Optical orbital angular momentum analogy to the Stern-Gerlach experiment.

Symmetry breaking has been shown to reveal interesting phenomena in physical systems. A notable example is the fundamental work of Otto Stern and Walther Gerlach [Stern and Zerlach, Z. Physik9, 349 (1922)10.1007/BF01326983] nearly 100 years ago demonstrating a spin angular momentum (SAM) deflection that differed from classical theory. Here we use non-separable states of SAM and orbital angular momentum (OAM), known as vector vortex modes, to demonstrate how a classical optics analogy can be used to reveal this non-separability, reminiscent of the work carried out by Stern and Gerlach. We show that by implementing a polarization insensitive device to measure the OAM, the SAM states can be deflected to spatially resolved positions.

Hepatitis a vaccine immunogenicity and boostability in adults receiving immunosuppressive therapy and adults living with HIV: a prospective single-Centre cohort study.

INTRODUCTION: Hepatitis A (hepA) vaccination is highly immunogenic in healthy individuals, however there is uncertainty about the immunogenicity in immunocompromised populations (ICPs). METHODS: In this prospective cohort study, people living with HIV (PLWH), patients on immunosuppressive mono- and combination therapy, and controls received two hepA vaccine doses at months 0 and 6-12, or three combined hepA/B vaccine doses at months 0, 1 and 6-12. Antibody levels were measured before and at different time-points post-vaccination (T2, 6, 8, 12 months). The primary endpoint was the seroconversion rate (SCR) at T8, defined as hepA antibodies ≥20 mIU/ml. To assess boostability, an additional vaccine dose was administered 1-5 years after T12 in those with antibodies < 50 mIU/ml, with antibody measurements before and seven days after the booster dose. RESULTS: We included 150 participants. At T2 SCRs ranged between 35-58% in ICPs versus 94% in controls. Among PLWH, patients on monotherapy, combination therapy and controls SCRs at T8 were 33/34 (97%), 32/34 (94%), 25/30 (83%) and 28/28 (100%) respectively. The booster dose resulted in 71% additional seroconversion (17/24), with only patients using combination therapy not responding. CONCLUSIONS: HepA vaccination is highly immunogenic in virologically suppressed PLWH and patients on immunosuppressive monotherapy, with SCRs after the complete hepA vaccination schedule similar to controls and adequate booster responses in case of waning immunity. However, patients using immunosuppressive combination therapy as well as all ICPs who did not receive the complete hepA vaccination schedule, are at risk of non-response to vaccination and post-vaccination antibody measurements are recommended.

Inherent uncertainty in pedestrian collision reconstruction: How evidence variability affects head kinematics and injury prediction.

Reconstructing individual cases from real-world collision data is used as a tool to better understand injury biomechanics and determine injury thresholds. However, real-world data tends to have inherent uncertainty within parameters, such as ranges of impact speed, pre-impact pedestrian stance or pedestrian anthropometric characteristics. The implications of this input parameter uncertainty on the conclusions made from case reconstruction about injury biomechanics and risk is not well investigated, with a 'best-fit' approach more frequently adopted, leaving uncertainty unexplored. This study explores the implications of uncertain parameters in real-world data on the biomechanical kinematic metrics related to head injury risk in reconstructed real-world pedestrian-car collisions. We selected six pedestrian-car cases involving seven pedestrians from the highly detailed GB Road Accident In-Depth Studies (RAIDS) database. The collisions were reconstructed from the images, damage measurements and dynamics available in RAIDS. For each case, we varied input parameters within uncertain ranges and report the range of head kinematic metrics from each case. This includes variations of reconstructed collision scenarios that fits within the constraints of the available evidence. We used a combination of multibody and finite element modelling in Madymo to test whether the effect of input data uncertainty is the same on the initial head-vehicle and latter head-ground impact phase. Finally, we assessed whether the predicted range of head kinematics correctly predicted the injuries sustained by the pedestrian. Varying the inputs resulted in a range of output head kinematic parameters. Real-world evidence such as CCTV footage enabled predicted simulated values to be further constrained, by ruling out unrealistic scenarios which do not fit the available evidence. We found that input data uncertainty had different implications for the initial head-vehicle and latter head-ground impact phase. There was a narrower distribution of kinematics associated with the head-vehicle impact (initial 400 ms of the collision) than in the latter head-ground impact. The mean head-vehicle kinematics were able to correctly predict the presence or absence of both subdural haematoma (using peak rotational acceleration) and skull vault fracture (using peak contact force) in all pedestrians presented. This study helps increase our understanding of the effects of uncertain parameters on head kinematics in pedestrian-car collision reconstructions. Extending this work to a broad range of pedestrian-vehicle collision reconstructions spanning broad population demographics will improve our understanding of injury mechanisms and risk, leading to more robust design of injury prevention measures.

