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In this study, a new drug carrier based on gelled-oil nanoparticles (GNPs) was designed and synthesized for the encapsulation and release of the model hydrophobic drug, berberine chloride (BCl). Two compositions with different oil phases were examined, sesame oil (SO) and cinnamaldehyde (Cin), which were emulsified with water, stabilized with Tween 80 (Tw80), and gelled using an N-alkylated primary oxalamide low-molecular-weight gelator (LMWG) to give stable dispersions of GNPs between 100 and 200 nm in size. The GNP formulation with Cin was significantly favored over SO due to (1) lower gel melting temperatures, (2) higher gel mechanical strength, and (3) significantly higher solubility, encapsulation efficiency, and loading of BCl. Also, the solubility and loading of BCl in Cin were significantly increased (at least 7-fold) with the addition of cinnamic acid. In vitro release studies showed that the release of BCl from the GNPs was independent of gelator concentration and lower than that for BCl solution and the corresponding nanoemulsion (no LWMG). Also, cell internalization studies suggested that the N-alkylated primary oxalamide LMWG did not interfere with the internalization efficiency of BCl into mouse mast cells. Altogether, this work demonstrates the potential use of these new GNP formulations for biomedical studies involving the encapsulation of drugs and nutraceuticals and their controlled release., Competing Interests: The authors declare no competing financial interest., (Crown © 2023. Published by American Chemical Society.)

The genus Thunnus (family Scombridae) comprises eight species of tunas of which all but one are targeted by industrialized fisheries. Although intact individuals of these species can be distinguished by morphological characteristics, researchers and managers often rely on dressed, frozen, juvenile or larval fish samples, which often necessitates the identification of molecular species. Here the authors investigate short amplicon (SA) and unlabelled probe high-resolution melting analysis (UP-HRMA) as a low-cost, high-throughput molecular genotyping assay capable of distinguishing between albacore tuna (Thunnus alalunga), blackfin tuna (Thunnus atlanticus), bigeye tuna (Thunnus obesus), Atlantic bluefin tuna (Thunnus thynnus) and yellowfin tuna (Thunnus albacares) in the Gulf of Mexico. Although SA-HRMA of variable regions in the NADH dehydrogenase subunit 4 (ND4) and subunit 5 (ND5), and subunit 6 (ND6) of the mtDNA genome did yield some species-specific diagnostic melting curves (e.g., ND4 assay can reliably distinguish Atlantic bluefin tuna), genotype masking produced excessive variation in melting curves for reliable multi-species identification. To minimize the genotyping masking of SA-HRMA a 26 base pair long UP containing four SNPs was developed within a 133 bp segment of ND4. The UP-HRMA is able to reliably distinguish Gulf of Mexico species T. thynnus, T. obesus, T. albacares and T. atlanticus by UP melting temperature at 67, 62, 59 and 57°C, respectively. The developed UP-HRMA assay is a lower-cost, higher-throughput, alternative to previously published molecular assays for tuna identification that can be easily automated for large data sets, including ichthyological larval surveys, fisheries specimens lacking distinguishing morphological characteristics or detection of fraudulent trading of tuna species., (© 2023 The Authors. Journal of Fish Biology published by John Wiley & Sons Ltd on behalf of Fisheries Society of the British Isles.)

Background: The protease BACE1 is a major drug target for Alzheimer's disease, but chronic BACE1 inhibition is associated with non-progressive cognitive worsening that may be caused by modulation of unknown physiological BACE1 substrates., Methods: To identify in vivo-relevant BACE1 substrates, we applied pharmacoproteomics to non-human-primate cerebrospinal fluid (CSF) after acute treatment with BACE inhibitors., Results: Besides SEZ6, the strongest, dose-dependent reduction was observed for the pro-inflammatory cytokine receptor gp130/IL6ST, which we establish as an in vivo BACE1 substrate. Gp130 was also reduced in human CSF from a clinical trial with a BACE inhibitor and in plasma of BACE1-deficient mice. Mechanistically, we demonstrate that BACE1 directly cleaves gp130, thereby attenuating membrane-bound gp130 and increasing soluble gp130 abundance and controlling gp130 function in neuronal IL-6 signaling and neuronal survival upon growth-factor withdrawal., Conclusion: BACE1 is a new modulator of gp130 function. The BACE1-cleaved, soluble gp130 may serve as a pharmacodynamic BACE1 activity marker to reduce the occurrence of side effects of chronic BACE1 inhibition in humans., (© 2023. The Author(s).)

Disrupted tau proteostasis and transneuronal spread is a pathological hallmark of Alzheimer's disease. Neurodegenerative diseases remain an unmet medical need and novel disease modifying therapeutics are paramount. Our objective was to develop a mechanistic mathematical model to enhance our understanding of tau antibody pharmacokinetics and pharmacodynamics in animals and humans. A physiologically-based pharmacokinetic-pharmacodynamic (PBPK-PD) modeling approach was employed to support the preclinical development and clinical translation of therapeutic antibodies targeting tau for the treatment of Alzheimer's disease. The pharmacokinetics of a tau antibody was evaluated in rat and non-human primate microdialysis studies. Model validation for humans was performed using publicly available clinical data for gosuranemab. In-silico analyses were performed to predict tau engagement in human brain for a range of tau antibody affinities and various dosing regimens. PBPK-PD modeling enabled a quantitative understanding for the relationship between dose, affinity, and target engagement, which supported lead candidate optimization and predictions of clinically efficacious dosing regimens., Competing Interests: Authors PB, DB-Y, JS, SG, BS, SA, MJ, GA, and KY were employed by Merck & Co., Inc., (Copyright © 2022 Bloomingdale, Bumbaca-Yadav, Sugam, Grauer, Smith, Antonenko, Judo, Azadi and Yee.)

More than 20 y ago, we developed an animal model for chronic and continuous collection of cerebrospinal fluid (CSF) from conscious rhesus macaques. Since our previous publication in 2003, we have successfully implanted 168 rhesus macaques using this approach. Our experience enables us to provide up-to-date information regarding the model, including refine- ments to our implant design, reductions in maintenance, and new procedures for dealing with contamination. The results of our experiences have reduced the number of surgeries required and helped to increase the longevity of the implant, with some functioning for more than 18 y. Building on our success in rhesus macaques, we attempted to develop similar animal models in the African green monkeys and dogs but have been unable to develop reliable chronic models for CSF collection in these species.

