928 research outputs found

    Restrictive Covenants in Maryland Employment Agreements: A Guide for Drafting

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    This article pro vides the Maryland lawyer with a practical guide for drafting restrictive covenants in employment agreements. The authors begin with a thorough analysis of the Maryland case law addressing this subject area. They recommend the types of provisions which will provide an employer with maximum protection against future competition by departing employees. The writers conclude with a section on suggested drafting techniques, keeping in mind that such provisions may have to withstand judicial scrutiny should litigation occur

    Inhibition of Glycogen Synthase Kinase-3 Increases the Cytotoxicity of Enzastaurin

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    Cutaneous T-cell lymphomas (CTCL) represent a spectrum of several distinct non-Hodgkin's lymphomas that are characterized by an invasion of the skin by malignant, clonal lymphocytes. Our laboratory has previously demonstrated that the protein kinase C (PKC) β inhibitor Enzastaurin increases apoptosis in malignant lymphocytes of CTCL. These results directly led to a clinical trial for Enzastaurin in CTCL in which it was well tolerated and showed modest activity. To ascertain a means of improving the efficacy of Enzastaurin, we investigated complementary signaling pathways and identified glycogen synthase kinase-3 (GSK3) as important in survival signaling in CTCL. Enzastaurin combined with GSK3 inhibitors demonstrated an enhancement of cytotoxicity. Treatment with a combination of Enzastaurin and the GSK3 inhibitor AR-A014418 resulted in upregulation of β-catenin total protein and β-catenin-mediated transcription. Inhibition of β-catenin-mediated transcription or small hairpin RNA (shRNA) knockdown of β-catenin decreased the cytotoxic effects of Enzastaurin plus AR-A014418. In addition, treatment with Enzastaurin and AR-A014418 decreased the mRNA levels and surface expression of CD44. shRNA knockdown of β-catenin also restored CD44 surface expression. Our observations provide a rationale for the combined targeting of PKC and GSK3 signaling pathways in CTCL to enhance the therapeutic outcome

    Stress-Related Psychopathology During the COVID-19 Pandemic

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    The COVID-19 pandemic has introduced widespread societal changes that have required ongoing adaptation. Unsurprisingly, stress-related psychopathology has increased during the pandemic, in both children and adults. We review these patterns through the lens of several leading conceptual models of the link between stress and psychopathology. Some of these models focus on characteristics of environmental stressors—including cumulative risk, specific stressor types, and stress sensitization approaches. Understanding the specific aspects of environmental stressors that are most likely to lead to psychopathology can shed light on who may be in most need of clinical intervention. Other models center on factors that can buffer against the onset of psychopathology following stress and the mechanisms through which stressors contribute to emergent psychopathology. These models highlight specific psychosocial processes that may be most usefully targeted by interventions to reduce stress-related psychopathology. We review evidence for each of these stress models in the context of other widescale community-level disruptions, like natural disasters and terrorist attacks, alongside emerging evidence for these stress pathways from the COVID-19 pandemic. We discuss clinical implications for developing interventions to reduce stress-related psychopathology during the pandemic, with a focus on brief, digital interventions that may be more accessible than traditional clinical services

    The sonographic quantitative assessment of the deltoid muscle to detect type 2 diabetes mellitus: a potential noninvasive and sensitive screening method?

