that governs the generation of sound indicates that optical sources moving in an absorbing fluid can produce sound as well. Here, the characteristics of the acoustic wave produced by a radially symmetric Gaussian source expanding outwardly from the origin are found. The unique feature of the photoacoustic effect from the spherical source is a trailing compressive wave that arises from reflection of an inwardly propagating component of the wave. Similar to the one-dimensional geometry, an unbounded amplification effect is found for the Gaussian source expanding at the sound speed.