Groundfish biodiversity change in northeastern Pacific waters under projected warming and deoxygenation.

In the coming decades, warming and deoxygenation of marine waters are anticipated to result in shifts in the distribution and abundance of fishes, with consequences for the diversity and composition of fish communities. Here, we combine fisheries-independent trawl survey data spanning the west coast of the USA and Canada with high-resolution regional ocean models to make projections of how 34 groundfish species will be impacted by changes in temperature and oxygen in British Columbia (BC) and Washington. In this region, species that are projected to decrease in occurrence are roughly balanced by those that are projected to increase, resulting in considerable compositional turnover. Many, but not all, species are projected to shift to deeper depths as conditions warm, but low oxygen will limit how deep they can go. Thus, biodiversity will likely decrease in the shallowest waters (less than 100 m), where warming will be greatest, increase at mid-depths (100-600 m) as shallow species shift deeper, and decrease at depths where oxygen is limited (greater than 600 m). These results highlight the critical importance of accounting for the joint role of temperature, oxygen and depth when projecting the impacts of climate change on marine biodiversity. This article is part of the theme issue 'Detecting and attributing the causes of biodiversity change: needs, gaps and solutions'.

Summary of Utah Project on Exfoliation Syndrome (UPEXS): using a large database to identify systemic comorbidities.

The purpose of the Utah Project on Exfoliation Syndrome (UPEXS) is to identify associations between exfoliation syndrome (XFS) and other diseases that share the commonality of abnormalities in elastin and Lysyl Oxidase-Like 1 gene regulation. The UPEXS is unique because it uses the Utah Population Database, which is linked to the Utah genealogy, that contains a compilation of large pedigrees of most families in the state of Utah that go back multiple generations (3 to ≥11). The health and medical records of these family members are linked to vital records and can be used effectively in studies focused on genetic disorders like XFS, where familial clustering of a disorder is a trend. There is increasing evidence that patients with XFS have a higher risk of certain systemic disorders that reflect the systemic tissue abnormalities of XFS. Epidemiological studies focused on patients with XFS have shown that there is an increased risk of these individuals developing other pathologies that have abnormalities in extracellular matrix metabolism and repair. UPEXS has focused on suspected comorbidities that involve abnormalities in elastin maintenance, a protein that plays a role in the makeup of the extracellular matrix. In this paper, the results from the analysis of chronic obstructive pulmonary disease, inguinal hernias, pelvic organ prolapse, obstructive sleep apnoea and atrial fibrillation are summarised along with the utility of using such a large dataset.

Simvastatin loaded chitosan guided bone regeneration membranes stimulate bone healing.

BACKGROUND AND OBJECTIVE: Electrospun chitosan membranes (ESCM) modified with short-chain fatty acids have the ability to control the release of simvastatin (SMV), an anti-cholesterol drug with osteogenic potential, for guided bone regeneration (GBR) applications. This study evaluated in vivo osteogenic effects of rapid short release of SMV (4 weeks) vs long sustained release (8 weeks) from acetic anhydride (AA)-and hexanoic anhydride (HA)-modified ESCMs, respectively. METHODS: AA ESCMs loaded with 10 or 50 µg SMV and HA ESCMs loaded with 50 µg SMV were evaluated for biocompatibility and bone formation at 4 and 8 weeks, in 5 mm critical size rat calvarial defects, using histological evaluation and micro-CT analysis. RESULTS: No severe inflammatory response was noticed around the ESCMs. Less hydrophobic AA membranes showed signs of resorption by week 4 and were almost completely resorbed by week 8 whereas the more hydrophobic HA membranes resorbed slowly, remaining intact over 8 weeks. In micro-CT analysis, 10 µg SMV-loaded AA membranes did not show significant bone formation as compared to non-loaded AA membranes at either evaluation time points. 50 µg SMV-loaded AA membranes stimulated significantly more bone formation than non-loaded AA membranes by week 4 (%bone = 31.0 ± 5.9% (AA50) vs 18.5 ± 13.7% (AA0)) but showed no difference at week 8. HA membranes with 50 µg SMV showed significantly more bone formation as compared to corresponding non-loaded membranes by week 8 (%bone = 61.7 ± 8.9% (HA50) vs 33.9 ± 29.7% (HA0)), though such an effect was not significant at week 4. CONCLUSION: These results indicate that modified ESCMs may be used to control the release of SMV and promote bone healing in GBR applications.

