Smaller body size under warming is not due to gill-oxygen limitation in a cold-water salmonid.

Declining body size in fishes and other aquatic ectotherms associated with anthropogenic climate warming has significant implications for future fisheries yields, stock assessments and aquatic ecosystem stability. One proposed mechanism seeking to explain such body-size reductions, known as the gill oxygen limitation (GOL) hypothesis, has recently been used to model future impacts of climate warming on fisheries but has not been robustly empirically tested. We used brook trout (Salvelinus fontinalis), a fast-growing, cold-water salmonid species of broad economic, conservation and ecological value, to examine the GOL hypothesis in a long-term experiment quantifying effects of temperature on growth, resting metabolic rate (RMR), maximum metabolic rate (MMR) and gill surface area (GSA). Despite significantly reduced growth and body size at an elevated temperature, allometric slopes of GSA were not significantly different than 1.0 and were above those for RMR and MMR at both temperature treatments (15°C and 20°C), contrary to GOL expectations. We also found that the effect of temperature on RMR was time-dependent, contradicting the prediction that heightened temperatures increase metabolic rates and reinforcing the importance of longer-term exposures (e.g. >6 months) to fully understand the influence of acclimation on temperature-metabolic rate relationships. Our results indicate that although oxygen limitation may be important in some aspects of temperature-body size relationships and constraints on metabolic supply may contribute to reduced growth in some cases, it is unlikely that GOL is a universal mechanism explaining temperature-body size relationships in aquatic ectotherms. We suggest future research focus on alternative mechanisms underlying temperature-body size relationships, and that projections of climate change impacts on fisheries yields using models based on GOL assumptions be interpreted with caution.

Stewardship-Guided T2Candida Testing Shortens Time to Antifungal Treatment and Reduces Antifungal Usage Among Medical Intensive Care Unit Patients With Septic Shock.

Background: Diagnosis of invasive candidiasis (IC) is limited by insensitivity and slow turnaround of cultures. Our objectives were to define the performance of T2Candida, a nonculture test, under guidance of a diagnostic stewardship program, and evaluate impact on time to antifungal initiation and antifungal utilization. Methods: This was a retrospective study of adult medical intensive care unit (MICU) patients with septic shock for whom T2Candida testing was performed from March 2017 to March 2020. Patients with positive T2Candida results during this period were compared to MICU patients who did not undergo T2Candida testing but had septic shock and blood cultures positive for Candida from January 2016 through March 2020. Results: Overall, 155 T2Candida tests from 143 patients were included. Nine percent of T2Candida tests were positive compared to 4.5% of blood cultures. Sensitivity, specificity, positive predictive value, and negative predictive value of T2Candida for proven and probable IC were 78%, 95%, 50%, and 99%, respectively. Patients who tested positive for T2Candida (n = 14) were diagnosed earlier and initiated on antifungal therapy sooner than patients with IC (n = 14) diagnosed by blood culture alone (median, 5.6 vs 60 hours; P < .0001). Median antifungal days of therapy/1000 patient-days were 23.3/month preimplementation and 15/month postimplementation (P  = .007). Following a negative T2Candida result, empiric antifungals were either not administered in 58% or discontinued within 72 hours in 96% of patients. Conclusions: Diagnostic stewardship guided T2Candida testing resulted in reduced time to IC diagnosis, faster initiation of antifungal therapy, and lower antifungal usage among MICU patients with septic shock.

Review of Deep Learning Approaches for Interleaved Photoacoustic and Ultrasound (PAUS) Imaging.

Photoacoustic (PA) imaging provides optical contrast at relatively large depths within the human body, compared to other optical methods, at ultrasound (US) spatial resolution. By integrating real-time PA and US (PAUS) modalities, PAUS imaging has the potential to become a routine clinical modality bringing the molecular sensitivity of optics to medical US imaging. For applications where the full capabilities of clinical US scanners must be maintained in PAUS, conventional limited view and bandwidth transducers must be used. This approach, however, cannot provide high-quality maps of PA sources, especially vascular structures. Deep learning (DL) using data-driven modeling with minimal human design has been very effective in medical imaging, medical data analysis, and disease diagnosis, and has the potential to overcome many of the technical limitations of current PAUS imaging systems. The primary purpose of this article is to summarize the background and current status of DL applications in PAUS imaging. It also looks beyond current approaches to identify remaining challenges and opportunities for robust translation of PAUS technologies to the clinic.

