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State-of-the-art laser frequency stabilization by high-finesse optical cavities is limited fundamentally by thermal noise-induced cavity length fluctuations. We present a novel design to reduce this thermal noise limit by an order of magnitude as well as an experimental realization of this new cavity system, demonstrating the most stable oscillator of any kind to date for averaging times of 0.1–10 s. The cavity spacer and the mirror substrates are both constructed from single-crystal silicon and are operated at 124 K, where the silicon thermal expansion coefficient is zero and the mechanical loss is small. The cavity is supported in a vibration-insensitive configuration, which, together with the superior stiffness of the silicon crystal, reduces the vibration-related noise. With rigorous analysis of heterodyne beat signals among three independent stable lasers, the silicon system demonstrates a fractional frequency instability of 1 × 10 −16 at short timescales and supports a laser linewidth of <40 mHz at 1.5 µm. Frequency stabilization in a high-finesse optical cavity is limited fundamentally by thermal-noise-induced cavity length fluctuations. Scientists have now developed a single-crystal silicon system that offers a fractional frequency instability of 1 × 10 −16 at short timescales and supports a laser linewidth of less than 40 mHz at 1.5 µm.

PurposeThe imaging of primary and metastatic brain tumours is very complex and relies heavily on advanced magnetic resonance imaging (MRI). Utilisation of these advanced imaging techniques is essential in helping clinicians determine tumour response after initiation of treatment. Many options are currently available to treat brain tumours, and each can significantly alter the brain tumour appearance on post-treatment imaging. In addition, there are several common and uncommon treatment-related complications that are important to identify on standard post-treatment imaging.MethodsThis article provides a review of the various post-treatment-related imaging appearances of brain neoplasms, including a discussion of advanced MR imaging techniques available and treatment response criteria most commonly used in clinical practice. This article also provides a review of the multitude of treatment-related complications that can be identified on routine post-treatment imaging, with an emphasis on radiation-induced, chemotherapy-induced, and post-surgical entities.Summary/ConclusionAlthough radiological evaluation of brain tumours after treatment can be quite challenging, knowledge of the various imaging techniques available can help the radiologist distinguish treatment response from tumour progression and has the potential to save patients from inappropriate alterations in treatment. In addition, knowledge of common post-treatment-related complications that can be identified on imaging can help the radiologist play a key role in preventing significant patient morbidity/mortality.Teaching points• Contrast enhancement does not reliably define tumour extent in many low-grade or infiltrative gliomas.• Focal regions of elevated cerebral blood volume (rCBV) on dynamic susceptibility contrast (DSC) perfusion-weighted imaging are suggestive of tumour growth/recurrence.• Brain tumour treatment response criteria rely on both imaging and clinical parameters.• Chemotherapeutic agents can potentiate many forms of radiation-induced injury.• Ipilimumab-induced hypophysitis results in transient diffuse enlargement of the pituitary gland.

Background Given the young age of patients with CNS WHO grade 2 and 3 oligodendrogliomas and the relevant risk of neurocognitive, functional, and quality-of-life impairment with the current aggressive standard of care treatment, chemoradiation with PCV, of the tumour located in the brain optimizing care is the major challenge. Methods NOA-18 aims at improving qualified overall survival (qOS) for adult patients with CNS WHO grade 2 and 3 oligodendrogliomas by randomizing between standard chemoradiation with up to six six-weekly cycles with PCV and six six-weekly cycles with lomustine and temozolomide (CETEG) ( n  = 182 patients per group accrued over 4 years) thereby delaying radiotherapy and adding the chemoradiotherapy concept at progression after initial radiation-free chemotherapy, allowing for effective salvage treatment and delaying potentially deleterious side effects. QOS represents a new concept and is defined as OS without functional and/or cognitive and/or quality of life deterioration regardless of whether tumour progression or toxicity is the main cause. The primary objective is to show superiority of an initial CETEG treatment followed by partial brain radiotherapy (RT) plus PCV (RT-PCV) at progression over partial brain radiotherapy (RT) followed by procarbazine, lomustine, and vincristine (PCV) chemotherapy (RT-PCV) and best investigators choice (BIC) at progression for sustained qOS. An event concerning a sustained qOS is then defined as a functional and/or cognitive and/or quality of life deterioration after completion of primary therapy on two consecutive study visits with an interval of 3 months, tolerating a deviation of at most 1 month. Assessments are done with a 3-monthly MRI, assessment of the NANO scale, HRQoL, and KPS, and annual cognitive testing. Secondary objectives are evaluation and comparison of the two groups regarding secondary endpoints (short-term qOS, PFS, OS, complete and partial response rate). The trial is planned to be conducted at a minimum of 18 NOA study sites in Germany. Discussion qOS represents a new concept. The present NOA trial aims at showing the superiority of CETEG plus RT-PCV over RT-PCV plus BIC as determined at the level of OS without sustained functional deterioration for all patients with oligodendroglioma diagnosed according to the most recent WHO classification. Trial registration Clinicaltrials.gov NCT05331521 . EudraCT 2018–005027-16.

