Modular variation, whereby the relative degree of connectivity varies within a system, is thought to evolve through a process of selection that favors the integration of certain traits and the ...decoupling of others. In this way, modularity may facilitate the pace of evolution and determine evolvability. Alternatively, conserved patterns of modularity may act to constrain the rate and direction of evolution by preventing certain functions from evolving. A comprehensive understanding of the potential interplay between these phenomena will require knowledge of the inheritance and the genetic basis of modularity. Here we explore these ideas in the cichlid mandible by investigating patterns of modularity at the clade and species levels and through the introduction of a new approach, the individual level. Specifically, we assessed patterns of covariation in Lake Malawi cichlid species that employ alternate “biting” and “suction-feeding” modes of feeding and in a hybrid cross between these two ecotypes. Across the suction-feeding clade, patterns of modularity were largely conserved and reflected a functionally based pattern. In contrast, the biting species displayed a pattern of modularity that more closely matched developmental modules. The pattern of modularity present in our F2 population was very similar to the pattern exhibited by the biter, suggesting a role for dominant inheritance. We demonstrate that our individual-level metric of modularity (IMM) is a valid quantitative trait that has a nonlinear relationship with shape. IMMs for each model were used as quantitative characters to map quantitative trait loci (QTL) that underlie modularity. Our QTL analysis offers new insights into the genetic basis of modularity in these fishes that may eventually lead to the discovery of the genetic processes that delineate particular modules. In all, our findings suggest that modularity is both a constraining and an evolvable force in cichlid evolution, as distinct patterns occur between species and variation exists among individuals.
Many central questions in ecology and evolutionary biology require characterizing phenotypes that change with time and environmental conditions. Such traits are inherently functions, and new ...‘function-valued’ methods use the order, spacing, and functional nature of the data typically ignored by traditional univariate and multivariate analyses. These rapidly developing methods account for the continuous change in traits of interest in response to other variables, and are superior to traditional summary-based analyses for growth trajectories, morphological shapes, and environmentally sensitive phenotypes. Here, we explain how function-valued methods make flexible use of data and lead to new biological insights. These approaches frequently offer enhanced statistical power, a natural basis of interpretation, and are applicable to many existing data sets. We also illustrate applications of function-valued methods to address ecological, evolutionary, and behavioral hypotheses, and highlight future directions.
Overactive bladder is a composite of lower urinary tract storage symptoms. Pharmacological treatment is widely employed despite markedly modest efficacy data, adverse effects, and costs for the ...health system.
To determine the 12-month efficacy of an intervention delivered by GPs on mirabegron revision and, if appropriate, discontinuation of treatment.
Multicentre, quasi-experimental study in Barcelona (Catalonia), Spain.
Two groups composed of 17 intervention and 34 control practices were formed. The follow-up period was 12 months, from 1 January to 31 December 2017. A structured intervention was designed consisting of initiatives with GPs and urology/gynaecology specialists. The primary outcome was mirabegron use at 12 months.
Of the 1932 patients, a significant discontinuation in treatment was observed at 12 months' follow-up in the intervention group (IG) (
= 433 out of 762, 56.8%), in contrast with the control one (CG) (
= 484 out of 1170, 41.4%) (
<0.001). There was also a reduced incorporation of new treatments in the IG (
= 214 out of 762, 28.1%) compared with the CG (
= 595 out of 1170, 50.9%) (
<0.001). In relation to patients with treatment at the beginning and end of the period, there was a decrease of 219 (28.7%) patients in the IG and an increase of 111 (9.5%) in the CG (
<0.001).
The structured intervention showed optimisation in the use of mirabegron. When considering discontinuation it is necessary to provide clear data on the benefits and/or risks for patients and their caregivers, as such information is a precondition for shared decision making.
Sixty cases of uterine adenomatoid tumors (ATs) are reported. All except four were incidental findings in hysterectomy specimens, three of these being discovered preoperatively as large multicystic ...tumors. ATs were classified into two distinctive macroscopic patterns: small, solid tumors and large, cystic ones. The 56 small, solid ATs ranged from 0.2 to 3.5 cm, (average 2.1 cm); 48 were nodular and 8 diffuse. The four large, cystic tumors ranged from 7 to 10 cm. Inflammation occurred in 65% of the tumors, and a smooth muscle reaction, identified by an increased Ki-67 index, was present in most cases. Both types were histologically similar except for the presence of short papillae in cystic tumors, which also showed serosal involvement. Both were immunoreactive for cytokeratins, calretinin, HMBE-1, and vimentin. Estrogen and progesterone nuclear receptors and EMA were negative. These tumors represent a spectrum ranging from small and solid to large and cystic ATs in the female genital tract, whereas outside the genital tract they are morphologically similar to multicystic mesothelioma. Although a reactive origin for ATs often seems plausible, especially when inflammation is present, their neoplastic nature should not be ignored.
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