Evolving Escherichia coli to use a tRNA with a non-canonical fold as an adaptor of the genetic code.

All known bacterial tRNAs adopt the canonical cloverleaf 2D and L-shaped 3D structures. We aimed to explore whether alternative tRNA structures could be introduced in bacterial translation. To this end, we crafted a vitamin-based genetic system to evolve Escherichia coli toward activity of structurally non-canonical tRNAs. The system reliably couples (escape frequency <10-12) growth with the activities of a novel orthogonal histidine suppressor tRNA (HisTUAC) and of the cognate ARS (HisS) via suppression of a GTA valine codon in the mRNA of an enzyme in thiamine biosynthesis (ThiN). Suppression results in the introduction of an essential histidine and thereby confers thiamine prototrophy. We then replaced HisTUAC in the system with non-canonical suppressor tRNAs and selected for growth. A strain evolved to utilize mini HisT, a tRNA lacking the D-arm, and we identified the responsible mutation in an RNase gene (pnp) involved in tRNA degradation. This indicated that HisS, the ribosome, and EF-Tu accept mini HisT ab initio, which we confirmed genetically and through in vitro translation experiments. Our results reveal a previously unknown flexibility of the bacterial translation machinery for the accepted fold of the adaptor of the genetic code and demonstrate the power of the vitamin-based suppression system.

Dissemination and outcome reporting bias in clinical malaria intervention trials: a cross-sectional analysis.

BACKGROUND: Dissemination and outcome reporting biases are a significant problem in clinical research, with far-reaching implications for both scientific understanding and clinical decision-making. This study investigates the prevalence of dissemination- and outcome reporting biases in registered interventional malaria research. METHODS: All malaria interventional trials registered on ClinicalTrials.gov from 2010 to 2020 were identified. Subsequently, publications that matched the registration were searched. The primary outcome measures were the percentage of registered studies that resulted in subsequent publication of study results, the concordance between registered outcomes, and reported outcomes. Secondary outcomes were compliance with WHO standards for timely publication (issued in 2017) of summary study results in the respective trial registry (within 12 months of study completion) or peer-reviewed publication (within 24 months of study completion) was evaluated. RESULTS: A total of 579 trials were identified on ClinicalTrials.gov, of which 544 met the inclusion criteria. Notably, almost 36.6% of these trials (199/544) were registered retrospectively, with 129 (23.7%) registered after the first patient enrolment and 70 (12.9%) following study completion. Publications were identified for 351 out of 544 registered trials (64.5%), involving 1,526,081 study participants. Conversely, publications were not found for 193 of the 544 registrations (35.5%), which aimed to enrol 417,922 study participants. Among these 544 registrations, 444 (81.6%) did not meet the WHO standard to post summary results within 12 months of primary study completion (the last visit of the last subject for collection of data on the primary outcome), while 386 out of 544 registrations (71.0%) failed to publish their results in a peer-reviewed journal within 24 months of primary study completion. Discrepancies were noted in the reported primary outcomes compared to the registered primary outcomes in 47.6% (222/466) of the published trials, and an even higher discordance rate of 73.2% (341/466 publications) for secondary outcomes. CONCLUSIONS: Non-dissemination remains a significant issue in interventional malaria research, with most trials failing to meet WHO standards for timely dissemination of summary results and peer-reviewed journal publications. Additionally, outcome reporting bias is highly prevalent across malaria publications. To address these challenges, it is crucial to implement strategies that enhance the timely reporting of research findings and reduce both non-dissemination and outcome reporting bias.

The burden of brooding on neural error processing: The role of repetitive negative thinking in major depressive disorder with and without comorbid anxiety disorders.