This paper describes the structure-activity-relationships of novel fluoroalkyl substituents at the C2 position of iminothiazine dioxide beta secretase inhibitors. Key discoveries include reduced amidine basicity and its effect on Pgp, cell potency, and efficacy in various preclinical in vivo efficacy animal models. Findings from these structure-activity-relationships are discussed., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Occupational and environmental medicine (OEM) departments in healthcare institutions can be quickly overwhelmed when COVID-19 infection rates rapidly and simultaneously increase in the workforce and the patients served. Our goal is to present a detailed toolkit of practical approaches for use by front-line OEM specialists to address workforce management tasks during pandemic surges., Methods: Specific focus is on tasks related to employee symptom triage, exposure risk assessment, workplace contact tracing, and work restrictions., Results: Tools include strategies used by customer call centers, two decision support algorithms (exposure due to cohabitation or non-cohabitation), a color-coded employee case tracking tool, a contact tracing protocol, and documentation templates that serve as memory aids for encounters., Conclusions: These tools are created with commonly used software. Implementation is feasible in most front-line OEM settings, including those with limited resources., Competing Interests: Conflict of interest: All authors, except for Yann Wester, have been employed by VA Loma Linda Healthcare (VALLHS) within the last 36 months. Yann Wester is an Occupational Medicine resident who is employed by the Loma Linda University Health residency program and was employed within the last 3 years in the internship program at Einstein Medical Center, Philadelphia. Within the last 36 months, Cesar Reis was employed at Kaiser Permanente Healthcare System. All other relationships between authors and the listed entities are academic appointments without compensation. All entities are medical training institutes and peer-reviewed publication of scholarly work is encouraged. Hall, Guo, Diaz-Caturan, Reis, Carritte, Smith, and Wester have no relationships/conditions/circumstances that present potential conflict of interest., (Copyright © 2021 American College of Occupational and Environmental Medicine.)

A four-wave-mixing, frequency-comb-based, hyperspectral imaging technique that is spectrally precise and potentially rapid, and can in principle be applied to any material, is demonstrated in a near-diffraction-limited microscopy application.

Background: Medical care provided by Special Operations Forces (SOF) combat medics is vital for establishing communication with local populations. In many of these communities, livestock hold a valuable position within the social, political, and cultural structure. The West Virginia University (WVU) Special Forces Medical Sergeant/Special Operations Independent Duty Corpsman (SFMS/SOIDC) Large Animal Module is designed to provide a foundational experience in livestock husbandry and veterinary procedures to SOF combat medic candidates. This study was conducted to determine the participants' base knowledge of food animal production and to evaluate if the program content was sufficient for increasing their knowledge of the subject matter., Methods: A quasi-experimental design utilizing pre-test and post-test instruments was used. The validity of the testing instruments was established by a panel of subject matter experts and the instruments' reliability was determined by a split-half analysis using SPSS® statistical software. The difference between the pre-test and post-test examinations were compared for 66 candidates who were assigned to WVU Health Sciences Center for the applied medical experience program and 46 counterparts assigned to other institutions by a match pair analysis., Results: Seventy-five percent of the subjects had no previous livestock exposure, and only 7% had previously participated in the 4-H program or Future Farmers of America (FFA). The average improvement in scores, pre-test versus post-test, was significantly greater for those that attended the module (18.5 versus 0.9)., Conclusion: Few SFMS/SOIDC candidates have prior knowledge of livestock husbandry practices. The large animal module successfully provides education on livestock husbandry practice to participants. Knowledge of livestock production can assist SOF medics in establishing rapport with indigenous populations while on mission., (2021.)

Background: Network analysis is an emerging approach in the study of psychopathology, yet few applications have been seen in eating disorders (EDs). Furthermore, little research exists regarding changes in network strength after interventions. Therefore the present study examined the network structures of ED and co-occurring depression and anxiety symptoms before and after treatment for EDs., Method: Participants from residential or partial hospital ED treatment programs (N = 446) completed assessments upon admission and discharge. Networks were estimated using regularized Graphical Gaussian Models using 38 items from the Eating Disorders Examination-Questionnaire, Quick Inventory of Depressive Symptomatology, and State-Trait Anxiety Inventory., Results: ED symptoms with high centrality indices included a desire to lose weight, guilt about eating, shape overvaluation, and wanting an empty stomach, while restlessness, self-esteem, lack of energy, and feeling overwhelmed bridged ED to depression and anxiety symptoms. Comparisons between admission and discharge networks indicated the global network strength did not change significantly, though symptom severity decreased. Participants with denser networks at admission evidenced less change in ED symptomatology during treatment., Conclusions: Findings suggest that symptoms related to shape and weight concerns and guilt are central ED symptoms, while physical symptoms, self-esteem, and feeling overwhelmed are links that may underlie comorbidities in EDs. Results provided some support for the validity of network approaches, in that admission networks conveyed prognostic information. However, the lack of correspondence between symptom reduction and change in network strength indicates that future research is needed to examine network dynamics in the context of intervention and relapse prevention.

Objective: Evidence suggests that eating disorders (EDs) may be under-detected in males. Commonly used measures of EDs such as the Eating Disorder Examination-Questionnaire (EDE-Q) were initially developed within female samples, raising concern regarding the extent to which these instruments may be appropriate for detecting EDs in males. The current study used receiver operating characteristic curve analysis to (a) examine the accuracy of the EDE-Q global score in correctly classifying males with and without clinically significant ED pathology, and (b) establish the optimal EDE-Q global clinical cutoff for males., Method: Participants were a clinical sample of 245 male ED patients and a control sample of 205 male undergraduates., Results: Eating Disorder Examination-Questionnaire global scores demonstrated moderate-high accuracy in predicting ED status (area under the curve = 0.85, 95% CI: 0.82-0.89). The optimal cutoff of 1.68 yielded a sensitivity of 0.77 and specificity of 0.77., Discussion: Overall, results provide preliminary support for the discriminant validity of EDE-Q scores among males. However, concerns remain regarding the measure's ability to comprehensively assess domains of disordered eating most relevant to males. Therefore, careful attention to the possibility for measurement bias and continued evaluation of the scale in males is encouraged., (© 2018 Wiley Periodicals, Inc.)

