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How can we look afresh at Shakespeare as a writer of sonnets? What new light might they shed on his career, personality, and sexuality? Shakespeare wrote sonnets for at least thirty years, not only for himself, for professional reasons, and for those he loved, but also in his plays, as prologues, as epilogues, and as part of their poetic texture. This ground-breaking book assembles all of Shakespeare's sonnets in their probable order of composition. An inspiring introduction debunks long-established biographical myths about Shakespeare's sonnets and proposes new insights about how and why he wrote them. Explanatory notes and modern English paraphrases of every poem and dramatic extract illuminate the meaning of these sometimes challenging but always deeply rewarding witnesses to Shakespeare's inner life and professional expertise. Beautifully printed and elegantly presented, this volume will be treasured by students, scholars, and every Shakespeare enthusiast.
Bipartite networks represent pairwise relationships between nodes belonging to two distinct classes. While established methods exist for analyzing unipartite networks, those for bipartite network analysis are somewhat obscure and relatively less developed. Community detection in such instances is frequently approached by first projecting the network onto a unipartite network, a method where edges between node classes are encoded as edges within one class. Here we test seven different projection schemes by assessing the performance of community detection on both: (i) a real-world dataset from social media and (ii) an ensemble of artificial networks with prescribed community structure. A number of performance and accuracy issues become apparent from the experimental findings, especially in the case of long-tailed degree distributions. Of the methods tested, the “hyperbolic” projection scheme alleviates most of these difficulties and is thus the most robust scheme of those tested. We conclude that any interpretation of community detection algorithm performance on projected networks must be done with care as certain network configurations require strong community preference for the bipartite structure to be reflected in the unipartite communities. Our results have implications for the analysis of detected community structure in projected unipartite networks.
Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged antipsychotic use. RE KINECT, a real-world screening study of antipsychotic-treated outpatients, included patients with movements that were clinician-confirmed as possible TD (Cohort 2) and patients with no involuntary movements (Cohort 1). Baseline data from the patient rated EuroQoL 5-Dimension 5-Level questionnaire (EQ-5D-5L) and Sheehan Disability Scale (SDS) were analyzed to evaluate health related quality of life (Cohort 2 vs. Cohort 1) and the effects of possible TD on quality of life (Cohort 2).
Assessments included EQ-5D-5L utility score (0=equivalent to death to 1=perfect health); SDS total score (0=no impact to 30=highest impact); patient- and clinician-rated severity of possible TD in 4 body regions (0=none, 1=some, and 2=a lot; summary score, 0 to 8); and patient-rated impact of possible TD in 7 daily activities (0=none, 1=some, and 2=a lot; summary score, 0 to 14). Populations included Cohort 1 (N=450); full Cohort 2 (N=204); and limited Cohort 2 (N=111, patients who self-reported “some” or “a lot” of TD severity in ≥1 body region). Mean differences between Cohort 2 and Cohort 1 in EQ-5D-5L utility and SDS total scores were analyzed using a generalized linear regression model that was adjusted for potentially confounding factors (e.g., age, sex, psychiatric diagnosis). Associations between TD summary scores (severity, impact) and quality of life (EQ-5D-5L utility, SDS total) were analyzed using a regression model.
The mean score difference between full Cohort 2 (N=204) and Cohort 1 (N=450) was significant for EQ-5D-5L utility (-0.037; P<0.05 [adjusted analysis]) but not SDS total (0.267; P>0.05). However, when limited to Cohort 2 patients who self-reported “a lot” of TD severity (n=53) or impact (n=33), both EQ 5D 5L utility and SDS total scores were significantly worse than in Cohort 1 (P<0.05). Regression coefficients indicated significant associations between patient-rated impact and EQ 5D-5L utility in the full Cohort 2 (-0.021, P<0.001) and limited Cohort 2 (-0.024, P<0.001). A significant association was also found with patient rated severity in limited Cohort 2 (P<0.05), but not with clinician-rated severity. Similar results were found for SDS total score.
RE-KINECT patients were consistent in evaluating the severity and impact of TD, whether based on subjective assessments or standardized patient-reported instruments (EQ-5D-5L, SDS). Clinician-rated severity of TD may not always correlate with patient perceptions of the significance of TD. Patient self-assessments (focused on symptom impact) can be clinically relevant; incorporating such measures into everyday practice may provide a more comprehensive approach to TD assessment and management.
