Prospective, multicenter study of P4HB (Phasix) mesh for hernia repair in cohort at risk for complications: 3-Year follow-up

Background: This study represents a prospective, multicenter, open-label study to assess the safety, performance, and outcomes of poly-4-hydroxybutyrate (P4HB, Phasix) mesh for primary ventral, primary incisional, or multiply-recurrent hernia in subjects at risk for complications. This study reports 3-year clinical outcomes. Materials and methods: P4HB mesh was implanted in 121 patients via retrorectus or onlay technique. Physical exam and/or quality of life surveys were completed at 1, 3, 6,12, 18, 24, and 36 months, with 5-year (60-month) follow-up ongoing. Results: A total of n = 121 patients were implanted with P4HB mesh (n = 75 (62%) female) with a mean age of 54.7 +/- 12.0 years and mean BMI of 32.2 +/- 4.5 kg/m(2) (+/-standard deviation). Comorbidities included: obesity (78.5%), active smokers (23.1%), COPD (28.1%), diabetes mellitus (33.1%), immunosuppression (8.3%), coronary artery disease (21.5%), chronic corticosteroid use (5.0%), hypo-albuminemia (2.5%), advanced age (5.0%), and renal insufficiency (0.8%). Hernias were repaired via retrorectus (n = 45, 37.2% with myofascial release (MR) or n = 43, 35.5% without MR), onlay (n = 8, 6.6% with MR or n = 24, 19.8% without MR), or not reported (n = 1, 0.8%). 82 patients (67.8%) completed 36-month follow-up. 17 patients (17.9% +/- 0.4%) experienced hernia recurrence at 3 years, with n = 9 in the retrorectus group and n = 8 in the onlay group. SSI (n = 11) occurred in 9.3% +/- 0.03% of patients. Conclusions: Long-term outcomes following ventral hernia repair with P4HB mesh demonstrate low recurrence rates at 3-year (36-month) postoperative time frame with no patients developing late mesh complications or requiring mesh removal. 5-year (60-month) follow-up is ongoing

The Arthrobacter Species FB24 Arth_1007 (DnaB) Intein Is a Pseudogene

An Arthrobacter species FB24 gene (locus tag Arth_1007) was previously annotated as a putative intein-containing DnaB helicase of phage origin (Arsp-FB24 DnaB intein). However, it is not a helicase gene because the sequence similarity is limited to inteins. In fact, the flanking exteins total only 66 amino acids. Therefore, the intein should be referred to as the Arsp-FB24 Arth_1007 intein. The Arsp-FB24 Arth_1007 intein failed to splice in its native precursor and in a model precursor. We previously noted that the Arsp-FB24 Arth_1007 intein is the only putative Class 3 intein that is missing the catalytically essential Cys at position 4 of intein Motif F, which is one of the three defining signature residues of this class. Additionally, a catalytically essential His in position 10 of intein Motif B is also absent; this His is the most conserved residue amongst all inteins. Splicing activity was not rescued when these two catalytically important positions were ‘reverted’ back to their consensus residues. This study restores the unity of the Class 3 intein signature sequence in active inteins by demonstrating that the Arsp-FB24 Arth_1007 intein is an inactive pseudogene

Prospective, multicenter study of P4HB (Phasix™) mesh for hernia repair in cohort at risk for complications: 3-Year follow-up

Background: This study represents a prospective, multicenter, open-label study to assess the safety, performance, and outcomes of poly-4-hydroxybutyrate (P4HB, Phasix™) mesh for primary ventral, primary incisional, or multiply-recurrent hernia in subjects at risk for complications. This study reports 3-year clinical outcomes. Materials and methods: P4HB mesh was implanted in 121 patients via retrorectus or onlay technique. Physical exam and/or quality of life surveys were completed at 1, 3, 6,12, 18, 24, and 36 months, with 5-year (60-month) follow-up ongoing. Results: A total of n = 121 patients were implanted with P4HB mesh (n = 75 (62%) female) with a mean age of 54.7 ± 12.0 years and mean BMI of 32.2 ± 4.5 kg/m2 (±standard deviation). Comorbidities included: obesity (78.5%), active smokers (23.1%), COPD (28.1%), diabetes mellitus (33.1%), immunosuppression (8.3%), coronary artery disease (21.5%), chronic corticosteroid use (5.0%), hypo-albuminemia (2.5%), advanced age (5.0%), and renal insufficiency (0.8%). Hernias were repaired via retrorectus (n = 45, 37.2% with myofascial release (MR) or n = 43, 35.5% without MR), onlay (n = 8, 6.6% with MR or n = 24, 19.8% without MR), or not reported (n = 1, 0.8%). 82 patients (67.8%) completed 36-month follow-up. 17 patients (17.9% ± 0.4%) experienced hernia recurrence at 3 years, with n = 9 in the retrorectus group and n = 8 in the onlay group. SSI (n = 11) occurred in 9.3% ± 0.03% of patients. Conclusions: Long-term outcomes following ventral hernia repair with P4HB mesh demonstrate low recurrence rates at 3-year (36-month) postoperative time frame with no patients developing late mesh complications or requiring mesh removal. 5-year (60-month) follow-up is ongoing

Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis

BACKGROUND Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P<0.001 for all comparisons of ixekizumab with placebo). In the UNCOVER-1 and UNCOVER-2 trials, among the patients who were randomly reassigned at week 12 to receive 80 mg of ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0% of the patients, respectively. Patients in the UNCOVER-3 trial received continuous treatment of ixekizumab from weeks 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response. Adverse events reported during ixekizumab use included neutropenia, candidal infections, and inflammatory bowel disease. CONCLUSIONS In three phase 3 trials involving patients with psoriasis, ixekizumab was effective through 60 weeks of treatment. As with any treatment, the benefits need to be weighed against the risks of adverse events. The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known

The population of merging compact binaries inferred using gravitational waves through GWTC-3

We report on the population properties of 76 compact binary mergers detected with gravitational waves below a false alarm rate of 1 per year through GWTC-3. The catalog contains three classes of binary mergers: BBH, BNS, and NSBH mergers. We infer the BNS merger rate to be between 10 $\rm{Gpc^{-3} yr^{-1}}$ and 1700 $\rm{Gpc^{-3} yr^{-1}}$ and the NSBH merger rate to be between 7.8 $\rm{Gpc^{-3}\, yr^{-1}}$ and 140 $\rm{Gpc^{-3} yr^{-1}}$ , assuming a constant rate density versus comoving volume and taking the union of 90% credible intervals for methods used in this work. Accounting for the BBH merger rate to evolve with redshift, we find the BBH merger rate to be between 17.9 $\rm{Gpc^{-3}\, yr^{-1}}$ and 44 $\rm{Gpc^{-3}\, yr^{-1}}$ at a fiducial redshift (z=0.2). We obtain a broad neutron star mass distribution extending from $1.2^{+0.1}_{-0.2} M_\odot$ to $2.0^{+0.3}_{-0.3} M_\odot$. We can confidently identify a rapid decrease in merger rate versus component mass between neutron star-like masses and black-hole-like masses, but there is no evidence that the merger rate increases again before 10 $M_\odot$. We also find the BBH mass distribution has localized over- and under-densities relative to a power law distribution. While we continue to find the mass distribution of a binary's more massive component strongly decreases as a function of primary mass, we observe no evidence of a strongly suppressed merger rate above $\sim 60 M_\odot$. The rate of BBH mergers is observed to increase with redshift at a rate proportional to $(1+z)^{\kappa}$ with $\kappa = 2.9^{+1.7}_{-1.8}$ for $z\lesssim 1$. Observed black hole spins are small, with half of spin magnitudes below $\chi_i \simeq 0.25$. We observe evidence of negative aligned spins in the population, and an increase in spin magnitude for systems with more unequal mass ratio

CEO succession and the CEO’s commitment to the status quo

Chief executive officer (CEO) commitment to the status quo (CSQ) is expected to play an important role in any firm’s strategic adaptation. CSQ is used often as an explanation for strategic change occurring after CEO succession: new CEOs are expected to reveal a lower CSQ than established CEOs. Although widely accepted in the literature, this relationship remains imputed but unobserved. We address this research gap and analyze whether new CEOs reveal lower CSQ than established CEOs. By analyzing the letters to the shareholders of German HDAX firms, we find empirical support for our hypothesis of a lower CSQ of newly appointed CEOs compared to established CEOs. However, our detailed analyses provide a differentiated picture. We find support for a lower CSQ of successors after a forced CEO turnover compared to successors after a voluntary turnover, which indicates an influence of the mandate for change on the CEO’s CSQ. However, against the widespread assumption, we do not find support for a lower CSQ of outside successors compared to inside successors, which calls for deeper analyses of the insiderness of new CEOs. Further, our supplementary analyses propose a revised tenure effect: the widely assumed relationship of an increase in CSQ when CEO tenure increases might be driven mainly by the event of CEO succession and may not universally and continuously increase over time, pointing to a “window of opportunity” to initiate strategic change shortly after the succession event. By analyzing the relationship between CEO succession and CEO CSQ, our results contribute to the CSQ literature and provide fruitful impulses for the CEO succession literature

Internal Hernia After Laparoscopic Antecolic Roux-en-Y Gastric Bypass

BACKGROUND: We evaluated the incidence and presentations of internal hernias (IH) after laparoscopic antecolic Roux-en-Y gastric bypass (RYGB) at our institution. METHODS: We retrospectively reviewed the records of 594 patients who underwent laparoscopic antecolic RYGB at our institution between December 2004 and December 2010. RESULTS: Five hundred ninety-four patients underwent laparoscopic antecolic RYGB with a mean follow-up of 50.5 months. Thirty-six patients developed 37 IH (6.2 %) requiring surgical intervention. Mean age of IH patients was 36.9 years. Thirty-one out of 36 were female. Mean preoperative BMI was 44.3 Kg/m(2). The mean time of presentation after their RYGB was 25.9 months. The mean % excess body weight loss at time of presentation was 54.0 %. Twenty-five out of 37 of IH occurred at Petersen\u27s space; 9/37 IH occurred under the jejunojejunostomy; three patients had hernias at both locations. Mesenteric swirling was the most common CT scan finding in 20/36 (55.6 %). Six out of 36 CT were initially read as normal; however, on retrospective review by a radiologist, abnormalities indicating IH were found in 4/6. Patients presented with different degrees of acuity: 6/37 with chronic abdominal pain and 28/37 with acute abdominal pain. Bowel necrosis was found in 3/37. CONCLUSION: IH is a serious and potentially fatal complication of RYGB. Presentation can vary from chronic abdominal pain to bowel necrosis. CT is helpful in providing diagnosis; however, careful attention to the specific signs of small bowel volvulus, such as mesenteric swirl sign, should be given. IH should be considered in RYGB patients who present with even vague symptoms