Improvements in speed and mass accuracy of mass spectrometers revolutionized proteomics, with high-throughput proteomics enabling the profiling of complete proteomes and thousands of ...posttranslational modification sites. The limits of high-throughput proteomics are constantly pushed to new frontiers, and mass spectrometry-based proteomics may eventually permit the analysis of protein expression profiles in less than a day. Increased data acquisition speed has led to a dramatic increase in the total number of tandem mass spectrometry (MS/MS) spectra, such that millions of MS/MS spectra are now acquired in a given set of analyses. Many of these spectra are insufficiently validated; instead, statistical tools are commonly used to estimate false-positive or false-discovery rates for these data sets. Many laboratories may not realize the costs associated with using these widely available, but minimally validated, data sets. The costs associated with use of these data can include missed opportunities for biological insight, the pollution of databases with increasing numbers of false-positive identifications, and time spent by biologists investigating false leads, resulting in a lack of faith in proteomics data. Improved strategies for data validation need to be implemented, along with a change in the culture of high-throughput proteomics, linking proteomics closer to biology.
Over the last decade, two lines of inquiry have emerged from earlier investigations of adolescent neighborhood effects. First, researchers began incorporating space‐time geography to study adolescent ...development within activity spaces or routine activity locations and settings. Second, cultural‐developmental researchers implicated neighborhood settings in cultural development, to capture neighborhood effects on competencies and processes that are salient or normative for minoritized youth. We review the decade’s studies on adolescent externalizing, internalizing, academic achievement, health, and cultural development within neighborhoods and activity spaces. We offer recommendations supporting decompartmentalization of cultural‐developmental and activity space scholarship to advance the science of adolescent development in context.
To perform a systematic review to determine the accuracy of computed tomographic (CT) angiography, magnetic resonance (MR) angiography, and transcranial Doppler ultrasonography (US) in depicting ...intracranial aneurysms.
A 1988-1998 literature search for studies with 10 or more subjects in which noninvasive imaging was compared with angiography was undertaken. Studies meeting initial criteria were evaluated by using intrinsically weighted standardized assessment to determine suitability for inclusion. Studies scoring greater than 50% were included.
Of 103 studies that met initial criteria, 38 scored greater than 50%. CT angiography and MR angiography had accuracies per aneurysm of 89% (95% CI: 87%, 91%) and 90% (95% CI: 87%, 92%), respectively. For US, data were scanty and accuracy was lower, although the CIs overlapped those of CT angiography and MR angiography. Sensitivity was greater for detection of aneurysms larger than 3 mm than for detection of aneurysms 3 mm or smaller-for CT angiography, 96% (95% CI: 94%, 98%) versus 61% (95% CI: 51%, 70%), and for MR angiography, 94% (95% CI: 90%, 97%) versus 38% (95% CI: 25%, 53%). Diagnostic accuracy was similar for anterior and posterior circulation aneurysms.
CT angiography and MR angiography depicted aneurysms with an accuracy of about 90%. Most studies were performed in populations with high aneurysm prevalence, which may have introduced bias toward noninvasive examinations.
To identify geographic and individual-level factors associated with healthcare access among transgender people in the United States.
Multilevel analyses were conducted to investigate lifetime ...healthcare refusal using national data from 5831 U.S. transgender adults. Hierarchical generalized linear models examined associations between individual (age, gender, race, income, insurance, and healthcare avoidance) and state-level factors (percent voting Republican, percent same-sex couple households, income inequality, and transgender protective laws) and lifetime refusal of care.
Results show that individual-level factors (being older; trans feminine; Native American, multiracial, or other racial/ethnic minority; having low income; and avoiding care due to discrimination) are positively associated with care refusal (all P-values <0.05). Adjusting for individual-level factors, variation was observed across U.S. states, with a greater proportion of states in the Southern and Western United States with transgender residents at increased odds of experiencing care refusal, relative to other regions of the United States. When adjusting for state-level factors, the percentage of the state population voting Republican was positively associated with care refusal among the transgender adults sampled (P < 0.01).
Transgender adults surveyed reported differential access to healthcare by geographic region. Identifying geographic and individual-level factors associated with healthcare barriers allows for the development of targeted educational and policy interventions to improve healthcare access for transgender people most in need of services.