Time of Emergence and Large Ensemble Intercomparison for Ocean Biogeochemical Trends.

Anthropogenically forced changes in ocean biogeochemistry are underway and critical for the ocean carbon sink and marine habitat. Detecting such changes in ocean biogeochemistry will require quantification of the magnitude of the change (anthropogenic signal) and the natural variability inherent to the climate system (noise). Here we use Large Ensemble (LE) experiments from four Earth system models (ESMs) with multiple emissions scenarios to estimate Time of Emergence (ToE) and partition projection uncertainty for anthropogenic signals in five biogeochemically important upper-ocean variables. We find ToEs are robust across ESMs for sea surface temperature and the invasion of anthropogenic carbon; emergence time scales are 20-30 yr. For the biological carbon pump, and sea surface chlorophyll and salinity, emergence time scales are longer (50+ yr), less robust across the ESMs, and more sensitive to the forcing scenario considered. We find internal variability uncertainty, and model differences in the internal variability uncertainty, can be consequential sources of uncertainty for projecting regional changes in ocean biogeochemistry over the coming decades. In combining structural, scenario, and internal variability uncertainty, this study represents the most comprehensive characterization of biogeochemical emergence time scales and uncertainty to date. Our findings delineate critical spatial and duration requirements for marine observing systems to robustly detect anthropogenic change.

Tracking Improvement in Simulated Marine Biogeochemistry Between CMIP5 and CMIP6.

Purpose of Review: The changes or updates in ocean biogeochemistry component have been mapped between CMIP5 and CMIP6 model versions, and an assessment made of how far these have led to improvements in the simulated mean state of marine biogeochemical models within the current generation of Earth system models (ESMs). Recent Findings: The representation of marine biogeochemistry has progressed within the current generation of Earth system models. However, it remains difficult to identify which model updates are responsible for a given improvement. In addition, the full potential of marine biogeochemistry in terms of Earth system interactions and climate feedback remains poorly examined in the current generation of Earth system models. Summary: Increasing availability of ocean biogeochemical data, as well as an improved understanding of the underlying processes, allows advances in the marine biogeochemical components of the current generation of ESMs. The present study scrutinizes the extent to which marine biogeochemistry components of ESMs have progressed between the 5th and the 6th phases of the Coupled Model Intercomparison Project (CMIP).

Variations of MRI-assessed peristaltic motions during radiation therapy.

PURPOSE: Understanding complex abdominal organ motion is essential for motion management in radiation therapy (RT) of abdominal tumors. This study investigates abdominal motion induced by respiration and peristalsis, during various time durations relevant to RT, using various CT and MRI techniques acquired under free breathing (FB) and breath hold (BH). METHODS: A series of CT and MRI images acquired with various techniques under free breathing and/or breath hold from 37 randomly-selected pancreatic or liver cancer patients were analyzed to assess the motion in various time frames. These data include FB 4DCT from 15 patients (for motion in time duration of 5 sec), FB 2D cine-MRI from 4 patients (time duration of 1.7 min, 1 second acquisition time per slice), FB cine-MRI acquired using MR-Linac from 6 patients in various fractions (acquisition time is less than 0.6 seconds per slice), FB 4DMRI from 2 patients (time duration of 2 min), respiration-gated T2 with gating at the end expiration (time duration of 3-5 min), and BH T1 with multiphase dynamic contrast in acquisition times of 17 seconds for each of five phases (pre-contrast, arterial, venous, portal venous and delayed post-contrast) from 10 patients. Motions of various organs including gallbladder (GB) and liver were measured based on these MRI data. The GB motion includes both respiration and peristalsis, while liver motion is primarily respiration. By subtracting liver motion (respiration) from GB motion (respiration and peristalsis), the peristaltic motion, along with small residual motion, was obtained. RESULTS: From cine-MRI, the residual motion beyond the respiratory motion was found to be up to 0.6 cm in superior-inferior (SI) and 0.55 cm in anterior-posterior (AP) directions. From 2D cine-MRI acquired by the MR-Linac, different peristaltic motions were found from different fractions for each patient. The peristaltic motion was found to vary between 0.3-1 cm. From BH T1 phase images, the average motions that were primarily due to peristalsis movements were found to be 1.2 cm in SI, 0.7 cm in AP, and 0.9 cm in left-right (LR) directions. The average motions assessed from 4DCT were 1.0 cm in SI and 0.3 cm in AP directions, which were generally smaller than the motions assessed from cine-MRI, i.e., 1.8 cm in SI and 0.6 cm in AP directions, for the same patients. However, average motions from 4DMRI, which are coming from respiratory were measured to be 1.5, 0.5, and 0.4 cm in SI, AP, and LR directions, respectively. CONCLUSION: The abdominal motion due to peristalsis can be similar in magnitude to respiratory motion as assessed. These motions can be irregular and persistent throughout the imaging and RT delivery procedures, and should be considered together with respiratory motion during RT for abdominal tumors.

