Demystifying Open Science in health psychology and behavioral medicine: a practical guide to Registered Reports and Data Notes.

Open Science practices are integral to increasing transparency, reproducibility, and accessibility of research in health psychology and behavioral medicine. Drives to facilitate Open Science practices are becoming increasingly evident in journal editorial policies, including the establishment of new paper formats such as Registered Reports and Data Notes. This paper provides: (i) an overview of the current state of Open Science policies within health psychology and behavioral medicine, (ii) a call for submissions to an Article Collection of Registered Reports and Data Notes as new paper formats within the journal of Health Psychology & Behavioral Medicine, (iii) an overview of Registered Reports and Data Notes, and (iv) practical considerations for authors and reviewers of Registered Reports and Data Notes.

Effectiveness of preoperative multimedia educational sessions on the levels of anxiety and satisfaction among women undergoing cesarean: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to explore the effectiveness of preoperative multimedia educational sessions on the levels of anxiety and satisfaction among women undergoing cesarean section (CS). The Scopus, PubMed, and Cochrane databases were searched without language limitations for eligible randomized controlled trials (RCTs) published from their inception up to October 15, 2023. A random-effect meta-analysis was conducted, and the quality of this meta-analysis was evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Seven RCTs (n = 1006 women) met the inclusion criteria. Preoperative multimedia sessions were found to significantly reduce anxiety levels (n = 6 RCTs, weighted mean difference: -3.10; 95 percent confidence intervals (CI): -4.48, -1.73; I2 = 44.24 percent, moderate certainty of evidence) compared to the control group. However, there was no significant difference between the two groups regarding women's satisfaction after surgery (n = 5 RCTs, risk ratio: 1.37; 95 percent CI: 0.76, 2.50; I2 = 98.26 percent, moderate certainty of evidence). Leave-one-out sensitivity analysis showed robustness of the outcomes. The findings of this meta-analysis suggest that providing multimedia educational programs before surgery could potentially have a beneficial effect on the levels of anxiety experienced by women undergoing CS. However, it is imperative to validate these results through larger samples and multi-centered RCTs.

Teaching open and reproducible scholarship: a critical review of the evidence base for current pedagogical methods and their outcomes.

In recent years, the scientific community has called for improvements in the credibility, robustness and reproducibility of research, characterized by increased interest and promotion of open and transparent research practices. While progress has been positive, there is a lack of consideration about how this approach can be embedded into undergraduate and postgraduate research training. Specifically, a critical overview of the literature which investigates how integrating open and reproducible science may influence student outcomes is needed. In this paper, we provide the first critical review of literature surrounding the integration of open and reproducible scholarship into teaching and learning and its associated outcomes in students. Our review highlighted how embedding open and reproducible scholarship appears to be associated with (i) students' scientific literacies (i.e. students' understanding of open research, consumption of science and the development of transferable skills); (ii) student engagement (i.e. motivation and engagement with learning, collaboration and engagement in open research) and (iii) students' attitudes towards science (i.e. trust in science and confidence in research findings). However, our review also identified a need for more robust and rigorous methods within pedagogical research, including more interventional and experimental evaluations of teaching practice. We discuss implications for teaching and learning scholarship.

Defining Pediatric Chronic Critical Illness: A Scoping Review.

OBJECTIVES: Children with chronic critical illness (CCI) are hypothesized to be a high-risk patient population with persistent multiple organ dysfunction and functional morbidities resulting in recurrent or prolonged critical care; however, it is unclear how CCI should be defined. The aim of this scoping review was to evaluate the existing literature for case definitions of pediatric CCI and case definitions of prolonged PICU admission and to explore the methodologies used to derive these definitions. DATA SOURCES: Four electronic databases (Ovid Medline, Embase, CINAHL, and Web of Science) from inception to March 3, 2021. STUDY SELECTION: We included studies that provided a specific case definition for CCI or prolonged PICU admission. Crowdsourcing was used to screen citations independently and in duplicate. A machine-learning algorithm was developed and validated using 6,284 citations assessed in duplicate by trained crowd reviewers. A hybrid of crowdsourcing and machine-learning methods was used to complete the remaining citation screening. DATA EXTRACTION: We extracted details of case definitions, study demographics, participant characteristics, and outcomes assessed. DATA SYNTHESIS: Sixty-seven studies were included. Twelve studies (18%) provided a definition for CCI that included concepts of PICU length of stay (n = 12), medical complexity or chronic conditions (n = 9), recurrent admissions (n = 9), technology dependence (n = 5), and uncertain prognosis (n = 1). Definitions were commonly referenced from another source (n = 6) or opinion-based (n = 5). The remaining 55 studies (82%) provided a definition for prolonged PICU admission, most frequently greater than or equal to 14 (n = 11) or greater than or equal to 28 days (n = 10). Most of these definitions were derived by investigator opinion (n = 24) or statistical method (n = 18). CONCLUSIONS: Pediatric CCI has been variably defined with regard to the concepts of patient complexity and chronicity of critical illness. A consensus definition is needed to advance this emerging and important area of pediatric critical care research.