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    BACKGROUND: In our previous published study, we demonstrated that a qualitatively assessed elevation in deltoid muscle echogenicity on ultrasound was both sensitive for and a strong predictor of a type 2 diabetes (T2DM) diagnosis. This study aims to evaluate if a sonographic quantitative assessment of the deltoid muscle can be used to detect T2DM. METHODS: Deltoid muscle ultrasound images from 124 patients were stored: 31 obese T2DM, 31 non-obese T2DM, 31 obese non-T2DM and 31 non-obese non-T2DM. Images were independently reviewed by 3 musculoskeletal radiologists, blinded to the patient\u27s category. Each measured the grayscale pixel intensity of the deltoid muscle and humeral cortex to calculate a muscle/bone ratio for each patient. Following a 3-week delay, the 3 radiologists independently repeated measurements on a randomly selected 40 subjects. Ratios, age, gender, race, body mass index, insulin usage and hemoglobin A(1c) were analyzed. The difference among the 4 groups was compared using analysis of variance or chi-square tests. Both univariate and multivariate linear mixed models were performed. Multivariate mixed-effects regression models were used, adjusting for demographic and clinical variables. Post hoc comparisons were done with Bonferroni adjustments to identify any differences between groups. The sample size achieved 90% power. Sensitivity and specificity were calculated based on set threshold ratios. Both intra- and inter-radiologist variability or agreement were assessed. RESULTS: A statistically significant difference in muscle/bone ratios between the groups was identified with the average ratios as follows: obese T2DM, 0.54 (P \u3c 0.001); non-obese T2DM, 0.48 (P \u3c 0.001); obese non-T2DM, 0.42 (P = 0.03); and non-obese non-T2DM, 0.35. There was excellent inter-observer agreement (intraclass correlation coefficient 0.87) and excellent intra-observer agreements (intraclass correlation coefficient 0.92, 0.95 and 0.94). Using threshold ratios, the sensitivity for detecting T2DM was 80% (95% CI 67% to 88%) with a specificity of 63% (95% CI 50% to 75%). CONCLUSIONS: The sonographic quantitative assessment of the deltoid muscle by ultrasound is sensitive and accurate for the detection of T2DM. Following further studies, this process could translate into a dedicated, simple and noninvasive screening method to detect T2DM with the prospects of identifying even a fraction of the undiagnosed persons worldwide. This could prove especially beneficial in screening of underserved and underrepresented communities

    A collection of bioconductor methods to visualize gene-list annotations

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    <p>Abstract</p> <p>Background</p> <p>Gene-list annotations are critical for researchers to explore the complex relationships between genes and functionalities. Currently, the annotations of a gene list are usually summarized by a table or a barplot. As such, potentially biologically important complexities such as one gene belonging to multiple annotation categories are difficult to extract. We have devised explicit and efficient visualization methods that provide intuitive methods for interrogating the intrinsic connections between biological categories and genes.</p> <p>Findings</p> <p>We have constructed a data model and now present two novel methods in a Bioconductor package, "GeneAnswers", to simultaneously visualize genes, concepts (a.k.a. annotation categories), and concept-gene connections (a.k.a. annotations): the "Concept-and-Gene Network" and the "Concept-and-Gene Cross Tabulation". These methods have been tested and validated with microarray-derived gene lists.</p> <p>Conclusions</p> <p>These new visualization methods can effectively present annotations using Gene Ontology, Disease Ontology, or any other user-defined gene annotations that have been pre-associated with an organism's genome by human curation, automated pipelines, or a combination of the two. The gene-annotation data model and associated methods are available in the Bioconductor package called "GeneAnswers " described in this publication.</p

    Report of the panel on earth rotation and reference frames, section 7

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    Objectives and requirements for Earth rotation and reference frame studies in the 1990s are discussed. The objectives are to observe and understand interactions of air and water with the rotational dynamics of the Earth, the effects of the Earth's crust and mantle on the dynamics and excitation of Earth rotation variations over time scales of hours to centuries, and the effects of the Earth's core on the rotational dynamics and the excitation of Earth rotation variations over time scales of a year or longer. Another objective is to establish, refine and maintain terrestrial and celestrial reference frames. Requirements include improvements in observations and analysis, improvements in celestial and terrestrial reference frames and reference frame connections, and improved observations of crustal motion and mass redistribution on the Earth

    Sonographic evaluation of the association between calcific tendinopathy and rotator cuff tear: a case-controlled comparison

