New Variants in the First Part of Dekker's "The Honest Whore"

The first part of "The Honest Whore" has an intriguing textual history. Two quarto editions of the play appeared in 1604. Both bear the imprint of Valentine Simmes, yet each appears to have been the work of no less than three different printing shops. What is more, only half of the second quarto (Q2) is a new edition, the rest being made up of 'standing-type' pages preserved from the first quarto (Q1). Interestingly, too, there are many substantial differences between the texts of Q1 and Q2; and these differences occur both in the standing-type pages and in the pages newly composed for Q2. A fairly high proportion of these variants appear to be authoritative, and may well be authorial

'There's scarce a thing but is both loved and loathed': "The Changeling" I.i.91-129

One of the most striking occurrences in the early scenes of Middleton and Rowley's "The Changeling" is Beatrice's extraordinarily vehement reaction to her father's servant, De Flores. The predominant point of Beatrice's speech appears to be that she wants to make it abundantly plain to De Flores that his presence is not welcome to her. In this article, the authors explore just why he is so unwelcome. For instance, consciously, Alsemero displays sexual love towards Beatrice while unconsciously he is afraid of her, or at least of her sexual impact. With Beatrice's feelings for De Flores matters are the other way round. Again, sex is `both loved and loathed'. She loathes De Flores at a conscious level, as her speeches in this scene have made very plain. But unconsciously she desires him

'Take Heed There's Giants Keep Em': "The Changeling" III.iii.178 and its Context

In Act III, scene iii of Middleton and Rowley's "The Changeling", Isabella, locked up in the asylum of her jealous husband, Alibius, and guarded by his 'man' Lollio, receives sexual attention first from Lollio, then Franciscus (disguised as a madman), and then Antonio (disguised as a fool). She rejects the advances of the first two would-be lovers, but in a minor way succumbs to Antonio's charms. It seems likely that one reason why she does find Antonio attractive is that she realizes that he is acting a part. In other words, given time and practice, Antonio may come to look like a fool, but at present his play-acting is not yet successful enough to take in those he is trying to deceive, including, it seems, the main target of his device, Isabella

Middleton and Rowley's "The Changeling"

Daalder and Moore focus on Act IV, ii, 89-103, and in particular Jasperino's comment "Like those that challenge interest in a woman" (line 102). The authors explore the possibility that the 'woman' described in this line is Beatrice, not Diaphanta; various interpretations of the passage, in regards to the complex sexual relationships in the tragedy, hinge on confirming the identity of this 'woman'

Mandrakes and Whiblins in 'The Honest Whore'

In Act I, scene ii of Thomas Dekker's The Honest Whore (1604), there occurs a dialogue between Viola, the wife of the linen-draper Candido, and her brother Fustigo. Fustigo comments that Candido must be either a mandrake or a whiblin. Daalder considers the context in detail in order to evaluate the correct meanings ascribed to these terms in the text

Antidepressant use and risk of adverse outcomes in people aged 20–64 years: cohort study using a primary care database

