Spatiotemporal Deep Learning-Based Cine Loop Quality Filter for Handheld Point-of-Care Echocardiography.

The reliability of automated image interpretation of point-of-care (POC) echocardiography scans depends on the quality of the acquired ultrasound data. This work reports on the development and validation of spatiotemporal deep learning models to assess the suitability of input ultrasound cine loops collected using a handheld echocardiography device for processing by an automated quantification algorithm (e.g. ejection fraction estimation). POC echocardiograms (n=885 DICOM cine loops from 175 patients) from two sites were collected using a handheld ultrasound device and annotated for image quality at the frame-level. Attributes of high-quality frames for left ventricular (LV) quantification included a temporally-stable LV, reasonable coverage of LV borders, and good contrast between the borders and chamber. Attributes of low-quality frames included temporal instability of the LV and/or imaging artifacts (e.g., lack of contrast, haze, reverberation, acoustic shadowing). Three different neural network architectures were investigated - (a) frame-level convolutional neural network (CNN) which operates on individual echo frames (VectorCNN), (b) single-stream sequence-level CNN which operates on a sequence of echo frames (VectorCNN+LSTM) and (c) two-stream sequence-level CNNs which operate on a sequence of echo and optical flow frames (VectorCNN+LSTM+Average, VectorCNN+LSTM+MinMax, and VectorCNN+LSTM+ConvPool). Evaluation on a sequestered test dataset containing 76 DICOM cine loops with 16,914 frames showed that VectorCNN+LSTM can effectively utilize both spatial and temporal information to regress the quality of an input frame (accuracy: 0.925, sensitivity = 0.860, specificity = 0.952), compared to the frame-level VectorCNN that only utilizes spatial information in that frame (accuracy: 0.903, sensitivity = 0.791, specificity = 0.949). Furthermore, an independent sample t-test indicated that the cine loops classified to be of adequate quality by the VectorCNN+LSTM model had a statistically significant lower bias in the automatically estimated EF (mean bias = - 3.73 ± 7.46 %, versus a clinically obtained reference EF) compared to the loops classified as inadequate (mean bias = -15.92 ± 12.17 %) (p = 0.007). Thus, cine loop stratification using the proposed spatiotemporal CNN model improves the reliability of automated point-of-care echocardiography image interpretation.

Pragmatic Evaluation of a Deep-Learning Algorithm to Automate Ejection Fraction on Hand-Held, Point-of-Care Echocardiography in a Cardiac Surgical Operating Room.

OBJECTIVE: To test the correlation of ejection fraction (EF) estimated by a deep-learning-based, automated algorithm (Auto EF) versus an EF estimated by Simpson's method. DESIGN: A prospective observational study. SETTING: A single-center study at the Hospital of the University of Pennsylvania. PARTICIPANTS: Study participants were ≥18 years of age and scheduled to undergo valve, aortic, coronary artery bypass graft, heart, or lung transplant surgery. INTERVENTIONS: This noninterventional study involved acquiring apical 4-chamber transthoracic echocardiographic clips using the Philips hand-held ultrasound device, Lumify. MEASUREMENTS AND MAIN RESULTS: In the primary analysis of 54 clips, compared to Simpson's method for EF estimation, bias was similar for Auto EF (-10.17%) and the experienced reader-estimated EF (-9.82%), but the correlation was lower for Auto EF (r = 0.56) than the experienced reader-estimated EF (r = 0.80). In the secondary analyses, the correlation between EF estimated by Simpson's method and Auto EF increased when applied to 27 acquisitions classified as adequate (r = 0.86), but decreased when applied to 27 acquisitions classified as inadequate (r = 0.46). CONCLUSIONS: Applied to acquisitions of adequate image quality, Auto EF produced a numerical EF estimate equivalent to Simpson's method. However, when applied to acquisitions of inadequate image quality, discrepancies arose between EF estimated by Auto EF and Simpson's method. Visual EF estimates by experienced readers correlated highly with Simpson's method in both variable and inadequate imaging conditions, emphasizing its enduring clinical utility.

The dermatologist identity crisis: a phenomenological analysis of dermatology trainee professional identity during generalist redeployment.