Possible depth-resolved reconstruction of shear moduli in the cornea following collagen crosslinking (CXL) with optical coherence tomography and elastography.

Corneal collagen crosslinking (CXL) is commonly used to prevent or treat keratoconus. Although changes in corneal stiffness induced by CXL surgery can be monitored with non-contact dynamic optical coherence elastography (OCE) by tracking mechanical wave propagation, depth dependent changes are still unclear if the cornea is not crosslinked through the whole depth. Here, phase-decorrelation measurements on optical coherence tomography (OCT) structural images are combined with acoustic micro-tapping (AµT) OCE to explore possible reconstruction of depth-dependent stiffness within crosslinked corneas in an ex vivo human cornea sample. Experimental OCT images are analyzed to define the penetration depth of CXL into the cornea. In a representative ex vivo human cornea sample, crosslinking depth varied from ∼100 µm in the periphery to ∼150 µm in the cornea center and exhibited a sharp in-depth transition between crosslinked and untreated areas. This information was used in an analytical two-layer guided wave propagation model to quantify the stiffness of the treated layer. We also discuss how the elastic moduli of partially CXL-treated cornea layers reflect the effective engineering stiffness of the entire cornea to properly quantify corneal deformation.

Possible depth-resolved reconstruction of shear moduli in the cornea following collagen crosslinking (CXL) with optical coherence tomography and elastography.

Corneal collagen crosslinking (CXL) is commonly used to prevent or treat keratoconus. Although changes in corneal stiffness induced by CXL surgery can be monitored with non-contact dynamic optical coherence elastography (OCE) by tracking mechanical wave propagation, depth dependent changes are still unclear if the cornea is not crosslinked through the whole depth. Here, phase-decorrelation measurements on optical coherence tomography (OCT) structural images are combined with acoustic micro-tapping (A$\mu$T) OCE to explore possible reconstruction of depth-dependent stiffness within crosslinked corneas in an ex vivo human cornea sample. Experimental OCT images are analyzed to define the penetration depth of CXL into the cornea. In a representative ex vivo human cornea sample, crosslinking depth varied from $\sim 100\mu m$ in the periphery to $\sim 150\mu m$ in the cornea center and exhibited a sharp in-depth transition between crosslinked and untreated areas. This information was used in an analytical two-layer guided wave propagation model to quantify the stiffness of the treated layer. We also discuss how the elastic moduli of partially CXL-treated cornea layers reflect the effective engineering stiffness of the entire cornea to properly quantify corneal deformation.

Noncontact Acoustic Micro-Tapping Optical Coherence Elastography for Quantification of Corneal Anisotropic Elasticity: In Vivo Rabbit Study.

Purpose: The purpose of this study was to demonstrate accurate measurement of corneal elastic moduli in vivo with noncontact and noninvasive optical coherence elastography. Methods: Elastic properties (in-plane Young's modulus, E, and both in-plane, µ, and out-of-plane, G, shear moduli) of rabbit cornea were quantified in vivo using noncontact dynamic acoustic micro-tapping optical coherence elastography (AµT-OCE). The intraocular pressure (IOP)-dependence of measured mechanical properties was explored in extracted whole globes following in vivo measurement. A nearly incompressible transverse isotropic (NITI) model was used to reconstruct moduli from AµT-OCE data. Independently, cornea elastic moduli were also measured ex vivo with traditional, destructive mechanical tests (tensile extensometry and shear rheometry). Results: Our study demonstrates strong anisotropy of corneal elasticity in rabbits. The in-plane Young's modulus, computed as E = 3µ, was in the range of 20 MPa to 44 MPa, whereas the out-of-plane shear modulus was in the range of 34 kPa to 261 kPa. Both pressure-dependent ex vivo OCE and destructive mechanical tests performed on the same samples within an hour of euthanasia strongly support the results of AµT-OCE measurements. Conclusions: Noncontact AµT-OCE can noninvasively quantify cornea anisotropic elastic properties in vivo. Translational Relevance: As optical coherence tomography (OCT) is broadly accepted in ophthalmology, these results suggest the potential for rapid translation of AµT-OCE into clinical practice. In addition, AµT-OCE can likely improve diagnostic criteria of ectatic corneal diseases, leading to early diagnosis, reduced complications, customized surgical treatment, and personalized biomechanical models of the eye.

