The brown dwarf desert as a consequence of orbital migration

We show that the dearth of brown dwarfs in short-period orbits around Solar-mass stars - the brown dwarf desert - can be understood as a consequence of inward migration within an evolving protoplanetary disc. Brown dwarf secondaries forming at the same time as the primary star have masses which are comparable to the initial mass of the protoplanetary disc. Subsequent disc evolution leads to inward migration, and destruction of the brown dwarf, via merger with the star. This is in contrast with massive planets, which avoid this fate by forming at a later epoch when the disc is close to being dispersed. Within this model, a brown dwarf desert arises because the mass at the hydrogen burning limit is coincidentally comparable to the initial disc mass for a Solar mass star. Brown dwarfs should be found in close binaries around very low mass stars, around other brown dwarfs, and around Solar-type stars during the earliest phases of star formation.Comment: MNRAS (Letters), in pres

Long-term treatment of uterine fibroids with ulipristal acetate

Objective: To investigate the efficacy and safety of ulipristal acetate (UPA) for long-term treatment of symptomatic uterine fibroids.<p></p> Design: Repeated intermittent open-label UPA courses, each followed by randomized double-blind norethisterone acetate (NETA) or placebo.<p></p> Setting: European clinical gynecology centers.<p></p> Patient(s): Two hundred and nine women with symptomatic fibroids including heavy menstrual bleeding.<p></p> Intervention(s): Patients received up to four 3-month courses of UPA 10 mg daily, immediately followed by 10-day double-blind treatment with NETA (10 mg daily) or placebo.<p></p> Main Outcome Measure(s): Amenorrhea, fibroid volume, endometrial histology.<p></p> Result(s): After the first UPA course, amenorrhea occurred in 79% of women, with median onset (from treatment start) of 4 days (interquartile range, 2–6 days). Median fibroid volume change was −45% (interquartile range, −66%; −25%). Amenorrhea rates were 89%, 88%, and 90% for the 131, 119, and 107 women who received treatment courses 2, 3, and 4, respectively. Median times to amenorrhea were 2, 3, and 3 days for treatment courses 2, 3, and 4, respectively. Median fibroid volume changes from baseline were −63%, −67%, and −72% after treatment courses 2, 3, and 4, respectively. All endometrial biopsies showed benign histology without hyperplasia; NETA did not affect fibroid volume or endometrial histology.<p></p> Conclusion(s): Repeated 3-month UPA courses effectively control bleeding and shrink fibroids in patients with symptomatic fibroids

Accounting for habitat structural complexity improves the assessment of performance in no-take marine reserves

Seascape variability may confound assessments on the effectiveness of no-take marine reserves (NTMRs) in conserving biodiversity. In most cases baseline data are lacking, resulting in evaluations of NTMR effectiveness being Control Impact (CI) assessments. Even with independent replicate areas among management zones, this approach can make it difficult to detect zone effects if seascape attributes, such as habitat structural complexity varies among experimental areas. To determine the importance of structural complexity in evaluations of NTMR effectiveness we performed assessments on the abundance of a targeted fish, yellowtail kingfish (Seriola lalandi), in the Lord Howe Island Marine Park (LHIMP). We compared assessments which did and did not account for structural complexity, quantified using high resolution multibeam bathymetry. Despite almost 3 times more S. lalandi in NTMRs, the traditional CI assessment explained only 3% of the variation in the abundance of S. lalandi and revealed no clear effect of protection. Incorporating structural complexity into the assessment increased the deviance explained to 65% and uncovered an important interaction between zone and structural complexity. Greater abundances of S. lalandi were detected in NTMRs compared to fished zones but only on highly complex reefs. By accounting for structural complexity, we demonstrate that the precision and accuracy of NTMR assessments can be improved, leading to a better understanding of ecological change in response to this conservation strategy. Consequently, where marine park zones vary greatly in structural complexity, we strongly advocate for quantifying and accounting for such variability in assessments of NTMR performance