Improving Communication Between Surgery and Critical Care Teams: Beyond the Handover.

BACKGROUND: Structured communication tools for postoperative surgical handover to the intensive care unit (ICU) have shown promise, yet little work has addressed ongoing daily communication between the surgery and ICU teams thereafter. OBJECTIVES: Evaluation of a novel, 2-part communication intervention between surgery and ICU teams focused on postoperative handover and ongoing daily communication. METHODS: A mixed-methods, pre- and postintervention survey study was conducted in a closed quaternary medical-surgical ICU. Study participants (N = 112) included ICU physicians, nurses, allied health professionals, and physicians on the surgical team. The intervention consisted of a handover checklist completed postoperatively on arrival in the ICU and a 5-item communication tool completed daily by the surgical team. RESULTS: Satisfaction improved significantly in the following areas: postoperative handover communication (P < .001), daily communication (P = .001), understanding the postoperative plan (P < .001), initiation of deep vein thrombosis prophylaxis (P = .008), initiation of feeding (P = .009), and daily primary resident contact (P = .008). No significant improvement was seen in communication regarding disposition or overall improvement in patient safety risk from communication errors. CONCLUSIONS: A simple handover checklist improved health care practitioner satisfaction with communication during postoperative handover to the ICU. Concise daily communication tools are an appropriate option for improving ongoing communication between surgeons and the ICU team thereafter.

Hierarchical attention networks for information extraction from cancer pathology reports.

OBJECTIVE: We explored how a deep learning (DL) approach based on hierarchical attention networks (HANs) can improve model performance for multiple information extraction tasks from unstructured cancer pathology reports compared to conventional methods that do not sufficiently capture syntactic and semantic contexts from free-text documents. MATERIALS AND METHODS: Data for our analyses were obtained from 942 deidentified pathology reports collected by the National Cancer Institute Surveillance, Epidemiology, and End Results program. The HAN was implemented for 2 information extraction tasks: (1) primary site, matched to 12 International Classification of Diseases for Oncology topography codes (7 breast, 5 lung primary sites), and (2) histological grade classification, matched to G1-G4. Model performance metrics were compared to conventional machine learning (ML) approaches including naive Bayes, logistic regression, support vector machine, random forest, and extreme gradient boosting, and other DL models, including a recurrent neural network (RNN), a recurrent neural network with attention (RNN w/A), and a convolutional neural network. RESULTS: Our results demonstrate that for both information tasks, HAN performed significantly better compared to the conventional ML and DL techniques. In particular, across the 2 tasks, the mean micro and macro F-scores for the HAN with pretraining were (0.852,0.708), compared to naive Bayes (0.518, 0.213), logistic regression (0.682, 0.453), support vector machine (0.634, 0.434), random forest (0.698, 0.508), extreme gradient boosting (0.696, 0.522), RNN (0.505, 0.301), RNN w/A (0.637, 0.471), and convolutional neural network (0.714, 0.460). CONCLUSIONS: HAN-based DL models show promise in information abstraction tasks within unstructured clinical pathology reports.

