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Background Pregnenolone, and related neurosteroids, may have antidepressant properties. Preclinical research proposes that microtubule associated protein 2 (MAP2) binding may be a mechanism for antidepressant properties of pregnenolone. Thus, MAP2 might be a novel target for antidepressant therapy. This clinical study is the first to examine serum MAP2 levels in people with bipolar depression and controls, and whether pregnenolone treatment is associated with a change in MAP2 levels. Methods Blood samples from a previously published clinical trial of pregnenolone for adult bipolar depression were analyzed at baseline and week 6 of treatment with pregnenolone or placebo for serum MAP2 levels using Western Blot. MAP2 levels from healthy controls were also obtained. Results MAP2 levels in the bipolar depressed patients (n=11) tended to be higher than in controls (n=4) (p=0.062). MAP2 levels decreased non-significantly from baseline to week 6 in placebo (n=5) and pregnenolone-treated patients (n=6). MAP2 level changes correlated positively with change in self-reported depressive symptom scores in the pregnenolone group (r=0.771, p=0.072) but not in the placebo group (r=0.000, p=1.000). Limitations This study, exploring relationships between MAP-2 in humans with mood disorders, is limited by the small sample size. Thus, the findings must be viewed with great caution. Conclusion These findings suggest possible differences in serum MAP-2 levels between bipolar depressed persons and controls and a relationship between changes in depressive symptoms and MAP-2 levels during pregnenolone therapy. Findings suggest additional research is needed on MAP-2 in mood disorders.

BackgroundPoor physical health in severe mental illness (SMI) remains a major issue for clinical practice.AimsTo use electronic health records of routinely collected clinical data to determine levels of screening for cardiometabolic disease and adverse health outcomes in a large sample (n= 7718) of patients with SMI, predominantly schizophrenia and bipolar disorder.MethodWe linked data from the Glasgow Psychosis Clinical Information System (PsyCIS) to morbidity records, routine blood results and prescribing data.ResultsThere was no record of routine blood monitoring during the preceding 2 years for 16.9% of the cohort. However, monitoring was poorer for male patients, younger patients aged 16–44, those with schizophrenia, and for tests of cholesterol, triglyceride and glycosylated haemoglobin. We estimated that 8.0% of participants had diabetes and that lipids levels, and use of lipid-lowering medication, was generally high.ConclusionsElectronic record linkage identified poor health screening and adverse health outcomes in this vulnerable patient group. This approach can inform the design of future interventions and health policy.

With the increasing need to build systems and products powered by machine learning inside organizations, it is critical to have a platform that provides machine learning practitioners with a unified environment to easily prototype, deploy, and maintain their models at scale. However, due to the diversity of machine learning libraries, the inconsistency between environments, and various scalability requirement, there is no existing work to date that addresses all of these challenges. Here, we introduce Bighead, a framework-agnostic, end-to-end platform for machine learning. It offers a seamless user experience requiring only minimal efforts that span feature set management, prototyping, training, batch (offline) inference, real-time (online) inference, evaluation, and model lifecycle management. In contrast to existing platforms, it is designed to be highly versatile and extensible, and supports all major machine learning frameworks, rather than focusing on one particular framework. It ensures consistency across different environments and stages of the model lifecycle, as well as across data sources and transformations. It scales horizontally and elastically in response to the workload such as dataset size and throughput. Its components include a feature management framework, a model development toolkit, a lifecycle management service with UI, an offline training and inference engine, an online inference service, an interactive prototyping environment, and a Docker image customization tool. It is the first platform to offer a feature management component that is a general-purpose aggregation framework with lambda architecture and temporal joins. Bighead is deployed and widely adopted at Airbnb, and has enabled the data science and engineering teams to develop and deploy machine learning models in a timely and reliable manner. Bighead has shortened the time to deploy a new model from months to days, ensured the stability of the models in production, facilitated adoption of cutting-edge models, and enabled advanced machine learning based product features of the Airbnb platform. We present two use cases of productionizing models of computer vision and natural language processing.