Flexible-dose fesoterodine in elderly adults with overactive bladder: results of the randomized, double-blind, placebo-controlled study of fesoterodine in an aging population trial

To assess the efficacy and safety of flexible-dose fesoterodine in elderly adults with overactive bladder (OAB). Twelve-week, randomized, double-blind, placebo-controlled trial. Sixty-one outpatient clinics in Europe, Israel, and Turkey. Seven hundred ninety-four individuals aged 65 and older (47% male) with OAB symptoms for 3 months or longer, mean of eight or more micturitions and three or more urgency episodes per 24 hours, at least some moderate problems on Patient Perception of Bladder Condition (PPBC), and Mini-Mental State Examination (MMSE) score of 20 or greater. Participants were randomized to fesoterodine or placebo for 12 weeks, with stratification according to age (>75 vs ≤ 75) and dosing time (morning vs evening). Participants receiving fesoterodine started on 4 mg and could increase to 8 mg at week 4 or 8 and de-escalate to 4 mg at week 8 (sham escalation for placebo). Changes from baseline in bladder-diary variables (primary endpoint, urgency episodes) and patient-reported outcomes including OAB Questionnaire, Treatment Benefit Scale (TBS), PPBC, Urgency Perception Scale (UPS), and OAB Satisfaction Questionnaire (OAB-S); all observed or reported adverse events. By week 8, 64% of fesoterodine-treated and 71% of placebo-treated participants opted for dose escalation. At week 12, the fesoterodine group had statistically significantly greater improvement than the placebo group in urgency episodes, micturitions, nocturnal micturitions, incontinence pad use, and OAB Questionnaire scores but not urgency urinary incontinence episodes. Responder rates on TBS, PPBC, UPS, and OAB-S were statistically significantly higher with fesoterodine. Improvements in most diary variables and participant-reported outcomes were greater with fesoterodine than placebo in participants in both age groups and when administered in the morning and evening. Rates of dry mouth and constipation were 34% and 9% with fesoterodine and 5% and 3% with placebo, respectively. Rates of adverse events and discontinuations were generally similar in participants in both age groups. There was no change in MMSE score. Fesoterodine was associated with significantly greater improvements in most diary variables and participant-reported outcomes than placebo and was generally well tolerated in older peopl

Ulipristal acetate versus placebo for fibroid treatment before surgery.

BACKGROUND: The efficacy and safety of oral ulipristal acetate for the treatment of symptomatic uterine fibroids before surgery are uncertain. METHODS: We randomly assigned women with symptomatic fibroids, excessive uterine bleeding (a score of >100 on the pictorial blood-loss assessment chart [PBAC, an objective assessment of blood loss, in which monthly scores range from 0 to >500, with higher numbers indicating more bleeding]) and anemia (hemoglobin level of </=10.2 g per deciliter) to receive treatment for up to 13 weeks with oral ulipristal acetate at a dose of 5 mg per day (96 women) or 10 mg per day (98 women) or to receive placebo (48 women). All patients received iron supplementation. The coprimary efficacy end points were control of uterine bleeding (PBAC score of <75) and reduction of fibroid volume at week 13, after which patients could undergo surgery. RESULTS: At 13 weeks, uterine bleeding was controlled in 91% of the women receiving 5 mg of ulipristal acetate, 92% of those receiving 10 mg of ulipristal acetate, and 19% of those receiving placebo (P<0.001 for the comparison of each dose of ulipristal acetate with placebo). The rates of amenorrhea were 73%, 82%, and 6%, respectively, with amenorrhea occurring within 10 days in the majority of patients receiving ulipristal acetate. The median changes in total fibroid volume were -21%, -12%, and +3% (P=0.002 for the comparison of 5 mg of ulipristal acetate with placebo, and P=0.006 for the comparison of 10 mg of ulipristal acetate with placebo). Ulipristal acetate induced benign histologic endometrial changes that had resolved by 6 months after the end of therapy. Serious adverse events occurred in one patient during treatment with 10 mg of ulipristal acetate (uterine hemorrhage) and in one patient during receipt of placebo (fibroid protruding through the cervix). Headache and breast tenderness were the most common adverse events associated with ulipristal acetate but did not occur significantly more frequently than with placebo. CONCLUSIONS: Treatment with ulipristal acetate for 13 weeks effectively controlled excessive bleeding due to uterine fibroids and reduced the size of the fibroids

