cssi/SciSciGPT-SciSciNet huggingface dataset:
Fluorescence visualization and modeling of a micelle-free zone formed at the interface between an oil and an aqueous micellar phase during interfacial surfactant transport.

This study examines the transport of surfactant that occurs when an aqueous micellar phase is placed in contact with a clean oil phase in which the surfactant is soluble. Upon contact with oil, surfactant monomer on the aqueous side of the interface adsorbs onto the oil/water interface and subsequently desorbs into the oil and diffuses away from the surface. The depletion of aqueous monomer underneath the interface disturbs the monomer−micelle equilibrium, and aggregates break down to replenish the monomer concentration and accelerate the interfacial transport. The depletion of monomer and micelles drives the diffusive flux of these species toward the surface, and the combined effects of diffusion and aggregate kinetic disassembly, alongside kinetic adsorption and desorption at the interface and diffusion away from the interface into the oil, determine the interfacial transport rate. This interfacial transport is examined here in the quasi-static limit in which the diffusion of monomer and micelles in the...
Anterolateral hypothalamic deafferentation prevents compensatory hypersecretion of ACTH following adrenalectomy in the rat.

SummaryComplete or anterolateral, but not anterior, basal hypothalamic deafferen-tation prevented the increased basal secretion of ACTH in chronically adrenalecto-mized rats. ACTH secretion in response to ether stress was at least as great in the de-afferented, adrenalectomized rats as in intact controls. The data suggest that extra-hypothalamic influences which enter the lateral basal hypothalamus are necessary to achieve a high basal ACTH secretion when plasma ghicocorticoids are depressed.
In vivo fate tracking of degradable nanoparticles for lung gene transfer using PET and Ĉerenkov imaging

Nanoparticles (NPs) play expanding roles in biomedical applications including imaging and therapy, however, their long-term fate and clearance profiles have yet to be fully characterized in vivo. NP delivery via the airway is particularly challenging, as the clearance may be inefficient and lung immune responses complex. Thus, specific material design is required for cargo delivery and quantitative, noninvasive methods are needed to characterize NP pharmacokinetics. Here, biocompatible poly(acrylamidoethylamine)-b-poly(dl-lactide) block copolymer-based degradable, cationic, shell-cross-linked knedel-like NPs (Dg-cSCKs) were employed to transfect plasmid DNA. Radioactive and optical beacons were attached to monitor biodistribution and imaging. The preferential release of cargo in acidic conditions provided enhanced transfection efficiency compared to non-degradable counterparts. In vivo gene transfer to the lung was correlated with NP pharmacokinetics by radiolabeling Dg-cSCKs and performing quantitative biodistribution with parallel positron emission tomography and Cerenkov imaging. Quantitation of imaging over 14 days corresponded with the pharmacokinetics of NP movement from the lung to gastrointestinal and renal routes, consistent with predicted degradation and excretion. This ability to noninvasively and accurately track NP fate highlights the advantage of incorporating multifunctionality into particle design.
Precise measurement method of shaft pulsation

The pulsation of each section is difficult to measure in the design of precise straightening press with the three-point bend straightening theory.To solve the problem,a new technology and the corresponding algorithm was raised.The key content of this technology is setting two sensors at the two ends of the shaft to measure the pulsation of the two pivots,and the circle fitting and line fitting are used in the corresponding algorithm.Finally,an example shows that the method can remove the effect of the pulsation at the bearing points,thus the pulsation of the shaft can be measured exactly.It can provide a foundation for deciding the press point,the pivot and the value of pressing.
Role of endothelin receptor subtypes in the in vivo regulation of renal function

Endothelin (ET) is a potent vasoconstrictor peptide of endothelial origin, which at low doses results in renal vasoconstriction and diuresis with variable actions on sodium excretion. The current study conducted in four groups of anesthetized dogs was designed to define the role of the ETA and ETB receptor subtypes in the renal actions of low-dose exogenous ET. Group 1 (n = 4) animals served as time controls. In group 2 (n = 6) a systemic ET-1 (5 ng.kg-1.min-1) infusion mediated renal vasoconstriction, antinatriuresis with increases in proximal fractional reabsorption of sodium, and diuresis with a decrease in urine osmolality. In group 3 (n = 6) intrarenal BQ-123 (4 micrograms.kg-1.min-1), a selective ETA antagonist, abolished the systemic ET-1-mediated changes in renal hemodynamics and unmasked a natriuretic action at the level of the proximal tubule. In contrast, the diuretic response of ET was not altered by BQ-123. In group 4 (n = 6) intrarenal sarafotoxin 6-c, a selective ETB receptor agonist, resulted in a diuretic response without a change in sodium excretion. These studies suggest that the ETA receptor contributes to the renal vasoconstriction, whereas the ETB receptor is largely responsible for the diuretic response during exogenous ET. This study also suggests that at low doses ET is natriuretic in vivo by decreasing proximal tubular reabsorption of sodium independent of ETA or ETB receptor activation.
Integrating Hyperspectral Likelihoods in a Multidimensional Assignment Algorithm for Aerial Vehicle Tracking