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    Objectives: To compare the incidence of rotator cuff (RC) tears on shoulder ultrasounds of patients with RC calcific tendinopathy (CaT) to that of a control group without CaT. Method: In this retrospective case-control study, 50 shoulder ultrasounds of patients with CaT were compared independently by 2 musculoskeletal radiologists to 50 patients from a control group without CaT to catalog the number and type of RC tears. RC tears in the CaT group were further characterized based on location, into tears in the specific tendon(s) containing calcium versus all tendon tears. Results: RC tears were diagnosed in 38% (19/50) of the control group (16 full-thickness) as compared to 22% (11/50) with CaT (6 full-thickness). The fewer full-thickness tears in the CaT group (12%, 6 of 50) compared to that in the control group (32%, 16 of 50) was statistically significant (P = 0.016, odds ratio 0.29). Only 7 of the 11 tears in the CaT group were in a calcium-containing tendon (3 full-thickness). The fewer calcium-containing tendon tears compared to tears in the control group was also statistically significant (P = 0.006, odds ratio 0.27). Furthermore, the fewer full-thickness calcium-containing tendon tears (6%, 3/50) compared to full-thickness tears in the control group (32%, 16/50) were yet more statistically significant (P = 0.001, odds ratio 0.14). Conclusions: In patients with shoulder pain and CaT, we observed a decreased number of RC tears and especially calcium-containing tendon tears, as compared to similar demographic patients with shoulder pain but without CaT. Key Points • Patients with rotator cuff calcific tendinopathy have few rotator cuff tears, especially full-thickness tears, compared to a control group without calcific tendinopathy. • The tendons containing the calcium hydroxyapatite deposition were the least likely to have a rotator cuff tear. • Future studies could evaluate if calcium hydroxyapatite deposition provides a protective mechanism against rotator cuff tears. • Musculoskeletal ultrasound is more sensitive than MRI in the evaluation of rotator cuff calcific tendinopathy

    Factors That Influence Medical Student Selection of an Emergency Medicine Residency Program: Implications for Training Programs

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    Objectives:  An understanding of student decision‐making when selecting an emergency medicine (EM) training program is essential for program directors as they enter interview season. To build upon preexisting knowledge, a survey was created to identify and prioritize the factors influencing candidate decision‐making of U.S. medical graduates. Methods:  This was a cross‐sectional, multi‐institutional study that anonymously surveyed U.S. allopathic applicants to EM training programs. It took place in the 3‐week period between the 2011 National Residency Matching Program (NRMP) rank list submission deadline and the announcement of match results. Results:  Of 1,525 invitations to participate, 870 candidates (57%) completed the survey. Overall, 96% of respondents stated that both geographic location and individual program characteristics were important to decision‐making, with approximately equal numbers favoring location when compared to those who favored program characteristics. The most important factors in this regard were preference for a particular geographic location (74.9%, 95% confidence interval [CI] = 72% to 78%) and to be close to spouse, significant other, or family (59.7%, 95% CI = 56% to 63%). Factors pertaining to geographic location tend to be out of the control of the program leadership. The most important program factors include the interview experience (48.9%, 95% CI = 46% to 52%), personal experience with the residents (48.5%, 95% CI = 45% to 52%), and academic reputation (44.9%, 95% CI = 42% to 48%). Unlike location, individual program factors are often either directly or somewhat under the control of the program leadership. Several other factors were ranked as the most important factor a disproportionate number of times, including a rotation in that emergency department (ED), orientation (academic vs. community), and duration of training (3‐year vs. 4‐year programs). For a subset of applicants, these factors had particular importance in overall decision‐making. Conclusions:  The vast majority of applicants to EM residency programs employed a balance of geographic location factors with individual program factors in selecting a residency program. Specific program characteristics represent the greatest opportunity to maximize the success of the immediate interview experience/season, while others provide potential for strategic planning over time. A working knowledge of these results empowers program directors to make informed decisions while providing an appreciation for the limitations in attracting applicants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91198/1/ACEM_1323_sm_DataSupplementS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/91198/2/j.1553-2712.2012.01323.x.pd
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