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Despite many interventions, science education remains highly inequitable throughout the world. Internet-enabled experimental learning has the potential to reach underserved communities and increase the diversity of the scientific workforce. Here, we demonstrate the use of lab-on-a-chip (LoC) technologies to expose Latinx life science undergraduate students to introductory concepts of computer programming by taking advantage of open-loop cloud-integrated LoCs. We developed a context-aware curriculum to train students at over 8000 km from the experimental site. Through this curriculum, the students completed an assignment testing bacteria contamination in water using LoCs. We showed that this approach was sufficient to reduce the students' fear of programming and increase their interest in continuing careers with a computer science component. Altogether, we conclude that LoC-based internet-enabled learning can become a powerful tool to train Latinx students and increase the diversity in STEM., (© 2024. The Author(s).)

Particle trapping and enrichment into confined volumes can be useful in particle processing and analysis. This review is an evaluation of the methods used to trap and enrich particles into constrained volumes in microfluidic and nanofluidic systems. These methods include physical, optical, electrical, magnetic, acoustic, and some hybrid techniques, all capable of locally enhancing nano- and microparticle concentrations on a microscale. Some key qualitative and quantitative comparison points are also explored, illustrating the specific applicability and challenges of each method. A few applications of these types of particle trapping are also discussed, including enhancing biological and chemical sensors, particle washing techniques, and fluid medium exchange systems.

Viral outbreaks can cause widespread disruption, creating the need for diagnostic tools that provide high performance and sample versatility at the point of use with moderate complexity. Current gold standards such as PCR and rapid antigen tests fall short in one or more of these aspects. Here, we report a label-free and amplification-free nanopore sensor platform that overcomes these challenges via direct detection and quantification of viral RNA in clinical samples from a variety of biological fluids. The assay uses an optofluidic chip that combines optical waveguides with a fluidic channel and integrates a solid-state nanopore for sensing of individual biomolecules upon translocation through the pore. High specificity and low limit of detection are ensured by capturing RNA targets on microbeads and collecting them by optical trapping at the nanopore location where targets are released and rapidly detected. We use this device for longitudinal studies of the viral load progression for Zika and Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infections in marmoset and baboon animal models, respectively. The up to million-fold trapping-based target concentration enhancement enables amplification-free RNA quantification across the clinically relevant concentration range down to the assay limit of RT-qPCR as well as cases in which PCR failed. The assay operates across all relevant biofluids, including semen, urine, and whole blood for Zika and nasopharyngeal and throat swab, rectal swab, and bronchoalveolar lavage for SARS-CoV-2. The versatility, performance, simplicity, and potential for full microfluidic integration of the amplification-free nanopore assay points toward a unique approach to molecular diagnostics for nucleic acids, proteins, and other targets., Competing Interests: Competing interests statement:A.R.H. and H.S. have a relevant patent filing (Systems and methods of delivering target molecules to a nanopore, US20200284783A1). A.R.H. and H.S. had a financial interest in Fluxus Inc., which commercializes optofluidic technology.

We present a design and a fabrication method for devices designed for rapid collection of nanoparticles in a fluid. The design uses nanofluidic channels as a passive size-based barrier trap to isolate particles near a central point in the channel, which is also covered by a thin membrane. Particles that enter the collection region are trapped with 100% efficiency within a 6-12  μ m radius from a central point. Flow rates for particle-free fluid range from 1.88 to 3.69 nl/s for the pressure and geometries tested. Particle trapping tests show that high trapped particle counts significantly impact flow rates. For suspensions as dilute as 30-300 aM (20-200 particles/ μ l), 8-80 particles are captured within 500 s., Competing Interests: The authors have no conflicts to disclose., (© 2023 Author(s).)

Integrated optofluidic devices have become subjects of high interest for rapid biosensor devices due to their unique ability to combine the fluidic processing of small volumes of microfluidics with the analysis capabilities of photonic structures. By integrating dynamically reconfigurable optofluidic lasers on-chip, complex coupling can be eliminated while further increasing the capabilities of sensors to detect an increasing number of target biomarkers. Here, we report a polydimethylsiloxane-based device with two on-chip fluidic distributed feedback (DFB) laser cavities that are integrated with an orthogonal analyte channel for multiplexed fluorescence excitation. One DFB grating is filled with 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran dissolved in dimethyl sulfoxide. The second grating is filled with rhodamine 6G dissolved in a diluted ethylene glycol solution. We present characterization of both lasers through analysis of the lasing spectra for spectral narrowing along with a power series to observe threshold behavior. We then demonstrate simultaneous detection of two different fluorescent microbeads as a proof of concept for scalable, single biomarker analysis using on-chip optofluidic lasers., (© 2023. Springer Nature Limited.)

Background: Histogram indices (HIs) and texture features (TFs) are considered to play an important role in future oncologic PET-imaging and it is unknown how these indices are affected by changes of tracer doses. A randomized undersampling of PET list mode data enables a simulation of tracer dose reduction. We performed a phantom study to compare HIs/TFs of simulated and measured tracer dose reductions and evaluated changes of HIs/TFs in the liver of patients with PETs from simulated reduced tracer doses. Overall, 42 HIs/TFs were evaluated in a NEMA phantom at measured and simulated doses (stepwise reduction of [18 F] from 100% to 25% of the measured dose). [18 F]-FDG-PET datasets of 15 patients were simulated from 3.0 down to 0.5 MBq/kgBW in intervals of 0.25 MBq/kgBW. HIs/TFs were calculated from two VOIs placed in physiological tissue of the right and left liver lobe and linear correlations and coefficients of variation analysis were performed., Results: All 42 TFs did not differ significantly in measured and simulated doses ( p > 0.05). Also, 40 TFs showed the same behaviour over dose reduction regarding differences in the same group (measured or simulated), and for 26 TFs a linear behaviour over dose reduction for measured and simulated doses could be validated. Out of these, 13 TFs could be identified, which showed a linear change in TF value in both the NEMA phantom and patient data and therefore should maintain the same informative value when transferred in a dose reduction setting. Out of this Homogeneity 2, Entropy and Zone size non-uniformity are of special interest because they have been described as preferentially considerable for tumour heterogeneity characterization., Conclusions: We could show that there was no significant difference of measured and simulated HIs/TFs in the phantom study and most TFs reveal a linear behaviour over dose reduction, when tested in homogeneous tissue. This indicates that texture analysis in PET might be robust to dose modulations.