Fabrication and characterization of UV-emitting nanoparticles as novel radiation sensitizers targeting hypoxic tumor cells.

Radiation therapy is one of the primary therapeutic techniques for treating cancer, administered to nearly two-thirds of all cancer patients. Although largely effective in killing cancer cells, radiation therapy, like other forms of cancer treatment, has difficulty dealing with hypoxic regions within solid tumors. The incomplete killing of cancer cells can lead to recurrence and relapse. The research presented here is investigating the enhancement of the efficacy of radiation therapy by using scintillating nanoparticles that emit UV photons. UV photons, with wavelengths between 230 nm and 280 nm, are able to inactivate cells due to their direct interaction with DNA, causing a variety of forms of damage. UV-emitting nanoparticles will enhance the treatment in two ways: first by generating UV photons in the immediate vicinity of cancer cells, leading to direct and oxygen-independent DNA damage, and second by down-converting the applied higher energy X-rays into softer X-rays and particles that are more efficiently absorbed in the targeted tumor region. The end result will be nanoparticles with a higher efficacy in the treatment of hypoxic cells in the tumor, filling an important, unmet clinical need. Our preliminary experiments show an increase in cell death using scintillating LuPO4:Pr nanoparticles over that achieved by the primary radiation alone. This work describes the fabrication of the nanoparticles, their physical characterization, and the spectroscopic characterization of the UV emission. The work also presents in vitro results that demonstrate an enhanced efficacy of cell killing with x-rays and a low unspecific toxicity of the nanoparticles.

Compact dual-mode diffuse optical system for blood perfusion monitoring in a porcine model of microvascular tissue flaps.

In reconstructive surgery, the ability to detect blood flow interruptions to grafted tissue represents a critical step in preventing postsurgical complications. We have developed and pilot tested a compact, fiber-based device that combines two complimentary modalities-diffuse correlation spectroscopy (DCS) and diffuse reflectance spectroscopy-to quantitatively monitor blood perfusion. We present a proof-of-concept study on an in vivo porcine model (n=8). With a controllable arterial blood flow supply, occlusion studies (n=4) were performed on surgically isolated free flaps while the device simultaneously monitored blood flow through the supplying artery as well as flap perfusion from three orientations: the distal side of the flap and two transdermal channels. Further studies featuring long-term monitoring, arterial failure simulations, and venous failure simulations were performed on flaps that had undergone an anastomosis procedure (n=4). Additionally, benchtop verification of the DCS system was performed on liquid flow phantoms. Data revealed relationships between diffuse optical measures and state of occlusion as well as the ability to detect arterial and venous compromise. The compact construction of the device, along with its noninvasive and quantitative nature, would make this technology suitable for clinical translation.

A capillary-mimicking optical tissue phantom for diffuse correlation spectroscopy.

Optical tissue phantoms are necessary for instrument benchmarking and providing a consistent baseline for experiments in various fields of tissue spectroscopy, including diffuse correlation spectroscopy (DCS). To provide the most useful comparisons, a phantom would ideally mimic tissue as closely as possible, including the geometry of static and dynamic scatterers. A branching design that keeps the capillary cross section constant ensures that the same flow velocity is found throughout the phantom while allowing for single input and output fittings to feed all of the capillaries simultaneously. The direction of each capillary is randomized every few millimeters by randomly allocating 2 by 2 "twisting" squares within each layer. These squares swap the locations of four adjacent artificial capillaries either clockwise or counterclockwise. Numerical simulations were used to verify the random walk-like behavior of the capillary paths resulting from this pattern. This is a step toward replicating the randomly varying directionality of actual capillaries. This design was verified by taking DCS measurements at different flow rates of Intralipid through the phantom, demonstrating the effect of the flow rate on the characteristic decay time of the autocorrelation.

Novel diffuse optics system for continuous tissue viability monitoring - extended recovery in vivo testing in a porcine flap model.

