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Asthma remains one of the most prevalent and costly diseases in the United States. Asthma accounts for a significant amount of direct medical expenditures and indirect cost from days lost at school and work. Modern understanding of its complex pathogenesis has allowed recognition of the heterogeneity of the disease across populations and the various inflammatory pathways that drive airway inflammation in asthma. Interleukins play important roles in both eosinophilic and noneosinophilic asthma, and anti-interleukin therapy will allow for a targeted, personalized approach to asthma management. With the success of anti-interleukin (IL) -4, IL-5, and IL-13 therapy in recent large trials among specific populations of asthmatics, it is likely that targeted anti-interleukin therapy will be approved for use in the near future. It will be important for clinicians and pharmacists to understand their risks, benefits, and proper indications. [ABSTRACT FROM AUTHOR]

Purpose: We hypothesize that Permacol™ may allow controlled integration over time while providing long-term mechanical stability and native tissue remodeling. The purpose of this report is to investigate these properties in an explanted piece of Permacol™ after 2 years in vivo.Methods: A 62-year-old female presented with a complex abdominal wall history having undergone a transverse rectus abdominis musculocutaneous (TRAM) flap breast reconstruction 10 years ago, followed by an abdominal wall repair with Marlex™ mesh for weakness 3 years later. Two years ago, she developed an abdominal bulge repaired with a Permacol™ overlay. Twenty-three months postoperatively, she presented with abdominal distension. Computed tomography (CT) scanning demonstrated a fluid collection behind the Permacol™. She underwent incision and drainage of the hematoma/bursa and quilting repair of the abdominal wall. A 1 × 6-cm Permacol™ section was resected as part of closure. Histology, immunohistochemistry, and mechanical testing of the Permacol™ explant were performed.Results: Histology showed fibroblast and blood vessel ingrowth with no cellular infiltrates reflective of inflammation. Immunohistochemistry for human-specific collagen types I and III and elastin detected staining throughout. Sections stained with non-specific control antibody exhibited no discernable staining. Elastin highlighted blood vessels. Native Permacol™ had a breaking strength of ~20 N, while for explanted Permacol™, it was ~33 N.Conclusions: Permacol™ maintained durability while allowing vascular ingrowth without residual inflammation. Explant demonstrated integration with human collagen and elastin remodeling throughout. Increase in mechanical strength may reflect newly synthesized collagen and elastin. These histologic findings and clinical result support the use of Permacol™ in complex abdominal wall reconstruction. [ABSTRACT FROM AUTHOR]

Choice can be driven both by rewards and stimuli that signal those rewards. Under certain conditions, pigeons will prefer options that lead to less probable reward when the reward is signaled. A recently quantified model, the Signal for Good News (SiGN) model, assumes that in the context of uncertainty, signals for a reduced delay to reward reinforce choice. The SiGN model provides an excellent fit to previous results from pigeons and the current studies are the first to test a priori quantitative predictions. Pigeons chose between a suboptimal alternative that led to signaled 20% food and an optimal alternative that led to 50% food. The duration of the choice period was manipulated across conditions in two experiments. Pigeons strongly preferred the suboptimal alternative at the shorter durations and strongly preferred the optimal alternative at the longer durations. The results from both experiments fit well with predictions from the SiGN model and show that altering the duration of the choice period has a dramatic effect in that it changes which of the two options pigeons prefer. More generally, these results suggest that the relative value of options is not fixed, but instead depends on the temporal context., (© 2024. The Author(s).)

As first reported several decades ago, pigeons ( Columba livia ) sometimes choose options that provide less food over options that provide more food. This behavior has been variously referred to as suboptimal, maladaptive, or paradoxical because it lowers overall food intake. A great deal of research has been directed at understanding the conditions under which animals and people make suboptimal choices and the mechanisms that drive this behavior. Here, we review the literature on suboptimal choice and the variables that play a role in this phenomenon. Suboptimal choice is most likely to occur when the outcomes following a choice are uncertain, when the outcomes are delayed after the choice, and when the outcomes are signaled only on the option that provides food less often. We propose a mathematical formalization of the signal for good news (SiGN) model which assumes that a signal for a reduction in delay to food reinforces choice. We generate predictions from the model about the effect of parameters that characterize suboptimal choice and we show that, even in the absence of free parameters, the SiGN model provides a very good fit to the choice proportions of birds from a large set of conditions across studies from numerous researchers. R code for SiGN predictions and the data set are available on the Open Science Framework (https://osf.io/39qtj). We discuss limitations of the model, propose directions for future research, and discuss the general applicability of this research to understanding how rewards and signals for reward may combine to reinforce behavior. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Riparian buffers are expedient interventions for water quality functions in agricultural landscapes. However, the choice of vegetation and management affects soil microbial communities, which in turn affect nutrient cycling and the production and emission of gases such as nitric oxide (NO), nitrous oxide (N 2 O), nitrogen gas (N 2 ) and carbon dioxide (CO 2 ). To investigate the potential fluxes of the above-mentioned gases, soil samples were collected from a cropland and downslope grass, willow and woodland riparian buffers from a replicated plot scale experimental facility. The soils were re-packed into cores and to investigate their potential to produce the aforementioned gases via potential denitrification, a potassium nitrate (KNO 3 - ) and glucose (labile carbon)-containing amendment, was added prior to incubation in a specialized laboratory DENItrification System (DENIS). The resulting NO, N 2 O, N 2 and CO 2 emissions were measured simultaneously, with the most NO (2.9 ± 0.31 mg NO m -2 ) and N 2 O (1413.4 ± 448.3 mg N 2 O m -2 ) generated by the grass riparian buffer and the most N 2 (698.1 ± 270.3 mg N 2  m -2 ) and CO 2 (27,558.3 ± 128.9 mg CO 2 m -2 ) produced by the willow riparian buffer. Thus, the results show that grass riparian buffer soils have a greater NO 3 - removal capacity, evidenced by their large potential denitrification rates, while the willow riparian buffers may be an effective riparian buffer as its soils potentially promote complete denitrification to N 2 , especially in areas with similar conditions to the current study., (© 2023 The Authors. Soil Use and Management published by John Wiley & Sons Ltd on behalf of British Society of Soil Science.)