Integrated optofluidic biosensors have demonstrated ultrasensitivity down to single particle detection and attomolar target concentrations. However, a wide dynamic range is highly desirable in practice and can usually only be achieved by using multiple detection modalities or sacrificing linearity. Here, we demonstrate an analysis technique that uses temporal excitation at two different time scales to simultaneously enable digital and analog detection of fluorescent targets. We demonstrated the seamless detection of nanobeads across eight orders of magnitude from attomolar to nanomolar concentration. Furthermore, a combination of spectrally varying modulation frequencies and a closed-loop feedback system that provides rapid adjustment of excitation laser powers enables multiplex analysis in the presence of vastly different concentrations. We demonstrated this ability to detect across scales via an analysis of a mixture of fluorescent nanobeads at femtomolar and picomolar concentrations. This technique advances the performance and versatility of integrated biosensors, especially toward point-of-use applications., Competing Interests: Disclosures. Authors Aaron R. Hawkins and Holger Schmidt had a competing interest in Fluxus Inc., which commercializes optofluidic technology. Author Vahid Ganjalizadeh has no competing interests.

Optofluidic biosensors have become an important medical diagnostic tool because they allow for rapid, high-sensitivity testing of small samples compared to standard lab testing. For these devices, the practicality of use in a medical setting depends heavily on both the sensitivity of the device and the ease of alignment of passive chips to a light source. This paper uses a model previously validated by comparison to physical devices to compare alignment, power loss, and signal quality for windowed, laser line, and laser spot methods of top-down illumination.

Multiplexed detection of biomarkers in real-time is crucial for sensitive and accurate diagnosis at the point of use. This scenario poses tremendous challenges for detection and identification of signals of varying shape and quality at the edge of the signal-to-noise limit. Here, we demonstrate a robust target identification scheme that utilizes a Deep Neural Network (DNN) for multiplex detection of single particles and molecular biomarkers. The model combines fast wavelet particle detection with Short-Time Fourier Transform analysis, followed by DNN identification on an AI-specific edge device (Google Coral Dev board). The approach is validated using multi-spot optical excitation of Klebsiella Pneumoniae bacterial nucleic acids flowing through an optofluidic waveguide chip that produces fluorescence signals of varying amplitude, duration, and quality. Amplification-free 3× multiplexing in real-time is demonstrated with excellent specificity, sensitivity, and a classification accuracy of 99.8%. These results show that a minimalistic DNN design optimized for mobile devices provides a robust framework for accurate pathogen detection using compact, low-cost diagnostic devices., (© 2023. The Author(s).)

Besides tremendous treatment success in advanced melanoma patients, the rapid development of oncologic treatment options comes with increasingly high costs and can cause severe life-threatening side effects. For this purpose, predictive baseline biomarkers are becoming increasingly important for risk stratification and personalized treatment planning. Thus, the aim of this pilot study was the development of a prognostic tool for the risk stratification of the treatment response and mortality based on PET/MRI and PET/CT, including a convolutional neural network (CNN) for metastasized-melanoma patients before systemic-treatment initiation. The evaluation was based on 37 patients (19 f, 62 ± 13 y/o) with unresectable metastasized melanomas who underwent whole-body 18F-FDG PET/MRI and PET/CT scans on the same day before the initiation of therapy with checkpoint inhibitors and/or BRAF/MEK inhibitors. The overall survival (OS), therapy response, metastatically involved organs, number of lesions, total lesion glycolysis, total metabolic tumor volume (TMTV), peak standardized uptake value (SULpeak), diameter (Dmlesion) and mean apparent diffusion coefficient (ADCmean) were assessed. For each marker, a Kaplan−Meier analysis and the statistical significance (Wilcoxon test, paired t-test and Bonferroni correction) were assessed. Patients were divided into high- and low-risk groups depending on the OS and treatment response. The CNN segmentation and prediction utilized multimodality imaging data for a complementary in-depth risk analysis per patient. The following parameters correlated with longer OS: a TMTV < 50 mL; no metastases in the brain, bone, liver, spleen or pleura; ≤4 affected organ regions; no metastases; a Dmlesion > 37 mm or SULpeak < 1.3; a range of the ADCmean < 600 mm2/s. However, none of the parameters correlated significantly with the stratification of the patients into the high- or low-risk groups. For the CNN, the sensitivity, specificity, PPV and accuracy were 92%, 96%, 92% and 95%, respectively. Imaging biomarkers such as the metastatic involvement of specific organs, a high tumor burden, the presence of at least one large lesion or a high range of intermetastatic diffusivity were negative predictors for the OS, but the identification of high-risk patients was not feasible with the handcrafted parameters. In contrast, the proposed CNN supplied risk stratification with high specificity and sensitivity.

We demonstrate an optofluidic device which utilizes the optical scattering and gradient forces for particle trapping in microchannels featuring 300 nm thick membranes. On-chip waveguides are used to direct light into microfluidic trapping channels. Radiation pressure is used to push particles into a protrusion cavity, isolating the particles from liquid flow. Two different designs are presented: the first exclusively uses the optical scattering force for particle manipulation, and the second uses both scattering and gradient forces. Trapping performance is modeled for both cases. The first design, referred to as the orthogonal force design, is shown to have a 80% capture efficiency under typical operating conditions. The second design, referred to as the gradient force design, is shown to have 98% efficiency under the same conditions.

Integrated biosensor platforms have become subjects of high interest for consolidated assay preparation and analysis to reduce sample-to-answer response times. By compactly combining as many biosensor processes and functions as possible into a single lab-on-chip device, all-in-one point-of-care devices can aid in the accessibility and speed of deployment due to their compact size and portability. Biomarker assay preparation and sensing are functionalities that are often carried out on separate devices, thus increasing opportunity of contamination, loss of sample volume, and other forms of error. Here, we demonstrate a complete lab-on-chip system combining sample preparation, on-chip optofluidic dye laser, and optical detection. We first show the integration of an on-chip distributed feedback dye laser for alignment-free optical excitation of particles moving through a fluidic channel. This capability is demonstrated by using Rhodamine 6G as the gain medium to excite single fluorescent microspheres at 575 nm. Next, we present an optofluidic PDMS platform combining a microvalve network (automaton) for sample preparation of nanoliter volumes, on-chip distributed feedback dye laser for target excitation, and optical detection. We conduct concurrent capture and fluorescence tagging of Zika virus nucleic acid on magnetic beads in 30 min. Target-carrying beads are then optically excited using the on-chip laser as they flow through an analysis channel, followed by highly specific fluorescence detection. This demonstration of a complete all-in-one biosensor is a tangible step in the development of a rapid, point-of-care device that can assist in limiting the severity of future outbreaks.

We demonstrate a method for fabricating and utilizing an optofluidic particle manipulator on a silicon chip that features a 300 nm thick silicon dioxide membrane as part of a microfluidic channel. The fabrication method is based on etching silicon channels and converting the walls to silicon dioxide through thermal oxidation. Channels are encapsulated by a sacrificial polymer which fills the length of the fluid channel by way of spontaneous capillary action. The sacrificial material is then used as a mold for the formation of a nanoscale, solid-state, silicon dioxide membrane. The hollow channel is primarily used for fluid and particle transport but is capable of transmitting light over short distances and utilizes radiation pressure for particle trapping applications. The optofluidic platform features solid-core ridge waveguides which can direct light on and off of the silicon chip and intersect liquid channels. Optical loss values are characterized for liquid and solid-core structures and at interfaces. Estimates are provided for the optical power needed to trap particles of various sizes.