The determination of the properties (i.e. line center, width, and amplitude) of a spectral line is simulated using a Monte Carlo method. For dual-comb spectroscopy, ideal repetition rates emerge for both the signal and LO combs that do not correspond to the repetition rates that possess the highest signal-to-noise ratio. The determination is even more accurate when the repetition rates have an arbitrary near-harmonic ratio. The simulation results are generalized to allow for the comparison of any two spectroscopic systems (i.e. not just comb-based systems) by performing the simulations as a function of the spectral point spacing and signal-to-noise ratio of the acquired data.

Despite evidence documenting relationships between eating disorder (ED) psychopathology, depression, and anxiety, little is known regarding how social anxiety is related to ED symptoms in treatment. Therefore this study examined associations between depression, general anxiety, social anxiety, and ED psychopathology at the beginning and end of treatment (EOT) among patients (N = 380) treated in a residential ED program. Participants completed measures of ED psychopathology and affective variables. Higher depression and general anxiety, but not social anxiety, were related to higher ED psychopathology at baseline. However, social anxiety emerged as a unique predictor of ED psychopathology at EOT such that participants with higher social anxiety evidenced less improvement in ED psychopathology. Findings suggest that social anxiety has specific relevance to treatment in EDs, which may reflect shared mechanisms and underlying deficits in emotion regulation.

Objective: To determine if participation in an online resilience program impacts resilience, stress, and somatic symptoms., Methods: Approximately 600 enrollees in the meQuilibrium resilience program received a series of brief, individually prescribed video, and text training modules in a user-friendly format. Regression models tested how time in the program affected change in resilience from baseline and how changes in resilience affected change in stress and reported symptoms., Results: A significant dose-response was detected, where increases in the time spent in training corresponded to greater improvements in resilience. Degree of change in resilience predicted the magnitude of reduction in stress and symptoms. Participants with the lowest resilience level at baseline experienced greater improvements., Conclusion: Interaction with the online resilience training program had a positive effect on resilience, stress, and symptoms in proportion to the time of use.

Objectives: The study measured the relative influence of the following 3 factors in consumers' choice of hospitals: (1) cost, (2) out-of-pocket cost, and (3) safety as measured by Leapfrog Hospital Safety Score letter grade., Methods: Two hospital-choice questions regarding a hypothetical medical procedure were administered to 2357 online respondents. In question 1, respondents were assigned a scenario in which hospital 1 grade (A through D), hospital 2 grade (B through F), and hospital 2 total cost (3 levels) were randomly varied across respondents. In all cases, hospital 2 had a lower safety grade than hospital 1, and hospital 1 cost was held constant. In question 2, scenarios varied out-of-pocket cost rather than total cost. Demographic characteristics, income level, health status, health literacy, and opinions about value were also measured., Results: On average, 94% and 88% of the respondents chose the safer hospital in questions 1 and 2, respectively. In all but 1 of 30 possible scenarios, where hospital 2 cost the individual $1000 less and was rated a B whereas hospital 1 was rated an A, respondents chose the safer hospital. Higher incomes, higher health literacy, and being female were associated with a stronger preference for hospital 1 (safer). There was a small effect suggesting that approximately 4% of the respondents selected a higher-cost hospital despite lower safety, but it was outweighed by predominant selections of the safer hospital., Conclusions: When shown Hospital Safety Score and cost information, consumers chose safer hospitals in 97% of cost and safety scenarios.

Successful police organizations rely on involved, satisfied, and committed workers. The concepts of job involvement (i.e., connection with the job), job satisfaction (i.e., affective feeling toward the job), and organizational commitment (i.e., bond with the employing organization) have been shown to significantly affect intentions and behaviors of employees. The current study used multivariate ordinary least squares (OLS) regression analysis on survey results from a sample of 827 Indian police officers to explore how perceptions of work environment factors affect officers' job involvement, job satisfaction, and organizational commitment. Organizational support, formalization (i.e., level of codified written rules and guidelines), promotional opportunities, institutional communication (i.e., salient work information is transmitted), and input into decision-making (i.e., having a voice in the process) significantly influenced the job involvement, job satisfaction, and organizational commitment of Indian police officers. Specifically, in the multivariate analysis, perceptions of formalization and instrumental communication had a positive relationship with job involvement; perceptions of organizational support, promotional opportunities, instrumental communication, and input into decision-making had positive associations with job satisfaction; and perceptions of organizational support, formalization, promotional opportunities, instrumental communication, and input into decision-making had positive relationships with organizational commitment.

Objective: Evidence indicates that males account for a significant minority of patients with eating disorders (EDs). However, prior research has been limited by inclusion of small and predominantly non-clinical samples of males. This study aimed to (1) provide male clinical norms for widely used ED measures (Eating Disorder Examination Questionnaire [EDE-Q] and Eating Disorder Inventory-3 [EDI-3]) and (2) examine sex differences in overall ED psychopathology., Method: Participants were 386 male and 1,487 female patients with an ED diagnosis aged 16 years and older who completed the EDE-Q and EDI-3 upon admission to a residential or partial hospital ED treatment program., Results: Normative data were calculated for the EDE-Q (global and subscales) and the EDI-3 (drive for thinness, body dissatisfaction, and bulimia). Analyses of variance (ANOVAs) used to examine sex, ED diagnosis, and their interaction in relation to overall ED psychopathology revealed a consistent pattern of greater severity among females for ED psychopathology., Discussion: This study provides clinical norms on the EDE-Q and the EDI-3 for males with clinically diagnosed EDs. It is unclear whether the greater severity observed in females reflects qualitative differences in ED presentation or true quantitative differences in ED severity. Additional research examining the underlying nature of these differences and utilizing male-specific ED measures with clinical samples is warranted., (© 2017 Wiley Periodicals, Inc.)