BACKGROUND: Dermatology faces a workforce crisis against a backdrop of wider medical education shifts towards generalism. A pivot towards generalism may have an impact on dermatology trainee professional identity, which, to our knowledge, has not been investigated and is known to have an impact on competence and conceptualization of ethics among physicians. Disruption because of the COVID-19 pandemic led to dermatology trainee redeployment and therefore presents a unique opportunity to examine dermatology trainee professional identity during times of pressure. AIM: To identify the impact of COVID-19 redeployment on dermatology trainee professional identity, the factors influencing identity and whether such factors affect trainees' perceptions about their future careers. METHODS: Ten trainees were purposively recruited to the study. Data were collected through semistructured interviews and were analysed phenomenologically using the template analysis method. Central and integrative themes were identified. RESULTS: Three central themes were identified: trainee identity and values; redeployment transitions; and future clarity. Three integrative themes were found: tribes; sense of purpose; and uncertainty. Trainees see competence and community as central to the dermatologist identity. Most trainees experienced a reaffirmation of their prior values, psychologically retreating to close-knit communities. However, some underwent disorienting dilemmas, later reflecting on their futures as dermatologists. CONCLUSION: Healthcare crises may have a significant impact on dermatology trainee professional identity and may lead to reaffirmation of prior tribal values or disorienting reflection upon future career trajectories. Improved support among diverse communities, minimization of uncertainty and fostering a sense of purpose among trainees may aid identity enrichment and safeguard the future dermatology consultant workforce.

Virtual Screening Approach to Identifying a Novel and Tractable Series of Pseudomonas aeruginosa Elastase Inhibitors.

Novel therapies are required to treat chronic bacterial infections in cystic fibrosis (CF) sufferers. The most common pathogen responsible for these infections is Pseudomonas aeruginosa, which persists within the lungs of CF sufferers despite intensive antibiotic treatment. P. aeruginosa elastase (also known as LasB or pseudolysin) is a key virulence determinant that contributes to the pathogenesis and persistence of P. aeruginosa infections in CF patients. The crucial role of LasB in pseudomonal virulence makes it a good target for the development of an adjuvant drug for CF treatment. Herein we discuss the discovery of a new series of LasB inhibitors by virtual screening and computer assisted drug design (CADD) and their optimization leading to compounds 29 and 39 (K i = 0.16 µM and 0.12 µM, respectively).

Molecular Recognition at Mineral Interfaces: Implications for the Beneficiation of Rare Earth Ores.

Ce-bastnäsite is the single largest mineral source for light rare-earth elements. In view of the growing industrial importance of rare-earth minerals, it is critical to develop more efficient methods for separating the valuable rare-earth-containing minerals from the surrounding gangue. In this work, we employ a combination of periodic density functional theory (DFT) and molecular mechanics (MM) calculations together with the de novo molecular design program HostDesigner to identify bis-phosphinate ligands that preferentially bind to the (100) Ce-bastnäsite surface rather than the (104) calcite surface. DFT calculations for a simple phosphinate ligand were employed to qualitatively understand key behaviors involved in ligand-metal, ligand-solvent, and solvent-metal interactions. These insights were then used to guide the search for flexible, rigid, and semirigid hydrocarbon linkers to identify candidate bis-phosphinate ligands with the potential to bind preferentially to Ce-bastnäsite. Among the five most promising bis-phosphinate ligands suggested by theoretical studies, three ligands were synthesized and their adsorption characteristics to bastnäsite (100) interfaces were characterized using vibrational sum-frequency (vSFG) spectroscopy, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, and isothermal titration calorimetry (ITC). The efficacy of the selective interfacial molecular binding was demonstrated by identifying a bis-phosphinate ligand capable of providing an overall higher surface coverage of alkyl groups relative to a monophosphinate ligand. The results highlight the interplay between adsorption binding strength and maximum surface coverage in determining ligand efficiency to render the mineral surface hydrophobic. DFT calculations further indicate that all tested ligands have higher affinity for Ce-bastnäsite than for calcite. This is consistent with the ITC data showing stronger adsorption enthalpy to bastnäsite than to calcite, making these ligands promising candidates for selective flotation of Ce-bastnäsite.

Augmentation of Tissue Perfusion in Patients With Peripheral Artery Disease Using Microbubble Cavitation.