Non-contact acoustic micro-tapping optical coherence elastography for quantification of corneal anisotropic elasticity: in vivo rabbit study.

PURPOSE: To demonstrate accurate measurement of corneal elastic moduli in vivo with non-contact and non-invasive optical coherence elastography. METHODS: Elastic properties (in-plane Young's modulus E and both in-plane, u, and out-of-plane, G, shear moduli) of rabbit cornea were quantified in vivo using non-contact dynamic Acoustic micro-Tapping Optical Coherence Elastography (AuT-OCE). The IOP-dependence of measured mechanical properties was explored in extracted whole globes following in vivo measurement. A nearly-incompressible transverse isotropic (NITI) model was used to reconstruct moduli from AuT-OCE data. Independently, cornea elastic moduli were also measured ex vivo with traditional, destructive mechanical tests (tensile extensometry and shear rheometry). RESULTS: Our study demonstrates strong anisotropy of corneal elasticity in rabbits. The in-plane Young's modulus, computer as E=3u, was in the range of 20-44 MPa, whereas the out-of-plane shear modulus was in the range of 34-261 kPa. Both pressure-dependent ex vivo OCE and destructive mechanical tests performed on the same samples within an hour of euthanasia strongly support the results of AuT-OCE measurements. CONCLUSIONS: Non-contact AuT-OCE can non-invasively quantify cornea anisotropic elastic properties in vivo. TRANSLATIONAL RELEVANCE: As OCT is broadly accepted in Ophthalmology, these results suggest the potential for rapid translation of AuT-OCE into clinical practice. In addition, AuT-OCE can likely improve diagnostic criteria of ectatic corneal diseases, leading to early diagnosis, reduced complications, customized surgical treatment, and personalized biomechanical models of the eye.

Neural correlates associated with conformity in adolescent and young adult men.

Social influence affects us throughout our lives, shaping our attitudes, behaviors, and preferences. Thus, the current study aimed to examine whether key age groups (adolescence versus young adulthood) were associated with differences in neural correlates associated with processing social feedback and conformity (i.e., conflict detection, positive valuation, and mentalizing) among young men. We recruited 153 participants across 5 studies, who completed a social influence task during an fMRI scan. Overall, participants were more likely to conform by changing their ratings when misaligned with others, and adolescents were more likely to conform when misaligned (compared to aligned) with others compared to young adults. Further, we found that adolescents showed increased activity in mentalizing (TPJ, dmPFC) and positive valuation regions (VS, vmPFC), compared to young adults, in response to misalignment with others. In contrast, young adults showed increased activity in conflict detection regions (AI, dACC) when exposed to feedback that they were misaligned with others and when conforming to that feedback. Overall, our results offer initial evidence that adolescent and young adult men engage different neural processes when they find out they are misaligned with others and when conforming to the recommendations of others, and this difference appears to track with brain responses in conflict detection, mentalizing and value regions. DATA STATEMENT: Raw data and analysis codes are available upon request.

Acoustic Micro-Tapping Optical Coherence Elastography to Quantify Corneal Collagen Cross-Linking: An Ex Vivo Human Study.