BACKGROUND: Repetitive negative thinking (RNT), particularly its brooding aspect, is a prominent feature in Major Depressive Disorder (MDD) with and without comorbid anxiety. Error processing, an adaptive cognitive operation, seems to be impaired in individuals with exaggerated RNT. This study measured a post-error neural response, error-related negativity (ERN), during an inhibitory task to examine the mechanism underlying the relationship between RNT and faulty error processing. METHODS: We examined current MDD patients with (n = 61) and without comorbid anxiety disorders (COM; n = 38), propensity-matched into High- or Low-RNT groups according to Ruminative Response Scale Brooding subscale scores. Using 32-channel electroencephalography (EEG) during a stop-signal task, we measured baseline-corrected ERN amplitude at FCz 0-100 ms after an incorrect response. A between-subjects ANOVA was conducted with group (High RNT, Low RNT) and comorbidity (MDD, COM) as factors. RESULTS: A significant group-by-comorbidity interaction (η2 = 0.07) was found, with MDD participants exhibiting high RNT revealing smaller (more positive) ERN amplitudes compared to their COM counterparts with high RNT (d = 0.77) and MDD participants with low RNT (d = 0.92). CONCLUSIONS: Non-anxious individuals with MDD and high RNT showed blunted post-error neural responses, potentially indicating a diminished adaptive neural mechanism for recognizing and correcting errors. However, the presence of comorbid anxiety disorders in individuals with high RNT appears to counteract this reduction, potentially through an enhanced neural response to errors, thereby maintaining a higher level of error-processing activity. Further understanding of these relationships is essential for developing targeted interventions for MDD, with particular focus on the detrimental impact of brooding RNT.

Perpendicular crossing chains enable high mobility in a noncrystalline conjugated polymer.

The nature of interchain π-system contacts, and their relationship to hole transport, are elucidated for the high-mobility, noncrystalline conjugated polymer C16-IDTBT by the application of scanning tunneling microscopy, molecular dynamics, and quantum chemical calculations. The microstructure is shown to favor an unusual packing motif in which paired chains cross-over one another at near-perpendicular angles. By linking to mesoscale microstructural features, revealed by coarse-grained molecular dynamics and previous studies, and performing simulations of charge transport, it is demonstrated that the high mobility of C16-IDTBT can be explained by the promotion of a highly interconnected transport network, stemming from the adoption of perpendicular contacts at the nanoscale, in combination with fast intrachain transport.

The relationship between pqs gene expression and acylhomoserine lactone signaling in Pseudomonas aeruginosa.

The opportunistic pathogen Pseudomonas aeruginosa has complex quorum sensing (QS) circuitry, which involves two acylhomoserine lactone (AHL) systems, the LasI AHL synthase and LasR AHL-dependent transcriptional activator system and the RhlI AHL synthase-RhlR AHL-responsive transcriptional activator. There is also a quinoline signaling system [the Pseudomonas quinolone signal (PQS) system]. Although there is a core set of genes regulated by the AHL circuits, there is strain-to-strain variation in the non-core QS regulon. A size reduction of the QS regulon occurs in laboratory evolution experiments with the model strain PAO1. We used transcriptomics to test the hypothesis that reductive evolution in the PAO1 QS regulon can in large part be explained by a null mutation in pqsR, the gene encoding the transcriptional activator of the pqs operon. We found that PqsR had very little influence on the AHL QS regulon. This was a surprising finding because the last gene in the PqsR-dependent pqs operon, pqsE, codes for a protein, which physically interacts with RhlR, and this interaction is required for RhlR-dependent activation of some genes. We used comparative transcriptomics to examine the influence of a pqsE mutation on the QS regulon and identified only three transcripts, which were strictly dependent on PqsE. By using reporter constructs, we showed that the PqsE influence on other genes was dependent on experimental conditions and we have gained some insight about those conditions. This work adds to our understanding of the plasticity of the P. aeruginosa QS regulon and to the role PqsE plays in RhlR-dependent gene activation.IMPORTANCEOver many generations of growth in certain conditions, Pseudomonas aeruginosa undergoes a large reductive evolution in the number of genes activated by quorum sensing. Here, we rule out one plausible route of the reductive evolution: that a mutation in a transcriptional activator PqsR or the PqsR activation of pqsE, which codes for a chaperone for the quorum sensing signal-responsive transcription factor RhlR, explains the finding. We further provide information about the influence of PqsR and PqsE on quorum sensing in P. aeruginosa.

Early drivers of clonal hematopoiesis shape the evolutionary trajectories of de novo acute myeloid leukemia.