Background: Antidepressants are one of the most commonly prescribed medications in young and middle-aged adults, but there is relatively little information on their safety across a range of adverse outcomes in this age group. This study aimed to assess associations between antidepressant treatment and several adverse outcomes in people aged 20–64 years diagnosed with depression. Methods: We conducted a cohort study in 238,963 patients aged 20–64 years registered with practices across the UK contributing to the QResearch primary care database. Only patients with a first diagnosis of depression were included. Outcomes were falls, fractures, upper gastrointestinal bleed, road traffic accidents, adverse drug reactions and all-cause mortality recorded during follow-up. Cox proportional hazards models were used to estimate hazard ratios associated with antidepressant exposure adjusting for potential confounding variables. Results: During 5 years of follow-up, 4651 patients had experienced a fall, 4796 had fractures, 1066 had upper gastrointestinal bleeds, 3690 had road traffic accidents, 1058 had experienced adverse drug reactions, and 3181 patients died. Fracture rates were significantly increased for selective serotonin reuptake inhibitors (adjusted hazard ratio 1.30, 95% CI 1.21–1.39) and other antidepressants (1.28, 1.11–1.48) compared with periods when antidepressants were not used. All antidepressant drug classes were associated with significantly increased rates of falls. Rates of adverse drug reactions were significantly higher for tricyclic and related antidepressants (1.54, 1.25–1.88) and other antidepressants (1.61, 1.22–2.12) compared with selective serotonin reuptake inhibitors. Trazodone was associated with a significantly increased risk of upper gastrointestinal bleed. All-cause mortality rates were significantly higher for tricyclic and related antidepressants (1.39, 1.22–1.59) and other antidepressants (1.26, 1.08–1.47) than for selective serotonin reuptake inhibitors over 5 years but not 1 year, and were significantly reduced after 85 or more days of treatment with selective serotonin reuptake inhibitors. Mirtazapine was associated with significantly increased mortality rates over 1 and 5 years of follow-up. Conclusions: Selective serotonin reuptake inhibitors had higher rates of fracture than tricyclic and related antidepressants but lower mortality and adverse drug reaction rates than the other antidepressant drug classes. The association between mirtazapine and increased mortality merits further investigation. These risks should be carefully considered and balanced against potential benefits for individual patients when the decision to prescribe an antidepressant is made

Antidepressant use and risk of suicide and attempted suicide or self harm in people aged 20 to 64: cohort study using a primary care database

Objective To assess the associations between different antidepressant treatments and the rates of suicide and attempted suicide or self harm in people with depression. Design Cohort study. Setting Patients registered with UK general practices contributing data to the QResearch database. Participants 238 963 patients aged 20 to 64 years with a first diagnosis of depression between 1 January 2000 and 31 July 2011, followed up until 1 August 2012. Exposures Antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, and duration of use, and commonly prescribed individual antidepressant drugs. Cox proportional hazards models were used to calculate hazard ratios adjusting for potential confounding variables. Main outcome measures Suicide and attempted suicide or self harm during follow-up. Results During follow-up, 87.7% (n=209 476) of the cohort received one or more prescriptions for antidepressants. The median duration of treatment was 221 days (interquartile range 79-590 days). During the first five years of follow-up 198 cases of suicide and 5243 cases of attempted suicide or self harm occurred. The difference in suicide rates during periods of treatment with tricyclic and related antidepressants compared with selective serotonin reuptake inhibitors was not significant (adjusted hazard ratio 0.84, 95% confidence interval 0.47 to 1.50), but the suicide rate was significantly increased during periods of treatment with other antidepressants (2.64, 1.74 to 3.99). The hazard ratio for suicide was significantly increased for mirtazapine compared with citalopram (3.70, 2.00 to 6.84). Absolute risks of suicide over one year ranged from 0.02% for amitriptyline to 0.19% for mirtazapine. There was no significant difference in the rate of attempted suicide or self harm with tricyclic antidepressants (0.96, 0.87 to 1.08) compared with selective serotonin reuptake inhibitors, but the rate of attempted suicide or self harm was significantly higher for other antidepressants (1.80, 1.61 to 2.00). The adjusted hazard ratios for attempted suicide or self harm were significantly increased for three of the most commonly prescribed drugs compared with citalopram: venlafaxine (1.85, 1.61 to 2.13), trazodone (1.73, 1.26 to 2.37), and mirtazapine (1.70, 1.44 to 2.02), and significantly reduced for amitriptyline (0.71, 0.59 to 0.85). The absolute risks of attempted suicide or self harm over one year ranged from 1.02% for amitriptyline to 2.96% for venlafaxine. Rates were highest in the first 28 days after starting treatment and remained increased in the first 28 days after stopping treatment. Conclusion Rates of suicide and attempted suicide or self harm were similar during periods of treatment with selective serotonin reuptake inhibitors and tricyclic and related antidepressants. Mirtazapine, venlafaxine, and trazodone were associated with the highest rates of suicide and attempted suicide or self harm, but the number of suicide events was small leading to imprecise estimates. As this is an observational study the findings may reflect indication biases and residual confounding from severity of depression and differing characteristics of patients prescribed these drugs. The increased rates in the first 28 days of starting and stopping antidepressants emphasise the need for careful monitoring of patients during these period

Antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: cohort study using primary care database

Objective To assess associations between different antidepressant treatments and rates of three cardiovascular outcomes (myocardial infarction, stroke or transient ischaemic attack, and arrhythmia) in people with depression. Design Cohort study. Setting UK general practices contributing to the QResearch primary care database. Participants 238 963 patients aged 20 to 64 years with a first diagnosis of depression between 1 January 2000 and 31 July 2011. Exposures Antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, duration of use, and commonly prescribed individual antidepressant drugs. Main outcome measures First diagnoses of myocardial infarction, stroke or transient ischaemic attack, and arrhythmia during five years’ follow-up. Cox proportional hazards models were used to estimate hazard ratios, adjusting for potential confounding variables. Results During five years of follow-up, 772 patients had a myocardial infarction, 1106 had a stroke or transient ischaemic attack, and 1452 were diagnosed as having arrhythmia. No significant associations were found between antidepressant class and myocardial infarction over five years’ follow-up. In the first year of follow-up, patients treated with selective serotonin reuptake inhibitors had a significantly reduced risk of myocardial infarction (adjusted hazard ratio 0.58, 95% confidence interval 0.42 to 0.79) compared with no use of antidepressants; among individual drugs, fluoxetine was associated with a significantly reduced risk (0.44, 0.27 to 0.72) and lofepramine with a significantly increased risk (3.07, 1.50 to 6.26). No significant associations were found between antidepressant class or individual drugs and risk of stroke or transient ischaemic attack. Antidepressant class was not significantly associated with arrhythmia over five years’ follow-up, although the risk was significantly increased during the first 28 days of treatment with tricyclic and related antidepressants (adjusted hazard ratio 1.99, 1.27 to 3.13). Fluoxetine was associated with a significantly reduced risk of arrhythmia (0.74, 0.59 to 0.92) over five years, but citalopram was not significantly associated with risk of arrhythmia even at high doses (1.11, 0.72 to 1.71 for doses ≥40 mg/day). Conclusions This study found no evidence that selective serotonin reuptake inhibitors are associated with an increased risk of arrhythmia or stroke/transient ischaemic attack in people diagnosed as having depression between the ages of 20 to 64 or that citalopram is associated with a significantly increased risk of arrhythmia. It found some indication of a reduced risk of myocardial infarction with selective serotonin reuptake inhibitors, particularly fluoxetine, and of an increased risk with lofepramine

Effect of ripple repetition rate on discrimination of ripple glide direction and the detection of brief tones in spectro-temporal ripple noise.

The effect of temporal repetition rate R on the discrimination and internal representation of stimuli with spectro-temporal ripples was examined. Experiment 1 measured the highest ripple density D at which upward- and downward-gliding ripples could be discriminated. Thresholds varied only slightly for R from 2 to 8 Hz, with a median threshold just above 5 ripples/oct. The threshold decreased (worsened) when R was increased to 16 and 32 Hz, suggesting that the limited temporal resolution of the auditory system plays a role for these higher values of R. Experiment 2 explored the internal representation of stimuli with static and downward-gliding spectral ripples by measuring the detection threshold for a brief tone presented at a peak or a valley in the stimulus spectrum. Thresholds were generally higher when the signal was at a peak than when it was at a valley. The peak-valley difference tended to decrease with increasing D, and the variation of thresholds with D was greater for low R than for high R. The results suggest that the discrimination of spectro-temporal ripples is limited mainly by frequency resolution for lower ripple rates (up to 4-8 Hz) but temporal resolution plays a major role for higher rates