Strategies to Mitigate and Treat Orthopaedic Device-Associated Infections.

Orthopaedic device implants play a crucial role in restoring functionality to patients suffering from debilitating musculoskeletal diseases or to those who have experienced traumatic injury. However, the surgical implantation of these devices carries a risk of infection, which represents a significant burden for patients and healthcare providers. This review delineates the pathogenesis of orthopaedic implant infections and the challenges that arise due to biofilm formation and the implications for treatment. It focuses on research advancements in the development of next-generation orthopaedic medical devices to mitigate against implant-related infections. Key considerations impacting the development of devices, which must often perform multiple biological and mechanical roles, are delineated. We review technologies designed to exert spatial and temporal control over antimicrobial presentation and the use of antimicrobial surfaces with intrinsic antibacterial activity. A range of measures to control bio-interfacial interactions including approaches that modify implant surface chemistry or topography to reduce the capacity of bacteria to colonise the surface, form biofilms and cause infections at the device interface and surrounding tissues are also reviewed.

Meta-Analysis on Utility of Bronchoscopy in Addition to Computed Tomography Thorax in the Investigation of Lung Cancer in Patients with Haemoptysis.

BACKGROUND: In patients with haemoptysis, many healthcare systems support bronchoscopy regardless of computed tomography (CT) findings. OBJECTIVE: This meta-analysis aimed to address whether a normal CT alone is sufficient to out-rule lung cancer in patients with haemoptysis. METHODS: A search was performed of the following databases: EBSCO (Medline), PubMed, Academic Search Complete, CINAHL, Cochrane Library, and Embase. Meta-Disc 1.4 and RevMan software were used to test for heterogeneity, risk of bias, and to summarize the test performance characteristics using forest plots and summary receiver operating characteristic (SROC) curves. SPSS was used to compare the diagnostic accuracy of CT and bronchoscopy. RESULTS: A total of 14 studies (2,960 patients) were included. The pooled sensitivities for detection of lung cancer using CT scan and bronchoscopy were 0.99 (95% CI: 0.97-1.00) and 0.84 (95% CI: 0.78-0.88), respectively. The sensitivity of CT was higher than that of bronchoscopy (p < 0.001). The pooled specificities for CT scan and bronchoscopy were 0.99 (95% CI: 0.99-1.00) and 1.00 (95% CI: 0.99-1.00), respectively. Of 2,960 patients, 257 had lung cancer (8.7%) at initial investigation. 254 of these had a CT thorax, and the CT scan was false negative in 4/255 (1.6%), with bronchoscopy only identifying one cancer with a normal CT (0.4%). CONCLUSION: CT scan showed a higher diagnostic accuracy than bronchoscopy. This study indicated that bronchoscopy offers an insignificant additional value in the investigation of lung cancer in patients with haemoptysis and a negative CT scan.

The Impact of the COVID-19 Pandemic and Associated Control Measures on the Mental Health of the General Population : A Systematic Review and Dose-Response Meta-analysis.