The major and minor salivary glands of the head and neck are important structures that contribute to many of the normal physiologic processes of the aerodigestive tract. The major salivary glands are routinely included within the field of view of standard neuroimaging, and although easily identifiable, salivary pathology is relatively rare and often easy to overlook. Knowledge of the normal and abnormal imaging appearance of the salivary glands is critical for forming useful differential diagnoses, as well as initiating proper clinical workup for what are often incidental findings. The purpose of this review is to provide a succinct image-rich article illustrating relevant anatomy and pathology of the salivary glands via an extensive review of the primary literature. In Part 1, we review anatomy as well as provide an in-depth discussion of the various infectious and inflammatory processes that can affect the salivary glands.

The Raman tensor of the dominant A 1 modes of the nonlinear optical crystalline material potassium dihydrogen phosphate and its 70% deuterated analog have been ascertained. Challenges in determining the A 1 mode tensor element values based on previous reports have been resolved using a specially designed experimental setup that makes use of spherical crystal samples. This novel experimental design enabled the determination of measurement artifacts, including polarization rotation of the pump and/or scattered light propagating through the sample and the contribution of additional overlapping phonon modes, which have hindered previous efforts. Results confirmed that the polarization tensor is diagonal, and matrix elements were determined with high accuracy.

To evaluate the influence of plum-, cranberry- and blackcurrant juice on urinary stone risk factors. Investigations were carried out in 12 healthy male subjects aged 18-38 y. All subjects received a standardized diet formulated according to the dietary recommendations of the German Society of Nutrition. The subjects provided 24 h urine collections in a control, three loading phases. In each loading phase a neutral mineral water was substituted for 330 ml of the particular juice. Cranberry juice decreased the urinary pH, whereas the excretion of oxalic acid and the relative supersaturation for uric acid were increased. Blackcurrant juice increased the urinary pH and the excretion of citric acid. The excretion of oxalic acid was increased too. All changes were statistically significant. The plum juice had no significant effect on the urinary composition. It is concluded that blackcurrant juice could support the treatment and metaphylaxis of uric acid stone disease because of its alkalizing effect. Since cranberry juice acidifies urine it could be useful in the treatment of brushite and struvite stones as well as urinary tract infection. Funded by our own Division respectively the University.

Genetic testing plays an increasing role in cardiovascular medicine. Advances in technology and the development of novel and more affordable (high throughput) methods have led to the identification of genetic risk factors in research and clinical practice. Also, this progress has simplified the screening of patients and individuals at risk. In case of rare monogenic diseases, diagnostics, risk stratification, and, in some cases, treatment decisions have become easier. For common, polygenic cardiovascular diseases, the situation is more complex due to interaction of modifiable external risk factors and nonmodifiable factors like genetic predisposition. Over the last few years, it has been shown that multiple genes are involved in the pathophysiology of these cardiovascular diseases rather than one single gene. In the following article, we give an overview of the genetic risk factors in polygenic cardiovascular diseases as atrial fibrillation, arterial hypertension and coronary artery disease. Furthermore, we aim to illustrate in which cases genetic testing is recommended in these diseases.

The concept of arming antibodies with bioactive payloads for a site-specific therapy of cancer has gained considerable interest in recent years. However, a successful antibody-based targeting approach critically relies on the availability of a tumor-associated target that is not only preferentially expressed in the tumor tissue but is also easily accessible for antibody therapeutics coming from the bloodstream. Here, we perfused the vasculature of healthy and acute myeloid leukemia (AML)-bearing rats with a reactive ester derivative of biotin and subsequently quantified the biotinylated proteins to identify AML-associated bone marrow (BM) antigens accessible from the bloodstream. In total, >1400 proteins were identified. Overall, 181 proteins were >100-fold overexpressed in AML as compared with normal BM. Eleven of the most differentially expressed proteins were further validated by immunohistochemistry and confocal microscopic analyses, including novel antigens highly expressed in AML cells (for example, adaptor-related protein complex 3 β2) and in the leukemia-modified extracellular matrix (ECM) (for example, collagen-VI-α-1). The presented atlas of targetable AML-associated BM proteins provides a valuable basis for the development of monoclonal antibodies that could be used as carriers for a site-specific pharmacodelivery of cytotoxic drugs, cytokines or radionuclides to the BM in AML.