The volume of high-quality evidence supporting exercise as beneficial to cancer survivors has grown exponentially; however, the potential harms of exercise remain understudied. Consequently, the trade-off between desirable and undesirable outcomes of engaging in exercise remains unclear to clinicians and people with cancer. Practical guidance on collecting and reporting harms in exercise oncology is lacking. We present a harms reporting protocol developed and refined through exercise oncology trials since 2015.Development of the Exercise Harms Reporting Method (ExHaRM) was informed by national and international guidelines for harms reporting in clinical trials involving therapeutic goods or medical devices, with adaptations to enhance applicability to exercise. The protocol has been adjusted via an iterative process of implementation and adjustment through use in multiple exercise oncology trials involving varied cancer diagnoses (types: breast, brain, gynaecological; stages at diagnosis I-IV; primary/recurrent), and heterogeneous exercise intervention characteristics (face to face/telehealth delivery; supervised/unsupervised exercise). It has also involved the development of terms (such as, adverse outcomes, which capture all undesirable physical, psychological, social and economic outcomes) that facilitate the harms assessment process in exercise.ExHaRM involves: step 1: Monitor occurrence of adverse outcomes through systematic and non-systematic surveillance; step 2: Assess and record adverse outcomes, including severity, causality, impact on intervention and type; step 3: Review of causality by harms panel (and revise as necessary); and step 4: Analyse and report frequencies, rates and clinically meaningful details of all-cause and exercise-related adverse outcomes.ExHaRM provides guidance to improve the quality of harms assessment and reporting immediately, while concurrently providing a framework for future refinement. Future directions include, but are not limited to, standardising exercise-specific nomenclature and methods of assessing causality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Long-term resorbable mesh represents a promising technology for ventral and incisional hernia repair (VIHR). This study evaluates poly-4-hydroxybutyrate mesh (P4HB; Phasix Mesh) among comorbid patients with CDC class I wounds., Study Design: This prospective, multi-institutional study evaluated P4HB VIHR in comorbid patients with CDC class I wounds. Primary outcomes included hernia recurrence and surgical site infection. Secondary outcomes included pain, device-related adverse events, quality of life, reoperation, procedure time, and length of stay. Evaluations were scheduled at 1, 3, 6, 12, 18, 24, 30, 36, and 60 months. A time-to-event analysis (Kaplan-Meier) was performed for primary outcomes; secondary outcomes were reported as descriptive statistics., Results: A total of 121 patients (46 male, 75 female) 54.7 ± 12.0 years old with a BMI of 32.2 ± 4.5 kg/m 2 underwent VIHR with P4HB Mesh (mean ± SD). Fifty-four patients (44.6%) completed the 60-month follow-up. Primary outcomes (Kaplan-Meier estimates at 60 months) included recurrence (22.0 ± 4.5%; 95% CI 11.7% to 29.4%) and surgical site infection (10.1 ± 2.8%; 95% CI 3.3 to 14.0). Secondary outcomes included seroma requiring intervention (n = 9), procedure time (167.9 ± 82.5 minutes), length of stay (5.3 ± 5.3 days), reoperation (18 of 121, 14.9%), visual analogue scale-pain (change from baseline -3.16 ± 3.35 cm at 60 months; n = 52), and Carolinas Comfort Total Score (change from baseline -24.3 ± 21.4 at 60 months; n = 52)., Conclusions: Five-year outcomes after VIHR with P4HB mesh were associated with infrequent complications and durable hernia repair outcomes. This study provides a framework for anticipated long-term hernia repair outcomes when using P4HB mesh., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Surgeons.)

Under certain conditions, pigeons will reliably prefer an alternative that leads to a lower probability of food over an alternative that leads to a higher probability of food (i.e., demonstrate suboptimal choice). A critical aspect of the typical procedure is that the alternative associated with less food provides differential stimuli that signal trial outcomes, but the alternative associated with more food does not. Few studies have investigated how partial signaling of an alternative influences preference. In Experiments 1-3, pigeons chose between two alternatives that each led to food 60% of the time with partially signaled trial outcomes. One alternative occasionally provided a stimulus that always preceded food (i.e., "good news") and the other alternative occasionally provided a stimulus that always preceded no food ("bad news"). Experiments 2 and 3 also assessed preference in conditions in which alternatives were either completely unsignaled (provided no differential stimuli) or always led to food. Pigeons consistently preferred the "good news" alternative over the "bad news" alternative and preferred 100% food over the "bad news" alternative. The results from conditions in which pigeons chose between the "bad news" alternative and an unsignaled alternative were inconclusive, but suggestive of a preference for bad news. The results are used to evaluate and distinguish between competing explanations of suboptimal choice., (© 2021. The Psychonomic Society, Inc.)

Buffer strips continue to feature in the management of agricultural runoff and water pollution in many countries. Existing research has explored their efficacy for reducing environmental problems in different geoclimatic settings but, the evidence on the efficacy of different vegetation treatments is less abundant than that for other buffer strip characteristics, including width, and is more contradictory in nature. With policy targets for various environmental outcomes including water or air quality and net zero pointing to the need for conversion of agricultural land, the need for robust experimental evidence on the relative benefits of different vegetation types in buffer strips is now renewed. Our experiment used a replicated plot scale facility to compare the efficacy of 12 m wide buffer strips for controlling runoff and suspended sediment loss during 15 sampled storms spanning 2017-2020. The buffer strips comprised three vegetation treatments: a deep rooting grass ( Festulolium cv. Prior), a short rotation coppice willow and native broadleaved woodland trees. Over the duration of the monitoring period, reductions in total runoff, compared with the experimental control, were in the order: willow buffer strips (49%); deciduous woodland buffer strips (46%); grass buffer strips (33%). The corresponding reductions in suspended sediment loss, relative to the experimental control, were ordered: willow buffer strips (44%) > deciduous woodland buffer strips (30%) > grass buffer strips (29%). Given the 3-year duration of our new dataset, our results should be seen as providing evidence on the impacts during the establishment phase of the treatments., (© 2022 The Authors. Hydrological Processes published by John Wiley & Sons Ltd.)

The influence of single option or forced-exposure (FE) trials was studied in the suboptimal choice task. Pigeons chose between an optimal alternative that led to food half of the time and a suboptimal alternative that led to food 20% of the time. Choice of the suboptimal alternative was compared across groups of subjects that received different numbers of FE trials during training. In Experiment 1, subjects received 100% FE trials, 67% FE trials, or only choice trials. Pigeons in the two groups that had FE trials developed extreme preference for the signaled suboptimal alternative over the unsignaled optimal alternative, while pigeons that had no FE trials showed pronounced individual differences. Experiment 2 compared 10% and 90% FE trials. When neither alternative signaled trial outcomes, both groups of subjects strongly preferred the optimal alternative. When the suboptimal alternative provided differential signals, the subjects in the 90% FE group developed strong preference for the suboptimal alternative and subjects in the 10% FE group maintained preference for the optimal alternative. The results of both experiments demonstrate that FE trials can have substantial effects on the development of preference in the suboptimal choice task., (© 2022. The Psychonomic Society, Inc.)