Background Facial palsy patients require reconstructive surgery because they suffer from an expressionless and deformed appearance especially during smiling. To gain a natural smile, various dynamic procedures rather than static procedures are performed. Through cadaveric studies with clinical implications on temporalis muscle and intraoral transposition, we were able to come up with a more effective and less invasive procedure than the conventional temporalis muscle transposition or lengthening temporalis myoplasty. The aim of this study is to describe our novel surgical technique for facial reanimation and evaluate its efficacy. Method Two intraoral incisions were made. Through the posterior incision, the tendinous portion of the temporalis was separated from the coronoid process and anterior border of the ramus. Through the anterior incision, submucosa tunneling was performed to fixate the temporalis tendon onto the new perioral site. Results 14 patients with facial palsy underwent intraoral temporalis transposition and their mouth corner excursion was measured for objective assessment after surgery. At resting state, mouth and cheek drooping was improved. At smiling, the excursion of the unaffected side was 10–17 mm. For the reconstructed side, 8 cases were considered excellent (exceeding 75% of normal side), 5 cases were considered good (exceeding 50%), and 1 case fair (exceeding 25%). Conclusion This temporalis transposition through the intraoral approach is a novel technique for facial reanimation reconstruction. It is s less invasive, immediately effective method with rapid recovery and minimal donor site morbidity without visible scar. Level of evidence IV.

Eyelid reconstruction is indicated in the setting of trauma, following cancer excision, for congenital deformities, and for age-related degeneration. As the eyelids have a large impact on the appearance of the eyes, the aesthetic result of reconstruction is as important as the restoration of eyelid function in ocular surface protection and lubrication. In this chapter, the authors discuss the operative care of patients with defects of varying extent involving the upper and lower eyelids, as well as common degenerative conditions such as eyelid margin malrotation and eyelid malposition, such as ptosis, retraction, entropion, and ectropion. Planning for repair should begin during the initial examination. The surgeon can evaluate the size of an eyelid lesion and attempt to predict the size of the possible defect after excision.

Upper and lower blepharoplasties are some of the most common cosmetic surgical procedures. The eyelids function in ocular protection and lubrication and are capable of expressing a wide range of emotions in nonverbal communication. As such, the goals of surgery are to impart a natural rejuvenated appearance with adequate symmetry while preserving the normal function of the eyelids. Patients seeking blepharoplasty can present with any number of chief complaints that can be categorized as functional or aesthetic in nature. The two are, however, intimately intertwined and the surgeon must consider both the function and appearance of the eyelids. Herein, we discuss various approaches to the clinical management of patients for blepharoplasty, including preoperative evaluation, operative approaches, and postoperative care.

A holistic system design approach is presented in this work which helps co-design and analyse a multi technology array of ICs, packages and PCBs. The proposed methodology provides the key functionality to simulate and thus co design an IC in context of its PCB and package parasitic models, at the same time, staying within the IC designers preferred design and simulation environment requiring minimal knowledge of packaging and PCB design techniques. It is, primarily, an IC centric co design environment and a simulation solution that allows the analog, RF, and mixed-signal designers to drive designs of package modules to their packaging teams and define simulation testbenches that include the native IC and its corresponding package, and PCB interconnect and component level parasitic models prior to tape-out. The breadth of this “one-ocean” solution caters equally to a wide array of applications including mm-wave RF, power management ICs and low power analog front ends.

This paper presents an investigation aimed at understanding the flaw size sensitivity in amorphous silica nanostructures. The investigation is carried out in LAMMPS via reactive molecular dynamics analyses by employing ReaxFF–SiO, a bond order-based force field. First, a validated procedure is developed to build the amorphous silica nanostructures via a melt, quench, and equilibration process. This procedure is seen to correctly reproduce the molecular structure as well as mechanical properties of silica. The best agreement to experimental data is obtained by using non-periodic boundary conditions with the isothermal–isobaric ensemble. The validated model is then used to analyze crack propagation in amorphous silica samples with varying flaw sizes subjected to mode I tensile fracture. The analyses reveal a marked transition from flaw sensitive to insensitive behavior with decreasing flaw size. The transition flaw size is found to be 20–25 A. Fracture propagation is found to be accompanied by the formation of several single atom thick strands near the crack tip, previously reported as “stress fibers.” This is proposed as a viable mechanism causing blunting of an initially sharp crack, analogous to blunting of a macroscale crack by an inelastic damage zone. The nanoscale fracture process zone estimated by probing near crack tip stresses is found to nearly equal the transition flaw size, providing an explanation for the transitional behavior. A semi-empirical, transitional flaw size effect law rooted in quasibrittle fracture mechanics is derived based on asymptotic matching and is found to capture well the nanoscale transitional behavior.

