A novel transflectance near infrared spectroscopy technique for monitoring hot melt extrusion

yesA transflectance near infra red (NIR) spectroscopy approach has been used to simultaneously measure drug and plasticiser content of polymer melts with varying opacity during hot melt extrusion. A high temperature reflectance NIR probe was mounted in the extruder die directly opposed to a highly reflective surface. Carbamazepine (CBZ) was used as a model drug, with polyvinyl pyrollidone-vinyl acetate co-polymer (PVP-VA) as a matrix and polyethylene glycol (PEG) as a plasticiser. The opacity of the molten extrudate varied from transparent at low CBZ loading to opaque at high CBZ loading. Particulate amorphous API and voids formed around these particles were found to cause the opacity. The extrusion process was monitored in real time using transflectance NIR; calibration and validation runs were performed using a wide range of drug and plasticiser loadings. Once calibrated, the technique was used to simultaneously track drug and plasticiser content during applied step changes in feedstock material. Rheological and thermal characterisations were used to help understand the morphology of extruded material. The study has shown that it is possible to use a single NIR spectroscopy technique to monitor opaque and transparent melts during HME, and to simultaneously monitor two distinct components within a formulation

Neoadjuvant chemotherapy in breast cancer-response evaluation and prediction of response to treatment using dynamic contrast-enhanced and diffusion-weighted MR imaging

Objective To explore the predictive value of MRI parameters and tumour characteristics before neoadjuvant chemotherapy (NAC) and to compare changes in tumour size and tumour apparent diffusion coefficient (ADC) during treatment, between patients who achieved pathological complete response (pCR) and those who did not. Methods Approval by the Regional Ethics Committee and written informed consent were obtained. Thirty-one patients with invasive breast carcinoma scheduled for NAC were enrolled (mean age, 50.7; range, 37–72). Study design included MRI before treatment (Tp0), after four cycles of NAC (Tp1) and before surgery (Tp2). Data in pCR versus non-pCR groups were compared and cut-off values for pCR prediction were evaluated. Results Before NAC, HER2 overexpression was the single significant predictor of pCR (p=0.006). At Tp1 ADC, tumour size and changes in tumour size were all significantly different in the pCR and non-pCR groups. Using 1.42×10−3 mm2/s as the cut-off value for ADC, pCR was predicted with sensitivity and specificity of 88% and 80%, respectively. Using a cut-off value of 83% for tumour volume reduction, sensitivity and specificity for pCR were 91% and 80%. Conclusion ADC, tumour size and tumour size reduction at Tp1 were strong independent predictors of pCR

The Acoustic Index User's Guide: a practical manual for defining, generating and understanding current and future acoustic indices

1. Ecoacoustics, the study of environmental sound, is a rapidly growing discipline offering ecological insights at scales ranging from individual organisms to whole ecosystems. Substantial methodological developments over the last 15 years have streamlined extraction of ecological information from audio recordings. One widely used set of methods are acoustic indices, which offer numerical summaries of the spectral, temporal and amplitude patterns in audio recordings. 2. Currently, the specifics of each index's background, methodology and the soundscape patterns they are designed to summarise, are spread across multiple sources. Critically, details of index calculation are sometimes scarce, making it challenging for users to understand how index values are generated. Discrepancies in understanding can lead to misuse of acoustic indices or reporting of spurious results. This hinders ecological inference, replicability and discourages adoption of these tools for conservation and ecosystem monitoring, where they might otherwise provide useful insight. 3. Here we present the Acoustic Index User's Guide—an interactive RShiny web app that defines and deconstructs eight of the most commonly used acoustic indices to facilitate consistent application across the discipline. We break the acoustic indices calculations down into easy-to-follow steps to better enable practical application and critical interpretation of acoustic indices. We demonstrate typical soundscape patterns using a suite of 91 example audio recordings: 66 real-world soundscapes from terrestrial, aquatic and subterranean systems around the world, and 25 synthetic files demonstrating archetypal soundscape patterns. Our interpretation figures signpost specific soundscape patterns likely to be reflected in acoustic indices' values. 4. This RShiny app is a living resource; additional acoustic indices will be added in the future through collaboration with authors of pre-existing and new indices. The app also serves as a best-practice template for the information required when publishing new acoustic indices, so that authors can facilitate the widest possible understanding and uptake of their indices. In turn, improved understanding of acoustic indices will aid effective hypothesis generation, application and interpretation in ecological research, ecosystem monitoring and conservation management