Objective: To examine whether resilience has a protective effect in difficult work environments., Methods: A survey of 2063 individuals measured individual resilience, stress, burnout, sleep problems, likelihood of depression, job satisfaction, intent to quit, absences, and productivity. It also measured work characteristics: job demands, job influence, and social support. Multivariate and logistic regression models examined the main effects and interactions of resilience and job characteristics., Results: High strain work environments (high demand, low influence, and low support) have an unfavorable effect on all outcomes. Resilience has a protective effect on all outcomes. For stress, burnout, and sleep, higher resilience has a more protective effect under low-strain conditions. For depression, absence and productivity, resilience has a more protective effect when job strain is high., Conclusions: Workers with high resilience have better outcomes in difficult work environments., Competing Interests: Dr Smith has no conflicts of interest to disclose.

We describe successful efforts to optimize the in vivo profile and address off-target liabilities of a series of BACE1 inhibitors represented by 6 that embodies the recently validated fused pyrrolidine iminopyrimidinone scaffold. Employing structure-based design, truncation of the cyanophenyl group of 6 that binds in the S3 pocket of BACE1 followed by modification of the thienyl group in S1 was pursued. Optimization of the pyrimidine substituent that binds in the S2'-S2″ pocket of BACE1 remediated time-dependent CYP3A4 inhibition of earlier analogues in this series and imparted high BACE1 affinity. These efforts resulted in the discovery of difluorophenyl analogue 9 (MBi-4), which robustly lowered CSF and cortex Aβ40 in both rats and cynomolgus monkeys following a single oral dose. Compound 9 represents a unique molecular shape among BACE inhibitors reported to potently lower central Aβ in nonrodent preclinical species.

Objective: The quality of mental health care provided by the U.S. Department of Veterans Affairs (VA) was compared with care provided to a comparable population treated in the private sector., Methods: Two cohorts of individuals with mental disorders (schizophrenia, bipolar disorder, posttraumatic stress disorder, major depression, and substance use disorders) were created with VA administrative data (N=836,519) and MarketScan data (N=545,484). The authors computed VA and MarketScan national means for seven process-based quality measures related to medication evaluation and management and estimated national-level performance by age and gender., Results: In every case, VA performance was superior to that of the private sector by more than 30%. Compared with individuals in private plans, veterans with schizophrenia or major depression were more than twice as likely to receive appropriate initial medication treatment, and veterans with depression were more than twice as likely to receive appropriate long-term treatment., Conclusions: Findings demonstrate the significant advantages that accrue from an organized, nationwide system of care. The much higher performance of the VA has important clinical and policy implications.

Objective: The objective of this study was to report on the validation of new scales [called the Altarum Consumer Engagement (ACE) Measure] that are indicative of an individual's engagement in health and healthcare decisions. The instrument was created to broaden the scope of how engagement is measured and understood, and to update the concept of engagement to include modern information sources, such as online health resources and ratings of providers and patient health., Methods: Data were collected through an online survey with a US population of 2079 participants. A combination of Principal Component Analysis (PCA) and detailed Rasch analyses were conducted to identify specific subscales of engagement. Results were compared to another commonly used survey instrument, and outcomes were compared for construct validity., Results: The PCA identified a four-factor structure composed of 21 items. The factors were named Commitment, Informed Choice, Navigation, and Ownership. Rasch analyses confirmed scale stability. Relevant outcomes were correlated in the expected direction, such as health status, lifestyle behaviors, medication adherence, and observed expected group differences., Conclusions: This study confirmed the validity of the new ACE Measure and its utility in screening for and finding group differences in activities related to patient engagement and health consumerism, such as using provider comparison tools and asking about medical costs.

Quality measures are currently reported almost exclusively at the facility level. Forthcoming physician quality data are expected to be reported primarily at the level of the group practice. Little is known about consumers' understanding of and interest in practice-level measures. The research team conducted 4 focus groups, half with individuals who had a chronic illness and half with individuals who did not. Most consumers correctly understand the concept of a physician practice. However, consumers exhibit little interest in practice-level characteristics, preferring information about their personal doctor. Understanding of and interest in practice-level quality does not differ by chronic disease status. Additional work must be done to design, develop, and test promotional and educational materials to accompany the planned reports to highlight the relevance of practice-level characteristics for consumer decision making., (© The Author(s) 2014.)

Previous genetic studies of Atlantic swordfish (Xiphias gladius L.) revealed significant differentiation among Mediterranean, North Atlantic and South Atlantic populations using both mitochondrial and nuclear DNA data. However, limitations in geographic sampling coverage, and the use of single loci, precluded an accurate placement of boundaries and of estimates of admixture. In this study, we present multilocus analyses of 26 single nucleotide polymorphisms (SNPs) within 10 nuclear genes to estimate population differentiation and admixture based on the characterization of 774 individuals representing North Atlantic, South Atlantic, and Mediterranean swordfish populations. Pairwise FST values, AMOVA, PCoA, and Bayesian individual assignments support the differentiation of swordfish inhabiting these three basins, but not the current placement of the boundaries that separate them. Specifically, the range of the South Atlantic population extends beyond 5°N management boundary to 20°N-25°N from 45°W. Likewise the Mediterranean population extends beyond the current management boundary at the Strait of Gibraltar to approximately 10°W. Further, admixture zones, characterized by asymmetric contributions of adjacent populations within samples, are confined to the Northeast Atlantic. While South Atlantic and Mediterranean migrants were identified within these Northeast Atlantic admixture zones no North Atlantic migrants were identified respectively in these two neighboring basins. Owing to both, the characterization of larger number of loci and a more ample spatial sampling coverage, it was possible to provide a finer resolution of the boundaries separating Atlantic swordfish populations than previous studies. Finally, the patterns of population structure and admixture are discussed in the light of the reproductive biology, the known patterns of dispersal, and oceanographic features that may act as barriers to gene flow to Atlantic swordfish.

Despite the availability of endorsed quality measures and widespread usage of hospice, hospice quality data are rarely available to consumers. Moreover, little is known about how consumers prioritize extant measures. This study drew on focus group and survey data collected in 5 metropolitan areas. The study found that consumers reported the hospice quality indicators we tested were easy to understand. Participants placed top priority on measures related to pain and symptom management. Relative to consumers with hospice experience, consumers without previous experience tended to place less value on spiritual support for patients and caregivers, emotional support for caregivers, and after-hours availability. The National Quality Forum-approved measures resonate well with consumers. Consumers also appear to be ready for access to data on the quality of hospice providers., (© The Author(s) 2014.)