BACKGROUND: To what extent the COVID-19 pandemic and its containment measures influenced mental health in the general population is still unclear. PURPOSE: To assess the trajectory of mental health symptoms during the first year of the pandemic and examine dose-response relations with characteristics of the pandemic and its containment. DATA SOURCES: Relevant articles were identified from the living evidence database of the COVID-19 Open Access Project, which indexes COVID-19-related publications from MEDLINE via PubMed, Embase via Ovid, and PsycInfo. Preprint publications were not considered. STUDY SELECTION: Longitudinal studies that reported data on the general population's mental health using validated scales and that were published before 31 March 2021 were eligible. DATA EXTRACTION: An international crowd of 109 trained reviewers screened references and extracted study characteristics, participant characteristics, and symptom scores at each timepoint. Data were also included for the following country-specific variables: days since the first case of SARS-CoV-2 infection, the stringency of governmental containment measures, and the cumulative numbers of cases and deaths. DATA SYNTHESIS: In a total of 43 studies (331 628 participants), changes in symptoms of psychological distress, sleep disturbances, and mental well-being varied substantially across studies. On average, depression and anxiety symptoms worsened in the first 2 months of the pandemic (standardized mean difference at 60 days, -0.39 [95% credible interval, -0.76 to -0.03]); thereafter, the trajectories were heterogeneous. There was a linear association of worsening depression and anxiety with increasing numbers of reported cases of SARS-CoV-2 infection and increasing stringency in governmental measures. Gender, age, country, deprivation, inequalities, risk of bias, and study design did not modify these associations. LIMITATIONS: The certainty of the evidence was low because of the high risk of bias in included studies and the large amount of heterogeneity. Stringency measures and surges in cases were strongly correlated and changed over time. The observed associations should not be interpreted as causal relationships. CONCLUSION: Although an initial increase in average symptoms of depression and anxiety and an association between higher numbers of reported cases and more stringent measures were found, changes in mental health symptoms varied substantially across studies after the first 2 months of the pandemic. This suggests that different populations responded differently to the psychological stress generated by the pandemic and its containment measures. PRIMARY FUNDING SOURCE: Swiss National Science Foundation. (PROSPERO: CRD42020180049).

Diagnostic test accuracy of remote, multidomain cognitive assessment (telephone and video call) for dementia.

BACKGROUND: Remote cognitive assessments are increasingly needed to assist in the detection of cognitive disorders, but the diagnostic accuracy of telephone- and video-based cognitive screening remains unclear. OBJECTIVES: To assess the test accuracy of any multidomain cognitive test delivered remotely for the diagnosis of any form of dementia. To assess for potential differences in cognitive test scoring when using a remote platform, and where a remote screener was compared to the equivalent face-to-face test. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialized Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, LILACS, and ClinicalTrials.gov (www. CLINICALTRIALS: gov/) databases on 2 June 2021. We performed forward and backward searching of included citations. SELECTION CRITERIA: We included cross-sectional studies, where a remote, multidomain assessment was administered alongside a clinical diagnosis of dementia or equivalent face-to-face test. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed risk of bias and extracted data; a third review author moderated disagreements. Our primary analysis was the accuracy of remote assessments against a clinical diagnosis of dementia. Where data were available, we reported test accuracy as sensitivity and specificity. We did not perform quantitative meta-analysis as there were too few studies at individual test level. For those studies comparing remote versus in-person use of an equivalent screening test, if data allowed, we described correlations, reliability, differences in scores and the proportion classified as having cognitive impairment for each test. MAIN RESULTS: The review contains 31 studies (19 differing tests, 3075 participants), of which seven studies (six telephone, one video call, 756 participants) were relevant to our primary objective of describing test accuracy against a clinical diagnosis of dementia. All studies were at unclear or high risk of bias in at least one domain, but were low risk in applicability to the review question. Overall, sensitivity of remote tools varied with values between 26% and 100%, and specificity between 65% and 100%, with no clearly superior test. Across the 24 papers comparing equivalent remote and in-person tests (14 telephone, 10 video call), agreement between tests was good, but rarely perfect (correlation coefficient range: 0.48 to 0.98). AUTHORS' CONCLUSIONS: Despite the common and increasing use of remote cognitive assessment, supporting evidence on test accuracy is limited. Available data do not allow us to suggest a preferred test. Remote testing is complex, and this is reflected in the heterogeneity seen in tests used, their application, and their analysis. More research is needed to describe accuracy of contemporary approaches to remote cognitive assessment. While data comparing remote and in-person use of a test were reassuring, thresholds and scoring rules derived from in-person testing may not be applicable when the equivalent test is adapted for remote use.

A network of change: united action on research integrity.