Mutations commonly found in AML such as DNMT3A, TET2 and ASXL1 can be found in the peripheral blood of otherwise healthy adults - a phenomenon referred to as clonal hematopoiesis (CH). These mutations are thought to represent the earliest genetic events in the evolution of AML. Genomic studies on samples acquired at diagnosis, remission, and at relapse have demonstrated significant stability of CH mutations following induction chemotherapy. Meanwhile, later mutations in genes such as NPM1 and FLT3, have been shown to contract at remission and in the case of FLT3 often are absent at relapse. We sought to understand how early CH mutations influence subsequent evolutionary trajectories throughout remission and relapse in response to induction chemotherapy. Here, we assembled a retrospective cohort of patients diagnosed with de novo AML at our institution that underwent genomic sequencing at diagnosis as well as at the time of remission and/or relapse (total n = 182 patients). Corroborating prior studies, FLT3 and NPM1 mutations were generally eliminated at the time of cytologic complete remission but subsequently reemerged upon relapse, whereas DNMT3A, TET2 and ASXL1 mutations often persisted through remission. Early CH-related mutations exhibited distinct constellations of co-occurring genetic alterations, with NPM1 and FLT3 mutations enriched in DNMT3A mut AML, while CBL and SRSF2 mutations were enriched in TET2 mut and ASXL1 mut AML, respectively. In the case of NPM1 and FLT3 mutations, these differences vanished at the time of complete remission yet readily reemerged upon relapse, indicating the reproducible nature of these genetic interactions. Thus, early CH-associated mutations that precede malignant transformation subsequently shape the evolutionary trajectories of AML through diagnosis, therapy, and relapse.

Asymptomatic vs Symptomatic Hypotension With Sacubitril/Valsartan in Heart Failure and Reduced Ejection Fraction in PARADIGM-HF.

BACKGROUND: Hypotension is an important clinical problem in heart failure (HF). OBJECTIVES: This study sought to examine the association between asymptomatic vs symptomatic hypotension and outcomes in PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure). METHODS: In a post hoc analysis of PARADIGM-HF, the efficacy and safety of sacubitril/valsartan compared to enalapril were estimated using time-updated Cox proportional hazards models. The primary outcome was cardiovascular death or HF hospitalization. RESULTS: Among 8,399 patients in PARADIGM-HF, 1,343 (16.0%) experienced only asymptomatic hypotension, and 936 (11.1%) experienced symptomatic hypotension at least once after randomization. Patients with symptomatic hypotension were older and more frequently had cardiovascular comorbidities compared to those developing only asymptomatic hypotension. By contrast, left ventricular ejection fraction was lower in those with asymptomatic hypotension. Patients who experienced either type of hypotension were at higher risk for all outcomes examined. However, the effect of sacubitril/valsartan on the primary outcome was not diminished in patients experiencing hypotension compared to those who did not: the HR for sacubitril/valsartan vs enalapril was 0.80 (95% CI: 0.72-0.89) for no hypotension, 0.87 (95% CI: 0.70-1.08) for asymptomatic hypotension, and 0.51 (95% CI: 0.38-0.69) for symptomatic hypotension (Pinteraction = 0.01), and this was also true for cardiovascular and all-cause deaths. The safety of sacubitril/valsartan vs enalapril was also maintained regardless of the occurrence of hypotension. Discontinuation of randomized treatment was less common with sacubitril/valsartan vs enalapril in patients experiencing asymptomatic and symptomatic hypotension. CONCLUSIONS: Although both asymptomatic and symptomatic hypotension during treatment with sacubitril/valsartan or enalapril were associated with worse outcomes, the benefits of sacubitril/valsartan were maintained (or even enhanced) in patients experiencing hypotension.

Pathobiology of the crystalline lens in Stickler syndrome.