Mindfulness-based stress reduction is a mindfulness-based intervention that is an effective treatment modality for many conditions including stress, anxiety, and depression. Using data from 23 patients who completed a short-form mindfulness-based stress reduction course at a federally qualified health center, a quasi-experimental design was used to assess the impact of participation on self-reported anxiety, stress, mindfulness, and quality of life. Mindfulness and stress showed improvements from pre- to posttests, but neither difference achieved statistical significance. Participants showed statistically significant decreases in anxiety (7-item Generalized Anxiety Disorder scale score: 7.8-4.4; P = .005) and improvements in health-related quality of life including the 36-item Medical Outcomes Study Short Form Health Survey Mental Component Summary (+9.1; P = .001), Physical Functioning (+6.6; P = .039), Vitality (+16.1; P = .001), Social Functioning (+16.9; P = .003), Role Physical (+16.8; P = .016), and Mental Health (+15.6; P < .001) subscales. These findings suggest that an abbreviated mindfulness-based stress reduction course can serve to reduce anxiety and improve quality of life in an underserved population.

Objective: We sought to describe the presentation of external head and neck lymphedema in patients treated for head and neck cancer and to examine their initial responses to complete decongestive therapy., Study Design: Case series with chart review., Setting: MD Anderson Cancer Center, Houston, Texas., Subjects and Methods: The charts of patients who were evaluated for head and neck cancer at MD Anderson Cancer Center after treatment (January 2007-January 2013) were retrospectively reviewed. Response to complete decongestive therapy was evaluated per changes in lymphedema severity rating or surface tape measures. Predictors of therapy response were examined on the basis of regression models., Results: The cases of 1202 patients were evaluated. Most patients (62%) had soft reversible pitting edema (MD Anderson Cancer Center stage 1b). Treatment response was evaluated for 733 patients; 439 (60%) improved after complete decongestive therapy. Treatment adherence independently predicted complete decongestive therapy response (P < .001)., Conclusions: These data support the effectiveness of a head and neck cancer-specific regimen of lymphedema therapy for cancer patients with external head and neck lymphedema. Our findings suggest that head and neck lymphedema is distinct from lymphedema that affects other sites, thus requiring adaptations in traditional methods of management and measurement., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.)

BACE, a β-secretase, is an attractive potential disease-modifying therapeutic strategy for Alzheimer's disease (AD) as it results directly in the decrease of amyloid precursor protein (APP) processing through the β-secretase pathway and a lowering of CNS amyloid-β (Aβ) levels. The interaction of the β-secretase and α-secretase pathway-mediated processing of APP in the rhesus monkey (nonhuman primate; NHP) CNS is not understood. We hypothesized that CNS inhibition of BACE would result in decreased newly generated Aβ and soluble APPβ (sAPPβ), with increased newly generated sAPPα. A stable isotope labeling kinetics experiment in NHPs was performed with a (13)C6-leucine infusion protocol to evaluate effects of BACE inhibition on CNS APP processing by measuring the kinetics of sAPPα, sAPPβ, and Aβ in CSF. Each NHP received a low, medium, or high dose of MBI-5 (BACE inhibitor) or vehicle in a four-way crossover design. CSF sAPPα, sAPPβ, and Aβ were measured by ELISA and newly incorporated label following immunoprecipitation and liquid chromatography-mass spectrometry. Concentrations, kinetics, and amount of newly generated APP fragments were calculated. sAPPβ and sAPPα kinetics were similar, but both significantly slower than Aβ. BACE inhibition resulted in decreased labeled sAPPβ and Aβ in CSF, without observable changes in labeled CSF sAPPα. ELISA concentrations of sAPPβ and Aβ both decreased and sAPPα increased. sAPPα increased by ELISA, with no difference by labeled sAPPα kinetics indicating increases in product may be due to APP shunting from the β-secretase to the α-secretase pathway. These results provide a quantitative understanding of pharmacodynamic effects of BACE inhibition on NHP CNS, which can inform about target development., (Copyright © 2014 the authors 0270-6474/14/348336-11$15.00/0.)

The introduction of portable in situ ultraviolet-visual spectrometers has made possible the collection of water quality parameters at a high frequency in dynamic systems such as tidal marshes. The usefulness of this technology is inhibited by fouling of the instrument's optics. In this study, a spectrometer fitted with manufacturer-recommended compressed air optical cleaning was installed in a brackish marsh to determine if fouling interfered with measurements between bi-weekly servicing. During a 2-wk period, the absorbance measured in air at 220 nm increased from 9 to 549 m, indicating major fouling. An antifouling system was developed that reduced the time of exposure of the optics to stream water and used a pressurized fresh water cleaning. After implementation of the system, the absorbance in air increased to at most 63 m after 2 wk of data collection. The dramatic reduction in fouling will allow quality long-term data to be collected using this technology., (Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.)

The exponential growth of genetic resources is fueled by continued advances in genomic technologies and the adoption of single nucleotide polymorphisms (SNPs) for population studies. Concomitant to these developments, there is growing need for rapid screening and subsequent genotyping of SNPs in non-model organisms. Here we provide a rapid and low-cost workflow utilizing high-resolution melting analysis (HRMA) for nuclear marker development and genotyping of 774 Atlantic and Mediterranean swordfish (Xiphias gladius) that is amendable to other species. Preliminary HRMA screening of amplicons (>290bp) for 10 nuclear loci revealed the presence of nucleotide polymorphisms, however, length and variability precluded diagnostic genotyping. Two variants of HRMA were therefore utilized to provide diagnostic genotyping assays. Short-amplicon HRMA (SA-HRMA), in which primers flank closely a SNP of interest, was identified as a low cost, rapid, closed-tube diagnostic genotyping assay that could distinguish between homozygous genotypes by ΔTm, and heterozygous genotypes by heteroduplex melting curve profiles. When the patterns of sequence variation were not suitable for SA-HRMA, unlabeled probe (UP)-HRMA was utilized. UP-HRMA has the advantage of being capable of genotyping multiple linked SNPs in a single closed-tube assay without Bayesian haplotype reconstruction, and can identify new SNPs while genotyping populations. Almost 37% of the SNPs genotyped via UP-HRMA were discovered while genotyping populations and not from preliminary screening. Analysis of swordfish in the North Atlantic (NA, n=419), South Atlantic (SA, n=296), and Mediterranean (MED, n=59) found no significant linkage disequilibrium. To assess whether deviations in HWE could be the result of genotyping error rather than population admixture only swordfish from reported spawning areas in the NA (n=49), MED (n=59), and SA (n=42) were analyzed and all loci were in Hardy-Weinberg equilibrium. Significant genetic differentiation (P<0.001) was identified among populations., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Stalking is a crime that can terrify its victims and ultimately take a severe emotional toll. Although a growing body of research has examined stalking experiences and reactions of victims, there has been far less research on whether men and women differ in their perceptions of stalking. Toward this end, a survey of college students at a large public 4-year Midwestern university was undertaken. We examined differences is how men and women view stalking and whether gender differences were moderated by prior stalking experience. Specifically, we examined whether there were gender differences in perceptions of the pervasiveness of stalking, the harm stalking does, who tends to be stalked, if stalking mainly involves former relational partners, possible motivations for stalking, the line between courtship and stalking, and notions of victim blaming. We found significant differences in stalking views between men and women on all the measures, except for perceptions of the line between courtship and stalking. Women tended to perceive stalking as more pervasive and harmful. Men were more likely to perceive stalking as involving strangers and to blame the victim for the stalking. Female and male respondents also differed in their perceptions of motivations for stalking. Prior victim stalking experience did not moderate the gender differences. Although being a prior stalking victim had a significant association with 4 of the 7 stalking perception variables, its effect sizes were smaller than that of gender.