OBJECTIVES: The authors investigated ideal acoustic conditions on a clinical scanner custom-programmed for ultrasound (US) cavitation-mediated flow augmentation in preclinical models. We then applied these conditions in a first-in-human study to test the hypothesis that contrast US can increase limb perfusion in normal subjects and patients with peripheral artery disease (PAD). BACKGROUND: US-induced cavitation of microbubble contrast agents augments tissue perfusion by convective shear and secondary purinergic signaling that mediates release of endogenous vasodilators. METHODS: In mice, unilateral exposure of the proximal hindlimb to therapeutic US (1.3 MHz, mechanical index 1.3) was performed for 10 min after intravenous injection of lipid microbubbles. US varied according to line density (17, 37, 65 lines) and pulse duration. Microvascular perfusion was evaluated by US perfusion imaging, and in vivo adenosine triphosphate (ATP) release was assessed using in vivo optical imaging. Optimal parameters were then used in healthy volunteers and patients with PAD where calf US alone or in combination with intravenous microbubble contrast infusion was performed for 10 min. RESULTS: In mice, flow was augmented in the US-exposed limb for all acoustic conditions. Only at the lowest line density was there a stepwise increase in perfusion for longer (40-cycle) versus shorter (5-cycle) pulse duration. For higher line densities, blood flow consistently increased by 3-fold to 4-fold in the US-exposed limb irrespective of pulse duration. High line density and long pulse duration resulted in the greatest release of ATP in the cavitation zone. Application of these optimized conditions in humans together with intravenous contrast increased calf muscle blood flow by >2-fold in both healthy subjects and patients with PAD, whereas US alone had no effect. CONCLUSIONS: US of microbubbles when using optimized acoustic environments can increase perfusion in limb skeletal muscle, raising the possibility of a therapy for patients with PAD. (Augmentation of Limb Perfusion With Contrast Ultrasound; NCT03195556).

WGS to determine the extent of Clostridioides difficile transmission in a high incidence setting in North Wales in 2015.

OBJECTIVES: Rates of Clostridioides (Clostridium) difficile infection (CDI) are higher in North Wales than elsewhere in the UK. We used WGS to investigate if this is due to increased healthcare-associated transmission from other cases. METHODS: Healthcare and community C. difficile isolates from patients across North Wales (February-July 2015) from glutamate dehydrogenase (GDH)-positive faecal samples underwent WGS. Data from patient records, hospital management systems and national antimicrobial use surveillance were used. RESULTS: Of the 499 GDH-positive samples, 338 (68%) were sequenced and 299 distinct infections/colonizations were identified, 229/299 (77%) with toxin genes. Only 39/229 (17%) toxigenic isolates were related within ≤2 SNPs to ≥1 infections/colonizations from a previously sampled patient, i.e. demonstrated evidence of possible transmission. Independent predictors of possible transmission included healthcare exposure in the last 12 weeks (P = 0.002, with rates varying by hospital), infection with MLST types ST-1 (ribotype 027) and ST-11 (predominantly ribotype 078) compared with all other toxigenic STs (P < 0.001), and cephalosporin exposure in the potential transmission recipient (P = 0.02). Adjusting for all these factors, there was no additional effect of ward workload (P = 0.54) or failure to meet cleaning targets (P = 0.25). Use of antimicrobials is higher in North Wales compared with England and the rest of Wales. CONCLUSIONS: Levels of transmission detected by WGS were comparable to previously described rates in endemic settings; other explanations, such as variations in antimicrobial use, are required to explain the high levels of CDI. Cephalosporins are a risk factor for infection with C. difficile from another infected or colonized case.

SQERT-T: alleviating kinetic Monte Carlo (KMC)-stiffness in transient KMC simulations.

Lattice based kinetic Monte Carlo (KMC) is often used for simulating the dynamics of systems at a supramolecular scale, based on molecular scale transitions. A common challenge in KMC simulations is rapid 'back-and-forth' reactions, which dominate the events executed during simulations and inhibit the ability for simulations to reach longer time scales. Such processes are fast frivolous processes (FFPs) and are one manifestation of a phenomenon referred to as KMC-stiffness. Here, an algorithm for staggered quasi-equilibrium rank-based throttling geared towards transient kinetics (SQERT-T) is presented. Within the SQERT-T methodology, a pace-restrictor reaction and an FFP floor are utilized along with throttling of the process transition rate constants to accelerate the KMC simulations while still retaining sufficient time resolution for sampling of the data. KMC simulations were performed for CO oxidation over RuO2(1 1 0) and over RuO2(1 1 1), and the results were compared to experimental data obtained using RuO2 powders. The experiments and simulations were for transient conditions: the system was subjected to a temperature program which included temperatures in the range of 363 to 453 K. The timescales that were achieved during the KMC simulations in this study would not have been accessible without KMC acceleration, and were enabled by the use of SQERT-T.