Application timing and environmental factors reportedly influence the efficacy of auxinic herbicides. In resistance-prone weed species such as Palmer amaranth (Amaranthus palmeri S. Watson), efficacy of auxinic herbicides recently adopted for use in resistant crops is of utmost importance to reduce selection pressure for herbicide-resistance traits. Growth chamber experiments were conducted comparing the interaction of different environmental effects with application time to determine the influence of these factors on visible phytotoxicity and hydrogen peroxide (H2O2) formation in A. palmeri. Temperature displayed a high degree of influence on 2,4-D and dicamba efficacy in general, with applications at the low-temperature treatment (31/20 C day/night) resulting in an increase in phytotoxicity compared with high-temperature treatments (41/30 C day/night). Application time across temperature treatments significantly affected 2,4-D–induced phytotoxicity, resulting in a ≥30% increase across rates with treatments at 4:00 PM compared with 8:00 AM. Temperature differential had a significant influence on dicamba efficacy based on visible phytotoxicity data, with a ≥46% increase with a high (37/20 C day/night) compared with a low differential (41/30 C day/night). Concentration of H2O2 in herbicide-treated plants was 34% higher under a high temperature differential compared with the low differential. Humidity treatments and application time interactions displayed undetected or inconsistent effects on visible phytotoxicity and H2O2 production. Overall, temperature-related influences seem to have the largest environmental effect on auxinic herbicides within conditions evaluated in this study. Leaf concentration of H2O2 appears to be generally correlated with phytotoxicity, providing a potentially useful tool in determining efficacy of auxinic herbicides in field settings.
Myocardial strain measurements are increasingly used to detect complications following heart transplantation. However, the temporal association of these changes with allograft rejection is not well defined. The aim of this study was to describe the evolution of strain measurements prior to the diagnosis of rejection in paediatric heart transplant recipients.
All paediatric heart transplant recipients (2004–2015) with at least one episode of acute rejection were identified. Longitudinal and circumferential strain measurements were assessed at the time of rejection and retrospectively on all echocardiograms until the most recent negative biopsy. Smoothing technique (LOESS) was used to visualise the changes of each variable over time and estimate the time preceding rejection at which alterations are first detectable.
A total of 58 rejection episodes were included from 37 unique patients. In the presence of rejection, there were decrements from baseline in global longitudinal strain (−18.2 versus −14.1), global circumferential strain (−24.1 versus −19.6), longitudinal strain rate (−1 versus −0.8), circumferential strain rate (−1.3 versus −1.1), peak longitudinal early diastolic strain rate (1.3 versus 1), and peak circumferential early diastolic strain rate (1.5 versus 1.3) (p<0.01 for all). The earliest detectable changes occurred 45 days prior to rejection with simultaneous alterations in myocardial strain and ejection fraction.
Changes in graft function can be detected non-invasively prior to the diagnosis of rejection. However, changes in strain occur concurrently with a decline in ejection fraction. Strain measurements aid in the non-invasive detection of rejection, but may not facilitate earlier diagnosis compared to more traditional measures of ventricular function.
Tardive dyskinesia (TD) is a hyperkinetic movement disorder associated with antipsychotic treatment. RE KINECT (NCT03062033), a real-world study of outpatients prescribed antipsychotics, was designed to identify the presence of possible TD and characterize the impact of involuntary movements on functioning and quality of life. Data from RE-KINECT were used to compare the impact of possible TD in patients with schizophrenia/schizoaffective disorder [SZD] versus mood/other psychiatric disorders [Mood].
Adults with ≥3months of lifetime exposure to antipsychotics and ≥1 psychiatric disorder were recruited. The presence of possible TD was based on clinicians’ observation of involuntary movements in 4 body regions (head, trunk, upper extremities, and lower extremities). Baseline outcomes included demographics, medication history, location/severity of abnormal movements, impact of abnormal movements on daily activities, the Sheehan Disability Scale (SDS), and the EuroQoL 5-Dimensional questionnaire (EQ-5D-5L).
Of 204 patients with clinician-confirmed possible TD, 111 (54.4%) had a SZD diagnosis and 93 (45.6%) had a mood/other psychiatric diagnosis. Significant differences found between groups (Mood vs SZD) included: mean age (56.9 vs 52.7 years; P=0.0263); male sex (33.3% vs 62.2%; P<0.0001); African-American race (7.5% vs 26.1%; P=0.0005); mean lifetime exposure to antipsychotics (9.5 vs 19.5 years; P<0.0001); and percentage of patients currently taking ≥2 psychiatric medications (93.5% vs 79.3%; P=0.0093). Based on clinician observation, there were no significant differences between diagnosis groups in the number of body regions impacted by abnormal movements, maximum severity score across all 4 regions, or patient awareness of possible TD. Over 30% of patients in both groups reported that involuntary movements had “some” or “a lot” of impact on their ability to continue usual activities, be productive, and socialize. No significant differences between the diagnosis groups (Mood vs SZD) were found for mean SDS total score (12.8 vs 10.8), SDS domain scores (work/school [4.1 vs 4.2], social life [4.3 vs 3.7], family life [4.1 vs 3.5]), EQ-5D-5L utility score (0.68 vs 0.74), or EQ-5D-5L health state VAS (64.8 vs 68.5).
In this cohort of outpatients with possible TD, those with Mood disorders were more likely to be older, female, and white than patients with SZD. The ability to function and quality of life were equally impaired in both groups. Further studies on the impact of TD are needed.
Funding Acknowledgements: Neurocrine Biosciences, Inc.