PURPOSE: The Stickler syndromes are a group of connective tissue disorders characterised by congenital myopia, giant retinal tear and retinal detachment, cleft palate, hearing loss and premature arthropathy. Patients with Stickler syndrome are also susceptible to abnormalities of the crystalline lens. Since neither type II or type XI collagen (those typically affected in the vast majority of Stickler patients) are highly expressed in the lens, this observational cohort study explores potential alternative mechanisms to explain why patients frequently exhibit such unusual but characteristic types of cataract. METHODS: Author observations drawn from a cohort of over 1,800 patients with genetically confirmed Stickler syndrome. RESULTS: 3 distinct lens pathologies were identified. Firstly, a congenital quadrantic lamellar opacity. This can be present in both type 1 (COL2A1) and type 2 (COL11A1) Stickler syndrome. Secondly, early onset Pantone 557 C blue-green nuclear cataract. Thirdly, congenital lens coloboma associated with localised zonule deficiency. CONCLUSIONS: The characteristic quadrantic lamellar lens opacity can be helpful in alerting to the possible diagnosis, particularly in sub-groups with an ocular-only phenotype. Temporal and spatial signalling pathways shared embryologically by both the developing vitreous body and crystalline lens suggest an ancillary role of the fibrillar collagens in cell signalling beyond their basic structural function. A common pathway of TGFb/BMP super-family dysregulation may be shared with allied disorders associated with both retinal detachment and cataract as well as the pathobiology linking retinal detachment and cataract in the population at large. Congenital lens coloboma associated with localised zonule deficiency can increase the difficulty and risks of cataract surgery. Strategies to mitigate such risks are presented.

Association between autoimmune diseases and Alzheimer's disease: Analysis using big data tools.

OBJECTIVE: The objective is to analyze the prevalence of Alzheimer's disease in patients with and without a diagnosis of different autoimmune diseases and the possible association between both pathologies. PATIENTS AND METHODS: A multicenter, retrospective, cohort study was conducted to study the prevalence of Alzheimer's disease among patients diagnosed with various autoimmune diseases compared to the general population. Data from electronic medical records from the Castilla-La Mancha healthcare system were analyzed using Natural Language Processing through the Savana Manager® artificial intelligence clinical platform. A total of 1,028,356 patients were analyzed, including 28,920 individuals with Alzheimer's disease and 999,436 control patients. RESULTS: Out of the 12 autoimmune diseases analyzed, 5 showed a significant association with Alzheimer's disease with p < 0.05. Myasthenia gravis had an increased prevalence of AD with OR 1.49 (95% CI 1.11-2), systemic lupus erythematosus with OR 2.42 (95% CI 2.02-2.88), rheumatoid arthritis with OR 1.38 (95% CI 1.24-1.54), polymyalgia rheumatica with OR 2.01 (95% CI 1.08-2.23), and pernicious anemia with OR 2.06 (95% CI 1.59-2.66). The remaining autoimmune diseases analyzed did not show a higher prevalence of Alzheimer's disease compared to the general population. CONCLUSIONS: There may be an association between certain systemic autoimmune diseases and Alzheimer's disease. Further studies are needed to confirm our findings, establish causality, and explore the underlying mechanisms of this association.

Neuroimaging Biomarkers in Addiction.

As a neurobiological process, addiction involves pathological patterns of engagement with substances and a range of behaviors with a chronic and relapsing course. Neuroimaging technologies assess brain activity, structure, physiology, and metabolism at scales ranging from neurotransmitter receptors to large-scale brain networks, providing unique windows into the core neural processes implicated in substance use disorders. Identified aberrations in the neural substrates of reward and salience processing, response inhibition, interoception, and executive functions with neuroimaging can inform the development of pharmacological, neuromodulatory, and psychotherapeutic interventions to modulate the disordered neurobiology. Based on our systematic search, 409 protocols registered on ClinicalTrials.gov include the use of one or more neuroimaging paradigms as an outcome measure in addiction, with the majority (N=268) employing functional magnetic resonance imaging (fMRI), followed by positron emission tomography (PET) (N=71), electroencephalography (EEG) (N=50), structural magnetic resonance imaging (MRI) (N=35) and magnetic resonance spectroscopy (MRS) (N=35). Furthermore, in a PubMed systematic review, we identified 61 meta-analyses including 30 fMRI, 22 structural MRI, 8 EEG, 7 PET, and 3 MRS meta-analyses suggesting potential biomarkers in addictions. These studies can facilitate the development of a range of biomarkers that may prove useful in the arsenal of addiction treatments in the coming years. There is evidence that these markers of large-scale brain structure and activity may indicate vulnerability or separate disease subtypes, predict response to treatment, or provide objective measures of treatment response or recovery. Neuroimaging biomarkers can also suggest novel targets for interventions. Closed or open loop interventions can integrate these biomarkers with neuromodulation in real-time or offline to personalize stimulation parameters and deliver the precise intervention. This review provides an overview of neuroimaging modalities in addiction, potential neuroimaging biomarkers, and their physiologic and clinical relevance. Future directions and challenges in bringing these putative biomarkers from the bench to the bedside are also discussed.