In reconstructive surgery, tissue perfusion/vessel patency is critical to the success of microvascular free tissue flaps. Early detection of flap failure secondary to compromise of vascular perfusion would significantly increase the chances of flap salvage. We have developed a compact, clinically-compatible monitoring system to enable automated, minimally-invasive, continuous, and quantitative assessment of flap viability/perfusion. We tested the system's continuous monitoring capability during extended non-recovery surgery using an in vivo porcine free flap model. Initial results indicated that the system could assess flap viability/perfusion in a quantitative and continuous manner. With proven performance, the compact form constructed with cost-effective components would make this system suitable for clinical translation.

In vivo preclinical verification of a multimodal diffuse reflectance and correlation spectroscopy system for sensing tissue perfusion.

In reconstructive surgery, impeded blood flow in microvascular free flaps due to a compromise in arterial or venous patency secondary to blood clots or vessel spasms can rapidly result in flap failures. Thus, the ability to detect changes in microvascular free flaps is critical. In this paper, we report progress on in vivo pre-clinical testing of a compact, multimodal, fiber-based diffuse correlation and reflectance spectroscopy system designed to quantitatively monitor tissue perfusion in a porcine model's surgically-grafted free flap. We also describe the device's sensitivity to incremental blood flow changes and discuss the prospects for continuous perfusion monitoring in future clinical translational studies.

Design verification of a compact system for detecting tissue perfusion using bimodal diffuse optical technologies.

It is essential to monitor tissue perfusion during and after reconstructive surgery, as restricted blood flow can result in graft failures. Current clinical procedures are insufficient to monitor tissue perfusion, as they are intermittent and often subjective. To address this unmet clinical need, a compact, low-cost, multimodal diffuse correlation spectroscopy and diffuse reflectance spectroscopy system was developed. We verified system performance via tissue phantoms and experimental protocols for rigorous bench testing. Quantitative data analysis methods were employed and tested to enable the extraction of tissue perfusion parameters. This design verification study assures data integrity in future in vivo studies.

Effects of cranberry components on IL-1ß-stimulated production of IL-6, IL-8 and VEGF by human TMJ synovial fibroblasts.

OBJECTIVE: Osteoarthritis (OA) in the TMJ is characterized by deterioration of articular cartilage and secondary inflammatory changes. Interleukin-1ß (IL-1ß) stimulates IL-6, IL-8, and vascular endothelial growth factor (VEGF) in synovial fluid of TMJ with internal derangement and bony changes. The cranberry (Vaccinium macrocarpon) contains polyphenolic compounds that inhibit production of pro-inflammatory molecules by gingival cells in response to several stimulators. This study examined effects of cranberry components on IL-1ß-stimulated IL-6, IL-8, and VEGF production by human TMJ synovial fibroblast-like cells. DESIGN: Cranberry high molecular weight non-dialyzable material (NDM) was derived from cranberry juice. Human TMJ synovial fibroblast-like cells from joints with degenerative OA and an ankylosed TMJ without degeneration were incubated with IL-1ß (0.001-1nM)±NDM (25-250µg/ml) (2h preincubation). Viability was assessed via activity of a mitochondrial enzyme. IL-6, IL-8, and VEGF in culture supernatants were measured by ELISA; NF-κB and AP-1 transcription factors were measured in nuclear extracts via binding to specific oligonucleotides. DATA ANALYSIS: ANOVA and Scheffe's F procedure for post hoc comparisons. RESULTS: NDM did not affect cell viability but inhibited IL-1ß stimulated IL-6, IL-8, and VEGF production in all cell lines (p<0.05). NDM partially reduced nuclear levels of NF-κB and AP-1 (p<0.04), depending upon cell line and time of exposure to IL-1ß+NDM. CONCLUSION: Cranberry NDM inhibition of IL-1ß-stimulated IL- 6, IL-8, and VEGF production by TMJ synovial fibroblast-like cells suggests that cranberry components may be useful as a host modulatory therapeutic agent to prevent or treat inflammatory arthropathies of the TMJ.

Instrument to detect syncope and the onset of shock.