Background: Some Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans experience serious mental health (MH) problems. As OEF/OIF soldiers leave active military duty, their growing numbers pose a challenge to the Department of Veterans Affairs (VA) in delivering high-quality mental health/substance-use disorder (MH/SUD) care., Objective: To determine whether the quality of MH/SUD care provided by the VA differs by OEF/OIF veteran status., Methods: Veterans with selected MH/SUDs were identified from administrative records using diagnostic codes. OEF/OIF service was determined based on Defense Manpower Data Center separation files. Eleven processes of care and 7 utilization performance indicators were examined. Regression analyses were adjusted for veteran demographic and clinical characteristics to test for differences in care by OEF/OIF status., Results: Of the 836,699 veterans with selected diagnoses who received MH/SUD treatment in FY2007, 52,870 (6.3%) were OEF/OIF veterans. In unadjusted analyses, OEF/OIF veterans were more likely to receive evidence-based care processes captured by 6 of the 11 dichotomous performance indicators examined; however, among those receiving psychotherapy encounters, OEF/OIF veterans received significantly fewer visits (6.9 vs. 9.7, P<0.0001). In adjusted analyses, only postdischarge follow-up remained meaningfully higher for OEF/OIF veterans., Conclusions: Efforts to maintain and/or increase OEF/OIF veteran participation in VA MH/SUD services should be informed by their characteristics, such as younger age and better physical health relative to other veterans.

Many veterans returning from service in Afghanistan or Iraq suffer from post-traumatic stress disorder or mild traumatic brain injury. Treating these conditions can be challenging because of high rates of relapse and associated memory impairments. We report on a pilot study that assessed the utility of mobile health (mHealth) technologies, including personal digital assistant-based ecological momentary assessment and two-way interactive text (SMS) messaging, for providing treatment feedback to clinicians, encouraging and motivating veterans throughout treatment, and monitoring participants for relapse after treatment discharge. The results of the pilot suggest that mHealth technologies are feasible adjuncts to traditional mental treatment in the veteran population. Additional work is needed to establish the degree of clinical and economic value.

Currently, there is considerable geographic variation in the data-collection requirements and procedures for US-permitted seismic surveys conducted for energy and research purposes. The development of standards to train PSOs, standardization of data collection, submission standards, and development of quality assurance and quality control standards will make data analysis more efficient and robust. The implementation of national standards for the Seismic Survey PSO Programs will increase the integrity of data collected and reported for more effective protected species management.

In 2006 the Department of Veterans Affairs commissioned the Altarum Institute and the RAND Corporation to do an evaluation of its mental health treatment system. We found that veterans with mental illness and substance use disorders represented 15.4 percent of all veterans using Veterans' Health Administration (VHA) services in 2007 and that they accounted for 32.9 percent ($12 billion) of VHA costs, of which the majority was for non-mental health conditions. The average cost for a veteran with mental illness and substance use in our study was $12,337, or 2.7 times the cost for an average veteran without these conditions. The quality of care for the veterans in our study, although similar to or better than the care given to comparable privately insured patients or those enrolled in Medicare or Medicaid, varied by as much as twenty-three percentage points among regional service networks. Performance on some indicators, such as whether those with alcohol dependence received pharmacotherapy, was low. There is a need for substantial improvement in the care of these veterans, particularly with respect to ensuring the delivery of evidence-based treatments.