Impulsivity, trauma history, and interoceptive awareness contribute to completion of a criminal diversion substance use treatment program for women.

Introduction: In the US, women are one of the fastest-growing segments of the prison population and more than a quarter of women in state prison are incarcerated for drug offenses. Substance use criminal diversion programs can be effective. It may be beneficial to identify individuals who are most likely to complete the program versus terminate early as this can provide information regarding who may need additional or unique programming to improve the likelihood of successful program completion. Prior research investigating prediction of success in these programs has primarily focused on demographic factors in male samples. Methods: The current study used machine learning (ML) to examine other non-demographic factors related to the likelihood of completing a substance use criminal diversion program for women. A total of 179 women who were enrolled in a criminal diversion program consented and completed neuropsychological, self-report symptom measures, criminal history and demographic surveys at baseline. Model one entered 145 variables into a machine learning (ML) ensemble model, using repeated, nested cross-validation, predicting subsequent graduation versus termination from the program. An identical ML analysis was conducted for model two, in which 34 variables were entered, including the Women's Risk/Needs Assessment (WRNA). Results: ML models were unable to predict graduation at an individual level better than chance (AUC = 0.59 [SE = 0.08] and 0.54 [SE = 0.13]). Post-hoc analyses indicated measures of impulsivity, trauma history, interoceptive awareness, employment/financial risk, housing safety, antisocial friends, anger/hostility, and WRNA total score and risk scores exhibited medium to large effect sizes in predicting treatment completion (p < 0.05; ds = 0.29 to 0.81). Discussion: Results point towards the complexity involved in attempting to predict treatment completion at the individual level but also provide potential targets to inform future research aiming to reduce recidivism.

Sensitivity analysis of transabdominal fetal pulse oximetry using MRI-based simulations.

Transabdominal fetal pulse oximetry offers a promising approach to improve fetal monitoring and reduce unnecessary interventions. Utilizing realistic 3D geometries derived from MRI scans of pregnant women, we conducted photon simulations to determine optimal source-detector configurations for detecting fetal heart rate and oxygenation. Our findings demonstrate the theoretical feasibility of measuring fetal signals at depths up to 30 mm using source-detector (SD) distances greater than 100 mm and wavelengths between 730 and 850 nm. Furthermore, we highlight the importance of customizing SD configurations based on fetal position and maternal anatomy. These insights pave the way for enhanced non-invasive fetal monitoring in clinical application.

Reporting checklists in neuroimaging: promoting transparency, replicability, and reproducibility.

Neuroimaging plays a crucial role in understanding brain structure and function, but the lack of transparency, reproducibility, and reliability of findings is a significant obstacle for the field. To address these challenges, there are ongoing efforts to develop reporting checklists for neuroimaging studies to improve the reporting of fundamental aspects of study design and execution. In this review, we first define what we mean by a neuroimaging reporting checklist and then discuss how a reporting checklist can be developed and implemented. We consider the core values that should inform checklist design, including transparency, repeatability, data sharing, diversity, and supporting innovations. We then share experiences with currently available neuroimaging checklists. We review the motivation for creating checklists and whether checklists achieve their intended objectives, before proposing a development cycle for neuroimaging reporting checklists and describing each implementation step. We emphasize the importance of reporting checklists in enhancing the quality of data repositories and consortia, how they can support education and best practices, and how emerging computational methods, like artificial intelligence, can help checklist development and adherence. We also highlight the role that funding agencies and global collaborations can play in supporting the adoption of neuroimaging reporting checklists. We hope this review will encourage better adherence to available checklists and promote the development of new ones, and ultimately increase the quality, transparency, and reproducibility of neuroimaging research.

The turbulent soundscape of intertidal oyster reefs.