Vegetated land areas play a significant role in determining the fate of carbon (C) in the global C cycle. Riparian buffer vegetation is primarily implemented for water quality purposes as they attenuate pollutants from immediately adjacent croplands before reaching freashwater systems. However, their prevailing conditions may sometimes promote the production and subsequent emissions of soil carbon dioxide (CO 2 ). Despite this, the understanding of soil CO 2 emissions from riparian buffer vegetation and a direct comparison with adjacent croplands they serve remain elusive. In order to quantify the extent of CO 2 emissions in such an agro system, we measured CO 2 emissions simultaneously with soil and environmental variables for six months in a replicated plot-scale facility comprising of maize cropping served by three vegetated riparian buffers, namely: (i) a novel grass riparian buffer; (ii) a willow riparian buffer, and; (iii) a woodland riparian buffer. These buffered treatments were compared with a no-buffer control. The woodland (322.9 ± 3.1 kg ha - 1 ) and grass (285 ± 2.7 kg ha - 1 ) riparian buffer treatments (not significant to each other) generated significantly ( p = < 0.0001 ) the largest CO 2 compared to the remainder of the treatments. Our results suggest that during maize production in general, the woodland and grass riparian buffers serving a maize crop pose a CO 2 threat. The results of the current study point to the need to consider the benefits for gaseous emissions of mitigation measures conventionally implemented for improving the sustainability of water resources., Competing Interests: Conflict of interestThe co-authors have no conflict of interest to declare., (© The Author(s) 2022.)

Purpose: Nitrous oxide (N 2 O) and methane (CH 4 ) are some of the most important greenhouse gases in the atmosphere of the 21st century. Vegetated riparian buffers are primarily implemented for their water quality functions in agroecosystems. Their location in agricultural landscapes allows them to intercept and process pollutants from adjacent agricultural land. They recycle organic matter, which increases soil carbon (C), intercept nitrogen (N)-rich runoff from adjacent croplands, and are seasonally anoxic. Thus processes producing environmentally harmful gases including N 2 O and CH 4 are promoted. Against this context, the study quantified atmospheric losses between a cropland and vegetated riparian buffers that serve it., Methods: Environmental variables and simultaneous N 2 O and CH 4 emissions were measured for a 6-month period in a replicated plot-scale facility comprising maize ( Zea mays L.). A static chamber was used to measure gas emissions. The cropping was served by three vegetated riparian buffers, namely: (i) grass riparian buffer; (ii) willow riparian buffer and; (iii) woodland riparian buffer, which were compared with a no-buffer control., Results: The no-buffer control generated the largest cumulative N 2 O emissions of 18.9 kg ha - 1 (95% confidence interval: 0.5-63.6) whilst the maize crop upslope generated the largest cumulative CH 4 emissions (5.1 ± 0.88 kg ha - 1 ). Soil N 2 O and CH 4 -based global warming potential (GWP) were lower in the willow (1223.5 ± 362.0 and 134.7 ± 74.0 kg CO 2 -eq. ha - 1 year - 1 , respectively) and woodland (1771.3 ± 800.5 and 3.4 ± 35.9 kg CO 2 -eq. ha - 1 year - 1 , respectively) riparian buffers., Conclusions: Our results suggest that in maize production and where no riparian buffer vegetation is introduced for water quality purposes (no buffer control), atmospheric CH 4 and N 2 O concerns may result., Competing Interests: Conflicts of interest/Competing interestsAuthors declared no conflicts of interest., (© The Author(s) 2022.)