Tracking vehicles through dense environments is an important and challenging task that is mostly tackled using visible and near IR wavelengths. Hyperspectral imaging is known to improve the robustness of target identification, but the massive increase in data created is usually prohibitive for tracking many targets. We present a persistent real-time aerial target tracking system, taking advantage of an adaptive, multimodal sensor concept and blending the hyperspectral likelihoods with kinematic likelihoods in a multidimensional assignment framework. The adaptive sensor is capable of providing wide field of view panchromatic images as well as the spectra of small number of pixels. The proposed system does not require large amount of hyperspectral data collection as we focus on tracking fewer number of targets with higher persistency. This overcomes the data challenge of hyperspectral tracking by following dynamic data-driven application systems (DDDAS) principles to control hyperspectral data collection where most beneficial. The DDDAS framework for controlling hyperspectral data collection is developed by incorporating prior information from the filter movement predictions and information from motion detection. The proposed multidimensional hyperspectral feature-aided tracker is compared to a 2-D hyperspectral feature-aided tracker and another cascaded hyperspectral data based tracker by generating a synthetic, realistic, aerial video on a dense scene.
Clinical Evaluation of Cerebral Perfusion in AVM Patients

The presence of an arteriovenous malformation (AVM) exerts a significant and occasionally profound effect on overall cerebral hemodynamic patterns. It is likely that the high-flow low-resistance nature of the shunt occasionally results in ischemic sequelae in surrounding brain tissue and may in some way relate to perioperative hyperemic consequences. In order to better understand the global and regional impact of these hemodynamic disturbances, 62 AVM patients referred to our Center who underwent microsurgical resection were subjected to preoperative single photon emission computed tomography (SPECT) regional cerebral blood flow (rCBF) quantitative measurements using xenon-133 inhalation. Attempts were made to correlate specific clinical, radiographic, and hemodynamic patterns with end points including the occurrence of perioperative hyperemia and outcome. In addition, 35 patients were studied preoperatively with and without acetazolamide activation in an attempt to identify patterns which might predict hemodynamic disturbances.
Prevalent and Incident Vertebral Deformities in Midlife Women: Results from the Study of Women's Health Across the Nation (SWAN).

Background Vertebral fractures are the most common type of osteoporotic fracture among women, but estimates of their prevalence and incidence during middle-age are limited. The development of vertebral morphometry (VM) using dual energy X-ray absorptiometry (DXA) makes it more feasible to measure VM in large, longitudinal, observational studies. We conducted this study to: 1) contribute to the scant knowledge of the prevalence, incidence and risk factors for vertebral deformities in middle-aged women; and 2) to evaluate the performance of DXA-based VM measurement in a large, community based sample. Methods The sample is derived from the Study of Women’s Health Across the Nation (SWAN), a multi-site, community-based, longitudinal cohort study of the MT. Using Hologic QDR 4500A instruments, we acquired initial VM measurements in 1446 women during calendar years 2004–2007; in 2012–2013, a follow-up VM was obtained in 1108. Annually, lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) were measured and participant characteristics were assessed with standardized instruments. Multivariable logistic regression models examined the relations between prevalent deformity and relevant characteristics. Analyses of characteristics associated with prevalent deformity were restricted to 824 women who had not taken bone active medications since SWAN baseline. We calculated incident deformity per person year (PY) of observation, standardized to 1000 person-years. Results The cranial portion of the VM image yielded the lowest proportions of readable vertebrae: from T4 through T6, between 43% and 63% of vertebral bodies were evaluable. Greater BMI was associated with fewer readable levels (B = -0.088, p<0.0001). In the baseline sample of 1446 women, the prevalence of vertebral deformity was 3.2% (95% CI: 2.3, 4.1). The relative odds of deformity increased by 61% per SD decrement in baseline LS BMD (p = 0.02) and were 67% greater per SD decrement in baseline FN BMD (p = 0.04). Odds of prevalent deformity increased by 21% per year increment in age (p = 0.02). On average, 1108 women were followed for 6.8 years (SD 0.5 years, range 5.1–8.3 years) and we observed an incidence of 1.98 vertebral deformities per 1000 PY. In the longitudinal sample, 628 participants had never used bone active medications; their vertebral deformity incidence was 2.8 per 1000 PY. Conclusion Prevalence of vertebral deformity in SWAN participants aged 50–60 years was low and lower bone density at the LS and FN was strongly related to greater risk of prevalent deformity. Only about half of the vertebral levels between T4-T6 could be adequately imaged by DXA. Greater BMI is associated with fewer readable vertebral levels.
A networking perspective of mobile parallel relays