Below-Room-Temperature C-H Bond Breaking on an Inexpensive Metal Oxide: Methanol to Formaldehyde on CeO2(111).

Upgrading of primary alcohols by C-H bond breaking currently requires temperatures of >200 °C. In this work, new understanding from simulation of a temperature-programmed reaction study with methanol over a CeO2(111) surface shows C-H bond breaking and the subsequent desorption of formaldehyde, even below room temperature. This is of particular interest because CeO2 is a naturally abundant and inexpensive metal oxide. We combine density functional theory and kinetic Monte Carlo methods to show that the low-temperature C-H bond breaking occurs via disproportionation of adjacent methoxy species. We further show from calculations that the same transition state with comparable activation energy exists for other primary alcohols; with ethanol, 1-propanol, and 1-butanol explicitly calculated. These findings indicate a promising class of transition states to search for in seeking low-temperature C-H bond breaking over inexpensive oxides.

Closed-loop control of targeted ultrasound drug delivery across the blood-brain/tumor barriers in a rat glioma model.

Cavitation-facilitated microbubble-mediated focused ultrasound therapy is a promising method of drug delivery across the blood-brain barrier (BBB) for treating many neurological disorders. Unlike ultrasound thermal therapies, during which magnetic resonance thermometry can serve as a reliable treatment control modality, real-time control of modulated BBB disruption with undetectable vascular damage remains a challenge. Here a closed-loop cavitation controlling paradigm that sustains stable cavitation while suppressing inertial cavitation behavior was designed and validated using a dual-transducer system operating at the clinically relevant ultrasound frequency of 274.3 kHz. Tests in the normal brain and in the F98 glioma model in vivo demonstrated that this controller enables reliable and damage-free delivery of a predetermined amount of the chemotherapeutic drug (liposomal doxorubicin) into the brain. The maximum concentration level of delivered doxorubicin exceeded levels previously shown (using uncontrolled sonication) to induce tumor regression and improve survival in rat glioma. These results confirmed the ability of the controller to modulate the drug delivery dosage within a therapeutically effective range, while improving safety control. It can be readily implemented clinically and potentially applied to other cavitation-enhanced ultrasound therapies.

Preclinical evaluation of a low-frequency transcranial MRI-guided focused ultrasound system in a primate model.

This study investigated thermal ablation and skull-induced heating with a 230 kHz transcranial MRI-guided focused ultrasound (TcMRgFUS) system in nonhuman primates. We evaluated real-time acoustic feedback and aimed to understand whether cavitation contributed to the heating and the lesion formation. In four macaques, we sonicated thalamic targets at acoustic powers of 34-560 W (896-7590 J). Tissue effects evaluated with MRI and histology were compared to MRI-based temperature and thermal dose measurements, acoustic emissions recorded during the experiments, and acoustic and thermal simulations. Peak temperatures ranged from 46 to 57 °C, and lesions were produced in 5/8 sonicated targets. A linear relationship was observed between the applied acoustic energy and both the focal and brain surface heating. Thermal dose thresholds were 15-50 cumulative equivalent minutes at 43 °C, similar to prior studies at higher frequencies. Histology was also consistent with earlier studies of thermal effects in the brain. The system successfully controlled the power level and maintained a low level of cavitation activity. Increased acoustic emissions observed in 3/4 animals occurred when the focal temperature rise exceeded approximately 16 °C. Thresholds for thermally-significant subharmonic and wideband emissions were 129 and 140 W, respectively, corresponding to estimated pressure amplitudes of 2.1 and 2.2 MPa. Simulated focal heating was consistent with the measurements for sonications without thermally-significant acoustic emissions; otherwise it was consistently lower than the measurements. Overall, these results suggest that the lesions were produced by thermal mechanisms. The detected acoustic emissions, however, and their association with heating suggest that cavitation might have contributed to the focal heating. Compared to earlier work with a 670 kHz TcMRgFUS system, the brain surface heating was substantially reduced and the focal heating was higher with this 230 kHz system, suggesting that a reduced frequency can increase the treatment envelope for TcMRgFUS and potentially reduce the risk of skull heating.

Effects of correlated parameters and uncertainty in electronic-structure-based chemical kinetic modelling.