Background: Eosinophilic granulomatosis with polyangiitis (EGPA), a rare vasculitis with substantial morbidity, is characterized by asthma, eosinophilia, sinusitis, pulmonary infiltrates, neuropathy, positivity for antineutrophil cytoplasmic antibody, and multiorgan vasculitis. Although treatment options previously included corticosteroids and immunosuppressants, anti-interleukin 5 therapies have gained interest in EGPA treatment. Mepolizumab was approved for and recently benralizumab was found to have safety and efficacy in EGPA., Objective: To determine the safety and efficacy of reslizumab in EGPA., Methods: In this open-label, pilot study, we evaluated the safety and efficacy of intravenous reslizumab (3 mg/kg) in EGPA in 10 subjects. Oral corticosteroid dose, adverse events, exacerbations, symptom control, disease activity, blood markers, and lung function were evaluated before, during, and after 7 monthly reslizumab treatments., Results: Reslizumab was tolerated and resulted in a significant reduction in daily oral corticosteroid (P < .05). Of the 10 subjects, 3 experienced an EGPA exacerbation during the treatment. One had a severe adverse event, requiring removal from the study., Conclusion: Yielding similar results to other anti-interleukin 5 biologic medications, reslizumab is generally a safe and effective treatment for EGPA that warrants further study., Trial Registration: ClinicalTrials.gov Identifier: NCT02947945., (Copyright © 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a vasculitis associated with significant morbidity and mortality that has historically been treated with systemic corticosteroids and immunosuppressants. The IL-5 antagonist mepolizumab was Food and Drug Administration approved in 2017 after demonstrating safety and efficacy in EGPA. We hypothesized that benralizumab, an IL-5 receptor antagonist approved for eosinophilic asthma, would demonstrate safety and efficacy in EGPA., Objectives: To determine the safety and efficacy of benralizumab in EGPA as measured by reduction in oral corticosteroid dose and EGPA exacerbations., Methods: We conducted a prospective 40-week open-label pilot study of benralizumab 30 mg administered subcutaneously in 10 patients with EGPA. Adverse events, oral corticosteroid dosing, exacerbations, and lung function were evaluated before, during, and after benralizumab treatment. Paired tests and tests derived from longitudinal models were used to compare outcome variables between phases or visits., Results: Benralizumab was well tolerated and resulted in reduction of median corticosteroid dose from 15 mg at the start to 2 mg at the end of treatment. Geometric mean corticosteroid dose was reduced from 11.6 mg during pretreatment to 6.3 mg during treatment phase. Five patients were able to achieve a dose of 0 mg. Mean annualized exacerbation rate was lowest during the treatment (1.5) compared with the pre- and posttreatment phases (4.6, P = .008 for treatment vs pre- and postphases combined)., Conclusions: Benralizumab was well tolerated, facilitated oral corticosteroid reduction, and reduced exacerbations in EGPA. Larger controlled trials are warranted to further evaluate the role of benralizumab in EGPA., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Dr. Roth reports a grant and consulting fees from C.R. Bard, Inc./Davol/Becton Dickinson (BD) during the conduct of this study. Dr. Roth also reports consulting fees (Johnson & Johnson) and stock (Miromatrix) outside of the current work. Dr. Anthone has no conflicts of interest to disclose related to this study. Dr. Anthone reports consulting fees and speaker honoraria (Becton Dickinson (BD)) outside of the current work. Dr. Selzer reports a grant from C.R. Bard, Inc./Davol/Becton Dickinson (BD) during the conduct of the study. Dr. Selzer also reports consulting fees (Cook Biotech, Inc.) outside of the current work. Dr. Poulose has no conflicts of interest to disclose related to the current study. Dr. Poulose reports salary support (Americas Hernia Society Quality Collaborative) and research support (Becton Dickinson (BD) and Advanced Medical Solutions) outside of the current work. Dr. Pierce has no conflicts of interest to disclose related to the current study. Dr. Pierce reports research support (Intuitive Surgical Solutions) outside of the current work and his spouse is a salaried employee of a medical device company (CareFusion) that falls under the overall umbrella of the parent company, Becton Dickinson (BD). Drs. Dunn, Bittner, Linn, Romanelli, and Sandler report a grant from C.R. Bard, Inc./Davol/Becton Dickinson (BD) during the conduct of the study but have nothing to disclose outside of the current work. Dr. Hope reports consulting fees and research support from C.R. Bard, Inc./Davol/Becton Dickinson (BD) during the conduct of the study. Dr. Hope also reports consulting fees, honoraria, and research support (Intuitive, W.L. Gore, and Medtronic) outside of the current work. Dr. Martindale has no conflicts of interest to disclose related to the current study. Dr. Martindale reports consulting fees (Allergan, C.R. Bard, Inc./Davol/Becton Dickinson (BD), and Nestle) and employment (OHSU) outside of the current work. Dr. Goldblatt reports a grant from C.R. Bard, Inc./Davol/Becton Dickinson (BD) during the conduct of the study. Dr. Goldblatt also reports consulting fees (W.L. Gore, Medtronic, and Allergan) and a grant (Medtronic) outside of the current work. Dr. Earle has no conflicts of interest to disclose related to the current study. Dr. Earle reports consulting fees (Becton Dickinson (BD) and Medtronic) and ownership stake/advisory board (Via Surgical) outside of the current work. Dr. Mancini has no conflicts of interest to disclose related to the current study. Dr. Mancini reports consulting fees (Stryker Endoscopy) and speakers’ fees (Gore Medical and Medtronic) outside of the current work. Dr. Greenberg reports a grant from C.R. Bard, Inc./Davol/Becton Dickinson (BD) during the conduct of the study. Dr. Greenberg also reports grants (Becton Dickinson (BD) and Medtronic), as well as course registration, travel, and lodging (Intuitive) outside of the current work. Dr. Parra-Davila has no conflicts of interest to disclose related to the current study. Dr. Parra-Davila reports consulting fees (C.R. Bard, Inc./Davol/Becton Dickinson (BD), Intuitive, Auris, Johnson & Johnson, and Titan), board membership (C.R. Bard, Inc./Davol/Becton Dickinson (BD)), and proctoring (Intuitive) outside of the current work. Dr. Deeken reports consulting fees from C.R. Bard, Inc./Davol/Becton Dickinson (BD) during the conduct of the study. Dr. Deeken also reports consulting fees from C.R. Bard, Inc./Davol/Becton Dickinson (BD), Surgical Innovation Associates, Americas Hernia Society Quality Collaborative, Colorado Therapeutics, TelaBio, and Aran Biomedical outside the submitted work, as well as grants from Ethicon, Inc. and TelaBio to support a book chapter outside the submitted work. In addition, Dr. Deeken is the owner of Covalent Bio, LLC and holds the following issued patents: 2009293001, 2334257, 2,334,257UK, 602009046407.8, 2,334,257FR, 16/043,849 and 2,737,542. Dr. Verbarg reports consulting fees from C.R. Bard, Inc./Davol/Becton Dickinson (BD) during the conduct of the study. Dr. Verbarg has no other conflict of interest to disclose outside of the current work. Drs. Salluzzo and Voeller have no conflicts of interest to disclose relative to the current study or any other work., (© 2020 The Authors. Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.)

Pigeons (n = 14) were trained in a concurrent-chains suboptimal choice procedure that tested the effect of an increased ratio requirement in the initial links. Fixed-ratio 1 and 25 conditions were manipulated within subjects in a counterbalanced order. In all conditions, distinct terminal-link stimuli on a suboptimal alternative signaled either primary reinforcement (20% of the time) or extinction (80% of the time). On an optimal alternative, two distinct terminal-link stimuli each signaled a 50% chance of primary reinforcement. Preference for the suboptimal alternative was significantly attenuated, and in some birds completely reversed, by the larger response requirement irrespective of condition order. This larger response requirement also generated a notable increase in between-subject variability. A measure of cumulative choice responding is introduced to mitigate the problems associated with traditional session averages. Ordinal predictions of some current theories of suboptimal choice are also considered in light of the results., (© 2019 Society for the Experimental Analysis of Behavior.)