Background: Anemia is a marker of worsened clinical outcome in patients with heart failure from left ventricular dysfunction. Pulmonary hypertension often results in right ventricular dysfunction. Accordingly we sought to examine the association of hemoglobin levels and long-term all-cause mortality in a cohort of patients with pulmonary hypertension., Methods: Baseline demographic information, clinical characteristics and fasting blood work were obtained in a cohort of 145 patients with pulmonary hypertension referred for pulmonary vasodilator testing. Data was retrospectively analyzed with Cox-proportional hazards analysis., Results: Baseline characteristics of the cohort included age (mean±SD) 55.8±14.6 years, 75% women, 50% with idiopathic pulmonary hypertension, mean pulmonary artery pressure 46.1±14.2 mm Hg and arterial O(2) saturation 91±6 %. The most commonly utilized pulmonary hypertension specific therapeutic agents in descending order of frequency were epoprostenol (27%), sildenafil (21%), bosentan (17%), and treprostinil (6%). Over a median follow-up of 2.1 years, there were 39 deaths (26.9%). Patients who died had significantly lower hemoglobin levels than those survived (12.2±2.3 vs. 13.7±2.0, p<0.001). After adjustment for known predictors of death and pulmonary hypertension etiology, anemic patients were 3.3 times more likely to die than non-anemic patients (95% CI [1.43-7.51], p=0.005)., Conclusions: Hemoglobin levels closely parallel survival in pulmonary hypertension. Modification of anemia in this disorder could alter the clinical course and calls for further research in this area., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: asthma and obesity continue to have a significant effect on public health. It is widely accepted that obesity may be an independent risk factor for asthma and affect asthma severity and quality of life (QOL)., Objective: to examine the relationship between body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]) and asthma severity, spirometry findings, health care utilization (HCU), and QOL., Methods: this 12-month prospective randomized controlled trial comparing disease management with traditional care enrolled 902 patients (473 pediatric and 429 adults) representing an underserved population. Data collected at baseline and at 6-month intervals included demographics, asthma severity, medication use, spirometry findings, and HCU. The QOL was assessed using the pediatric and adult versions of the Asthma Quality of Life Questionnaire and the 36-Item Short Form Health Survey. All HCU was determined by means of patient interview and extensive medical record review. Data were analyzed using negative binomial regression and analysis of variance., Results: in children, 45% were overweight/obese (17% with BMIs >85th percentile; 28% with BMIs ≥ 95th percentile). In adults, 58% were obese (BMIs ≥ 30). There was no relationship in children between BMI and severity of asthma, spirometry findings, QOL, or HCU. In adults, there was no relationship between BMI and asthma severity or HCU. Higher BMI was associated with a significant reduction in QOL (P < .001). The BMI had an inverse relationship with forced vital capacity but with no other spirometric values., Conclusions: obesity was not associated with worse asthma severity, spirometry findings, QOL, or HCU in children. In adults with asthma, obesity was associated with lower forced vital capacity and QOL but not with severity or HCU.

Recent attention has focused on validity and feasibility of different approaches to developing performance indicators for the purposes of quality improvement and value-based purchasing. This paper presents the methodology used to develop a comprehensive set of performance indicators that will be used for a national evaluation of the mental healthcare provided by the Veterans Health Administration. The paper report on the indicators' technical specifications and the United States Public Health System Task Force defined strength of supporting evidence. Indicators were reviewed iteratively for meaningfulness, utility, feasibility, and supporting evidence until a final set of measures of acceptable validity and feasibility was produced with technical specifications. Fifty-seven mental health performance indicators that use information from both the medical record and administrative data (hybrid indicators) and 31 administrative-data only indicators are presented. Of the 57 hybrid indicators, 13 indicators are supported by Agency for Healthcare Research and Quality grade I evidence, 5 indicators are grade II, and 39 indicators are grade III. This paper describes the methodology used to develop 88 performance indicators of the quality of mental health and substance abuse treatment, and presents the technical specifications associated with each indicator., (© 2010 National Association for Healthcare Quality.)

In this paper we present the conceptual framework and research design of a national evaluation of the quality of mental healthcare provided to veterans by the Veterans Health Administration, and present results on the reported availability of evidence-based practices. We used the Donabedian paradigm to design a longitudinal evaluation of the quality of mental healthcare. To evaluate the structure of care we used a combination of survey and administrative data and designed a web-based facility survey to examine the availability and characteristics of 12 evidence-based practices and other mental health services. We identified 138 unique facilities that provided mental healthcare to 783,280 veterans. With the exception of opiate substitution therapies, every evidence-based practice was reported in at least one location in each service network. We use maps to estimate the maximum number of veterans that might benefit from expanding the availability of an evidence-based practice. We demonstrate the feasibility of overcoming several major challenges typically associated with measuring the quality of healthcare systems. This framework for evaluation of mental healthcare delivery provides a model upon which other stakeholders can continue to build and expand., (© 2010 National Association for Healthcare Quality.)

Purpose of Review: Head and neck lymphedema (HNL) is a common and often debilitating cancer treatment effect that is under-researched and ill defined. We examined current literature and reviewed historical treatment approaches. We propose a model for evaluation and treatment of HNL used at The University of Texas M. D. Anderson Cancer Center (MDACC) for patients with head and neck cancer (HNC)., Recent Findings: Despite the morbidity associated with HNL in patients with HNC, to our knowledge, no article has been published within the past 18 months whose primary focus is HNL. Eight publications included HNL but only as a secondary focus related to treatment effect, risk of dysphagia, prognostic indicator of underlying disease, and quality of life. A potential benefit of selenium treatment to reduce HNL was reported., Summary: This article highlights the recent literature regarding HNL in patients treated for HNC. Although HNL is reported as a potential complication of HNC treatment, no clear definition of the disease or its management are published. Our early experience using an objective evaluation and treatment protocol holds promise for a better understanding of HNL in patients treated for head and neck malignancy.

Objective: The study aimed to characterize the demographics, diagnostic makeup and aspects of patient management for the inpatient population of a large aged psychiatry service., Method: Sociodemographic and clinical variables were retrospectively collated from inpatient files and discharge summaries over a 3-year period. Age, gender, country of birth, diagnostic group, length of stay, involuntary care status and number of admissions were described and analysed. A total of 604 patients were included in the study, with complete data available for 516., Results: Approximately half of the patients were aged 65-75 years and 59.3% were female. More than half had been born outside of Australia. The primary diagnosis was an affective disorder in 39.0% of admissions, dementia in 27.5% and psychotic illnesses in 25.8%. The median length of stay was 28 days; 60.8% had a period of involuntary care and 79.8% had only one admission., Conclusion: In the near future, aged psychiatry services will face increased numbers of patients and rising expectations. To best respond to these challenges, we need to have an understanding of current patient and service profiles. The findings of this study illustrate a range of patient, diagnostic and management variables in aged psychiatry practice. This information can be used for comparison with other services and in planning for future development of services.