The last decade has seen renewed concern within the scientific community over the reproducibility and transparency of research findings. This paper outlines some of the various responsibilities of stakeholders in addressing the systemic issues that contribute to this concern. In particular, this paper asserts that a united, joined-up approach is needed, in which all stakeholders, including researchers, universities, funders, publishers, and governments, work together to set standards of research integrity and engender scientific progress and innovation. Using two developments as examples: the adoption of Registered Reports as a discrete initiative, and the use of open data as an ongoing norm change, we discuss the importance of collaboration across stakeholders.

Roleplay as an Educational Strategy in Palliative Care: A Systematic Integrative Review.

INTRODUCTION: Simulation activities, such as roleplay, have become established in undergraduate and graduate education in several subjects of healthcare. The objective of this study was to synthesize the evidence available in the literature on the use of roleplay as an educational strategy in palliative care. METHODS: Using the method proposed by Whittemore and Knafl, this integrative systematic review was carried out based on the following guiding question: "What is the available evidence in the literature on the use of roleplay as an educational strategy in the teaching of palliative care?" The databases used for the selection of articles were the following: Web of Science, Scopus, Cochrane Library, PubMed, CINAHL, EMBASE, and LILACS. There were no limitations regarding the year of publication or language. RESULTS: The articles (n = 34) were grouped into 3 categories, according to the purpose of roleplay use: 1) Use of roleplay as an educational strategy to teach communication in palliative care; 2) Use of roleplay as an educational strategy to teach the communication of bad news, and 3) Use of roleplay as an educational strategy to teach end-of-life care. CONCLUSION: Roleplay has been employed in the teaching of palliative care in order to develop skills related to communication and to the provision of end-of-life care. These educational activities have mainly been directed to healthcare students and professionals. Future investigations should further evaluate the efficacy of this teaching strategy, based on studies with more robust designs that allow the establishment of cause-and-effect relationships.

A decade of theory as reflected in Psychological Science (2009-2019).

The dominant belief is that science progresses by testing theories and moving towards theoretical consensus. While it's implicitly assumed that psychology operates in this manner, critical discussions claim that the field suffers from a lack of cumulative theory. To examine this paradox, we analysed research published in Psychological Science from 2009-2019 (N = 2,225). We found mention of 359 theories in-text, most were referred to only once. Only 53.66% of all manuscripts included the word theory, and only 15.33% explicitly claimed to test predictions derived from theories. We interpret this to suggest that the majority of research published in this flagship journal is not driven by theory, nor can it be contributing to cumulative theory building. These data provide insight into the kinds of research psychologists are conducting and raises questions about the role of theory in the psychological sciences.

Professional characteristics and the prevalence of advance directives among palliative care professionals: A cross-sectional study.

OBJECTIVE: This study aimed to investigate the association between professional characteristics and the prevalence of advance directives among palliative care professionals. METHODS: This is a descriptive cross-sectional study. A diverse sample of 327 healthcare professionals completed an online survey investigating demographic variables, length of time working in palliative care, post-graduate qualifications in palliative care, and development of their own advance directives. RESULTS: The prevalence of advance directives among professionals working in palliative care was associated with factors such as higher academic qualifications, holding a post-graduate qualification in palliative care, and working in palliative care for a longer time. Furthermore, psychologists were most likely to have registered their own advance directives, compared with other healthcare professionals. SIGNIFICANCE OF RESULTS: Post-graduate palliative care education and professional experience in this area appear to be important factors associated with palliative care professionals writing of their own advance directives. However, our study suggests that just being involved in or familiar with the context of palliative and end-of-life care does not guarantee that health professionals register their advance directives.

Conceptualising a model to guide nursing and midwifery in the community guided by an evidence review.

