How novel phenotypes evolve is challenging to imagine because traits are often underlain by numerous integrated phenotypic components, and changes to any one form can disrupt the function of the ...entire module. Yet novel phenotypes do emerge, and research on adaptive phenotypic evolution suggests that complex traits can diverge while either maintaining existing form–function relationships or through innovations that alter form–function relationships. How these alternate routes contribute to sexual signal evolution is poorly understood, despite the role of sexual signals in generating biodiversity. In Hawaiian populations of the Pacific field cricket, male song attracts both female crickets and a deadly acoustically orienting parasitoid fly. In response to this conflict between natural and sexual selection, male crickets have evolved altered wing morphologies multiple times, resulting in loss and dramatic alteration of sexual signals. More recently, we and others have observed a radical increase in sexual signal variation and the underlying morphological structures that produce song. We conducted the first combined analysis of form (wing morphology), function (emergent signal), and receiver responses to characterize novel variation, test alternative hypotheses about form–function relationships (Form–Function Continuity vs. Form–Function Decoupling), and investigate underlying mechanistic changes and fitness consequences of novel signals. We identified three sound‐producing male morphs (one previously undescribed, named “rattling”) and found that relationships between morphology and signals have been rewired (Form–Function Decoupling), rapidly and repeatedly, through the gain, loss, and alteration of morphological structures, facilitating the production of signals that exist in novel phenotypic space. By integrating across a hierarchy of phenotypes, we uncovered divergent morphs with unique solutions to the challenge of attracting mates while evading fatal parasitism.
This study examines how high-quality professional development can promote the diffusion of effective teaching strategies among teachers through collaboration. Drawing on longitudinal and sociometric ...data from a study of writing professional development in 39 schools, this study shows that teachers' participation in professional development is associated with providing more help to colleagues on instructional matters. Further, the influence of professional development on participants' instructional practice diffuses through the network of helping. These findings suggest that in addition to direct effects, spillover effects of professional development can occur through collegial interactions. Evidence presented in this study potentially helps educational leaders develop highquality professional development programs and distribute professional development participants within schools to enhance all teachers' instructional practices.
We present a detailed description of a new hadronic multiparticle production model for use in neutrino interaction simulations. Its validity spans a wide invariant mass range starting from the pion ...production threshold. This model focuses on the low invariant mass region which is probed in few-GeV neutrino interactions and is of particular importance to neutrino oscillation experiments using accelerator and atmospheric fluxes. It exhibits reasonable agreement with a wide variety of experimental data. We also describe measurements that can be made in upcoming experiments that can improve modeling in areas where uncertainties are currently large.
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The development of solid dosage forms and manufacturing processes are governed by complex physical properties of the powder and the type of pharmaceutical unit operation the ...manufacturing processes employs. Suitable powder flow properties and compactability are crucial bulk level properties for tablet manufacturing by direct compression. It is also generally agreed that small scale powder flow measurements can be useful to predict large scale production failure. In this study, predictive multilinear regression models were effectively developed from critical material properties to estimate static powder flow parameters from particle size distribution data for a single component and for binary systems. A multilinear regression model, which was successfully developed for ibuprofen, also efficiently predicted the powder flow properties for a range of batches of two other active pharmaceutical ingredients processed by the same manufacturing route. The particle size distribution also affected the compactability of ibuprofen, and the scope of this work will be extended to the development of predictive multivariate models for compactability, in a similar manner to the approach successfully applied to flow properties.
Patients and families report experiencing a multitude of harms from medical errors resulting in physical, emotional, and financial hardships. Little is known about the duration and nature of these ...harms and the type of support needed to promote patient and family healing after such events. We sought to describe the long-term impacts (LTIs) reported by patients and family members who experienced harmful medical events 5 or more years ago.
We performed a content analysis on 32 interviews originally conducted with 72 patients or family members about their views of the factors contributing to their self-reported harmful event. Interviews selected occurred 5 or more years after the harmful event and were grouped by time since event, 5 to 9 years (22 interviews) or 10 or more years (10 interviews) for analysis. We analyzed these interviews targeting spontaneous references of ongoing impacts experienced by the participants.
Participants collectively described the following four LTIs: psychological, social/behavioral, physical, and financial. Most cited psychological impacts with half-reporting ongoing anger and vivid memories. More than half reported ongoing physical impacts and one-third experienced ongoing financial impacts. Long-term social and behavioral impacts such as alterations in lifestyle, self-identity, and healthcare seeking behaviors were the most highly reported.
These patients and families experienced many profound LTIs after their harmful medical event. For some, these impacts evolved into secondary harms ongoing 10 years and more after the event. Our results draw attention to the persistent impacts patients and families may experience long after harmful events and the need for future research to understand and support affected patients and families.