Purpose: To evaluate changes in the anisotropic elastic properties of ex vivo human cornea treated with ultraviolet cross-linking (CXL) using noncontact acoustic micro-tapping optical coherence elastography (AµT-OCE). Design: Acoustic micro-tapping OCE was performed on normal and CXL human donor cornea in an ex vivo laboratory study. Subjects: Normal human donor cornea (n = 22) divided into 4 subgroups. All samples were stored in optisol. Methods: Elastic properties (in-plane Young's, E, and out-of-plane, G, shear modulus) of normal and ultraviolet CXL-treated human corneas were quantified using noncontact AµT-OCE. A nearly incompressible transverse isotropic model was used to reconstruct moduli from AµT-OCE data. Independently, cornea elastic moduli were also measured with destructive mechanical tests (tensile extensometry and shear rheometry). Main Outcome Measures: Corneal elastic moduli (in-plane Young's modulus, E, in-plane, µ, and out-of-plane, G, shear moduli) can be evaluated in both normal and CXL treated tissues, as well as monitored during the CXL procedure using noncontact AµT-OCE. Results: Cross-linking induced a significant increase in both in-plane and out-of-plane elastic moduli in human cornea. The statistical mean in the paired study (presurgery and postsurgery, n = 7) of the in-plane Young's modulus, E = 3 µ , increased from 19 MPa to 43 MPa, while the out-of-plane shear modulus, G, increased from 188 kPa to 673 kPa. Mechanical tests in a separate subgroup support CXL-induced cornea moduli changes and generally agree with noncontact AµT-OCE measurements. Conclusions: The human cornea is a highly anisotropic material where in-plane mechanical properties are very different from those out-of-plane. Noncontact AµT-OCE can measure changes in the anisotropic elastic properties in human cornea as a result of ultraviolet CXL.

Genetic and Morphological Variation in Hypodontia of Maxillary Lateral Incisors.

(1) Background: Hypodontia has a multifactorial aetiology, in which genetic factors are a major component. Associated with this congenital absence, the formed teeth may show differences in size and shape, which may vary with the specific genetic variants and with the location of the missing teeth. The aims of the present study were to investigate a specific variant of MSX1, derive morphometric tooth measurements in a sample of patients with isolated maxillary lateral incisor agenesis and matched controls, and model the findings. (2) Methods: Genotyping of the MSX1 rs8670 genetic variant and morphometric measurements with a 2D image analysis method were performed for 26 hypodontia patients and 26 matched controls. (3) Results: The risk of upper lateral incisor agenesis was 6.9 times higher when the T allele was present. The morphometric parameters showed significant differences between hypodontia patients and controls and between the unilateral and bilateral agenesis cases. The most affected crown dimension in the hypodontia patients was the bucco-lingual dimension. In crown shape there was significant variation the Carabelli trait in upper first molars. (4) Conclusions: The MSX1 rs8670 variant was associated with variations in morphological outcomes. The new findings for compensatory interactions between the maxillary incisors indicate that epigenetic and environmental factors interact with this genetic variant. A single-level directional complex interactive network model incorporates the variations seen in this study.

Design and Conduct of Randomized Clinical Trials Evaluating Surgical Innovations in Ophthalmology: A Systematic Review.

PURPOSE: Surgical innovations are necessary to improve patient care. After an initial exploratory phase, novel surgical technique should be compared with alternative options or standard care in randomized controlled trials (RCTs). However, surgical RCTs have unique methodological challenges. Our study sought to investigate key aspects of the design, conduct, and reporting of RCTs of novel surgeries. DESIGN: Systematic review. METHODS: The protocol was prospectively registered in PROSPERO (CRD42021253297). RCTs evaluating novel surgeries for cataract, vitreoretinal, glaucoma, and corneal diseases were included. Medline, EMBASE, Cochrane Library, and Clinicaltrials.gov were searched. The search period was January 1, 2016, to June 16, 2021. RESULTS: A total of 52 ophthalmic surgery RCTs were identified in the fields of glaucoma (n = 12), vitreoretinal surgery (n = 5), cataract (n = 19), and cornea (n = 16). A description defining the surgeon's experience or level of expertise was reported in 30 RCTs (57%) and was presented in both control and intervention groups in 11 (21%). Specification of the number of cases performed in the particular surgical innovation being assessed prior to the trial was reported in 10 RCTs (19%) and an evaluation of quality of the surgical intervention in 7 (13%). Prospective trial registration was recorded in 12 RCTs (23%) and retrospective registration in 13 (25%); and there was no registration record in the remaining 28 (53%) studies. CONCLUSIONS: Important aspects of the study design such as the surgical learning curve, surgeon's previous experience, quality assurance, and trial registration details were often missing in novel ophthalmic surgical procedures. The Idea, Development, Exploration, Assessment, Long-term follow-up (IDEAL) framework aims to improve the quality of study design.