Turbulence and sound are important cues for oyster reef larval recruitment. Numerous studies have found a relationship between turbulence intensity and swimming behaviors of marine larvae, while others have documented the importance of sounds in enhancing larval recruitment to oyster reefs. However, the relationship between turbulence and the reef soundscape is not well understood. In this study we made side-by-side acoustic Doppler velocimeter turbulence measurements and hydrophone soundscape recordings over 2 intertidal oyster reefs (1 natural and 1 restored) and 1 adjacent bare mudflat as a reference. Sound pressure levels (SPL) were similar across all three sites, although SPL > 2000 Hz was highest at the restored reef, likely due to its larger area that contained a greater number of sound-producing organisms. Flow noise (FN), defined as the mean of pressure fluctuations recorded by the hydrophone at f < 100 Hz, was significantly related to mean flow speed, turbulent kinetic energy, and turbulence dissipation rate (ε), agreeing with theoretical calculations for turbulence. Our results also show a similar relationship between ε and FN to what has been previously reported for ε vs. downward larval swimming velocity (w b ), with both FN and w b demonstrating rapid growth at ε > 0.1 cm2 s-3. These results suggest that reef turbulence and sounds may attract oyster larvae in complementary and synergistic ways.

Whole-brain mechanism of neurofeedback therapy: predictive modeling of neurofeedback outcomes on repetitive negative thinking in depression.

Real-time fMRI neurofeedback (rtfMRI-NF) has emerged as a promising intervention for psychiatric disorders, yet its clinical efficacy remains underexplored due to an incomplete mechanistic understanding. This study aimed to delineate the whole-brain mechanisms underpinning the effects of rtfMRI-NF on repetitive negative thinking in depression. In a double-blind randomized controlled trial, forty-three depressed individuals underwent NF training targeting the functional connectivity (FC) between the posterior cingulate cortex and the right temporoparietal junction, linked to rumination severity. Participants were randomly assigned to active or sham groups, with the sham group receiving synthesized feedback mimicking real NF signal patterns. The active group demonstrated a significant reduction in brooding rumination scores (d = -1.52, p < 0.001), whereas the sham group did not (d = -0.23, p = 0.503). While the target FC did not show discernible training effects or group differences, connectome-based predictive modeling (CPM) analysis revealed that the interaction between brain activity during regulation and brain response to the feedback signal was the critical factor in explaining treatment outcomes. The model incorporating this interaction successfully predicted rumination changes across both groups. The FCs significantly contributing to the prediction were distributed across brain regions, notably the frontal control, salience network, and subcortical reward processing areas. These results underscore the importance of considering the interplay between brain regulation activities and brain response to the feedback signal in understanding the therapeutic mechanisms of rtfMRI-NF. The study affirms rtfMRI-NF's potential as a therapeutic intervention for repetitive negative thinking and highlights the need for a nuanced understanding of the whole-brain mechanisms contributing to its efficacy.

The unique face of comorbid anxiety and depression: Increased frontal, insula and cingulate cortex response during Pavlovian fear-conditioning.

BACKGROUND: Dysregulation of fear processing through altered sensitivity to threat is thought to contribute to the development of anxiety disorders and major depressive disorder (MDD). However, fewer studies have examined fear processing in MDD than in anxiety disorders. The current study used propensity matching to examine the hypothesis that comorbid MDD and anxiety (AnxMDD) shows greater neural correlates of fear processing than MDD, suggesting that the co-occurrence of AnxMDD is exemplified by exaggerated defense related processes. METHODS: 195 individuals with MDD (N = 65) or AnxMDD (N = 130) were recruited from the community and completed multi-level assessments, including a Pavlovian fear learning task during functional imaging. Visual images paired with threat (conditioned stimuli: CS+) were compared to stimuli not paired with threat (CS-). RESULTS: MDD and AnxMDD showed significantly different patterns of activation for CS+ vs CS- in the dorsal anterior insula/inferior frontal gyrus (partial eta squared; ηp2 = 0.02), dorsolateral prefrontal cortex (ηp2 = 0.01) and dorsal anterior/mid cingulate cortex (ηp2 = 0.01). These differences were driven by greater activation to the CS+ in AnxMDD versus MDD. LIMITATIONS: Limitations include the cross-sectional design, a scream US rather than shock and half the number of MDD as AnxMDD participants. CONCLUSIONS: AnxMDD showed a pattern of increased activation in regions identified with fear processing. Effects were consistently driven by threat, further suggesting fear signaling as the emergent target process. Differences emerged in regions associated with salience processing, attentional orienting/conflict, self-relevant processing and executive functioning in comorbid anxiety and depression, thereby highlighting potential treatment targets for this prevalent and treatment resistant group.