For mobile ad hoc networking, relaying is one of the most fundamental functions. The traditional relaying strategy is serial, where data packets hop from a single node to another, and the nodes neighboring a transmitting node or a receiving node are suppressed from transmission to avoid radio interference. We consider a parallel relaying strategy where neighboring nodes may act as parallel relays with space-time modulation. We demonstrate the feasibility of parallel relaying in ad hoc networks by presenting a generic route discovery algorithm for establishing routes of parallel relays. We also formulate a link layer protocol for forwarding packets through parallel relays. We then provide analytical results of packet loss rate and link delay time to highlight some of the potential benefits of parallel relays. With N parallel relays at each link, a diversity factor, N-squared, is achievable. A power saving of 10 dB or more is possible from serial relaying to parallel relaying.
Introduction to Case Presentation

The following case presentation was used at The Greenbrier Conference in August 1991 as a stimulus to the invited experts. The questions were prepared to be consistent with the type of problems commonly encountered by clinicians caring for patients who have undergone a bone marrow transplant. The questions were designed to be straightforward yet raise issues for which the answer is frequently controversial. There was lively discussion regarding most answers, a summary of which is given at the end of this monograph.
Patient Symptoms Are the Most Frequent Indicators of Recurrence in Patients with American Joint Committee on Cancer Stage II Melanoma

Background Patients with stage II melanoma have a considerable risk for recurrence. Current guidelines are imprecise as to optimal follow-up. We hypothesized that by examining recurrence patterns, we could help to better inform guidelines. Study Design We queried IRB-approved melanoma databases of Thomas Jefferson University and University of North Carolina, identifying 581 patients with stage II melanoma between 1996 and 2015 with at least 1 year of follow-up. Data included location of first recurrence and how recurrence was detected (ie patient symptom, physician examination, or routine surveillance imaging). Cox regression with backward elimination was used for multivariable analysis. Results One hundred and seventy-one patients had a recurrence (29.4%), the incidence increased considerably by stage sub-group. Significant predictors of recurrence included male sex (p = 0.003), ulceration (p = 0.03), and stage (p Conclusions The majority of recurrences in stage II melanoma are detected by patients and their physicians and rarely by routine imaging. As such, clinical follow-up and patient education are critical factors in detection of recurrence. With the prevalence of regional nodal recurrences, ultrasound might prove to be an important strategy in early recurrence detection.
Pharmacists’ earnings determination: are part-time practitioners homogeneous in their response?

Background Evidence suggests that part-time pharmacists possess different characteristics from those exhibited by full-time pharmacists. Practitioners working fewer hours per week are driven almost exclusively by pay, whereas full-time practitioners show a more comprehensive approach to their work experience. Objective Compare wage-and-salary responses to the number of hours worked, human-capital stock, job-related preferences and job-opinion variables across three employment-status groups: full-time and two kinds of part-time pharmacists. Methods The study was based on self-reported survey data collected from a random sample of licensed pharmacists practicing throughout the USA. The analysis sample consisted of 411 full-time pharmacists, 119 part-time pharmacists working an average of 30–39 h per week and 78 part-time pharmacists working an average of <30 h per week. Using ordinary least squares, the model estimated, separately for each employment-status group, annual wage-and-salary earnings as a function of ten explanatory variables. Key findings Responses to earnings determinants varied not only between full-time and part-time pharmacists but also across part-time practitioners. The responsiveness of wages and salaries to an additional hour of work per week drops as pharmacists work more hours. Full-time and both types of part-time practitioners differ in the way they transform human-capital stock, job-related preferences and job-opinion variables into wages and salaries. Conclusion The empirical evidence reported here is expected to be used by healthcare managers and policymakers to facilitate communication, promote teamwork within pharmacy and foster better relations with other healthcare professionals.
Direct observation of nanoparticle migration in epoxy based fiber reinforced composites using fluorescence microscopy

The preferential accumulation of nanoparticles at carbon fiber surfaces, induced by the addition of a thermoplastic “migrating agent” to an epoxy resin, was monitored via in situ fluorescence microscopy. (3-Glydidyloxypropyl)trimethoxysilane functionalized fluorescent silica nanoparticles (GFCSP) were synthesized by a modified Stober method to track the spatiotemporal abundance of nanoparticles. Single carbon fibers were embedded in an uncured epoxy mixture consisting of tetraglycidyl-4,4-diaminodiphenylmethane and 4,4’-diamnodiphenyl sulfone, as well as thermoplastic migrating agent, poly(ether sulfone), and GFCSP. A heated microscope stage was used to monitor the fluorescence in the local vicinity of the fiber as the epoxy begins to cross-link and solidify upon heating. Our results show that the synthesized GFCSP accumulate at fiber surfaces only in the presence of poly(ether sulfone), as verified using scanning electron micrographs of Mode I fiber fracture surfaces.
Evaluating Which Dose-Function Metrics Are Most Critical for Functional-Guided Radiation Therapy