Many sensors operate by detecting and identifying individual events in a time-dependent signal which is challenging if signals are weak and background noise is present. We introduce a powerful, fast, and robust signal analysis technique based on a massively parallel continuous wavelet transform (CWT) algorithm. The superiority of this approach is demonstrated with fluorescence signals from a chip-based, optofluidic single particle sensor. The technique is more accurate than simple peak-finding algorithms and several orders of magnitude faster than existing CWT methods, allowing for real-time data analysis during sensing for the first time. Performance is further increased by applying a custom wavelet to multi-peak signals as demonstrated using amplification-free detection of single bacterial DNAs. A 4x increase in detection rate, a 6x improved error rate, and the ability for extraction of experimental parameters are demonstrated. This cluster-based CWT analysis will enable high-performance, real-time sensing when signal-to-noise is hardware limited, for instance with low-cost sensors in point of care environments., (© 2022. The Author(s).)

Integrated optofluidic biosensors can fill the need for sensitive, amplification-free, multiplex single molecule detection which is relevant for containing the spread of infectious diseases such as COVID-19. Here, we demonstrate a rapid sample-to-answer scheme that uses a field programmable gate array (FPGA) to enable live monitoring of single particle fluorescence analysis on an optofluidic chip. Fluorescent nanobeads flowing through a micro channel are detected with 99% accuracy and particle concentrations in clinically relevant ranges from 3.4×10 4 to 3.4 × 10 6 /ml are determined within seconds to a few minutes without the need for post-experiment data extraction and analysis. In addition, other extract salient experimental parameters such as dynamic flow rate changes can be monitored in real time. The sensor is validated with real-time fluorescence detection of single bacterial plasmid DNA at attomolar concentrations, showing excellent promise for implementation as a point of care (POC) diagnostic tool.

Ultrasensitive, versatile sensors for molecular biomarkers are a critical component of disease diagnostics and personalized medicine as the COVID-19 pandemic has revealed in dramatic fashion. Integrated electrical nanopore sensors can fill this need via label-free, direct detection of individual biomolecules, but a fully functional device for clinical sample analysis has yet to be developed. Here, we report amplification-free detection of SARS-CoV-2 RNAs with single molecule sensitivity from clinical nasopharyngeal swab samples on an electro-optofluidic chip. The device relies on optically assisted delivery of target carrying microbeads to the nanopore for single RNA detection after release. A sensing rate enhancement of over 2,000x with favorable scaling towards lower concentrations is demonstrated. The combination of target specificity, chip-scale integration and rapid detection ensures the practicality of this approach for COVID-19 diagnosis over the entire clinically relevant concentration range from 10 4 -10 9 copies/mL., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: A sense of security is important in palliative home care. Yet, knowledge about which components contribute most to feeling secure from the patients' and family caregivers' perspectives, especially since the introduction of specialist palliative home care, is sparse. The goal of the current study was to determine the key components contributing to a sense of security and how they relate to each other as experienced by patients and family caregivers in specialist and generalist palliative home care., Methods: The current sub-study, as part of a larger study, was performed in different regions in Germany. Palliative care patients and family caregivers of at least 18 years of age, being cared for at home were interviewed using semi-structured interview guides following a three-factor model and analyzed by using a combined quantitative-qualitative-content approach., Results: One hundred and ninty-seven patients and 10 carers completed interviews between December 2017 and April 2019. The majority of patients were diagnosed with an oncological disease. Sense of security was mentioned particularly often suggesting its high relevance. We identified nine subcategories that were all mentioned more frequently by specialist than generalist palliative home care recipients in the following order of priority and relation: (i) patient-centeredness: availability, provision of information/education, professional competence, patient empowerment, and trust (ii) organizational work: comprehensive responsibility, external collaboration, and internal cooperation, and (iii) direct communication., Significance of Results: The work of specialist palliative home care services in particular was perceived as very effective and beneficial. Our findings confirm a previously developed three-factor model allowing for generalizability and revealed that availability was most important for improving the sense of security for effective palliative home care.

Smarter Medicine in Headache Care - presentation and discussion of 5 recommendations Abstract. An unequivocal headache diagnosis cannot always be made. The lack of diagnostic tests able to prove primary headaches often prompts physicians to perform unnecessary examinations to reduce their uncertainty. When setting out the therapeutic strategy, again, insecurity often leads to mendable choices. In this Delphi study, members of the therapy commission of the Swiss Headache Society collected, rated, and re-rated doubtful and questionable procedures. Five recommendations that resulted from this survey are presented and reviewed in this article. The recommendations are: (A) no repeated cerebral imaging in headaches with unchanged phenotype; (B) no computed tomography in the work-up of non-acute headaches; (C) no tooth extraction to treat persistent idiopathic facial pain, (D) no migraine surgery; (E) no removal of amalgam fillings to treat headache disorders.

High sensitivity and easy integration with microfabrication techniques has made silicon photonics one of the leading technologies used to build biosensors for diagnostic applications. Here we introduce a new silicon dioxide based optofluidic platform having a planar solid-core (SC) waveguide orthogonally intersecting a liquid-core (LC) waveguide with high refractive index ZnI2 salt solution as core. This enables both more uniform collection of particle fluorescence by the core mode and its propagation to an off-chip detector. This approach results in ultra-high sensitivity performance, demonstrated by achieving 8X enhancement in signal-to-noise ratio, a 45x increase in detection efficiency, and a 100x lower detection limit of 80 aM of fluorescent nanobeads. This represents a key step towards an ultrasensitive biosensor system for analyzing pathogens at clinical concentrations.

The advent of single-molecule probing techniques has revolutionized the biomedical and life science fields and has spurred the development of a new class of labs-on-chip based on powerful biosensors. Nanopores represent one of the most recent and most promising single molecule sensing paradigms that is seeing increased chip-scale integration for improved convenience and performance. Due to their physical structure, nanopores are highly sensitive, require low sample volume, and offer label-free, amplification-free, high-throughput real-time detection and identification of biomolecules. Over the last 25 years, nanopores have been extensively employed to detect a variety of biomolecules with a growing range of applicatons ranging from nucleic acid sequencing to ultrasensitive diagnostics to single-molecule biophysics. Nanopores, in particular those in solid-state membranes, also have the potential for integration with other technologies such as optics, plasmonics, microfluidics, and optofluidics to perform more complex tasks for an ever-expanding demand. A number of breakthrough results using integrated nanopore platforms have already been reported, and more can be expected as nanopores remain the focus of innovative research and are finding their way into commercial instruments. This review provides an overview of different aspects and challenges of nanopore technology with a focus on chip-scale integration of solid-state nanopores for biosensing and bioanalytical applications.