Kinetic models based on first principles are becoming common place in heterogeneous catalysis because of their ability to interpret experimental data, identify the rate-controlling step, guide experiments and predict novel materials. To overcome the tremendous computational cost of estimating parameters of complex networks on metal catalysts, approximate quantum mechanical calculations are employed that render models potentially inaccurate. Here, by introducing correlative global sensitivity analysis and uncertainty quantification, we show that neglecting correlations in the energies of species and reactions can lead to an incorrect identification of influential parameters and key reaction intermediates and reactions. We rationalize why models often underpredict reaction rates and show that, despite the uncertainty being large, the method can, in conjunction with experimental data, identify influential missing reaction pathways and provide insights into the catalyst active site and the kinetic reliability of a model. The method is demonstrated in ethanol steam reforming for hydrogen production for fuel cells.

A novel management of post-oesophagectomy gastro-pleural fistula.

Oesophageal anastomotic leak and fistula are major and life-threatening complications of oesophagectomy with resultant increased mortality. Non-operative approach of such cases should be the initial strategy. Re-operative surgery and/or stent insertion are considered if conservative measures failed. Although oesophageal stenting is a safe option for the leaks, stent migration and failure to completely cover large anastomotic leaks are the main complications and pitfalls of the procedure. These can be overcome by using multiple or larger stents. We describe a case of a 73-year-old man who underwent a laparoscopic oesophagectomy for an oesophageal adenocarcinoma. The procedure was complicated by a large gastro-pleural fistula and anastomotic leak, resulting into a chronic empyema. The initial conservative treatment and a conventional oesophageal stent insertion failed to heal the fistula and to resolve the empyema. Re-operative surgery was ruled out because of the patient's poor general health and high surgical risk. Due to the changed oesophago-gastric anatomy and a potential risk of migration of the additional conventional stent, a mega stent was deployed with successful closure of the oesophageal leak. Post-stenting contrast studies and an out-patient follow up review of the case confirmed no further anastomotic leakage.

Refining the Candidate Environment: Interpersonal Stress, the Serotonin Transporter Polymorphism, and Gene-Environment Interactions in Major Depression.

Meta-analytic evidence supports a gene-environment (G×E) interaction between life stress and the serotonin transporter polymorphism (5-HTTLPR) on depression, but few studies have examined factors that influence detection of this effect, despite years of inconsistent results. We propose that the "candidate environment" (akin to a candidate gene) is key. Theory and evidence implicate major stressful life events (SLEs)-particularly major interpersonal SLEs-as well as chronic family stress. Participants (N = 400) from the Youth Emotion Project (which began with 627 high school juniors oversampled for high neuroticism) completed up to five annual diagnostic and life stress interviews and provided DNA samples. A significant G×E effect for major SLEs and S-carrier genotype was accounted for significantly by major interpersonal SLEs but not significantly by major non-interpersonal SLEs. S-carrier genotype and chronic family stress also significantly interacted. Identifying such candidate environments may facilitate future G×E research in depression and psychopathology more broadly.

Ultrasound-mediated drug delivery for cardiovascular disease.

INTRODUCTION: Ultrasound (US) has been developed as both a valuable diagnostic tool and a potent promoter of beneficial tissue bioeffects for the treatment of cardiovascular disease. These effects can be mediated by mechanical oscillations of circulating microbubbles, or US contrast agents, which may also encapsulate and shield a therapeutic agent in the bloodstream. Oscillating microbubbles can create stresses directly on nearby tissue or induce fluid effects that effect drug penetration into vascular tissue, lyse thrombi or direct drugs to optimal locations for delivery. AREAS COVERED: The present review summarizes investigations that have provided evidence for US-mediated drug delivery as a potent method to deliver therapeutics to diseased tissue for cardiovascular treatment. In particular, the focus will be on investigations of specific aspects relating to US-mediated drug delivery, such as delivery vehicles, drug transport routes, biochemical mechanisms and molecular targeting strategies. EXPERT OPINION: These investigations have spurred continued research into alternative therapeutic applications, such as bioactive gas delivery and new US technologies. Successful implementation of US-mediated drug delivery has the potential to change the way many drugs are administered systemically, resulting in more effective and economical therapeutics, and less-invasive treatments.

Clot retraction affects the extent of ultrasound-enhanced thrombolysis in an ex vivo porcine thrombosis model.