BACKGROUND: Successful models of nursing and midwifery in the community delivering healthcare throughout the lifespan and across a health and illness continuum are limited, yet necessary to guide global health services. Primary and community health services are the typical points of access for most people and the location where most care is delivered. The scope of primary healthcare is complex and multifaceted and therefore requires a practice framework with sound conceptual and theoretical underpinnings. The aim of this paper is to present a conceptual model informed by a scoping evidence review of the literature. METHODS: A scoping evidence review of the literature was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Databases included CINAHL, MEDLINE, PsycINFO and SocINDEX using the EBSCO platform and the Cochrane Library using the keywords: model, nursing, midwifery, community, primary care. Grey literature for selected countries was searched using the Google 'advanced' search interface. Data extraction and quality appraisal for both empirical and grey literature were conducted independently by two reviewers. From 127 empirical and 24 non-empirical papers, data extraction parameters, in addition to the usual methodological features, included: the nature of nursing and midwifery; the population group; interventions and main outcomes; components of effective nursing and midwifery outcomes. RESULTS: The evidence was categorised into six broad areas and subsequently synthesised into four themes. These were not mutually exclusive: (1) Integrated and Collaborative Care; (2) Organisation and Delivery of Nursing and Midwifery Care in the Community; (3) Adjuncts to Nursing Care and (4) Overarching Conceptual Model. It is the latter theme that is the focus of this paper. In essence, the model depicts a person/client on a lifespan and preventative-curative trajectory. The health related needs of the client, commensurate with their point position, relative to both trajectories, determines the nurse or midwife intervention. Consequently, it is this need, that determines the discipline or speciality of the nurse or midwife with the most appropriate competencies. CONCLUSION: Use of a conceptual model of nursing and midwifery to inform decision-making in primary/community based care ensures clinical outcomes are meaningful and more sustainable. Operationalising this model for nursing and midwifery in the community demands strong leadership and effective clinical governance.

Normalising breastfeeding within a formula feeding culture: An Irish qualitative study.

BACKGROUND: Breastfeeding rates in Ireland are among the lowest in Europe. Breastfeeding groups can provide support, information, and friendship for women. However, there is little research exploring community breastfeeding groups led by Public Health Nurses providing universal maternal and child care to all postnatal mothers in the community in Ireland. AIM: The aim of this study was to explore breastfeeding women's experiences of a Public Health Nurse led support group. METHODS: A qualitative descriptive design to explore women's experiences of a community breastfeeding support group was conducted. Data were collected using one to one interviews with breastfeeding women (n=7) in a primary healthcare setting. Transcripts were analysed using Burnard's thematic content analysis. RESULTS: The overall theme identified was 'normalising breastfeeding' which emerged from the subthemes 'socialising and sharing', 'information and support seeking', 'building confidence', 'overcoming embarrassment', 'negative perceptions of others', and 'promoting breastfeeding to others'. DISCUSSION: Women who attended the PHN led breastfeeding support group found it to be a cocoon of 'normality', whereas breastfeeding was considered almost something to be ashamed of in other circumstances. Many women attributed their success with breastfeeding to the support group. CONCLUSION: Facilitating a sense of normalcy for breastfeeding women at individual, community and societal levels was essential in promoting breastfeeding. The community support group was influential in normalising breastfeeding for a sample of women, by minimising the potential for embarrassment, promoting social interaction and sharing, building confidence and knowledge. This buffered the effects of negative attitudes of others and personal feelings of shame.

Exploring the impact of drug properties on the extent of intestinal lymphatic transport - in vitro and in vivo studies.

PURPOSE: Intestinal lymphatic transport of specific lipophilic drugs offers therapeutic advantages and maximises oral bioavailability. The aims of this study were; to compare intestinal lymphatic transport of a range of drugs and to investigate the influence of cyclosporine A on the mechanism/extent of lymphatic transport. METHODS: Caco2 cells and an anaesthetised mesenteric lymphatic cannulated rat model were used for in vitro and in vivo studies. Lymphatic transport of three lipophilic drugs was directly compared in a long chain fatty acid formulation. In addition, the impact of cyclosporine A on triglyceride turnover was evaluated in vivo and in vitro. RESULTS: The extent of intestinal lymphatic transport in rats was positively correlated with drug solubility in triglyceride and negatively correlated with drug aqueous solubility. Cyclosporine A displayed non-linear lymphatic transport kinetics and reduced intestinal lymph triglyceride. In vitro experiments indicated that the cellular processes affected were intracellular lipid processing and/or lipid secretion. CONCLUSIONS: The linear correlations obtained using a range of lipophilic drugs confirm that the simplified approach of determining aqueous or triglyceride drug solubility is useful in predicting the extent of lymphatic transport. In vitro experiments correlated with in vivo observations, demonstrating the usefulness of the Caco-2 model for mechanistic investigations.

Nanoparticles and the blood-brain barrier: advancing from in-vitro models towards therapeutic significance.