Identifying mechanisms underlying individual body size increases in a changing, highly seasonal environment: The growing trout of West brook.

As air temperature increases, it has been suggested that smaller individual body size may be a general response to climate warming. However, for ectotherms inhabiting cold, highly seasonal environments, warming temperatures may increase the scope for growth and result in larger body size. In a long-term study of individual brook trout Salvelinus fontinalis and brown trout Salmo trutta inhabiting a small stream network, individual lengths increased over the course of 15 years. As size-selective gains and losses to the population acted to reduce body sizes and mean body size at first tagging in the autumn (<60 mm) were not observed to change substantially over time, the increase in body size was best explained by higher individual growth rates. For brook trout, increasing water temperatures during the spring (when both trout species accomplish most of their total annual growth) was the primary driver of growth rate for juvenile fish and the environmental factor which best explained increases in individual body size over time. For brown trout, by contrast, reduction in and subsequent elimination of juvenile Atlantic salmon Salmo salar midway through the study period explained most of the increases in juvenile growth and body size. In addition to these major trends, a considerable amount of interannual variation in trout growth and body size was explained by other abiotic (stream flow) and biotic (population density) factors with the direction and magnitude of these effects differing by season, age-class and species. For example, stream flow was the dominant growth rate driver for adult fish with strong positive effects in the summer and autumn, but flow variation could not explain increases in body size as we observed no trend in flow. Overall, our work supports the general contention that for high-latitude ectotherms, increasing spring temperatures associated with a warming climate can result in increased growth and individual body size (up to a point), but context-dependent change in other factors can substantially contribute to both interannual variation and longer-term effects.

Current Source Density Imaging Using Regularized Inversion of Acoustoelectric Signals.

Acoustoelectric (AE) imaging can potentially image biological currents at high spatial (~mm) and temporal (~ms) resolution. However, it does not directly map the current field distribution due to signal modulation by the acoustic field and electric lead fields. Here we present a new method for current source density (CSD) imaging. The fundamental AE equation is inverted using truncated singular value decomposition (TSVD) combined with Tikhonov regularization, where the optimal regularization parameter is found based on a modified L-curve criterion with TSVD. After deconvolution of acoustic fields, the current field can be directly reconstructed from lead field projections and the CSD image computed from the divergence of that field. A cube phantom model with a single dipole source was used for both simulation and bench-top phantom studies, where 2D AE signals generated by a 0.6 MHz 1.5D array transducer were recorded by orthogonal leads in a 3D Cartesian coordinate system. In simulations, the CSD reconstruction had significantly improved image quality and current source localization compared to AE images, and performance further improved as the fractional bandwidth (BW) increased. Similar results were obtained in the phantom with a time-varying current injected. Finally, a feasibility study using an in vivo swine heart model showed that optimally reconstructed CSD images better localized the current source than AE images over the cardiac cycle.

Spatial resolution in optical coherence elastography of bounded media.

Dynamic optical coherence elastography (OCE) tracks mechanical wave propagation in the subsurface region of tissue to image its shear modulus. For bulk shear waves, the lateral resolution of the reconstructed modulus map (i.e., elastographic resolution) can approach that of optical coherence tomography (OCT), typically a few tens of microns. Here we perform comprehensive numerical simulations and acoustic micro-tapping OCE experiments to show that for the typical situation of guided wave propagation in bounded media, such as cornea, the elastographic resolution cannot reach the OCT resolution and is mainly defined by the thickness of the bounded tissue layer. We considered the excitation of both broadband and quasi-harmonic guided waves in a bounded, isotropic medium. Leveraging the properties of broadband pulses, a robust method for modulus reconstruction with minimum artifacts at interfaces is demonstrated. In contrast, tissue bounding creates large instabilities in the phase of harmonic waves, leading to serious artifacts in modulus reconstructions.

Brain system integration and message consistent health behavior change.