The overall pharmaceutical market is changing. A more personalised medicine approach is replacing the concept of blockbuster drugs and the "one size fits all" model. The two main forces that fuel the ...growth of nano-enabled drug technologies are the low aqueous solubility of new chemical entities and the pharmaceutical market itself, as the development of novel drug delivery systems can extend the drug patent lifetime. Classical solubilisation techniques, such as salt formation and the use of cyclodextrins can only be applied to drugs with ionisable groups or specific molecular weight ranges in order to fit in the cavity of the cyclodextrin. However, drug nanonisation, or particle size reduction into the nanosize range, is a versatile technique that can be applied to a wide range of pharmaceutical compounds. Nano-drugs exhibit higher surface area per unit of volume, which leads to faster dissolution kinetics and hence potentially improved bioavailability. Marketed nano-drugs are mostly crystalline due to the improved physical stability afforded by the crystalline state whereas amorphous nano-drugs have been largely neglected in spite of generating higher saturation solubility compared to their crystalline counterparts. Due to the vast potential in the global pharmaceutical market, many technologies have been licensed to produce nano-drugs. Among them, the most successful by far is Nanocrystal(®); Technology based on wet milling methods. In this review, the main methods to generate and characterise nano-drugs are covered and also, the biopharmaceutical characteristics of the marketed nano-drugs are discussed.
Diabet. Med. 27, 203–209 (2010)
Aims Incorrect classification, diagnosis and coding of the type of diabetes may have implications for patient management and limit our ability to measure quality. The ...aim of the study was to measure the accuracy of diabetes diagnostic data and explore the scope for identifying errors.
Method We used two sets of anonymized routinely collected computer data: the pilot used Cutting out Needless Deaths Using Information Technology (CONDUIT) study data (n = 221 958), which we then validated using 100 practices from the Quality Improvement in Chronic Kidney Disease (QICKD) study (n = 760 588). We searched for contradictory diagnostic codes and also compatibility with prescription, demographic and laboratory test data. We classified errors as: misclassified—incorrect type of diabetes; misdiagnosed—where there was no evidence of diabetes; or miscoded—cases where it was difficult to infer the type of diabetes.
Results The standardized prevalence of diabetes was 5.0 and 4.0% in the CONDUIT and the QICKD data, respectively: 13.1% (n = 930) of CONDUIT and 14.8% (n = 4363) QICKD are incorrectly coded; 10.3% (n = 96) in CONDUIT and 26.2% (n = 1143) in QICKD are misclassified; nearly all of these cases are people classified with Type 1 diabetes who should be classified as Type 2. Approximately 5% of T2DM in both samples have no objective evidence to support a diagnosis of diabetes. Miscoding was present in approximately 7.8% of the CONDUIT and 6.1% of QICKD diabetes records.
Conclusions The prevalence of miscoding, misclassification and misdiagnosis of diabetes is high and there is substantial scope for further improvement in diagnosis and data quality. Algorithms which identify likely misdiagnosis, misclassification and miscoding could be used to flag cases for review.
Cardiovascular disease is the leading cause of death worldwide. It remains one of the greatest challenges to global health and will continue to dominate mortality trends in the future. Acute ...myocardial infarction results in 7.4 million deaths globally per annum. Current management strategies are centered on restoration of coronary blood flow via percutaneous coronary intervention, coronary artery bypass grafting and administration of anti-platelet agents. Such myocardial reperfusion accounts for 40–50 % of the final infarct size in most cases. Signaling transducer and activator of transcription 3 (STAT3) has been shown to have cardioprotective effects via canonical and non-canonical activation and modulation of mitochondrial and transcriptional responses. A significant body of in vitro and in vivo evidence suggests that activation of the STAT3 signal transduction pathway results in a cardio protective response to ischemia and attempts have been made to modulate this with therapeutic effect. Not only is STAT3 important for cardiomyocyte function, but it also modulates the cardiac microenvironment and communicates with cardiac fibroblasts. To this end, we here review the current evidence supporting the manipulation of STAT3 for therapeutic benefit in cardiac ischemia and identify areas for future research.
ABSTRACTBackground Few situations are as stressful for dentists as when a harmful error has occurred in their care of a patient. Embarrassment, fear of litigation, and uncertainty about what to say ...and how the patient will react can complicate the response. While most dentists are committed to responding to problems with transparency and accountability, turning these principles into practice can be difficult.Description In this article, we discuss the lessons that dentistry can learn from the field of Medicine about being more transparent with patients about care problems and aligning this transparency with broader efforts to promote a culture of safety where openness and accountability drive learning and improvement. Transparency is recognized as a precondition to a culture of safety, and has many elements including open communication with patients and families, colleagues, and organizations about problems. While fear of litigation is a frequent concern when clinicians are contemplating being open with a patient about something that went wrong, robust evidence suggests that transparency, when approached in a disciplined and thoughtful manner, can actually reduce the chances of lawsuits. Communication and Resolution Programs are structured processes that can support dentists in their response to problems in care. The Dental Patient Safety Foundation is another important resource all dentists should know about and partner with to improve their practice. We provide practical suggestions that dentists can apply to their practice now to reduce the chances of harm events happening and to be better prepared to respond effectively when harm events occur.
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