Currently the diagnosis of hemorrhagic shock is essentially clinical, relying on the expertise of nurses and doctors. One of the first measurable physiological changes that marks the onset of hemorrhagic shock is a decrease in capillary blood flow. Diffuse correlation spectroscopy (DCS) quantifies this decrease. DCS collects and analyzes multiply scattered, coherent, near infrared light to assess relative blood flow. This work presents a preliminary study using a DCS instrument with human subjects undergoing a lower body negative pressure (LBNP) protocol. This work builds on previous successful DCS instrumentation development and we believe it represents progress toward understanding how DCS can be used in a clinical setting.

A disposable, flexible skin patch for clinical optical perfusion monitoring at multiple depths.

Stable, relative localization of source and detection fibers is necessary for clinical implementation of quantitative optical perfusion monitoring methods such as diffuse correlation spectroscopy (DCS) and diffuse reflectance spectroscopy (DRS). A flexible and compact device design is presented as a platform for simultaneous monitoring of perfusion at a range of depths, enabled by precise location of optical fibers in a robust and secure adhesive patch. We will discuss preliminary data collected on human subjects in a lower body negative pressure model for hypovolemic shock. These data indicate that this method facilitates simple and stable simultaneous monitoring of perfusion at multiple depths and within multiple physiological compartments.

A scalable correlator for multichannel diffuse correlation spectroscopy.

Diffuse correlation spectroscopy (DCS) is a technique which enables powerful and robust non-invasive optical studies of tissue micro-circulation and vascular blood flow. The technique amounts to autocorrelation analysis of coherent photons after their migration through moving scatterers and subsequent collection by single-mode optical fibers. A primary cost driver of DCS instruments are the commercial hardware-based correlators, limiting the proliferation of multi-channel instruments for validation of perfusion analysis as a clinical diagnostic metric. We present the development of a low-cost scalable correlator enabled by microchip-based time-tagging, and a software-based multi-tau data analysis method. We will discuss the capabilities of the instrument as well as the implementation and validation of 2- and 8-channel systems built for live animal and pre-clinical settings.

A compact instrument to measure perfusion of vasculature in transplanted maxillofacial free flaps.

The vascularization and resulting perfusion of transferred tissues are critical to the success of grafts in buried free flap transplantations. To enable long-term clinical monitoring of grafted tissue perfusion during neovascularization and endothelialization, we are developing an implantable instrument for the continuous monitoring of perfusion using diffuse correlation spectroscopy (DCS), and augmented with diffuse reflectance spectroscopy (DRS). This work discusses instrument construction, integration, and preliminary results using a porcine graft model.

A Study of Position-Sensitive Solid-State Photomultiplier Signal Properties.

We present an analysis of the signal properties of a position-sensitive solid-state photomultiplier (PS-SSPM) that has an integrated resistive network for position sensing. Attractive features of PS-SSPMs are their large area and ability to resolve small scintillator crystals. However, the large area leads to a high detector capacitance, and in order to achieve high spatial resolution a large network resistor value is required. These inevitably create a low-pass filter that drastically slows what would be a fast micro-cell discharge pulse. Significant changes in the signal shape of the PS-SSPM cathode output as a function of position are observed, which result in a position-dependent time delay when using traditional time pick-off methods such as leading edge discrimination and constant fraction discrimination. The timing resolution and time delay, as a function of position, were characterized for two different PS-SSPM designs, a continuous 10 mm × 10 mm PS-SSPM and a tiled 2 × 2 array of 5 mm × 5 mm PS-SSPMs. After time delay correction, the block timing resolution, measured with a 6 × 6 array of 1.3 × 1.3 × 20 mm3 LSO crystals, was 8.6 ns and 8.5 ns, with the 10 mm PS-SSPM and 5 mm PS-SSPM respectively. The effect of crystal size on timing resolution was also studied, and contrary to expectation, a small improvement was measured when reducing the crystal size from 1.3 mm to 0.5 mm. Digital timing methods were studied and showed great promise for allowing accurate timing by implementation of a leading edge time pick-off. Position-dependent changes in signal shape on the anode side also are present, which complicates peak height data acquisition methods used for positioning. We studied the effect of trigger position on signal amplitude, flood histogram quality, and depth-of-interaction resolution in a dual-ended readout detector configuration. We conclude that detector timing and positioning can be significantly improved by implementation of digital timing methods and by accounting for changes in the shape of the signals from PS-SSPMs.