This study argues that several metrics are necessary to build up a picture of yield gain and nitrogen losses for ryegrass sheep pastures. Metrics of resource use efficiency, nitrous oxide emission factor, leached and emitted nitrogen per unit product are used to encompass yield gain and losses relating to nitrogen. These metrics are calculated from field system simulations using the DAYCENT model, validated from field sensor measurements and observations relating to crop yield, fertilizer applied, ammonium in soil and nitrate in soil and water, nitrous oxide and soil moisture. Three ryegrass pastures with traditional management for sheep grazing and silage are studied. As expected, the metrics between long-term ryegrass swards in this study are not very dissimilar. Slight differences between simulations of different field systems likely result from varying soil bulk density, as revealed by a sensitivity analysis applied to DAYCENT. The field with the highest resource use efficiency was also the field with the lowest leached inorganic nitrogen per unit product, and vice versa. Field system simulation using climate projections indicates an increase in nitrogen loss to water and air, with a corresponding increase in biomass. If we simulate both nitrogen loss by leaching and by gaseous emission, we obtain a fuller picture. Under climate projections, the field with the lowest determined nitrous oxide emissions factor, had a relatively high leached nitrogen per product amongst the three fields. When management differences were investigated, the amount of nitrous oxide per unit biomass was found to be significantly higher for an annual management of grazing only, than a silage harvest plus grazing, likely relating to the increased period of livestock on pasture. This work emphasizes how several metrics validated by auto-sampled data provide a measure of nitrogen loss, efficiency and best management practise., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Our food security depends on finding a sustainable alternative to rock phosphate for fertilizer production. Furthermore, over 2 billion people worldwide are currently affected by micronutrient deficiencies, and crop concentrations of essential minerals are declining. This paper examines whether a novel multi-element fertilizer, Thallo®, can produce crop yields comparable to conventional rock phosphate derived fertilizers, and have an additional benefit of increasing essential mineral concentrations. Thallo®, produced from abattoir and recycled industrial by-products, was tested against conventional mineral fertilizers in a pot trial with wheat and grass. In soil, yields were comparable between the fertilizer types, but, in a low-nutrient substrate, Thallo® showed a yield benefit. Elemental concentrations in the plant material typically reflected the relative concentrations in the fertilizer, and Thallo® fertilized plants contained significantly more of some essential elements, such as selenium and zinc. Furthermore, concentrations of the toxic element cadmium were significantly lower in Thallo® fertilized crops. Among the fertilizers, manganese concentrations were greatest in the Thallo®, but within the fertilized plants, they were greatest under the mineral fertilizer, showing the complexity of assessing whether nutrients will be taken up by crops. In summary, fertilizers from livestock waste have the potential to improve wheat and grass concentrations of essential elements while maintaining yields., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Elemental Digest Systems, who manufacture Thallo® fertilizer, funded the experimental work and the time of Robert Dunn. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Pigeons chose between two options on a concurrent-chains task with a single response requirement in the initial link. The suboptimal option ended with food 20% of the time whereas the optimal option ended with food 80% of the time. During a Sig-Both condition, terminal-link stimuli on both options signaled whether or not food would occur. During a Sig-Sub condition, terminal-link stimuli on the suboptimal option provided differential signals, but stimuli on the optimal option did not differentially signal the food and no food outcomes. Initial-link choices revealed a clear preference for the optimal option in the Sig-Both condition, but preference shifted toward suboptimality in the Sig-Sub condition. These findings show that pigeon suboptimal choice is not singularly driven by signal value, as has been suggested, but also by reinforcer frequency., (© 2018 Society for the Experimental Analysis of Behavior.)

Background: Long-term resorbable mesh represents a promising technology for complex ventral and incisional hernia repair (VIHR). Preclinical studies indicate that poly-4-hydroxybutyrate (P4HB) resorbable mesh supports strength restoration of the abdominal wall. This study evaluated outcomes of high-risk subjects undergoing VIHR with P4HB mesh., Methods: This was a prospective, multi-institutional study of subjects undergoing retrorectus or onlay VIHR. Inclusion criteria were CDC Class I, defect 10-350 cm 2 , ≤ 3 prior repairs, and ≥ 1 high-risk criteria (obesity (BMI: 30-40 kg/m 2 ), active smoker, COPD, diabetes, immunosuppression, coronary artery disease, chronic corticosteroid use, hypoalbuminemia, advanced age, and renal insufficiency). Physical exam and/or quality of life surveys were performed at regular intervals through 18 months (to date) with longer-term, 36-month follow-up ongoing., Results: One hundred and twenty-one subjects (46M, 75F) with an age of 54.7 ± 12.0 years and BMI of 32.2 ± 4.5 kg/m 2 (mean ± SD), underwent VIHR. Comorbidities included the following: obesity (n = 95, 78.5%), hypertension (n = 72, 59.5%), cardiovascular disease (n = 42, 34.7%), diabetes (n = 40, 33.1%), COPD (n = 34, 28.1%), malignancy (n = 30, 24.8%), active smoker (n = 28, 23.1%), immunosuppression (n = 10, 8.3%), chronic corticosteroid use (n = 6, 5.0%), advanced age (n = 6, 5.0%), hypoalbuminemia (n = 3, 2.5%), and renal insufficiency (n = 1, 0.8%). Hernia types included the following: primary ventral (n = 17, 14%), primary incisional (n = 54, 45%), recurrent ventral (n = 15, 12%), and recurrent incisional hernia (n = 35, 29%). Defect and mesh size were 115.7 ± 80.6 and 580.9 ± 216.1 cm 2 (mean ± SD), respectively. Repair types included the following: retrorectus (n = 43, 36%), retrorectus with additional myofascial release (n = 45, 37%), onlay (n = 24, 20%), and onlay with additional myofascial release (n = 8, 7%). 95 (79%) subjects completed 18-month follow-up to date. Postoperative wound infection, seroma requiring intervention, and hernia recurrence occurred in 11 (9%), 7 (6%), and 11 (9%) subjects, respectively., Conclusions: High-risk VIHR with P4HB mesh demonstrated positive outcomes and low incidence of hernia recurrence at 18 months. Longer-term 36-month follow-up is ongoing.

In this study, we evaluated the ability of the SPACSYS model to simulate water run-off, soil moisture, N 2 O fluxes and grass growth using data generated from a field of the North Wyke Farm Platform. The field-scale model is adapted via a linked and grid-based approach (grid-to-grid) to account for not only temporal dynamics but also the within-field spatial variation in these key ecosystem indicators. Spatial variability in nutrient and water presence at the field-scale is a key source of uncertainty when quantifying nutrient cycling and water movement in an agricultural system. Results demonstrated that the new spatially distributed version of SPACSYS provided a worthy improvement in accuracy over the standard (single-point) version for biomass productivity. No difference in model prediction performance was observed for water run-off, reflecting the closed-system nature of this variable. Similarly, no difference in model prediction performance was found for N 2 O fluxes, but here the N 2 O predictions were noticeably poor in both cases. Further developmental work, informed by this study's findings, is proposed to improve model predictions for N 2 O. Soil moisture results with the spatially distributed version appeared promising but this promise could not be objectively verified.

Elderly asthmatics are at a higher risk for morbidity and mortality from their asthma than younger patients. There are important age-related physiologic and immunologic changes that complicate the presentation, diagnosis, and management of asthma in the aged population. Evidence suggests that elderly asthmatics are more likely to be underdiagnosed and undertreated. Additionally, elderly patients with asthma have highest rates of morbidity and mortality from their disease than younger patients. The underlying airway inflammation of asthma in this age group likely differs from younger patients and is felt to be non-type 2 mediated. While elderly patients are underrepresented in clinical trials, subgroup analysis of large clinical trials suggests they may be less likely to respond to traditional asthma therapies (ie, corticosteroids). As the armamentarium of pharmacologic asthma therapies expands, it will be critical to include elderly asthmatics in large clinical trials so that therapy may be better tailored to this at-risk and growing population., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Pigeons and other animals sometimes deviate from optimal choice behavior when given informative signals for delayed outcomes. For example, when pigeons are given a choice between an alternative that always leads to food after a delay and an alternative that leads to food only half of the time after a delay, preference changes dramatically depending on whether the stimuli during the delays are correlated with (signal) the outcomes or not. With signaled outcomes, pigeons show a much greater preference for the suboptimal alternative than with unsignaled outcomes. Key variables and research findings related to this phenomenon are reviewed, including the effects of durations of the choice and delay periods, probability of reinforcement, and gaps in the signal. We interpret the available evidence as reflecting a preference induced by signals for good news in a context of uncertainty. Other explanations are briefly summarized and compared., (© 2016 Society for the Experimental Analysis of Behavior.)