Optofluidic sensors have enabled single molecule sensing using planar, waveguide dependent multi-spot fluorescence excitation. Here, we demonstrate a new approach to single-particle fluorescence sensing using free-space, top-down illumination of liquid-core antiresonant reflecting optical waveguide (ARROW) devices using two different multi-spot excitation techniques. First, the liquid core ARROW waveguide is excited with a focused beam through a slit pattern milled into an opaque aluminum film, showing comparable performance for single bead fluorescence detection as in-plane, multi-mode interference waveguide based excitation. The second top-down illumination technique images the spot pattern from a Y-splitter SiO 2 waveguide chip directly onto the detection device for efficient power utilization and circumventing the need for an opaque cover, producing a further 2.7x improvement in signal-to-noise ratio. The two top-down approaches open up new possibilities for chip-based optical particle sensing with relaxed alignment tolerances.

Optofluidic flow-through biosensors are being developed for single particle detection, particularly as a tool for pathogen diagnosis. The sensitivity of the biosensor chip depends on design parameters, illumination format (side vs. top), and flow configuration (parabolic, two- and three-dimensional hydrodynamic focused (2DHF and 3DHF)). We study the signal differences between various combinations of these design aspects. Our model is validated against a sample of physical devices. We find that side-illumination with 3DHF produces the strongest and consistent signal, but parabolic flow devices process a sample volume more quickly. Practical matters of optical alignment are also discussed, which may affect design choice.

Infectious disease outbreaks such as Ebola and other Viral Hemorrhagic Fevers (VHF) require low-complexity, specific, and differentiated diagnostics as illustrated by the recent outbreak in the Democratic Republic of Congo. Here, we describe amplification-free spectrally multiplex detection of four different VHF total RNA samples using multi-spot excitation on a multimode interference waveguide platform along with combinatorial fluorescence labeling of target nucleic acids. In these experiments, we observed an average of 8-fold greater fluorescence signal amplitudes for the Ebola total RNA sample compared to three other total RNA samples: Lake Victoria Marburg Virus, Ravn Marburg Virus, and Crimean-Congo Hemorrhagic Fever. We have attributed this amplitude amplification to an increased amount of RNA during synthesis of soluble glycoprotein in infection. This hypothesis is confirmed by single molecule detection of the total RNA sample after heat-activated release from the carrier microbeads. From these experiments, we observed at least a 5.3x higher RNA mass loading on the Ebola carrier microbeads compared to the Lake Victoria Marburg carrier microbeads, which is consistent with the known production of soluble glycoprotein during infection.

The urgency for the development of a sensitive, specific, and rapid point-of-care diagnostic test has deepened during the ongoing COVID-19 pandemic. Here, we introduce an ultrasensitive chip-based antigen test with single protein biomarker sensitivity for the differentiated detection of both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A antigens in nasopharyngeal swab samples at diagnostically relevant concentrations. The single-antigen assay is enabled by synthesizing a brightly fluorescent reporter probe, which is incorporated into a bead-based solid-phase extraction assay centered on an antibody sandwich protocol for the capture of target antigens. After optimization of the probe release for detection using ultraviolet light, the full assay is validated with both SARS-CoV-2 and influenza A antigens from clinical nasopharyngeal swab samples (PCR-negative spiked with target antigens). Spectrally multiplexed detection of both targets is implemented by multispot excitation on a multimode interference waveguide platform, and detection at 30 ng/mL with single-antigen sensitivity is reported., Competing Interests: Competing interest statement: J.W.P., A.R.H., and H.S. have a financial interest in Fluxus Inc., which is developing optofluidic devices., (Copyright © 2021 the Author(s). Published by PNAS.)

We present a model and simulation for predicting the detected signal of a fluorescence-based optical biosensor built from optofluidic waveguides. Typical applications include flow experiments to determine pathogen concentrations in a biological sample after tagging relevant DNA or RNA sequences. An overview of the biosensor geometry and fabrication processes is presented. The basis for the predictive model is also outlined. The model is then compared to experimental results for three different biosensor designs. The model is shown to have similar signal statistics as physical tests, illustrating utility as a pre-fabrication design tool and as a predictor of detection sensitivity., Competing Interests: Disclosures A.R.H. and H.S. have a financial interest in Fluxus Inc., which commercializes optofluidic technology.

Objectives: The purpose of this study was to evaluate the feasibility and diagnostic performance of prostate-specific membrane antigen (PSMA) based 18 F-DCFPyL PET/CT-ultrasound (PET/CT-US) or PET/MRI-ultrasound (PET/MRI-US) fusion targeted biopsy for intra-prostatic PET-positive lesions., Methods: From April 2018 to November 2019, we prospectively enrolled 55 candidates to perform PET/CT-US or PET/MRI-US fusion targeted biopsies for solitary PET-positive prostate lesions (two to four cores/lesion). The positive rates of prostate cancer based on patients and biopsy cores were calculated respectively. With reference to the pathological results of biopsy cores, the MR signal characteristics in the area of the PET-positive lesion were analyzed for the patients who underwent PET/MRI., Results: A total of 178 biopsy cores were taken on the 55 patients. One hundred forty-six biopsy cores (82.0%, 146/178) from 51 (92.7%, 51/55) patients were positive for prostate cancer; 47 (85.5%, 47/55) were clinically significant prostate cancer. It is noteworthy that nine patients underwent both 18 F-DCFPyL PET/CT and PET/MRI examinations; the seven patients with prostate cancer showed abnormal MR signal in the area of the PET-positive lesion while the other two patients with prostatic hyperplasia and prostatitis showed normal MR signal in the area of the PET-positive lesion., Conclusion: This study indicated that 18 F-DCFPyL PET/CT-US or PET/MRI-US fusion targeted prostate biopsies may be valuable for prostate cancer diagnosis and have a high detection rate of clinically significant prostate cancer for PET-positive lesions. PET/MR can rule out some false PET-positive lesions, which may potentially reduce unnecessary prostate biopsies., Competing Interests: Author ML was employed by company Siemens Healthineers Ltd., China. Author HS was employed by company Siemens Healthcare GmbH, Germany. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Yu, Liu, Zhang, Lin, Schmidt, Gao and Xu.)