OBJECTIVE: Modifiable behaviors, including physical activity and sedentary behavior, are important determinants of health, and messages are important tools for influencing these behaviors. Functional neuroimaging research suggests that activity in regions of the brain's default mode and salience systems are independently associated with attending to health promoting messages. However, it remains unclear how these brain systems interact during exposure to persuasive messages and how this interaction relates to subsequent behavior change. Here, we examine how between-person differences in the relative integration between default mode and salience systems while viewing health messages relates to changes in health behavior. METHOD: Using wrist-worn accelerometers, we logged physical activity in 150 participants (mean age = 33.17 years, 64% women; 43% Black, 37% white, 7% Asian, 5% Hispanic, and 8% other) continuously for an average of 10 days. Participants then viewed health messages encouraging physical activity while undergoing functional MRI (fMRI) and completed an additional month where physical activity was logged and the health messages were reinforced with daily text reminders. RESULTS: Individuals with higher default mode and salience system integration during health message exposure were more likely to decrease their sedentary behavior and increase light physical activity in the month following fMRI than participants with lower brain integration. CONCLUSIONS: Interactions between the salience and default mode systems are associated with message receptivity and subsequent behavior change, highlighting the value of expanding the focus from the role of single brain regions in studying health behavior change to larger-scale connectivity. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The Effects of Tobacco Coverage in the Public Communication Environment on Young People's Decisions to Smoke Combustible Cigarettes.

In today's complex media environment, does media coverage influence youth and young adults' (YYA) tobacco use and intentions? We conceptualize the "public communication environment" and effect mediators, then ask whether over time variation in exogenously measured tobacco media coverage from mass and social media sources predicts daily YYA cigarette smoking intentions measured in a rolling nationally representative phone survey (N = 11,847 on 1,147 days between May 2014 and June 2017). Past week anti-tobacco and pro-tobacco content from Twitter, newspapers, broadcast news, Associated Press, and web blogs made coherent scales (thetas = 0.77 and 0.79). Opportunities for exposure to anti-tobacco content in the past week predicted lower intentions to smoke (Odds ratio [OR] = 0.95, p < .05, 95% confidence interval [CI] = 0.91-1.00). The effect was stronger among current smokers than among nonsmokers (interaction OR = 0.88, p < .05, 95% CI = 0.77-1.00). These findings support specific effects of anti-tobacco media coverage and illustrate a productive general approach to conceptualizing and assessing effects in the complex media environment.

Screening for Ocular Candidiasis Among Patients With Candidemia: Is It Time to Change Practice?

Ocular candidiasis (OC) complicates approximately 10% of candidemia and carries potentially severe morbidity. There are conflicting recommendations about the need for routine funduscopic examinations of candidemic patients. Indirect funduscopy is accurate and safe in diagnosing OC, and positive findings change recommended treatment. However, conclusive evidence that treatment changes improve outcomes is lacking. Bringing perspectives as infectious diseases physicians and ophthalmologists, we review controversies about OC and endorse routine screening during candidemia. We acknowledge difficulties in obtaining inpatient ophthalmologic consults and recommend studies to evaluate digital fundus photography and teleophthalmology as an alternative to funduscopic examinations by ophthalmologists in asymptomatic patients.

Probing elastic anisotropy of human skin in vivo with light using non-contact acoustic micro-tapping OCE and polarization sensitive OCT.

Skin broadly protects the human body from undesired factors such as ultraviolet radiation and abrasion and helps conserve body temperature and hydration. Skin's elasticity and its level of anisotropy are key to its aesthetics and function. Currently, however, treatment success is often speculative and subjective, and is rarely based on skin's elastic properties because there is no fast and accurate non-contact method for imaging of skin's elasticity. Here we report on a non-contact and non-invasive method to image and characterize skin's elastic anisotropy. It combines acoustic micro-tapping optical coherence elastography (AµT-OCE) with a nearly incompressible transversely isotropic (NITI) model to quantify skin's elastic moduli. In addition, skin sites were imaged with polarization sensitive optical coherence tomography (PS-OCT) to help define fiber orientation. Forearm skin areas were investigated in five volunteers. Results clearly demonstrate elastic anisotropy of skin in all subjects. AµT-OCE has distinct advantages over competitive techniques because it provides objective, quantitative characterization of skin's elasticity without contact, which opens the door for broad translation into clinical use. Finally, we demonstrate that a combination of multiple OCT modalities (structural OCT, OCT angiography, PS-OCT and AµT-OCE) may provide rich information about skin and can be used to characterize scar.