Purpose Four-dimensional (4D) computed tomography (CT) ventilation imaging is increasingly being used to calculate lung ventilation and implement functional-guided radiation therapy in clinical trials. There has been little exhaustive work evaluating which dose-function metrics should be used for treatment planning and plan evaluation. The purpose of our study was to evaluate which dose-function metrics best predict for radiation pneumonitis (RP). Methods and Materials Seventy lung cancer patients who underwent 4D CT imaging and pneumonitis grading were assessed. Pretreatment 4D CT scans of each patient were used to calculate ventilation images. We evaluated 3 types of dose-function metrics that combined the patient's 4D CT ventilation image and treatment planning dose distribution: (1) structure-based approaches; (2) image-based approaches using the dose-function histogram; and (3) nonlinear weighting schemes. Log-likelihood methods were used to generate normal tissue complication probability models predicting grade 3 or higher (ie, grade 3+) pneumonitis for all dose-function schemes. The area under the curve (AUC) was used to assess the predictive power of the models. All techniques were compared with normal tissue complication probability models based on traditional, total lung dose metrics. Results The most predictive models were structure-based approaches that focused on the volume of functional lung receiving ≥20 Gy (AUC, 0.70). Probabilities of grade 3+ RP of 20% and 10% correspond to V20 (percentage of volume receiving ≥20 Gy) to the functional subvolumes of 26.8% and 9.3%, respectively. Imaging-based analysis with the dose-function histogram and nonlinear weighted ventilation values yielded AUCs of 0.66 and 0.67, respectively, when we evaluated the percentage of functionality receiving ≥20 Gy. All dose-function metrics outperformed the traditional dose metrics (mean lung dose, AUC of 0.55). Conclusions A full range of dose-function metrics and functional thresholds was examined. The calculated AUC values for the most predictive functional models occupied a narrow range (0.66-0.70), and all showed notable improvements over AUC from traditional lung dose metrics (0.55). Identifying the combinations most predictive of grade 3+ RP provides valuable data to inform the functional-guided radiation therapy process.
Konflik Hukum Antara Ketentuan Hukum Pidana Islam dan Hak-Hak Sipil? (Telaah Konsep HAM dan Implementasi Ratifikasi ICCPR dan CAT di Indonesia)

Can death penalty or corporal punishment be imposed by a state since it is required by the Shariah, but, at the same time, it is against state’s obligation to guarantee civil rights as documented in such international human right laws as ICCPR and CAT? This article is to analyse the so called conflict of law between the requirements of Islamic criminal law and civil rights in Indonesia with particular reference to its implementation in Nanggroe Aceh Darussalam province. There are growing demands of some Muslims to the implementation of hudud in Indonesia and several Qanun Provinsi Nanggroe Aceh Darussalam have been enacted too. According to the proponent of such implementation, this depicts that the state respects its citizens’ belief and culture which is guaranted under the aegis of the right to self determination. However, Indonesia has ratified some international human right laws which require the state to respect the right to life and prohibit torture and cruel, inhuman or degrading punishment. How should the state react? this article argues that an alternative approach which is able to bridge prolonged polemic between universalims and cultural relativisms with regards to the validity of international human rights norms when being implemented to different legal cultures is very much needed. This is important in order to reduce resistence against international human right laws which are important to safeguard civil rights especially when the criminal justice system of a country has not fulfilled the due process of law.
The Evolution of Weapons Policies on College Campuses in the 21st Century

A conservatively-minded campus, Liberty University's administrators have, like many college campuses, struggled with creating an appropriate weapons policy. The policies in existence prior to 2011 were more traditionally anti-weapon, while those created after 2011 have been more forgiving. This article examines the background, both national and local, for these shifts in policy.
Role of testosterone in the treatment of cardiovascular disease

Cardiovascular disease (CVD) is the most prevalent non-communicable cause of death worldwide. Testosterone is a sex hormone that is predominant in males but also occurs in lower concentrations in females. It has effects directly on the blood vessels of the cardiovascular system and on the heart, as well as effects on risk factors for CVD. Serum testosterone concentrations are known to decrease with age and reduced testosterone levels are linked to premature coronary artery disease, unfavourable effects on CVD risk factors and increased risk of cardiovascular mortality independent of age. A significant number of men with heart failure demonstrate reduced serum testosterone concentrations and there is early evidence suggesting that low testosterone levels affect cardiac repolarisation. Any association between endogenous testosterone concentrations and CVD in women has yet to be established. Testosterone replacement is used to treat men with hypogonadism but also has cardiovascular effects. This review will present the current evidence, expert opinion and controversies around the role of testosterone in the pathophysiology of CVD and surrounding the use of testosterone treatment and its effects on the cardiovascular system and CVD.
Challenges and Opportunities for the Subcutaneous Delivery of Therapeutic Proteins

Biotherapeutics is a rapidly growing drug class, and over 200 biotherapeutics have already obtained approval, with about 50 of these being approved in 2015 and 2016 alone. Several hundred protein therapeutic products are still in the pipeline, including interesting new approaches to treatment. Owing to patients' convenience of at home administration and reduced number of hospital visits as well as the reduction in treatment costs, subcutaneous (SC) administration of biologics is of increasing interest. Although several avenues for treatment using biotherapeutics are being explored, there is still a sufficient gap in knowledge regarding the interplay of formulation conditions, immunogenicity, and pharmacokinetics (PK) of the absorption of these compounds when they are given SC. This review seeks to highlight the major concerns and important factors governing this route of administration and suggest a holistic approach for effective SC delivery.
Probing kinetic enhancement of β-galactosidase-nanoparticle complexes (Conference Presentation)