Efficacy and safety of repeated use of ulipristal acetate in uterine fibroids.

OBJECTIVE: To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily of ulipristal acetate for intermittent treatment of symptomatic uterine fibroids. DESIGN: Double-blind, randomized administration of two 12-week courses of ulipristal acetate. SETTING: Gynecology centers. PATIENT(S): A total of 451 patients with symptomatic uterine fibroid(s) and heavy bleeding. INTERVENTION(S): Two repeated 12-week treatment courses of daily 5 or 10 mg of ulipristal acetate. MAIN OUTCOME MEASURE(S): Amenorrhea, controlled bleeding, fibroid volume, quality of life (QoL), pain. RESULT(S): In the 5- and 10-mg treatment groups (62% and 73% of patients, respectively) achieved amenorrhea during both treatment courses. Proportions of patients achieving controlled bleeding during two treatment courses were >80%. Menstruation resumed after each treatment course and was diminished compared with baseline. After the second treatment course, median reductions from baseline in fibroid volume were 54% and 58% for the patients receiving 5 and 10 mg of ulipristal acetate, respectively. Pain and QoL improved in both groups. Ulipristal acetate was well tolerated with less than 5% of patients discontinuing treatment due to adverse events. CONCLUSION(S): Repeated 12-week courses of daily oral ulipristal acetate (5 and 10 mg) effectively control bleeding and pain, reduce fibroid volume, and restore QoL in patients with symptomatic fibroids

A New Perspective on the Nitrate-Phosphodiesterase Type 5 Inhibitor Interaction.

BACKGROUND Nitrates and nitrate-containing compounds are vasodilators used for the treatment of angina and heart failure. Phosphodiesterase type 5 inhibitors used for the treatment of erectile dysfunction are also vasodilators, and when taken together with nitrates, synergistic effects that enhance hypotensive effects may occur. Phosphodiesterase type 5 inhibitors are therefore contraindicated in patients taking organic nitrates. METHODS AND RESULTS A literature review was performed to provide a historical overview of different phosphodiesterase type 5 inhibitors and nitrates and their interaction. The pharmacologic characteristics of phosphodiesterase type 5 inhibitors and nitrates are reviewed, and clinical recommendations for treating cardiovascular disease in men taking phosphodiesterase type 5 inhibitors are discussed. Pharmacologic and adverse drug reactions between nitrates and phosphodiesterase type 5 inhibitors are dependent on many variables. Organic nitrates remain an absolute contraindication in men treated with phosphodiesterase type 5 inhibitors. In general, nitrates may be taken 24 hours after the last dose of short-acting phosphodiesterase type 5 inhibitors and 48 hours after the last dose of long-acting phosphodiesterase type 5 inhibitors. CONCLUSIONS This literature review determined that the use of phosphodiesterase type 5 inhibitors with nitrates is a contraindication, with the duration between the last dose of phosphodiesterase inhibitor and nitrate use generally varying between short- and long-acting phosphodiesterase type 5 formulations. Patients receiving nitrates who wish to use phosphodiesterase type 5 inhibitors should be educated regarding the interaction and should be evaluated to determine whether nitrate treatment can be discontinued. Further research is needed to determine how soon phosphodiesterase type 5 inhibitors can be restarted after a patient has taken a nitrate and the effect of high and low phosphodiesterase type 5 inhibitor doses on the interaction effect