Pigeons chose between an (optimal) alternative that sometimes provided food after a 10-s delay and other times after a 40-s delay and another (suboptimal) alternative that sometimes provided food after 10 s but other times no food after 40 s. When outcomes were not signaled during the delays, pigeons strongly preferred the optimal alternative. When outcomes were signaled, choices of the suboptimal alternative increased and most pigeons preferred the alternative that provided no food after the long delay despite the cost in terms of obtained food. The pattern of results was similar whether the short delays occurred on 25% or 50% of the trials. Shortening the 40-s delay to food sharply reduced suboptimal choices, but shortening the delay to no food had little effect. The results suggest that a signaled delay to no food does not punish responding in probabilistic choice procedures. The findings are discussed in terms of conditioned reinforcement by signals for good news., (© Society for the Experimental Analysis of Behavior.)

Background: Seroma formation is a well-recognized complication associated with many operative procedures. Despite its ubiquity, a lack of definitive scientific understanding of the etiology, natural history, and biochemistry of seromas remains. We endeavored to create and examine seromas in a rat model in the setting of commonly used biologic implants and to examine the role of quilting sutures/mechanical fixation in mitigating seroma development., Methods: Female Sprague-Dawley rats were assigned to either Quilting or Nonquilting groups then subdivided into one of 3 porcine dermal implant groups (Permacol Surgical Implant, Strattice Reconstructive Tissue Matrix, or XCM Biologic Tissue Matrix) or control group. A 5-cm midline back incision was made, the skin reflected and the latissimus dorsi muscle resected bilaterally. Implants were sutured into the surgical bed using a running suture. The skin of nonquilted rats was closed with a running subcuticular suture. Quilted rats underwent placement of absorbable quilting sutures spaced 2 cm apart between the skin and underlying implant or muscle before skin closure. Postoperatively, rats were monitored for seroma formation with fluid aspirated as needed. At 28 or 90 days, rats were euthanized. Seroma and implants were examined grossly and under light microscopy., Results: Of nonquilted rats, 42/54 (78%) developed seromas compared with 19/46 (41%) of quilted rats (P < 0.05), defined by bursa cavity present at necropsy. When a biologic implant was present, 28/35 (80%) of nonquilted rats developed seromas compared with 12/33 (36%) of quilted rats (P < 0.05). In the control group, 14/19 (74%) of nonquilted rats developed seromas compared with 7/13 (54%) of quilted rats. This difference was not statistically significant. Bursa presence was confirmed histologically in all cases, with no difference in bursa character seen between groups., Conclusions: This study confirms a reliable rat model of seroma formation, with most of the rats exhibiting at least subclinical seromas. There was no difference in seroma formation rate in the presence of biologic implants, and no differences in bursa character between implants. Mechanical fixation with quilting sutures decreased seroma rate significantly in all subgroups. All rats with seromas at necropsy had histological evidence of a bursa with no difference in appearance between groups.

Rationale: Age and sex are associated with differences in asthma prevalence and morbidity., Objectives: To determine if age and sex associate with distinct phenotypes and a variable response to therapy in subjects with mild to moderate asthma., Methods: We used Asthma Clinical Research Network data to determine the impact of age and sex on phenotypes and treatment failures among subjects participating in 10 trials from 1993 to 2003., Measurements and Main Results: A total of 1,200 subjects were identified (median age, 30.4 yr; male, 520 [43.3%]; female, 680 [56.7%]) and analyzed. A higher proportion of subjects greater than or equal to 30 years old experienced treatment failures (17.3% vs. 10.3%; odds ratio [OR], 1.82; confidence interval [CI], 1.30-2.54; P < 0.001), and rates increased proportionally with increasing age older than 30 across the cohort (OR per yr, 1.02 [CI, 1.01-1.04]; OR per 5 yr, 1.13 [CI, 1.04-1.22]; P < 0.001). Lower lung function and longer duration of asthma were associated with a higher risk of treatment failures. A higher proportion of subjects greater than or equal to 30 years old receiving controller therapy experienced treatment failures. When stratified by specific therapy, treatment failures increased consistently for every year older than age 30 in subjects on inhaled corticosteroids (OR per year, 1.03; CI, 1.01-1.07). Females had a slightly higher FEV1 % predicted (84.5% vs. 81.1%; P < 0.001) but similar asthma control measures. There was not a statistically significant difference in treatment failures between females and males (15.2% vs. 11.7%; P = 0.088)., Conclusions: Older age is associated with an increased risk of treatment failure, particularly in subjects taking inhaled corticosteroids. There was no significant difference in treatment failures between sexes.

We recently reported results that erythropoiesis-stimulating agent (ESA)-related thrombotic toxicities in preclinical species were not solely dependent on a high hematocrit (HCT) but also associated with increased ESA dose level, dose frequency, and dosing duration. In this article, we conclude that sequelae of an increased magnitude of ESA-stimulated erythropoiesis potentially contributed to thrombosis in the highest ESA dose groups. The results were obtained from two investigative studies we conducted in Sprague-Dawley rats administered a low (no thrombotic toxicities) or high (with thrombotic toxicities) dose level of a hyperglycosylated analog of recombinant human erythropoietin (AMG 114), 3 times weekly for up to 9 days or for 1 month. Despite similarly increased HCT at both dose levels, animals in the high-dose group had an increased magnitude of erythropoiesis measured by spleen weights, splenic erythropoiesis, and circulating reticulocytes. Resulting prothrombotic risk factors identified predominantly or uniquely in the high-dose group were higher numbers of immature reticulocytes and nucleated red blood cells in circulation, severe functional iron deficiency, and increased intravascular destruction of iron-deficient reticulocyte/red blood cells. No thrombotic events were detected in rats dosed up to 9 days suggesting a sustained high HCT is a requisite cofactor for development of ESA-related thrombotic toxicities.