Enhancement in enzymatic activity after attachment to nanoparticle surfaces has been observed in numerous enzyme systems, although the underlying mechanism for these enhancements remains largely unknown. This work explores the utility of a model based on a reaction scheme that takes into account some of the many interactions between substrate, product, and nanoparticle that can occur. This model was utilized to make predictions about the type of behavior that should manifest itself with quantum dots peripherally displayed around beta-galactosidase (&beta-gal) and confirmed empirically. &beta-gal is a homotetrameric enzyme which at ~465 kDa is significantly larger than the 4.2 nm diameter green emitting quantum dots utilized to decorate its periphery. Because &beta-gal operates near the diffusion limit, this provides an opportunity to selectively investigate certain aspects of enzyme enhancement when attached to a nanoparticle with minimal perturbation to the native enzyme structure. Enzymatic assays were performed with both free enzyme and quantum dot-decorated enzymes in a side-by-side format where kinetic processes were challenged by increasing viscosity with glycerol and competitive inhibitors such as lactose. The results from this model suggest it is possible to achieve significant enhancements in a diffusion limited enzyme’s catalytic rate ( k cat ) after NP attachment without substantial changes to the enzyme’s structure or function. Because cell free synthetic biology is gaining importance, this approach will yield insights on how enzymes can be utilized ex vivo and how being attached to NP scaffolds yields kinetic enhancement, possibly through enhanced product dissociation.
Nerve excitability: transition from descriptive phenomenology to chemical analysis of mechanisms.

The electrical activity by which impulses are conducted along nerve and muscle fibers, is carried by Na- and K-ions moving across the excitable membranes due to increased ion permeability. — A biochemical approach, initiated to elucidate the mechanism of the permeability changes, centered around the analysis of the properties and functions of the proteins, including enzymes, directly associated with the role of AcCh, in the excitable membrane. The results necessitated a fundamentally reformed concept of the role of AcCh. The four proteins specifically associated with the function of AcCh form a cycle which controls the rapid ion permeability changes of the membrane and permits the ion fluxes through dynamic gateways. A model has been elaborated that integrates biochemical, biophysical, and thermodynamic data; it permits the interpretation of many electrophysiological data in molecular terms. AcCh has basically the same function in conducting and synaptic parts of excitable membranes. The new concept has replaced the purely descriptive phenomenology of nerve impulse propagation by the analysis of the chemical mechanisms of nerve excitability and bioelectricity.
Natural selection without survival of the fittest

Susan Mills and John Beatty proposed a propensity interpretation of fitness (1979) to show that Darwinian explanations are not circular, but they did not address the critics' chief complaint that the principle of the survival of the fittest is either tautological or untestable. I show that the propensity interpretation cannot rescue the principle from the critics' charges. The critics, however, incorrectly assume that there is nothing more to Darwin's theory than the survival of the fittest. While Darwinians all scoff at this assumption, they do not agree about what role, if any, this principle plays in Darwin's theory of natural selection. I argue that the principle has no place in Darwin's theory. His theory does include the idea that some organisms are fitter than others. But greater reproductive success is simply inferred from higher fitness. There is no reason to embody this inference in the form of a special principle of the survival of the fittest.
Law and Law Enforcement

The academic study of law and geography is primarily concerned with investigating the relationships of geographical or socio-spatial phenomena to forms of social power and modes of meaning production associated with distinctively legal practices, institutions, ideologies, and forms of consciousness. This article traces the emergence of legal geography against a backdrop of changing scholarly conceptions of both law and geography. It then surveys some of the ways in which legal and geographical phenomena are co-conditioning. Examples are presented concerning the legal constitution of ‘home’ and of more extensive geographies of power. The final section discusses some of the primary tasks and methodological questions that shape the doing of legal geography.
Rural Occupational Health and Safety

Approximately 20% of the U.S. population, or 53 million Americans, reside in rural areas, but as with many issues in rural health, there is little published information in occupational safety and health specifically for rural residents. In Colorado, between 1982 and 1987, 16% of the total workforce was employed in rural counties (Colorado Department of Health, 1990). The majority of rural residents who do not commute to urban areas are likely to work in the production of goods and they are often self-employed. Because small businesses are primary employers in rural areas, information is not readily available from the Bureau of Labor Statistics, which focuses largely on businesses that employ 11 or more workers who are 14 years of age or older (Pratt, 1990). The most extensive work on occupational safety and health in rural areas has been done among agricultural workers (Donham et al, 1997), including migrant and seasonal workers, yet this group makes up only about 2% to 5% of the total population and a small percentage of all rural workers.
Depressive symptoms in relation to clinical symptom onset of mild cognitive impairment.