Despite effective prevention programs targeting cardiovascular risk factors, coronary artery disease (CAD) remains the leading cause of death. Novel biomarkers are needed for improved risk stratification and primary prevention. To assess for independent associations between plasma metabolites and specific CAD plaque phenotypes we performed liquid chromatography mass-spectrometry on plasma from 1002 patients in the BioHEART-CT study. Four metabolites were examined as candidate biomarkers. Dimethylguanidino valerate (DMGV) was associated with presence and amount of CAD (OR) 1.41 (95% Confidence Interval [CI] 1.12–1.79, p = 0.004), calcified plaque, and obstructive CAD (p &lt, 0.05 for both). The association with amount of plaque remained after adjustment for traditional risk factors, ß-coefficient 0.17 (95% CI 0.02–0.32, p = 0.026). Glutamate was associated with the presence of non-calcified plaque, OR 1.48 (95% CI 1.09–2.01, p = 0.011). Phenylalanine was associated with amount of CAD, ß-coefficient 0.33 (95% CI 0.04–0.62, p = 0.025), amount of calcified plaque, (ß-coefficient 0.88, 95% CI 0.23–1.53, p = 0.008), and obstructive CAD, OR 1.84 (95% CI 1.01–3.31, p = 0.046). Trimethylamine N-oxide was negatively associated non-calcified plaque OR 0.72 (95% CI 0.53–0.97, p = 0.029) and the association remained when adjusted for traditional risk factors. In targeted metabolomic analyses including 53 known metabolites and controlling for a 5% false discovery rate, DMGV was strongly associated with the presence of calcified plaque, OR 1.59 (95% CI 1.26–2.01, p = 0.006), obstructive CAD, OR 2.33 (95% CI 1.59–3.43, p = 0.0009), and amount of CAD, ß-coefficient 0.3 (95% CI 0.14–0.45, p = 0.014). In multivariate analyses the lipid and nucleotide metabolic pathways were both associated with the presence of CAD, after adjustment for traditional risk factors. We report novel associations between CAD plaque phenotypes and four metabolites previously associated with CAD. We also identified two metabolic pathways strongly associated with CAD, independent of traditional risk factors. These pathways warrant further investigation at both a biomarker and mechanistic level.

Calgary offers many public transportation options, including light rail transit (LRT), bus rapid transit (BRT), and local buses as well as facilities for non-motorized travelers. Yet the individual and synergistic effects of these mobility options on residential property values in Calgary have not been clearly understood. By using a multilevel hedonic modeling approach, we examine the independent and interactive economic impacts of different transportation options on Calgary's residential properties in 2017. Our findings suggest that proximity to LRT and better neighborhood walkability can appreciate residential property values, whereas proximity to major roads and bus service tend to depreciate the values, although the degree and significance vary by property type. When proximity to LRT is coupled with high walkability, more appreciation of property values is expected, particularly in the case of attached houses and apartment properties. Our results imply that urban planners and city officials should strive to create safe and pedestrian-friendly environments near LRT stations that could lead to more dynamic civic activities.