Introduction: Stroke has a long-term impact on functional status and quality of life in multiple health domains. A well-coordinated managed care program for stroke patients is crucial for ameliorating patients' health and cost-efficient use of resources. The aim of this study is the implementation and evaluation of an optimised cross-sectoral, coordinated and managed care program for stroke patients bridging secondary and tertiary care., Methods: In this multi-center mixed method sequentially controlled intervention study, stroke patients with ischemic stroke (I63), transient ischemic attack and related syndromes (G45), or intracerebral haermorrhage (I64) will be invited to participate. For a 12-months period, 235 consecutive patients are expected to be enrolled and assigned standard of care treatment as an active control group. During the following 12 months, 235 consecutive patients will be enrolled and assigned to a post stroke intervention program. The StroCare intervention consists of repeated outpatient visits with specialized stroke teams, the implementation of a case manager, the use of an electronical tool for communication between acute care, rehabilitation facilities, and out-patient care, and the definition of individualized treatment targets. Patients will be followed up for 24 months. The primary outcome is health-related quality of life measured by the Patient-Reported Outcomes Measurement Information System 10-Question Short Form (PROMIS-10) at 12 months after the index event, i.e. stroke or TIA. For the qualitative survey of the implementation process, 21 patients in the intervention group will be interviewed after implementation of the interventions. In addition, 20 health care providers and staff members will be interviewed before and after implementation. Additionally, economic outcomes will be evaluated after 6 and 12 months., Perspective: The study will not only provide information about the tested intervention but is likely to be helpful for clinicians, suppliers of reimbursement, and researchers in implementing and evaluating complex interventions in stroke care in general. With this program, the health care system will have a reference model at its disposal for transfer to other regions and settings., Trial Registration: The trial is registered at ClinicalTrials.gov ( NCT04159324 ). Approval of the local ethics committee (Ethik-Kommission der Ärztekammer Hamburg, Niedersachsen, Schleswig-Holstein) has been obtained.

Chronic hepatitis C virus (HCV) infection is a highly prevalent systemic disease, which can cause a variety of neurological complications. The HCV-associated symptoms can be differentiated into central and peripheral nervous systems as well as the musculature. Important pathomechanisms are HCV-associated autoimmunity (e.g. mixed cryoglobulinemia with polyneuropathy) and direct neurotoxic effects of the virus (e.g. HCV-associated cognitive deficits). Distal symmetric polyneuropathies, small fiber neuropathies and cognitive deficits are the most prevalent neurological manifestations. Furthermore, HCV infection is a risk factor for ischemic and hemorrhagic stroke as well as Parkinson's disease. As HCV infection has become a permanently curable disease in >90% of patients, early identification and antiviral treatment of HCV positive patients is of utmost importance.

Silica waveguides are often etched by reactive ion etch (RIE) processes. These processes can leave residual topography that can increase optical loss. We investigated the relation between optical loss and various RIE etch. A wet etch step meant to remove microstructures was also considered and compared. Ridge waveguides were fabricated in plasma enhanced chemical vapor deposited films by three different RIE processes, each with a different gas composition, pressure setting, and applied power setting. Half of each set of waveguides were also subjected to a hydrofluoric acid (HF) solution. The waveguides were tested for optical transmission via the cutback method. The transmission vs waveguide length measurements were plotted to fit an exponential curve and the optical loss and measurement uncertainty for each waveguide set was calculated. Clear distinctions in optical loss were found between the different RIE processes. The HF treatment also has an effect, significantly reducing optical loss for two processes and increasing it for the third. Of the tested RIE processes, one can be suggested for silica waveguides. It results in the lowest optical loss and coincidently has the fastest etch rate., Competing Interests: Disclosures A.R.H. and H.S. have a financial interest in Fluxus Inc., which commercializes optofluidic technology.

Polydimethylsiloxane-based optofluidics provides a powerful platform for a complete analytical lab-on-chip. Here, we report on a novel on-chip laser source that can be integrated with sample preparation and analysis functions. A corrugated sidewall structure is integrated into a microfluidic channel to form a distributed feedback (DFB) laser using rhodamine 6G dissolved in an ethylene glycol and water solution. Lasing is demonstrated with a threshold pump power of 87.9 µW, corresponding to a pump intensity of 52.7 m W / c m 2 . Laser threshold and output power are optimized with respect to rhodamine 6G concentration and core index and found to be in good agreement with a rate equation model. Additionally, the laser can be switched on and off mechanically using a pneumatic cell inducing positive pressure on the grating.

We present a method to create robust, nanoscale solid-state membranes using the natural shape of a liquid meniscus as a template. A narrow, open channel is etched into a silicon substrate and then a photoresist polymer is introduced into the channel through spontaneous capillary action. The natural concave meniscus formed by the polymer is then covered by a thin chemical vapor deposited membrane. The polymer is removed by sacrificial etching, leaving behind a suspended membrane. Membranes as large as 20 μm by 9 mm can be fabricated with a thickness as low as 50 nm.

Dementia syndrome is common and expected to increase significantly among older people and characterized by the loss of cognitive, psychological and physical functions. Palliative care is applicable for people with dementia, however they are less likely to have access to palliative care. This narrative review summarizes specifics of palliative care in advanced dementia. Most people with advanced dementia live and die in institutional care and they suffer a range of burdensome symptoms and complications. Shortly before dying people with advanced dementia suffer symptoms as pain, eating problems, breathlessness, neuropsychiatric symptoms, and complications as respiratory or urinary infections and frequently experience burdensome transitions. Pharmacological and nonpharmacological interventions may reduce symptom burden. Sensitive observation and appropriate assessment tools enable health professionals to assess symptoms and needs and to evaluate interventions. Due to lack of decisional capacity, proxy decision making is often necessary. Advanced care planning is an opportunity establishing values and preferences and is associated with comfort and decrease of burdensome interventions. Family carers are important for people with advanced dementia they also experience distress and are in need for support. Recommendations refer to early integration of palliative care, recognizing signs of approaching death, symptom assessment and management, advanced care planning, person-centered care, continuity of care, and collaboration of health care providers., (Copyright © 2020 Eisenmann, Golla, Schmidt, Voltz and Perrar.)

Purpose: Evaluate the feasibility of fluorine-18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET) and magnetic resonance (MR) imaging in patients with gastric cancer by optimizing the scan protocol and to compare the image quality to 18 F FDG PET and computed tomography (CT)., Methods: The PET/CT and PET/MR imaging were sequentially performed in 30 patients with gastric cancer diagnosed by gastroscope using a single-injection-with-dual-imaging protocol. After intravenous injection of 18 F-FDG (mean, 249 MBq), PET/CT imaging including low-dose CT was performed (mean uptake time, 47 ± 6 min), and PET/MR imaging including a T1-weighted Dixon sequence for attenuation correction and two different T2-weighted sequences was subsequently acquired (88 ± 15 min after 18 F-FDG injection). Four series of images (CT from PET/CT, T1W, T2W Half-Fourier acquisition single-shot turbo spin-echo [T2W-HASTE] and T2W-BLADE from PET/MR) were visually evaluated using a 3-4 points scale for: (1) image artifacts, (2) lesion conspicuity and (3) image fusion quality. The characteristics of the primary lesions were assessed and compared between the PET/CT and PET/MR acquisitions., Results: The image quality and lesion conspicuity of the T2W-HASTE images were significantly improved compared to that of the T2W-BLADE images. A significantly higher number of artifacts were seen in the T2W-HASTE images compared with the T1W and CT images (p < 0. 05). No differences in the accuracy of image fusion between PET/MR and PET/CT (p > 0. 05); however, significant difference was seen in the lesion conspicuity measurements (p < 0.05) with T2W-HASTE being superior. For information about the primary lesion characteristics, the T2W-HASTE images provided the most successful identifications compared with those of the T1W and PET/CT (13vs7vs5) images., Conclusions: PET/MR with the T2W-HASTE was better at revealing the details of local stomach lesions compared with PET/CT imaging. Combining the PET/MR with the T2W-HASTE technique is a promising imaging method for diagnosing and staging gastric cancer.