ABSTRACTObjective:There is increasing evidence of an association between depressive symptoms and mild cognitive impairment (MCI) in cross-sectional studies, but the longitudinal association between depressive symptoms and risk of MCI onset is less clear. The authors investigated whether baseline symptom severity of depression was predictive of time to onset of symptoms of MCI. Method These analyses included 300 participants from the BIOCARD study, a cohort of individuals who were cognitively normal at baseline (mean age = 57.4 years) and followed for up to 20 years (mean follow-up = 2.5 years). Depression symptom severity was measured using the Hamilton Depression Scale (HAM-D). The authors assessed the association between dichotomous and continuous HAM-D and time to onset of MCI within 7 years versus after 7 years from baseline (reflecting the mean time from baseline to onset of clinical symptoms in the cohort) using Cox regression models adjusted for gender, age, and education. Results At baseline, subjects had a mean HAM-D score of 2.2 (SD = 2.8). Higher baseline HAM-D scores were associated with an increased risk of progression from normal cognition to clinical symptom onset ≤ 7 years from baseline (p = 0.043), but not with progression g 7 years from baseline (p = 0.194). These findings remained significant after adjustment for baseline cognition. Conclusions These results suggest that low levels of depressive symptoms may be predictive of clinical symptom onset within approximately 7 years among cognitively normal individuals and may be useful in identifying persons at risk for MCI due to Alzheimer's disease.
Defining and operationalizing the phenomena of recovery: a working definition from the recovery science research collaborative

A number of definitions exist for the concept of “recovery” in both the substance use disorder (SUD) and mental health (MH) fields. Previous attempts to define recovery have not reached consensus a...
A New Framework for CNN-Based Speech Enhancement in the Time Domain

This paper proposes a new learning mechanism for a fully convolutional neural network (CNN) to address speech enhancement in the time domain. The CNN takes as input the time frames of noisy utterance and outputs the time frames of the enhanced utterance. At the training time, we add an extra operation that converts the time domain to the frequency domain. This conversion corresponds to simple matrix multiplication, and is hence differentiable implying that a frequency domain loss can be used for training in the time domain. We use mean absolute error loss between the enhanced short-time Fourier transform (STFT) magnitude and the clean STFT magnitude to train the CNN. This way, the model can exploit the domain knowledge of converting a signal to the frequency domain for analysis. Moreover, this approach avoids the well-known invalid STFT problem since the proposed CNN operates in the time domain. Experimental results demonstrate that the proposed method substantially outperforms the other methods of speech enhancement. The proposed method is easy to implement and applicable to related speech processing tasks that require time-frequency masking or spectral mapping.
What’s New in Obstetric Anesthesia? The 2017 Gerard W. Ostheimer Lecture

The "What's New in Obstetric Anesthesia Lecture" is presented every year at the annual meeting of the Society for Obstetric Anesthesia and Perinatology. This lecture was established in 1975 to update the membership on the most relevant articles that were published in the preceding calendar year. In 1995, the lecture was renamed as the "Ostheimer Lecture" in honor of Gerard W. Ostheimer, an obstetric anesthesiologist from the Brigham and Women's Hospital with significant contributions in the field. This review summarizes key articles published in 2017 that were presented in the 2018 Ostheimer Lecture with a focus on opioid prescriptions, anesthesia for external cephalic version, labor analgesia, maternal morbidity, and global health. A proposed list of action items based on the 2017 literature is also presented.
DOMINO: Data-driven Optimization of bi-level Mixed-Integer NOnlinear Problems

The Data-driven Optimization of bi-level Mixed-Integer NOnlinear problems (DOMINO) framework is presented for addressing the optimization of bi-level mixed-integer nonlinear programming problems. In this framework, bi-level optimization problems are approximated as single-level optimization problems by collecting samples of the upper-level objective and solving the lower-level problem to global optimality at those sampling points. This process is done through the integration of the DOMINO framework with a grey-box optimization solver to perform design of experiments on the upper-level objective, and to consecutively approximate and optimize bi-level mixed-integer nonlinear programming problems that are challenging to solve using exact methods. The performance of DOMINO is assessed through solving numerous bi-level benchmark problems, a land allocation problem in Food-Energy-Water Nexus, and through employing different data-driven optimization methodologies, including both local and global methods. Although this data-driven approach cannot provide a theoretical guarantee to global optimality, we present an algorithmic advancement that can guarantee feasibility to large-scale bi-level optimization problems when the lower-level problem is solved to global optimality at convergence.
DEVELOPMENT OF A PREDICTION MODEL FOR INCIDENT MYOCARDIAL INFARCTION USING MACHINE LEARNING APPLIED TO HARMONIZED ELECTRONIC HEALTH RECORD DATA

With the burden of cardiovascular disease expected to increase considerably, substantial research has focused on the development of prediction tools to assess who might develop disease. Machine learning offers a means to mobilize large amounts of EHR data for this purpose. Here we compare deep
Selecting a theoretical framework to explore the social and cognitive uncertainty that hepatitis C treatment represents for people who inject drugs