Background: Inhaled corticosteroids and long-acting beta-agonists (LABAs) are recommended for treating moderate to severe persistent asthma. The Food and Drug Administration has issued a black box warning (BBW) for LABAs., Objective: To investigate physician knowledge of the BBW and its effect on the practice of specialists (pulmonologists and allergists) and primary care physicians (PCPs) (internists and family physicians)., Methods: A total of 1,107 physicians responded to a questionnaire to determine their awareness of the BBW and whether it changed their practice., Results: The group comprised 429 pulmonologists (38.8%), 395 allergists (35.7%), 141 internists (12.7%), 132 family physicians (11.9%), and 10 pediatricians (0.9%). Comparing specialists with PCPs, there was approximately a 10% difference in the rate of knowledge concerning the BBW (99.0% vs 90.8%, P < .001). Approximately a quarter of specialists agreed with the BBW compared with 52.9% of family physicians and 40.3% of internists. Twice as many PCPs vs specialists agreed with the warning (45.6% vs 24.2%, P < .001). The PCPs were more likely to alter their prescribing habits than were specialists (40.1% vs 34.6%, P < .005). Specialists were more likely to discuss the warning with patients than were PCPs (87.4% vs 64.8%, P < .001). For mild persistent asthma, most respondents chose inhaled corticosteroids as the preferred first-line therapy, but 11.4% of PCPs and 2.1% of specialists identified LABA monotherapy as their first choice. For moderate to severe asthma, the pattern of response was similar., Conclusion: Although most physicians were aware of the BBW for LABAs, there was a difference in how specialists and PCPs approached it and altered their prescribing habits.

The primary pathophysiology of peripheral artery occlusive disease is associated with impaired perfusion to the lower extremities. The lack of effective pharmacologic agents to treat this disease emphasizes the need for well-characterized animal models that can be used to evaluate the efficacy of emerging therapies. A major limitation with the current animal models of peripheral artery occlusive disease is that the variety of surgical methods employed to reduce peripheral blood flow produce differences in the severity and time course of the resting and reserve blood flow deficits. Furthermore, the methods used to evaluate the restoration of peripheral flow are often not suitable for serial measurements. This study used laser Doppler imaging to serially evaluate resting blood flow and the development of a functional collateral circulation after the induction of hind limb ischemia in the rat. Reserve blood flow was assessed by measuring hyperemic blood flow in the hind paw after temporary arterial occlusion. The magnitude of the hyperemic response was found to be dependent upon both the duration of arterial occlusion and the measurement time after release of the occluder. After ligation of the common iliac artery, but at a time when resting blood flow was reestablished, hyperemic tests unmasked a sustained deficit in reserve blood flow capacity that persisted for at least 14 days. Therefore, the use of a noninvasive vascular occluder and laser Doppler imaging represents a sensitive and consistent technique to measure peripheral blood flow status to assess the development of functional collateral vessels. These findings will enhance the ability to effectively study pharmacologic therapies aimed at promoting the growth and development of collateral vessels.

Background: Although congestive heart failure (CHF) is a primary target for disease management programs, previous studies have generated mixed results regarding the effectiveness and cost savings of disease management when applied to CHF., Objective: We estimated the long-term impact of systolic heart failure disease management from the results of an 18-month clinical trial., Methods: We used data generated from the trial (starting population distributions, resource utilization, mortality rates, and transition probabilities) in a Markov model to project results of continuing the disease management program for the patients' lifetimes. Outputs included distribution of illness severity, mortality, resource consumption, and the cost of resources consumed. Both cost and effectiveness were discounted at a rate of 3% per year. Cost-effectiveness was computed as cost per quality-adjusted life year (QALY) gained., Results: Model results were validated against trial data and indicated that, over their lifetimes, patients experienced a lifespan extension of 51 days. Combined discounted lifetime program and medical costs were $4850 higher in the disease management group than the control group, but the program had a favorable long-term discounted cost-effectiveness of $43,650/QALY. These results are robust to assumptions regarding mortality rates, the impact of aging on the cost of care, the discount rate, utility values, and the targeted population., Conclusions: Estimation of the clinical benefits and financial burden of disease management can be enhanced by model-based analyses to project costs and effectiveness. Our results suggest that disease management of heart failure patients can be cost-effective over the long term.

Background: The goal of disease management (DM) is to improve health outcomes and reduce cost through decreasing health care utilization. Although some studies have shown that DM improves asthma outcomes, these interventions have not been examined in a large randomized controlled trial., Objective: To compare the effectiveness of 2 previously successful DM programs with that of traditional care., Methods: Nine hundred two individuals with asthma (429 adults; 473 children) were randomly assigned to telephonic DM, augmented DM (ADM; DM plus in-home visits by a respiratory therapist), or traditional care. Data were collected at enrollment and at 6 and 12 months. Primary outcomes were time to first asthma-related event, quality of life (QOL), and rates of asthma-related health care utilization. Secondary outcomes included rate of controller medication initiation, number of oral corticosteroid bursts, asthma symptom scores, and number of school days missed., Results: There were no significant differences between groups in time to first asthma-related event or health care utilization. Adult participants in the ADM group had greater improvement in QOL (P = .04) and a decrease in asthma symptoms (P = .001) compared with other groups. Of children not receiving controller medications at enrollment (13%), those in the intervention groups were more likely to have controller medications initiated than the control group (P = .01). Otherwise, there were no differences in outcomes., Conclusions: Overall, participation in asthma DM did not result in significant differences in utilization or clinical outcomes. The only significant impact was a higher rate of controllermedication initiation in children and improvement in asthma symptoms and QOL in adults who received ADM.

Background: Trial recruitment is challenging for researchers, who frequently overestimate the pool of qualified, willing participants. Little has been written about recruitment and the comparative success of recruitment strategies. We describe one center's experience with recruitment in two regional single-center clinical trials with a combined total of 1971 participants., Methods: The heart failure trial was conducted between 1999 and 2003. The asthma trial was performed between 2003 and 2006. Trial databases were queried for referral source of each individual. Data were analyzed for effectiveness of referral source using three measures: percentage of enrollment due to that source, subject commitment to the trial (retention rate), and economics (cost per enrollee)., Results: 47.8% of CHF enrollees came from computer-generated lists or from healthcare provider referrals. Average marketing cost for enrollees and completers was $29.20 and $41.96 respectively. The most economical marketing strategy was self-referral in response to flyers. Most asthma participants (53.5%) were referred from healthcare providers, mailings to lists from local healthcare institutions, or self-referred in response to flyers. Average marketing cost for enrollees and completers was $20.44 and $38.10 respectively. The most economical marketing strategy was patient mailings. Retention rates were not markedly different among referral sources in either trial., Conclusion: In order to be considered effective, a recruitment strategy must demonstrate a balance between response to recruitment, retention rates, and economics. Despite the differences between these two clinical trials, the most effective recruitment strategies in both trials were mailings to locally-generated, targeted lists, and referrals from healthcare providers.