Optofluidic devices are capable of detecting single molecules, but greater sensitivity and specificity is desired through hydrodynamic focusing (HDF). Three-dimensional (3D) hydrodynamic focusing was implemented in 10-μm scale microchannel cross-sections made with a single sacrificial layer. HDF is achieved using buffer fluid to sheath the sample fluid, requiring four fluid ports to operate by pressure driven flow. A low-pressure chamber, or pit, formed by etching into a substrate, enables volumetric flow ratio-induced focusing at a low flow velocity. The single layer design simplifies surface micromachining and improves device yield by 1.56 times over previous work. The focusing design was integrated with optical waveguides and used in order to analyze fluorescent signals from beads in fluid flow. The implementation of the focusing scheme was found to narrow the distribution of bead velocity and fluorescent signal, giving rise to 33% more consistent signal. Reservoir effects were observed at low operational vacuum pressures and a balance between optofluidic signal variance and intensity was achieved. The implementation of the design in optofluidic sensors will enable higher detection sensitivity and sample specificity.

Background: In three randomized, controlled laboratory efficacy studies, the efficacy in the prevention of patent infections of a topical combination of imidacloprid 10%/moxidectin 1% (Advocate® spot-on formulation for cats, Bayer Animal Health GmbH) against larval stages and immature adults of Aelurostrongylus abstrusus, as well as the treatment efficacy of a single or three monthly treatments against adult A. abstrusus, were evaluated., Methods: Cats were experimentally inoculated with 300-800 third-stage larvae (L3). Each group comprised 8 animals and the treatment dose was 10 mg/kg bodyweight (bw) imidacloprid and 1 mg/kg bw moxidectin in each study. Prevention of the establishment of patent infections was evaluated by two treatments at a monthly interval at three different time points before and after challenge infection. Curative efficacy was tested by one or three treatments after the onset of patency. Worm counts at necropsy were used for efficacy calculations., Results: In Study 1, the control group had a geometric mean (GM) of 28.8 adult nematodes and the single treatment group had a GM of 3.4 (efficacy 88.3%). In Study 2, the control group had a GM of 14.3, the prevention group had a GM of 0 (efficacy 100%), while the treatment group had a GM of 0.1 (efficacy 99.4%). In Study 3, the GM worm burden in the control group was 32.6 compared to 0 in all three prevention groups (efficacy 100% for all of those groups)., Conclusions: The monthly administration of Advocate® reliably eliminated early larval stages and thereby prevented lung damage from and patent infections with A. abstrusus in cats. Regarding treatment, a single application of Advocate® reduced the worm burden, but it did not sufficiently clear the infection. In contrast, three monthly treatments were safe and highly efficacious against A. abstrusus.

Porcine parvovirus 1 (PPV1) viral protein (VP) 2 is the primary antigen responsible for inducing specific protective immunity, so it is a desirable target for development of recombinant subunit vaccines to prevent PPV1 disease. The objective of this study was to evaluate repeated doses of a novel VP2-based PPV1 subunit vaccine, namely ReproCyc® ParvoFLEX, for safety in bred pigs and in offspring under experimental settings. Therefore, the investigation of safety at all breeding stages was evaluated in four independent studies involving: pre-breeding gilts (study A), breeding-age gilts and boars (study B), early and late gestating sows and offspring (study C) and lactating sows and offspring (study D). In all four studies, animals were free from PPV1 based on serology and PCR prior to inclusion. All studies comprised one or two vaccinated groups that received the PPV1 subunit vaccine and a negative control group. Thus, safety was established due to the lack of significant differences between the vaccinated groups and the corresponding unvaccinated (negative control) groups. Gilts, sows and boars were evaluated for local and systemic reactions after vaccination as well as for reproductive performance. The survival rate and average daily weight gain (ADWG) from birth to weaning in offspring was evaluated in studies C and D. Additionally, serology was determined in studies A, C and D. The vaccine was shown to be safe with no relevant significant differences between vaccinated and unvaccinated groups in any experiment. Therefore, repeated doses of ReproCyc® ParvoFLEX were safe in target animals at different stages of the reproductive cycle and in offspring, placing this vaccine as a suitable candidate for mass vaccination programs in breeding herds., (© 2019 The Author(s).)

3D hydrodynamic focusing was implemented with channel cross-section dimensions smaller than 10 μm. Microchannels were formed using sacrificial etching of two photoresist layers on a silicon wafer. The photoresist forms a plus-shaped prismatic focusing fluid junction which was coated with plasma-enhanced chemical-vapor-deposited oxide. Buffer fluid carried to the focusing junction envelopes an intersecting sample fluid, resulting in 3D focusing of the sample stream. The design requires four fluid ports and operates across a wide range of fluid velocities through pressure-driven flow. The focusing design was integrated with optical waveguides to interrogate fluorescing particles and confirm 3D focusing. Particle diffusion away from a focused stream was characterized., Competing Interests: Conflict of interest ARH and HS have a financial interest in Fluxus Inc. which commercializes optofluidic technology.

Polaritons are widely investigated quasiparticles with fundamental and technological significance due to their unique properties. They have been studied most extensively in semiconductors when photons interact with various elementary excitations. However, other strongly coupled excitations demonstrate similar dynamics. Specifically, when magnon and phonon modes are coupled, a hybridized magnon-phonon quasiparticle can form. Here, we report on the direct observation of coupled magnon-phonon dynamics within a single thin nickel nanomagnet. We develop an analytic description to model the dynamics in two dimensions, enabling us to isolate the parameters influencing the frequency splitting. Furthermore, we demonstrate tuning of the magnon-phonon interaction into the strong coupling regime via the orientation of the applied magnetic field.