The blood-brain barrier is a unique cell-based restrictive barrier that prevents the entry of many substances, including most therapeutics, into the central nervous system. A wide range of nanoparticulate delivery systems have been investigated with the aim of targeting therapeutics (drugs, nucleic acids, proteins) to the brain following administration by various routes. This review provides a comprehensive description of the design and formulation of these nanoparticles including the rationale behind individual approaches. In addition, the ability of currently available in-vitro BBB models to accurately predict the in-vivo performance of targeted nanoparticles is critically assessed.

Orthogonal identification of gunshot residue with complementary detection principles of voltammetry, scanning electron microscopy, and energy-dispersive X-ray spectroscopy: sample, screen, and confirm.

Field-deployable voltammetric screening coupled with complementary laboratory-based analysis to confirm the presence of gunshot residue (GSR) from the hands of a subject who has handled, loaded, or discharged a firearm is described. This protocol implements the orthogonal identification of the presence of GSR utilizing square-wave stripping voltammetry (SWSV) as a rapid screening tool along with scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) to confirm the presence of the characteristic morphology and metal composition of GSR particles. This is achieved through the judicious modification of the working electrode of a carbon screen-printed electrode (CSPE) with carbon tape (used in SEM analysis) to fix and retain a sample. A comparison between a subject who has handled and loaded a firearm and a subject who has had no contact with GSR shows the significant variations in voltammetric signals and the presence or absence of GSR-consistent particles and constituent metals. This initial electrochemical screening has no effect on the integrity of the metallic particles, and SEM/EDX analysis conducted prior to and postvoltammetry show no differences in analytical output. The carbon tape is instrumental in retaining the GSR sample after electrochemical analysis, supported by comparison with orthogonal detection at a bare CSPE. This protocol shows great promise as a two-tier detection system for the presence of GSR from the hands of a subject, whereby initial screening can be conducted rapidly onsite by minimally trained operators; confirmation can follow at the same substrate to substantiate the voltammetric results.

Biophysical and structural characterisation of nucleic acid complexes with modified cyclodextrins using circular dichroism.

Modified cyclodextrins (CDs) have shown great promise as non-viral gene and siRNA delivery vectors in a range of in vitro and in vivo studies. In the current study, structural and biophysical characterisation of selected CDs was carried out to enhance our understanding of their interaction with nucleic acids. The methods used for such characterisation were dynamic light scattering, zeta potential measurements and circular dichroism. Variations in the chemistries of individual CDs and in the type of formulation were shown to affect key properties of complexes such as size, surface charge and nucleic acid conformation. Furthermore, the effects of temperature and pH on the conformation of nucleic acids were investigated. pH studies were intended to mimic the conditions encountered by cationic complexes during endocytosis. Circular dichroism studies revealed that changes occurred in DNA and siRNA conformation upon complexation with CDs and when exposed to increasing temperature and decreasing pH. Overall, siRNA appeared to be more susceptible to conformational changes although complexation of siRNA with CDs tended to have a stabilising effect.

Gastrointestinal gene delivery by cyclodextrins--in vitro quantification of extracellular barriers.

Local gene delivery represents a promising therapeutic approach for diseases of the intestine. However, the gastrointestinal tract poses significant challenges to successful gene delivery. Cyclodextrins (CDs) have been extensively investigated as non-viral vectors. Here, we assessed the suitability of an amphiphilic cationic CD for intestinal gene transfer, with particular focus on extracellular barriers. Stability and transfection efficiency of CD·DNA complexes were assessed post incubation in simulated gastric and intestinal fluids, bile salts and mucin, or with intestinal enzymes to represent extracellular barriers to intestinal gene delivery. Stability was determined by gel electrophoresis and transfection was measured by luciferase expression in intestinal epithelial cells (Caco-2). Transfection efficiency of CD·DNA complexes was enhanced after incubation in bile salts but was reduced after incubation in gastric and intestinal fluids and mucin. CD·DNA complexes were stable after incubation with pancreatic enzymes and with a model lower intestinal enzyme. Furthermore, the CD protected pDNA from degradation by DNase. In summary, physiologically relevant in vitro models were established and used to quantify the barriers posed by the intestinal extracellular environment to gene delivery. This systematic assessment identified the advantages and limitations of the CD vector and facilitated the proposal of formulation strategies to overcome these barriers.