ObjectivesThe study aim was to explore experiences of patients with pleural mesothelioma of follow-up care in three National Health Service (NHS) Trusts to develop recommendations for practice.DesignThe study design was qualitative and comprised three interlinked phases: a documentary analysis, interviews and consultation meetings. Altheide and Johnson’s Analytic Realism theoretical framework guided the thematic data analysis process.SettingThe study was conducted in three NHS Trusts in South England. Two were secondary care settings and the third was a tertiary centre.ParticipantsThe secondary care trusts saw 15–20 patients with new mesothelioma per year and the tertiary centre 30–40. The tertiary centre had a designated mesothelioma team. Twenty-one patients met the inclusion criteria: >18 years, mesothelioma diagnosis and in follow-up care. Non-English speaking participants, those unable to provide written informed consent or those whom the clinical team felt would find participation too distressing were excluded. All participants were white, 71% were 70–79 years old and 71% were men. Three consultation meetings were conducted with key stakeholders including mesothelioma nurse specialists, patients with mesothelioma, carers and local clinical commissioning group members.Main outcome measuresSpecific outcomes were to gain a detailed understanding of mesothelioma follow-up care pathways and processes and to develop coproduced recommendations for practice.ResultsMesothelioma pathways were not always distinct from lung cancer care pathways. All trusts provided follow-up information and resources but there was varied information on how to access local support groups, research or clinical trial participation. Five themes were developed relating to people; processes; places; purpose and perception of care. Coproduced recommendations for improving mesothelioma follow-up pathways were developed following the consultation meetings.ConclusionsThis study has developed recommendations which identify the need for patients with pleural mesothelioma to access consistent, specialist, streamlined mesothelioma care, centred around specialist mesothelioma nurses and respiratory consultants, with input from the wider multidisciplinary team.

To describe radiographic evidence of radiation pneumonitis (rRP) and fibrosis (rRF) and determine what dosimetric parameters correlate with rRP and rRF after stereotactic ablative radiation therapy (SABR) to the lung. Ninety-eight follow-up computed tomography (CT) scans from 32 patients treated by SABR were retrospectively reviewed for CT appearance of rRP and rRF determined by the Ikezoe (≤6 months) and Koenig (≥7 months) systems. The dosimetric correlations for rRP, rRF, and fibrotic volume were analyzed. There was a 55 % incidence of rRP and 59 % incidence of rRF with a median follow-up of 10 months. Only the low-dose parameters V 2.5, V 5, V 7, and V 10 (the volume of lung receiving more than 2.5, 5, 7, and 10 Gy of radiation, respectively) were correlated to the development of rRP (p

Haun saussy opens his influential discussion of past and present conceptions of comparative literature, “exquisite cadavers Stitched from Fresh Nightmares,” by linking them in an apparently historic claim to victory: “Comparative literature has, in a sense, won its battles” (3). The ambiguous nature of that claim, and the real subject of Saussy's ensuing discussion, is indicated, however, by the qualifying phrase “in a sense.” In another sense, Saussy implies, the achievements of comparative literature remain open to debate. For, despite the widespread adoption by national-literature departments of comparative literature's theoretical methods of inquiry, comparative approaches to literature continue to be considered inessential or secondary to the defining aim of national-literature departments—investigating and describing the reality of historically grounded national traditions and identities. Saussy's “sense” of victory is thus snatched from the jaws of an unapologetic sense of defeat:What needs propagating is the comparative reflex, the comparative way of thinking, not the departmental name; and if those are to spread at the cost of identity and institutional reward, so much the worse for identity.—It so happens that identity is the pivot of our triumph—and our wraithlikeness. (5)

Background: Nurses experience poor quality of life due to workload and role stress. In this study, a spirituality-based intervention was administered to nurse managers. Method: A total of 45 nurse managers participated in the study; 24 were assigned to the experimental group, and 21 were assigned to a control group. The Holy Name Meditation Program was provided solely to the experimental group. Pretest, posttest 1 (5 weeks after the intervention), posttest 2 (12 weeks after the intervention), and posttest 3 (24 weeks after the intervention) data were gathered on seven variables, including spiritual well-being, spiritual needs, job satisfaction, leadership, burnout, depression, and self-efficacy. Results: The experimental group showed significant improvement in spiritual well-being ( p < .001), spiritual needs ( p = .029), and job satisfaction ( p = .005) until the 24-week follow-up. Burnout ( p < .001), depression and anxiety ( p = .034), and self-efficacy ( p = .024) showed significant improvement until the 12-week follow-up. Depression and anxiety ( p = .053) showed decreasing tendency until the 24-week follow-up. Conclusion: Evidence suggests this program promotes spiritual and psychosocial well-being of nurse managers. [ J Contin Educ Nurs . 2020;51(5):215–224.]