The frequency of extreme drought and heavy rain events during the vegetation period will increase in Central Europe according to future climate change scenarios, which will affect the functioning of terrestrial ecosystems in multiple ways. In this study, we simulated an extreme drought event (40 days) at two different vegetation periods (spring and summer) to investigate season-related effects of drought and subsequent rewetting on nitrifiers and denitrifiers in a grassland soil. Abundance of the microbial groups of interest was assessed by quantification of functional genes (amoA, nirS/nirK and nosZ) via quantitative real-time PCR. Additionally, the diversity of ammonia-oxidizing archaea was determined based on fingerprinting of the archaeal amoA gene. Overall, the different time points of simulated drought and rewetting strongly influenced the obtained response pattern of microbial communities involved in N turnover as well as soil ammonium and nitrate dynamics. In spring, gene abundance of nirS was irreversible reduced after drought whereas nirK and nosZ remained unaffected. Furthermore, community composition of ammonia-oxidizing archaea was altered by subsequent rewetting although amoA gene abundance remained constant. In contrast, no drought/rewetting effects on functional gene abundance or diversity pattern of nitrifying archaea were observed in summer. Our results showed (I) high seasonal dependency of microbial community responses to extreme events, indicating a strong influence of plant-derived factors like vegetation stage and plant community composition and consequently close plant-microbe interactions and (II) remarkable resistance and/or resilience of functional microbial groups involved in nitrogen cycling to extreme weather events what might indicate that microbes in a silty soil are better adapted to stress situations as expected.

Planar optofluidics provide a powerful tool for facilitating chip-scale light-matter interactions. Silicon-based liquid core waveguides have been shown to offer single molecule sensitivity for efficient detection of bioparticles. Recently, a PDMS based planar optofluidic platform was introduced that opens the way to rapid development and prototyping of unique structures, taking advantage of the positive attributes of silicon dioxide-based optofluidics and PDMS based microfluidics. Here, hydrodynamic focusing is integrated into a PDMS based optofluidic chip to enhance the detection of single H1N1 viruses on-chip. Chip-plane focusing is provided by a system of microfluidic channels to force the particles towards a region of high optical collection efficiency. Focusing is demonstrated and enhanced detection is quantified using fluorescent polystyrene beads where the coefficient of variation is found to decrease by a factor of 4 with the addition of hydrodynamic focusing. The mean signal amplitude of fluorescently tagged single H1N1 viruses is found to increase with the addition of focusing by a factor of 1.64.

Detection of molecular biomarkers with high specificity and sensitivity from biological samples requires both sophisticated sample preparation and subsequent analysis. These tasks are often carried out on separate platforms which increases required sample volumes and the risk of errors, sample loss, and contamination. Here, we present an optofluidic platform which combines an optical detection section with single nucleic acid strand sensitivity, and a sample processing unit capable of on-chip, specific extraction and labeling of nucleic acid and protein targets in complex biological matrices. First, on-chip labeling and detection of individual lambda DNA molecules down to concentrations of 8 fM is demonstrated. Subsequently, we demonstrate the simultaneous capture, fluorescence tagging and detection of both Zika specific nucleic acid and NS-1 protein targets in both buffer and human serum. We show that the dual DNA and protein assay allows for successful differentiation and diagnosis of Zika against cross-reacting species like dengue.

Multimode interference (MMI) waveguides can be used to create wavelength-dependent spot patterns which enables simultaneous analyte detection on a single optofluidic chip, useful for disease diagnostics. The fidelity of such multi-spot patterns is important for high sensitivity and accurate target identification. Buried rib structures have been incorporated into these SiO 2 -based waveguides to improve environmental stability. Through experiments and simulation, this letter explores design parameters for a buried MMI rib waveguide based on anti-resonant reflecting optical waveguides in order to produce high-fidelity spot patterns. Optimal rib heights and widths are reported in the context of available microfabrication etch technology and performance for an optimized biosensor is shown.

Background: To satisfy the increasing demand of mechanical thrombectomy (MT) for acute ischemic stroke treatment, new organizational concepts for patient care are required. This study evaluates time intervals of acute stroke management in two stroke care models, including one based on transportation of the interventionalist from a comprehensive stroke center (CSC) to treat patients in two primary stroke centers (PSC). We hypothesized that time intervals were not inferior for the 'drip-and-drive' concept compared with the traditional 'drip-and-ship' concept., Methods: Patients treated with MT at the PSC ('drip-and-drive', 'D+D group') were compared with patients transferred from PSC to CSC for MT ('drip-and-ship', 'D+S group') with regard to time delays. Time intervals assessed were: symptom onset to initial CT, to angiography, and to recanalization; time from initial CT to telephone call activation, to arrival, and to angiography; and time from telephone call activation to arrival and from arrival to angiography., Results: 42 patients were treated at the PSC after transfer of the interventionalist, and 32 patients were transferred to the CSC for MT. The groups did not differ with regard to median Onset-CT and CT-Phone times. Significant differences between the groups were found for the primary outcome measure CT-Arrival time ('D+D group': median 121 (IQR 108-134) min vs 181 (157-219) min for the 'D+S group'; P<0.001). Time difference between the groups increased to more than 2 hours for median CT-Angio times (median 123 (IQR 93-147) min vs 252 (228-275) min; P<0.001)., Conclusion: Time intervals for the 'D+D group' were not inferior to those of the 'D+S group'. Moreover, under certain conditions, the 'drip-and-drive' concept might even be superior., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aim To evaluate voxelwise computed diffusion-weighted imaging (vcDWI) for the detection of cytotoxic oedema in brain imaging and to quantify the benefit of lesion contrast in comparison to standard b = 1000 s/mm 2 by the example of acute ischaemic stroke. Materials and methods A retrospective evaluation of 66 patients (63 ± 15.9 years) suspected for acute ischaemic stroke who received diffusion-weighted magnetic resonance imaging and fluid-attenuated inversion recovery sequence. A neuroradiologist evaluated all examinations for acute ischaemic stroke based on diffusion-weighted imaging, the apparent diffusion coefficient and fluid-attenuated inversion recovery (reference standard) and 6 weeks later the vcDWI in a randomised manner. Time of analysis was noted. Signal intensities were acquired in lesions, in healthy tissue as well as in the cerebrospinal fluid. Contrast ratios and coefficients of variation were computed. Results A total of 218 lesions was found in 46/66 patients. vcDWI identified all patients and lesions correctly. The median evaluation time was 36 seconds (4-126 s) for the vcDWI and 44 seconds (9-186 s; P < 0.001) for the diffusion-weighted imaging/apparent diffusion coefficient reading. The contrast ratio in vcDWI (mean value 2.57, range 1.73-4.11) was higher than in b = 1000 s/mm 2 (2.33, 0.83-3.85, P = 0.03) and the apparent diffusion coefficient map (1.83, 1.00-3.00, P < 0.001), respectively. Coefficients of variation in lesions and tissue did not differ significantly between vcDWI and b = 1000 s/mm 2 ( P = 0.81/ P = 0.26). The signal intensity of cerebrospinal fluid was lower in vcDWI than in b = 1000 mm 2 /s (0.08 and 34.8, P < 0.001). Conclusion It could be shown that vcDWI has the potential to accelerate the detection of diffusion-restricted lesions in neuroimaging by improving the contrast ratios and reducing the T2 shine-through effect in comparison to standard diffusion-weighted imaging in brain imaging.