We previously reported an increased incidence of thrombotic toxicities in Sprague-Dawley rats administered the highest dose level of a hyperglycosylated analog of recombinant human erythropoietin (AMG 114) for 1 month as not solely dependent on high hematocrit (HCT). Thereafter, we identified increased erythropoiesis as a prothrombotic risk factor increased in the AMG 114 high-dose group with thrombotic toxicities, compared to a low-dose group with no toxicities but similar HCT. Here, we identified pleiotropic cytokines as prothrombotic factors associated with AMG 114 dose level. Before a high HCT was achieved, rats in the AMG 114 high, but not the low-dose group, had imbalanced hemostasis (increased von Willebrand factor and prothrombin time, decreased antithrombin III) coexistent with cytokines implicated in thrombosis: monocyte chemotactic protein 1 (MCP-1), MCP-3, tissue inhibitor of metalloproteinases 1, macrophage inhibitory protein-2, oncostatin M, T-cell-specific protein, stem cell factor, vascular endothelial growth factor, and interleukin-11. While no unique pathway to erythropoiesis stimulating agent-related thrombosis was identified, cytokines associated with increased erythropoiesis contributed to a prothrombotic intravascular environment in the AMG 114 high-dose group, but not in lower dose groups with a similar high HCT.

We conducted a retrospective analysis of publicly available preclinical toxicology studies with erythropoiesis-stimulating agents (ESAs) to examine common adverse events in rats, Beagle dogs, and cynomolgus monkeys. Mortality and/or thrombotic events were reported sporadically in a subset of studies and attributed to the high hematocrit (HCT) achieved in the animals. However, similarly high HCT was achieved in both high-dose and low-dose groups, but there were no reported adverse events in the low-dose group suggesting HCT was not the sole contributing factor leading to toxicity. Our analysis indicated that increased dose, dose frequency, and dosing duration in addition to high HCT contributed to mortality and thrombosis. To further evaluate this relationship, the incidence of toxicities was compared in rats administered an experimental hyperglycosylated analog of recombinant human erythropoietin (AMG 114) at varying dosing schedules in 1-month toxicity studies. The incidence of mortality and thrombotic events increased in higher dose groups and when dosed more frequently, despite a similarly high HCT in all animals. The results from the investigative study and retrospective analysis demonstrate that ESA-related toxicities in preclinical species are associated with dose level, dose frequency, and dosing duration, and not solely dependent upon a high HCT.

The purpose of this primer is to provide the clinical surgeon with a survey overview of the basic biochemistry of collagen and the methods and rationale of collagen cross-linking in the processing and preparation of bioprosthetics for surgical implantation. The author highlights the critical biologic factors, such as strength over time, integration, and rate, and type of remodeling, that are to an extent controllable by the cross-linking of collagen tissues so that clinicians may be better capable of understanding differences among the devices, which may be more applicable to their clinical indications.

Purpose: The purpose of this study was to compare inflammatory responses, tissue integration, and strength of the acellular dermal collagen matrices AlloDerm(®)* Regenerative Tissue Matrix, Permacol™**Surgical Implant (Permacol), and CollaMend™*** Implant in a rat model for ventral hernia repair., Methods: Rats were randomized into four groups and abdominal wall defects repaired with an inlay graft of AlloDerm, Permacol, or CollaMend. Rats were sacrificed at six time points and the defect area was removed and analyzed for tissue integration and physical strength., Results: Variable cell infiltration was seen for the three implant groups. At of the all time points examined, cellular infiltration was most rapid in the AlloDerm implants and slowest for CollaMend. At 14 days, significant cell infiltration along with putative blood vessel formation was observed for AlloDerm, while Permacol implants exhibited a moderate level of infiltration. Very few cells penetrated CollaMend implants at 2 weeks. Cells had reached the center of the Permacol implants by 1 month, whereas CollaMend implants were encapsulated with a loose coat of disconnected cells, with very few cells infiltrating past the surface. At 6 months, AlloDerm and Permacol had evidence of cell penetration throughout the implants, while the CollaMend samples exhibited limited infiltration. Animals for each implant developed seromas: AlloDerm 40%, Permacol 33%, and CollaMend 83%. Mechanical testing revealed that AlloDerm at 6 months showed the lowest tensile strength, CollaMend the highest, and Permacol an intermediate level., Conclusions: The three biologics exhibited different patterns and rates of cellular and vascular permeation in our rat model. AlloDerm implants exhibited the most rapid and extensive cellular infiltration, followed by Permacol. However, on gross examination, the AlloDerm implants thinned significantly by 6 months. In contrast, the Permacol and CollaMend implants appeared to be largely intact.

Hybrid organisms may fail to develop, be sterile or they may be more vigorous than either of the parents. Examples of hybrid vigour or hybrid necrosis in the F1 are often not inherited stably in subsequent generations if they are associated with overdominance. There can also be transgressive phenotypes that are inherited stably in these later generations, but the underlying mechanisms are not well understood. Here we have investigated the possibility that stable transgressive phenotypes in the progeny of crosses between cultivated tomato (Solanum lycopersicum cv. M82) and a wild relative (Solanum pennellii, accession LA716) are associated with micro or small interfering(si) RNAs. We identified loci from which these small(s)RNAs were more abundant in hybrids than in either parent and we show that accumulation of such transgressive sRNAs correlated with suppression of the corresponding target genes. In one instance this effect was associated with hypermethylation of the corresponding genomic DNA. Our results illustrate a potential role of transgressive sRNAs in plant breeding and in natural evolution with wild plants.

Background: Plastic surgeons are faced with increasing numbers of patients presenting for insurance-covered skin excision procedures following bariatric surgery. Panniculectomy for symptomatic relief of rashes is commonly performed, but an isolated infraumbilical amputation-type panniculectomy is a highly unaesthetic procedure, leaving many patients deeply dissatisfied. It may be also fraught with complications due to large incisions and potential for dead-space. In these patients, many surgeons avoid the fleur-de-lis panniculectomy, despite the body contour aesthetic advantage, because of increased time, more scarring, and a perceived increase in complications., Methods: This is a retrospective chart review of 130 consecutive postbariatric surgery patients who had panniculectomy over a 2-year period at our institution., Results: A total of 30 patients underwent a traditional panniculectomy and 100 patients had a fleur-de-lis panniculectomy. Mean weight loss from bariatric surgery to panniculectomy was 58.2 kg, with an average body mass index (BMI) of 30. Fifty-seven patients had additional procedures performed at the time of panniculectomy. Twenty-two patients (17%) had complications, with 5 in the traditional group (17%) and 17 in the fleur-de-lis group (17%) (P = 1.0). Six males (40%) had more complications compared with 18 females (15.7%) (P = 0.034). Patients with BMI <30 had 10 complications compared with patients with BMI ≥30 had 15 complications., Conclusions: There are many benefits of fleur-de-lis over traditional panniculectomy, even for medical necessity cases. There is limited undermining of tissue which minimizes/eliminates skin necrosis. Our experience with primarily fleur-de-lis panniculectomies shows a complication rate lower than most published data. Fleur-de-lis potentially creates a better symptom correction and cosmetic outcome by resecting maximal skin in both vertical and horizontal directions. These findings must be balanced against a potentially longer operation.