Emerging research models for hepatitis C eradication suggest a social network-based treatment approach among people who inject drugs. It is essential for nurses to critically examine the influence of these social networks among people who inject drugs and the impact on their hepatitis C treatment decisions. The purpose of this paper is to describe the process of selecting a theoretical framework to guide a mixed methods study exploring the perceived uncertainty of individual hepatitis C treatment behaviors existing within the social networks of people who inject drugs. Using Walker and Avant's framework for theory analysis, four established theories and models from nursing science and psychology were reviewed. Aspects of both the Social Cognitive Theory and Uncertainty in Illness Theory were combined to form a theoretical framework, the Socio-Cognitive Uncertainty Model. This new theoretical framework describes the social and cognitive uncertainty that hepatitis C virus treatment represents for people who inject drugs. Taken together, social influence and social selection can inform the nurse's understanding of hepatitis C treatment acceptability among this high-risk social network- an important consideration in the pursuit of disease eradication.
Abstract B36: A novel model of osteosarcomagenesis reveals dysregulation of oxidative phosphorylation

The purpose of this study is to develop a new model to study osteosarcoma in order to elucidate cellular pathways important in osteosarcomagenesis that are potential therapeutic targets. Osteosarcoma is the most common bone malignancy in childhood and early adolescence. Thirty percent of patients with the rare genetic disorder Type II Rothmund-Thomson syndrome (RTS) develop osteosarcoma. Patients with RTS have biallelic mutations in the RECQL4 gene, which encodes an ATP-dependent DNA helicase. Unfortunately, many attempts to model RTS-associated osteosarcoma have not been successful. Here, we describe a patient-derived induced pluripotent stem cell (iPSC) model capable of recapitulating the process of osteosarcomagenesis. Briefly, RTS patient fibroblasts are reprogrammed to iPSCs, then subsequently differentiated to mesenchymal stem cells. These cells are validated and further differentiated to early and late osteoblasts, the potential precursors of osteosarcoma. Because the iPSC-derived osteoblasts retain the genetic fidelity of the patient from which they were derived, we believe these cells are the ideal model to study the molecular mechanism associated with RTS-associated osteosarcoma. Utilizing the patient-derived osteoblasts, we have performed RNAseq and subsequent GSEA analyses to explore the transcriptome of RTS osteoblasts and found the dysregulation of oxidative phosphorylation in RTS osteoblasts. Interestingly, it has been reported that specific vacuolar ATPases are upregulated in patient cells. It has been reported that vacuolar ATPases function to increase proton concentration within the mitochondria and also within the extracellular environment. Understanding key mechanisms of osteosarcomagenesis is critical to making steps toward novel therapeutics. Citation Format: Brittany E. Jewell, An Xu, Ruoji Zhou, Dandan Zhu, Linchao Lu, Ruying Zhao, Lisa L. Wang, Dung-Fang Lee. A novel model of osteosarcomagenesis reveals dysregulation of oxidative phosphorylation [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B36.
Abstract 4025: New candidate therapy for BAP1-mutant cancer identified using novel screen

Inactivation of the oncogene BAP1 is associated with poor prognosis in many cancers, including uveal melanoma (UM). Therapies for mediating the detrimental effects of BAP1 mutations have yet to be developed. Previously, we found that BAP1 depletion in Xenopus causes a striking developmental phenotype and a global dysregulation of differentiation markers across the genetic landscape. This was caused by impaired promoter assembly at commitment genes, marked by decreased H3K27ac levels. Inhibition of HDAC4 protein rescues the affected BAP1-depleted phenotype and genetic regulations, further emphasizing the role of H3K27ac in BAP1 function. Pairing these findings with a lab-devised multitiered screening process, we identified an epigenetic compound that successfully reverses the detrimental effects of the BAP1 deficient phenotype back to phenotypically normal conditions. This multitiered screening process tests prospective compounds for the ability to mediate transcriptional aberrations caused by BAP1 loss in UM cells (phase 1), rescue the BAP1 loss phenotype in Xenopus (phase 2), and provide significant inhibition of UM tumor growth in a mouse model (phase 3). These findings reveal a new application for a promising epigenetic compound as a therapeutic and reversing agent for BAP1 mutant UM. Furthermore, our streamlined process for the testing of promising therapeutic agents can accelerate the testing of such agents and getting them to clinical trials in a timely manner. Citation Format: DAWN A. OWENS, Jeffim N. Kuznetsov, Andy Lopez, Stefan Kurtenbach, Daniel Bilbao, Evan R. Roberts, Claude-Henry Volmar, Claes R. Wahlestedt, Shaun P. Brothers, J. William Harbour. New candidate therapy for BAP1-mutant cancer identified using novel screen [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4025.
A Randomized, Placebo-Controlled Trial of Mirtazapine for the Treatment of Posttraumatic Stress Disorder in Veterans.