Liquid-core waveguide-based optofluidic devices have proven to be valuable tools for analysis of biological samples in fluid. They have enabled single bioparticle sensitivity while maintaining in-plane detection via light-induced fluorescence. The incorporation of multi-spot excitation with multimode interference (MMI) waveguides has enabled spatially and spectrally multiplexed detection of single viruses on an oxide-based optofluidic platform. Here, we introduce a new way of MMI-based multiplexing where multiple analysis channels are placed within a single multi-spot pattern. This stacked channel design enables both velocity and spectral multiplexing of single particles. The principle is demonstrated with differentiated detection of single H3N2 and H1N1 viruses on a polydimethylsiloxane platform.

Background and Purpose: Functional PET/MRI has great potential to improve radiotherapy planning (RTP). However, data integration requires imaging with radiotherapy-specific patient positioning. Here, we investigated the feasibility and image quality of radiotherapy-customized PET/MRI in head-and-neck cancer (HNC) patients using a dedicated hardware setup., Material and Methods: Ten HNC patients were examined with simultaneous PET/MRI before treatment, with radiotherapy and diagnostic scan setup, respectively. We tested feasibility of radiotherapy-specific patient positioning and compared the image quality between both setups by pairwise image analysis of 18 F-FDG-PET, T1/T2-weighted and diffusion-weighted MRI. For image quality assessment, similarity measures including average symmetric surface distance (ASSD) of PET and MR-based tumor contours, MR signal-to-noise ratio (SNR) and mean apparent diffusion coefficient (ADC) value were used., Results: PET/MRI in radiotherapy position was feasible - all patients were successfully examined. ASSD (median/range) of PET and MR contours was 0.6 (0.4-1.2) and 0.9 (0.5-1.3) mm, respectively. For T2-weighted MRI, a reduced SNR of -26.2% (-39.0--11.7) was observed with radiotherapy setup. No significant difference in mean ADC was found., Conclusions: Simultaneous PET/MRI in HNC patients using radiotherapy positioning aids is clinically feasible. Though SNR was reduced, the image quality obtained with a radiotherapy setup meets RTP requirements and the data can thus be used for personalized RTP., (Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to demonstrate the feasibility of voxel-wise multiparametric characterization of head and neck squamous cell carcinomas (HNSCC) using hybrid multiparametric magnetic resonance imaging and positron emission tomography with [ 18 F]-fluorodesoxyglucose (FDG-PET/MRI) in a radiation treatment planning setup., Methods: Ten patients with locally advanced HNSCC were examined with a combined FDG-PET/MRI in an irradiation planning setup. The multiparametric imaging protocol consisted of FDG-PET, T2-weighted transverse short tau inversion recovery sequence (STIR) and diffusion-weighted MRI (DWI). Primary tumours were manually segmented and quantitative imaging parameters were extracted. PET standardized uptake values (SUV) and DWI apparent diffusion coefficients (ADC) were correlated on a voxel-wise level., Results: Images acquired in this specialised radiotherapy planning setup achieved good diagnostic quality. Median tumour volume was 4.9 [1.1-42.1] ml. Mean PET SUV and ADC of the primary tumours were 5 ± 2.5 and 1.2 ± 0.3 10 -3  mm 2 /s, respectively. In voxel-wise correlation between ADC values and corresponding FDG SUV of the tumours, a significant negative correlation was observed (r = -0.31 ± 0.27, p < 0.05)., Conclusion: Multiparametric voxel-wise characterization of HNSCC is feasible using combined PET/MRI in a radiation planning setup. This technique may provide novel insights into tumour biology with regard to radiation therapy in the future.

Objective: Aim of the study was to evaluate the influence of the selection of measured b-values on the precision of cDWI in the upper abdomen as well as on the lesion contrast of PET-positive liver metastases in cDWI and vcDWI., Methods: We performed a retrospective analysis of 10 patients (4 m, 63.5 ± 12.9 y/o) with PET-positive liver metastases examined in 3 T-PET/MRI with b = 100,600,800,1000 and 1500s/mm 2 . cDWI (cb1000/cb1500) and vcDWI were computed based on following combinations: i) b = 100/600 s/mm 2 , ii) b = 100/800 s/mm 2 , iii) b = 100/1000s/mm 2 , iv) b = 100/600/1000s/mm 2 v) all measured b-values. Mean signal intensity (SI) and standard deviation (SD) in the liver, spleen, kidney, bone marrow and in liver lesions were acquired. The coefficient of variation (CV = SD/SI), the differences of SI between measured and calculated high b-value images and the lesion contrast (SI lesion/liver) were computed., Results: With increasing upper measured b-values, the CV in cDWI and vcDWI decreased (CV in the liver in cb1500: 0.42 with b100/600 s/mm 2 and 0.28 with b100/b1000s/mm 2 ) while the differences of measured and calculated b-value images decreased (in the liver in cb1500: 30.7% with b = 100/600 s/mm 2 , 19.7% with b100/b1000s/mm 2 ). In diffusion-restricted lesions, lesion contrast was at least 1.6 in cb1000 and 1.4 in cb1500, respectively, with an upper measured b-value of b = 800 s/mm 2 and 2.1 for vcDWI with an upper measured b-value of b = 1000s/mm 2 . Overall, the lesion contrast was superior in cb1500 and vcDWI compared to cb1000 (15% and 11%, respectively)., Conclusion: Measuring higher upper b-values seems to lead to more precise computed high b-value images and a decrease of CV. vcDWI provides a comparable lesion contrast to b = 1500s/mm 2 and offers additionally the reduction of T2 shine-through effects. For vcDWI, measuring b = 1000s/mm 2 as upper b-value seems to be necessary to guarantee good lesion visibility in the liver based on our preliminary results.

The recent massive Zika virus (ZIKV) outbreak illustrates the need for rapid and specific diagnostic techniques. Detecting ZIKV in biological samples poses unique problems: antibody detection of ZIKV is insufficient due to cross-reactivity of Zika antibodies with other flaviviruses, and nucleic acid and protein biomarkers for ZIKV are detectable at different stages of infection. Here, we describe a new optofluidic approach for the parallel detection of different molecular biomarkers using multimode interference (MMI) waveguides. We report differentiated, multiplex detection of both ZIKV biomarker types using multi-spot excitation at two visible wavelengths with over 98% fidelity by combining several analysis techniques., Competing Interests: J.W.P., A.R.H., and H.S. have financial interest in Fluxus Inc. which is developing optofluidic devices.