Background: The adductor magnus musculocutaneous perforator flap is a medial thigh flap whose utility is often overshadowed by that of its anatomic neighbor, the gracilis flap. It has a large, reliable pedicle and associated skin paddle. Few reports have been published describing the use of this flap as a local or free tissue transfer. The purpose of this study is to revisit and further characterize the anatomy of this extremely versatile yet underutilized flap., Materials/methods: A total of 13 cadavers (n = 26 thighs) were dissected to identify the musculocutaneous perforators that supply the skin of the posteriomedial thigh. The vascular anatomy was studied using multiple modalities. Based on the anatomic data, a local V-Y advancement flap was designed. A total of 8 patients (n = 10 flaps) underwent reconstruction of locoregional defects., Results: Our anatomic studies confirmed the presence of multiple parallel musculocutaneous perforators that travel through the adductor magnus muscle and course obliquely in a posterior-inferior direction. We found that the primary perforator is reliably found approximately 8 cm distal to the groin crease and 2 cm posterior to the posterior border of the gracilis muscle. We discovered that it is consistently accompanied by a separate perforator located 2 cm distally. Minimal dissection into the muscle revealed a Y-configuration of these 2 perforators. This configuration was present in 100% of the cadaveric dissections and is supplied by the first medial branch of the profunda femoris artery. Computed tomography angiograms depicted vascular arborization of the perforators supplying the flap. Clinical experience showed that complete flap survival was achieved in all of the cases., Conclusion: The adductor magnus perforator flap is a reliable flap that offers robust blood supply, through a consistent vascular pedicle, to an extensive skin territory. Our anatomic studies revealed the consistent presence of 2 proximal perforators in the medial thigh that are linked by an intramuscular Y-configuration that provides enhanced blood supply to a local V-Y advancement flap design. The location of the skin paddle on the proximal medial thigh allows for minimal donor-site morbidity as it can be closed primarily with a V-Y advancement flap design, obviating the need for skin grafting.

Frontal sinus fractures have traditionally been repaired through a bicoronal approach. This incision provides a wide exposure, but is not without complications, particularly in the patient with or at risk for hairline recession. We present a series of 15 patients who underwent open reduction and internal fixation of anterior table frontal sinus fractures through a frontalis rhytid forehead incision and their results based on the scar appearance, forehead contour, frontalis function, sensation and fracture reduction. Paresthesias cranial to the incision in the supraorbital or supratrochlear distribution were noted in 12 of the 15 patients with resolution in all except 1 patient who did not regain sensation at 4 months follow-up. In all patients, satisfactory forehead contour and fracture reduction were achieved, as were scar appearance and frontalis function at 4 months follow-up. We thus recommend this approach in the treatment of anterior table frontal sinus fractures, with special consideration for the patient with or at risk for anterior hairline recession.

Objectives: Negative pressure wound therapy (NPWT) is a useful therapy in the preparation of wounds prior to application of a split-thickness skin graft (STSG) both "pregraft" and "postgraft" on top of the STSG. Customarily, a foam-based NPWT has been used, but gauze-based therapy is finding an increasing use. Gauze is easy to apply and forgiving of complicated wound geometries so it can be an ideal material in this indication. The aim of this study was to quantitatively assess the clinical efficacy of gauze-based NPWT as an adjunctive therapy to STSG procedures., Methods: A prospective, noncomparative, multicenter evaluation was carried out to assess the performance of gauze-based NPWT. Twenty-one patients had NPWT applied prior to definitive closure by STSG or flap techniques (pregraft group). A further 21 patients underwent an STSG procedure and had gauze-based NPWT placed immediately on top of the STSG (postgraft group). Negative pressure was applied at -80 mm Hg., Results: In the pregraft group, NPWT was used for a median of 12 days. Improvement in quality of wound bed with decreased nonviable tissue (from 20% to 0% median wound area) and increased granulation tissue (from 20% to 90% median wound area) was observed. In the postgraft group, median duration of therapy was 5 days at which point median percentage skin graft-take was 96%., Conclusions: Gauze-based NPWT appears to be an effective addition to the care and management of wounds intended for definitive closure by STSG.

The fibula flap is commonly used to reconstruct the tibia. This has risk of postoperative fracture despite long-term non-weight bearing. A flap using noncircumferential distal femur is proposed. This study is to determine the circumference of femur required to produce greater strength than the fibular flap. Femurs and fibulas were harvested from eight cadavers. The structural strength of fibula and femur flaps was assessed using three-point bend. Compression testing was performed on osteotomized and whole femurs to assess donor site morbidity. The 35% flap (mean maximum force at fracture 869 N) was not significantly stronger than the fibula flap (626 N; P > 0.05). The 40% flap (1225 N) was significantly stronger than the fibula flap ( P < 0.01). There was no significant difference between forces at fracture for whole femurs (3978 N), femurs with 35% osteotomies (3604 N), and femurs with 40% osteotomies (3493 N; P = 0.87). Change occurred in the fracture pattern of femurs following osteotomies. Whole femurs consistently fractured at the femoral neck, and osteotomized femurs consistently fractured obliquely from the osteotomy. A flap consisting of 40% of the circumference of the distal femur exceeds the structural strength of the fibular flap. Taking such a flap changes the femur's structural integrity; fixation may be prudent following harvest., ((c) Thieme Medical Publishers.)

Argonaute (AGO) effectors of RNA silencing bind small RNA (sRNA) molecules and mediate mRNA cleavage, translational repression, or epigenetic DNA modification. In many organisms, these targeting mechanisms are devolved to different products of AGO multigene families. To investigate the basis of AGO functional diversification, we characterized three closely related Arabidopsis thaliana AGOs (AGO4, AGO6, and AGO9) implicated in RNA-directed DNA methylation. All three AGOs bound 5' adenosine 24-nucleotide sRNAs, but each exhibited different preferences for sRNAs from different heterochromatin-associated loci. This difference was reduced when AGO6 and AGO9 were expressed from the AGO4 promoter, indicating that the functional diversification was partially due to differential expression of the corresponding genes. However, the AGO4-directed pattern of sRNA accumulation and DNA methylation was not fully recapitulated with AGO6 or AGO9 expressed from the AGO4 promoter. Here, we show that sRNA length and 5' nucleotide do not account for the observed functional diversification of these AGOs. Instead, the selectivity of sRNA binding is determined by the coincident expression of the AGO and sRNA-generating loci, and epigenetic modification is influenced by interactions between the AGO protein and the different target loci. These findings highlight the importance of tissue specificity and AGO-associated proteins in influencing epigenetic modifications.