Ensembl Genomes 2022: an expanding genome resource for non-vertebrates

Ensembl Genomes (https://www.ensemblgenomes.org) provides access to non-vertebrate genomes and analysis complementing vertebrate resources developed by the Ensembl project (https://www.ensembl.org). The two resources collectively present genome annotation through a consistent set of interfaces spanning the tree of life presenting genome sequence, annotation, variation, transcriptomic data and comparative analysis. Here we present our largest increase in plant, metazoan and fungal genomes since the project’s inception creating one of the world’s most comprehensive genomic resources and describe our efforts to reduce genome redundancy in our Bacteria portal. We also detail our new efforts in gene annotation, our emerging support for pangenome analysis and efforts to accelerate data dissemination through the Ensembl Rapid Release resource. We also present our new AlphaFold visualisation. Finally, we present details of our future plans including updates on our integration with Ensembl, and how we plan to improve our support for the microbial research community. Software and data are made available without restriction via our website, online tools platform and programmatic interfaces (available under an Apache 2.0 license). Data updates are synchronised with Ensembl’s release cycle

MRI/PET Brain Imaging

Multimodal brain imaging has become an established clinical and research tool for diagnosis and disease progression of brain disorders. Among available imaging modalities, magnetic resonance imaging (MRI) and positron-emission tomography (PET) can provide a wide spectrum of data for the in vivo mapping of neurobiological functions and brain morphology while demonstrating to relationships between behavioral and neurobiological factors. Since MRI mostly uses endogenous contrast mechanisms to visualize and quantify tissue characteristics, optimal sequence design is essential for the diagnostic information of MRI. On the other hand, PET imaging is always based on the exogenous contrast of an injected PET tracer. Therefore, characteristics of the PET tracer determine the quantitative and diagnostic potential of PET. This chapter will focus on both of these modalities and shortly discuss the potential of multimodal or hybrid MR/PET imaging. We will not cover MR spectroscopy nor specific applications of H215O PET since this will be discussed in other chapters of this book.</p

Pituitary microadenomas: diagnosis with two-and three-dimensional MR imaging at 1.5 T before and after injection of gadolinium.

The usefulness of different magnetic resonance (MR) imaging sequences (coronal and sagittal spin-echo [SE] and three-dimensional fast low-angle shot [3D FLASH]) in the detection of pituitary microadenomas before and after gadolinium injection was prospectively evaluated in 28 patients with surgical confirmation. When evaluated separately, the most useful sequences in the detection of these microadenomas were coronal pregadolinium T1-weighted SE, coronal pregadolinium 3D FLASH, coronal postgadolinium T1-weighted SE, and coronal postgadolinium 3D FLASH. The combination of pre- and postgadolinium T1-weighted sequences with pre-and postgadolinium 3D FLASH sequences produced the highest number of true-positive findings (90%) and the lowest number of false-positive findings (5%). When a 1.5-T imaging unit with a high signal-to-noise ratio allowing useful three-dimensional acquisition is used, the authors advocate a coronal T1-weighted SE sequence, followed (if necessary) by a coronal 3D FLASH sequence, both without injection of gadolinium, in the diagnosis of pituitary microadenomas. When no confident diagnosis is reached, the same sequences should be performed after the injection of gadolinium. The sagittal pre- and postgadolinium T1-weighted SE and long-TR SE sequences are useful only in specific cases

Contrast behavior between microadenoma and normal pituitary gland after gadolinium injection as a function of time at 1.5 T.

The behavior of contrast enhancement between a microadenoma and the normal pituitary gland after gadolinium injection was evaluated in 12 operatively confirmed cases using a repetitive sequence of four coronal T1-weighted spin echo series (T1 SE) (continuous acquisition, TR = 400 ms), followed by conventional coronal T1 SE (TR = 600 ms) and a three-dimensional fast low-angle shot sequence. The first and second acquisitions were useful with respect to delayed scans only in 3 cases (25%). Nevertheless, in these cases confident diagnosis could also be made on pre-contrast studies, which diminishes the real advantage of this finding. For a 1.5 T MRI unit we advocate starting with coronal T1 SE 30 s after a rapid injection of gadolinium