Objective The aim of this study was to determine the efficacy of mirtazapine, a tetracyclic antidepressant, as monotherapy for the treatment of posttraumatic stress disorder (PTSD). Methods This multisite, randomized, double-blind, placebo-controlled trial was conducted between April 2006 and November 2010 at the Tuscaloosa and Birmingham Veterans Affairs Medical Centers in Alabama. US military veterans who met DSM-IV criteria for PTSD were randomly assigned to placebo (n = 39) or mirtazapine (n = 39) titrated up to 45 mg/d for an 8-week double-blind period followed by an 8-week open-label phase of mirtazapine treatment. The primary outcome efficacy measure was the Structured Interview for Posttraumatic Stress Disorder (SIP). Secondary measures included other measures of PTSD, depression, and sleep. Analyses of treatment groups involved mixed-model procedures using a random intercept to test the hypotheses that mirtazapine would be more effective than placebo in reducing symptoms of PTSD and depression and improving quality of sleep. Results Seventy-eight participants were randomized with 61 completing the 8-week controlled phase and 48 completing the open-label phase. No significant differences were observed between groups on the primary outcome of SIP scores during the controlled phase (P = .418). In secondary outcomes, significant improvements per the Clinical Global Impressions-Improvement scale were found for the mirtazapine group compared to the placebo group (P = .041). The 8-week open-label phase demonstrated significant symptom improvement in SIP total score (P = .0003) and in scores on the SIP re-experiencing (P = .0007), avoidance (P = .0309), and hyperarousal (P = .0014) subscales. There were no significant differences in the occurrence of adverse events between groups. Conclusions This study did not show efficacy of mirtazapine monotherapy in the treatment of PTSD. Identification of more effective treatments, either as monotherapy or adjunctive, for PTSD is imperative. Trial registration ClinicalTrials.gov identifier: NCT00302107.
Packed Like Sardines – How Surface Crowdedness Impacts Accessibility to Peptidoglycan of Staphylococcus aureus

Bacterial cell walls are essential barriers that protect bacteria against the onslaught of potentially lethal molecules from the outside. Small molecule therapeutics, proteins from bacterial foes, and host immune proteins must navigate past a dense layer of bacterial biomacromolecules (e.g., capsular proteins, teichoic acids, and anchored proteins) to reach the peptidoglycan (PG) layer of Gram-positive bacteria. A subclass of molecules (e.g., antibiotics with intracellular cellular targets) must also permeate through the PG (in a molecular sieving manner) to reach the cytoplasmic membrane. In the case of Staphylococcus aureus (S. aureus), teichoic acids are the major biopolymers that decorate bacterial cell surfaces. Despite the biological and therapeutic importance of surface accessibility, systematic analyses in live bacterial cells have been lacking. We describe a novel live cell fluorescence assay that reports on the permeability of molecules to and within the PG scaffold. The assay has robust reproducibility, is readily adoptable to any Gram-positive organism, and is compatible with high-throughput sample processing. Analysis of the factors controlling permeability to S. aureus and the drug resistant methicillin resistant MRSA revealed that molecular flexibility plays a central role in molecular permeability. Moreover, teichoic acids impeded permeability of molecules of a wide range of sizes and chemical composition.
Basic Principles of MR Imaging

Summary Magnetic resonance imaging is a safe, noninvasive imaging technique that relies on the interactions of hydrogen nuclei in various tissues to high-strength magnetic fields and RF pulses and produces images that allow one to evaluate the soft-tissues of the head and body in ways never before available. Although one cannot get a histologic diagnosis of all tissues types, one can gain a significant amount of clinically useful information to help detect the presence and extent of abnormalities more readily and plan the necessary treatment more precisely. Future advances in three-dimensional imaging and dynamic scanning will enhance the use of this imaging technique even further.
Deleterious effects of whole-body vibration on the spine: A review of in vivo, ex vivo, and in vitro models

Occupational exposure to whole-body vibration is associated with the development of musculoskeletal, neurological, and other ailments. Low back pain and other spine disorders are prevalent among those exposed to whole-body vibration in occupational and military settings. Although standards for limiting exposure to whole-body vibration have been in place for decades, there is a lack of understanding of whole-body vibration-associated risks among safety and healthcare professionals. Consequently, disorders associated with whole-body vibration exposure remain prevalent in the workforce and military. The relationship between whole-body vibration and low back pain in humans has been established largely through cohort studies, for which vibration inputs that lead to symptoms are rarely, if ever, quantified. This gap in knowledge highlights the need for the development of relevant in vivo, ex vivo, and in vitro models to study such pathologies. The parameters of vibrational stimuli (eg, frequency and direction) play critical roles in such pathologies, but the specific cause-and-effect relationships between whole-body vibration and spinal pathologies remain mostly unknown. This paper provides a summary of whole-body vibration parameters; reviews in vivo, ex vivo, and in vitro models for spinal pathologies resulting from whole-body vibration; and offers suggestions to address the gaps in translating injury biomechanics data to inform clinical practice.