Perils and pitfalls of mixed-effects regression models in biology

This is the final version. Available on open access from PeerJ via the DOI in this recordData Availability: The following information was supplied regarding data availability: The R code used to conduct all simulations in the paper is available in the Supplemental Files.Biological systems, at all scales of organisation from nucleic acids to ecosystems, are inherently complex and variable. Biologists therefore use statistical analyses to detect signal among this systemic noise. Statistical models infer trends, find functional relationships and detect differences that exist among groups or are caused by experimental manipulations. They also use statistical relationships to help predict uncertain futures. All branches of the biological sciences now embrace the possibilities of mixed-effects modelling and its flexible toolkit for partitioning noise and signal. The mixed-effects model is not, however, a panacea for poor experimental design, and should be used with caution when inferring or deducing the importance of both fixed and random effects. Here we describe a selection of the perils and pitfalls that are widespread in the biological literature, but can be avoided by careful reflection, modelling and model-checking. We focus on situations where incautious modelling risks exposure to these pitfalls and the drawing of incorrect conclusions. Our stance is that statements of significance, information content or credibility all have their place in biological research, as long as these statements are cautious and well-informed by checks on the validity of assumptions. Our intention is to reveal potential perils and pitfalls in mixed model estimation so that researchers can use these powerful approaches with greater awareness and confidence. Our examples are ecological, but translate easily to all branches of biology.University of Exete

The changing landscape of professional practice in podiatry, lessons to be learned from other professions about the barriers to change – a narrative review

Background: The delivery of healthcare is changing and aligned with this, the podiatry profession continues to change with evidence informed practice and extending roles. As change is now a constant, this gives clinicians the opportunity to take ownership to drive that change forward. In some cases, practitioners and their teams have done so, where others have been reluctant to embrace change. It is not clear to what extent good practice is being shared, whether interventions to bring about change have been successful, or what barriers exist that have prevented change from occurring. The aim of this article is to explore the barriers to changing professional practice and what lessons podiatry can learn from other health care professions. Main body: A literature search was carried out which informed a narrative review of the findings. Eligible papers had to (1) examine the barriers to change strategies, (2) explore knowledge, attitudes and roles during change interventions, (3) explore how the patients/service users contribute to the change process (4) include studies from predominantly primary care in developed countries. Ninety-two papers were included in the final review. Four papers included change interventions involving podiatrists. The barriers influencing change were synthesised into three themes (1) the organisational context, (2) the awareness, knowledge and attitudes of the professional, (3) the patient as a service user and consumer. Conclusions: Minimal evidence exists about the barriers to changing professional practice in podiatry. However, there is substantial literature on barriers and implementation strategies aimed at changing professional practices in other health professions. Change in practice is often resisted at an organisational, professional or service user level. The limited literature about change in podiatry, a rapidly changing healthcare workforce and the wide range of contexts that podiatrists work, highlights the need to improve the ways in which podiatrists can share successful attempts to change practice

Implicated reading: a method for reflecting on practice

This paper evaluates an attempt by the author to operationalise the theory of reflective practice within the context of initial teacher education. Whilst an integral element of many teacher education programmes, the problematic of ‘how’ to reflect on practice remains a concern. In response, and taking inspiration from the work of Deleuze and Guattari, specifically their critique of representational thought and common understandings of text, the author experiments with a method for reflecting called implicated reading. The method involves the reading of students’ lived experiences as beginning teachers (recorded in written form), against a variety of other texts. The author draws on interview data to analyse and discuss the merits of the approach. The paper concludes that the method of implicated reading has the potential to unsettle the common tendency to focus on meaning and interpretation when reflecting on events and experiences. It is argued that the student teachers involved in the project instead begin to experience reflection as a process of connectivity, rethinking pedagogy as a result

Mass Drug Administration and beyond: how can we strengthen health systems to deliver complex interventions to eliminate neglected tropical diseases?