We investigated ultrasound-enhanced thrombolysis in two whole-blood clot models using a Food and Drug Administration-approved contrast agent (Definity, Lantheus Medical Imaging; Billerica, MA USA) and thrombolytic drug (recombinant tissue-type plasminogen activator [rt-PA]) (Genentech; South San Francisco, CA USA). Porcine venous blood was collected from donor hogs and coagulated in vials made of two different materials. This method produced clots with differing compositional properties, as determined by routine scanning electron microscopy and histology. Clots were deployed in an ex vivo porcine thrombosis model, and exposed to an intermittent ultrasound scheme previously developed to maximize stable cavitation while acoustic emissions were detected. Exposure to 3.15 µg/mL rt-PA promoted lysis in both clot models, compared with exposure to plasma alone. However, only unretracted clots experienced significant enhancement of thrombolysis in the presence of rt-PA, Definity, and ultrasound, compared with treatment with rt-PA. In these clots, microscopy revealed loose erythrocyte aggregates, a significantly less extensive fibrin network and a higher porosity, which may facilitate increased penetration of thrombolytics by cavitation.

Layer-by-layer templated assembly of silica at the nanoscale.

Bioinspired bottom-up assembly and layer-by-layer (LbL) construction of inorganic materials from lithographically defined organic templates enables the fabrication of nanostructured systems under mild temperature and pH conditions. Such processes open the door to low-impact manufacturing and facile recycling of hybrid materials for energy, biology, and information technologies. Here, templated LbL assembly of silica was achieved using a combination of electron beam lithography, chemical lift-off, and aqueous solution chemistry. Nanopatterns of lines, honeycomb-lattices, and dot arrays were defined in polymer resist using electron beam lithography. Following development, exposed areas of silicon were functionalized with a vapor deposited amine-silane monolayer. Silicic acid solutions of varying pH and salt content were reacted with the patterned organic amine-functional templates. Vapor treatment and solution reaction could be repeated, allowing LbL deposition. Conditions for the silicic acid deposition had a strong effect on thickness of each layer, and the morphology of the amorphous silica formed. "Defects" in the arrays of silica nanostructures were minor and do not affect the overall organization of the layers. The bioinspired method described here facilitates the bottom-up assembly of inorganic nanostructures defined in three dimensions and provides a path, via LbL processing, for the construction of layered hybrid materials under mild conditions.

A longitudinal examination of stress generation in depressive and anxiety disorders.

The current study compared two competing theories of the stress generation model of depression (stress causation vs. stress continuation) using interview-based measures of episodic life stress, as well as interpersonal and noninterpersonal chronic life stress. We also expanded on past research by examining anxiety disorders as well as depressive disorders. In addition, we examined the role of neuroticism and extraversion in these relationships. Participants were 627 adolescents enrolled in a two-site, longitudinal study of risk factors for depressive and anxiety disorders. Baseline and follow-up assessments were approximately one year apart. Results supported the stress causation theory for episodic stress generation for anxiety disorders, with neuroticism partially accounting for this relationship. The stress causation theory was also supported for depression, but only for more moderate to severe stressors; neuroticism partially accounted for this relationship as well. Finally, we found evidence for interpersonal and noninterpersonal chronic life stress continuation in both depressive and anxiety disorders. The present findings have implications regarding the specificity of the stress generation model to depressive disorders, as well as variables involved in the stress generation process.

The Relationships of Personality and Cognitive Styles with Self-Reported Symptoms of Depression and Anxiety.

Many studies have reported concurrent relationships between depressive symptoms and various personality, cognitive, and personality-cognitive vulnerabilities, but the degree of overlap among these vulnerabilities is unclear. Moreover, whereas most investigations of these vulnerabilities have focused on depression, their possible relationships with anxiety have not been adequately examined. The present study included 550 high school juniors and examined the cross-sectional relationships among neuroticism, negative inferential style, dysfunctional attitudes, sociotropy, and autonomy, with a wide range of anxiety and depressive symptoms, as well as the incremental validity of these different putative vulnerabilities when examined simultaneously. Correlational analyses revealed that all five vulnerabilities were significantly related to symptoms of both anxiety and depression. Whereas neuroticism accounted for significant unique variance in all symptom outcomes, individual cognitive and personality-cognitive vulnerabilities accounted for small and only sometimes statistically significant variance across outcomes. Importantly, however, for most outcomes the majority of symptom variance was accounted for by shared aspects of the vulnerabilities rather than unique aspects. Implications of these results for understanding cognitive and personality-cognitive vulnerabilities to depression and anxiety are discussed.