Glioblastoma multiforme (GBM) is the most aggressive malignant primary brain tumor, with a dismal mean survival even with the current standard of care. Although in vitro cell systems can provide ...mechanistic insight into the regulatory networks governing GBM cell proliferation and migration, clinical samples provide a more physiologically relevant view of oncogenic signaling networks. However, clinical samples are not widely available and may be embedded for histopathologic analysis. With the goal of accurately identifying activated signaling networks in GBM tumor samples, we investigated the impact of embedding in optimal cutting temperature (OCT) compound followed by flash freezing in LN2 vs immediate flash freezing (iFF) in LN2 on protein expression and phosphorylation-mediated signaling networks. Quantitative proteomic and phosphoproteomic analysis of 8 pairs of tumor specimens revealed minimal impact of the different sample processing strategies and highlighted the large interpatient heterogeneity present in these tumors. Correlation analyses of the differentially processed tumor sections identified activated signaling networks present in selected tumors and revealed the differential expression of transcription, translation, and degradation associated proteins. This study demonstrates the capability of quantitative mass spectrometry for identification of in vivo oncogenic signaling networks from human tumor specimens that were either OCT-embedded or immediately flash-frozen.
OBJECTIVES:The goal of this study was to examine the prevalence and perceptions of electronic cigarette use among Canadian youth and young adults.
METHODS:A sample of 1,188 youth and young adults age ...16–30 years were recruited from an online panel of Canadians in 2012. After viewing an image of an e-cigarette, respondents answered questions regarding their use and perceptions of e-cigarettes.
RESULTS:Close to half of respondents (43.4%) had seen e-cigarettes advertised or for sale. A total of 16.1% reported trying an e-cigarette (5.2% non-smokers, 18.9% former smokers, and 34.5% current smokers), and 5.7% reported use in the past 30 days (0.8% non-smokers, 1.4% former smokers, and 15.0% current smokers). Compared to non-smokers, former smokers and current smokers were more likely to have tried e-cigarettes (OR=4.25 and OR=9.84, respectively), and current smokers were more likely to have tried e-cigarettes than former smokers (OR=2.32). Current smokers were also more likely to be current users of e-cigarettes than both former smokers (OR=15.15) and non-smokers (OR=4.43). Smokers were interested in trying e-cigarettes to help them quit smoking (80.4%), as a long-term replacement for cigarettes (77.8%), or to use in places where they cannot smoke (80.9%).
CONCLUSIONS:Awareness of e-cigarettes among surveyed youth and young adults is quite high. Almost one fifth (16.1%) of participants reported trying e-cigarettes, with evidence of use among non-smokers.
Persons with serious mental illness are often reluctant to disclose their disability to an employer because of the intense stigma associated with their illness. Yet, disclosure may be desirable to ...gain access to employer-provided job accommodations, or to achieve other goals. In this article, we aimed to (1) describe the contexts in which workers in regular employment disclose a mental illness to their employer and (2) describe employer responses to disclosure, as perceived by the workers themselves. Semi-structured interviews were conducted with 40 workers, who were currently or formerly employed in a mainstream, regular job, post-onset of mental illness. Workers were asked to describe the circumstances that led to disclosure, and to describe their employers’ responses to disclosure. Conventional content analysis was applied to identify common themes in the transcribed interviews. Analyses revealed five mutually exclusive disclosure contexts: seeking job accommodations, seeking protection, seeking understanding, responding to an employer’s symptom-based inquiries, or being exposed by a third party or event. Analyses also revealed a wider range of employer responses—positive, negative, and ambiguous—than has been suggested by studies in which employers described their reactions to worker disclosure. Some themes were more prevalent among current versus former workers. Overall, the disclosure process appeared to be more complex than has been described by extant frameworks to date, and the linkages between disclosure contexts and employer response themes suggested that many workers did not receive the responses they were seeking from their employers.
Identical regions of partially reduced TiO2(110) surfaces with bridge-bonded oxygen vacancy (BBOV) concentrations of ∼10% ML (1 ML = 5.2 × 1014 cm-2) were imaged using scanning tunneling microscopy ...(STM) before and after dosing H2O at ambient temperature (∼300 K). Atomically resolved images confirm that H2O adsorbs dissociatively on the BBOV sites, producing two hydroxyl species, one positioned at BBOV and denoted OHV and the other, denoted OHB, formed by protonation at either of the two nearest-neighbor bridge-bonded oxygen atoms. Hydrogen hopping along the 001 direction is observed at ambient temperature, with a strong preference for OHB (∼10×) hydrogen motion. This powerful imbalance demonstrates the inequality of OHV and OHB and suggests differences in their charge and/or binding configuration.
A Pd(II)/sulfoxide-catalyzed sequential allylic C−H oxidation/vinylic C−H arylation of α-olefins to furnish E-arylated allylic esters in high regio- and E:Z selectivities (>20:1) is reported. The ...broad scope of this method with respect to the α-olefin, carboxylic acid, and aryl boronic acid enables the rapid assembly of densely functionalized fragments for complex molecule synthesis from cheap, abundant hydrocarbon starting materials. The Pd(II)/sulfoxide-catalyzed vinylic C−H arylation of electronically unbiased olefins with aryl boronic acids proceeds under oxidative, acidic conditions and mild temperatures (room temperature to 45 °C).
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