Rayleigh-B\'enard convection is simulated to study the effects of inertial, nonisothermal particles on buoyancy-driven turbulent fluid. Distinct particle characteristics, such as gravitational settling and specific heat, are isolated to infer which are dominant in affecting the fluid.

Trigeminal nerves collecting sensory information from the orofacial area synapse on second-order neurons in the dorsal horn of subnucleus caudalis and cervical C1/C2 spinal cord (Vc/C2, or trigeminocervical complex), which is critical for sensory information processing. Injury to the trigeminal nerves may cause maladaptive changes in synaptic connectivity that plays an important role in chronic pain development. Here we examined whether injury to the infraorbital nerve, a branch of the trigeminal nerves, led to synaptic ultrastructural changes when the injured animals have developed neuropathic pain states. Transmission electron microscopy was used to examine synaptic profiles in Vc/C2 at 3 weeks postinjury, corresponding to the time of peak behavioral hypersensitivity following chronic constriction injury to the infraorbital nerve (CCI-ION). Using established criteria, synaptic profiles were classified as associated with excitatory (R-), inhibitory (F-), and primary afferent (C-) terminals. Each type was counted within the superficial dorsal horn of the Vc/C2 and the means from each rat were compared between sham and injured animals; synaptic contact length was also measured. The overall analysis indicates that rats with orofacial pain states had increased numbers and decreased mean synaptic length of R-profiles within the Vc/C2 superficial dorsal horn (lamina I) 3 weeks post-CCI-ION. Increases in the number of excitatory synapses in the superficial dorsal horn of Vc/C2 could lead to enhanced activation of nociceptive pathways, contributing to the development of orofacial pain states.

Technical committees for industry consensus standards involve multiple stakeholders. These stakeholders are experts who assess and perceive benefits and risks differently due to differences in their experiences, training, and cultural worldviews. Decision-making on technical committees is premised on information sharing and communications between these experts. We seek to understand how these worldviews drive decision-making criteria. Specifically, we aim to test the hypothesis that technical experts’ worldviews are diagnostic of their technical preferences. In this paper, we surveyed members of the National Aerospace Standards Committee (NASC). We report preliminary results in our efforts to develop a survey that can reliably measure their cultural worldviews. Our approach was inspired by measures used by Kahan’s cultural cognition paradigm, a method of categorizing individuals’ worldviews and associated risk perceptions on a combination of Douglas’s cultural theory of risk, and Slovic’s Psychometric Paradigm. Preliminary results indicate support for the existence of different worldviews on the NASC.

Purpose/background In animal models, levels of the neurosteroid pregnenolone increase after tetrahydrocannabinol (THC) administration and pregnenolone appears to attenuate the brain effects of THC. Given these interactions between pregnenolone and THC, we evaluated baseline neurosteroid levels in participants with a history of a cannabis use disorders (CUDs). Methods/procedures Bipolar depressed participants were enrolled in a randomized placebo-controlled clinical trial to evaluate the efficacy of add-on pregnenolone for depression and before receiving pregnenolone or placebo. Baseline serum levels of neurosteroids (pregnenolone, allopregnanolone, pregnanolone, and androsterone) were analyzed in 53 participants with highly sensitive and specific gas chromatography/mass spectrometry. Current, active substance use disorders, or a positive baseline urine drug screen, were exclusionary. Participants were classified by past cannabis abuse or dependence diagnosis using the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Data were analyzed by independent t tests for separate neurosteroids. Findings/results Participants with a history of CUD had higher serum pregnanolone, lower allopregnanolone, a higher pregnanolone to allopregnanolone ratio, and a lower pregnenolone to pregnanolone ratio compared with those without a history of cannabis use. Similar findings were not observed based on a history of other substance use disorders with the exception of lower allopregnanolone in those with opioid use disorders. Notably, the majority of those with an opioid use disorder also had a CUD (75%). Implications/conclusions These findings potentially suggest either enduring changes in neurosteroids in people with past CUDs or represent a vulnerability marker for a CUD.