Achieving the 2020 goals for Neglected Tropical Diseases (NTDs) requires scale-up of Mass Drug Administration (MDA) which will require long-term commitment of national and global financing partners, strengthening national capacity and, at the community level, systems to monitor and evaluate activities and impact. For some settings and diseases, MDA is not appropriate and alternative interventions are required. Operational research is necessary to identify how existing MDA networks can deliver this more complex range of interventions equitably. The final stages of the different global programmes to eliminate NTDs require eliminating foci of transmission which are likely to persist in complex and remote rural settings. Operational research is required to identify how current tools and practices might be adapted to locate and eliminate these hard-to-reach foci. Chronic disabilities caused by NTDs will persist after transmission of pathogens ceases. Development and delivery of sustainable services to reduce the NTD-related disability is an urgent public health priority. LSTM and its partners are world leaders in developing and delivering interventions to control vector-borne NTDs and malaria, particularly in hard-to-reach settings in Africa. Our experience, partnerships and research capacity allows us to serve as a hub for developing, supporting, monitoring and evaluating global programmes to eliminate NTDs

Motile cilia defects in diseases other than primary ciliary dyskinesia:The contemporary diagnostic and research role for transmission electron microscopy

Ultrastructural studies have underpinned the cell biological and clinical investigations of the varied roles of motile cilia in health and disease, with a long history since the 1950s. Recent developments from transmission electron microscopy (TEM; cryo-electron microscopy, electron tomography) have yielded higher resolution and fresh insights into the structure and function of these complex organelles. Microscopy in ciliated organisms, disease models, and in patients with ciliopathy diseases has dramatically expanded our understanding of the ubiquity, multisystem involvement, and importance of cilia in normal human development. Here, we review the importance of motile cilia ultrastructural studies in understanding the basis of diseases other than primary ciliary dyskinesia

Breathlessness and opioid prescribing in COPD in general practice: a cross-sectional, observational study.

Chronic breathlessness is a disabling syndrome, prevalent in people with advanced chronic obstructive pulmonary disease (COPD). Regular, low-dose, oral sustained-release morphine is approved in Australia to reduce symptomatic chronic breathlessness. We aimed to determine the current prescribing patterns of opioids for chronic breathlessness in COPD in Australian general practice and to define any associated patient and practitioner characteristics. Five years (2011 to 2016) of the Bettering the Evaluation and Care of Health database, an Australian national, continual, cross-sectional study of clinical care in general practice were used. The database included 100 consecutive clinical encounters from almost 1000 general practitioners annually (n=488 100 encounters). Descriptive analyses with subsequent regression models were generated. Breathlessness as a patient-defined reason for encounter was identified in 621 of 4522 encounters where COPD was managed. Opioids were prescribed in 309 of 4522 encounters where COPD was managed (6.8%; (95% CI) 6.1-7.6), of which only 17 were prescribed for breathlessness, and the rest for other conditions almost entirely related to pain. Patient age (45-64 years versus age 80+ years, OR 1.68; 1.19-2.36), Commonwealth Concession Card holders (OR 1.70; 1.23-2.34) and socioeconomic disadvantage (OR 1.30; 1.01-1.68) were associated with increased likelihood of opioid prescription at COPD encounters. The rate of opioid prescriptions rose over the 5 years of study. In primary care encounters for COPD, opioids were prescribed in 6.8% of cases, but almost never for breathlessness. These data create a baseline against which to compare changes in prescribing as the treatment of chronic breathlessness evolves

A scattering rate approach to the understanding of absorption line broadening in near-infrared AlGaN/GaN quantum wells

There has been much interest in the advancement of III-Nitride growth technology to fabricate AlGaN/GaN heterostructures for intersubband transitions (ISBTs). The large conduction band offset in these structures (up to 2 eV) allows transition energies in the near- to the far-infrared region, which have applications from telecommunications, such as in all-optical switches, to infra-red detectors for sensing and imaging. To date, ISBT electroluminescence has been elusive and absorption measurements remain an important method to verify band structure calculations. The growth quality can be inferred from the absorption spectrum, which will have line broadening with contributions that are both inhomogeneous (large-scale interface roughness, and non-parabolicity) and homogeneous (electron scattering related lifetime broadening). In the present work we calculated the contributions of various homogeneous broadening mechanisms (electron interaction with longitudinal-optical (LO) phonons, acoustic phonons, impurities and alloy disorder) to the full linewidth, and also the contribution of band non-parabolicity, which contributes to the inhomogeneous broadening. Calculations are then compared to the measured absorption spectra of several samples