Motivations of assessment item writers in medical programs : a qualitative study

Background: The challenge of generating sufficient quality items for medical student examinations is a common experience for medical program coordinators. Faculty development strategies are commonly used, but there is little research on the factors influencing medical educators to engage in item writing. To assist with designing evidence-based strategies to improve engagement, we conducted an interview study informed by self-determination theory (SDT) to understand educators' motivations to write items. Methods: We conducted 11 semi-structured interviews with educators in an established medical program. Interviews were transcribed verbatim and underwent open coding and thematic analysis. Results: Major themes included; responsibility for item writing and item writer motivations, barriers and enablers; perceptions of the level of content expertise required to write items; and differences in the writing process between clinicians and non-clinicians. Conclusions: Our findings suggest that flexible item writing training, strengthening of peer review processes and institutional improvements such as improved communication of expectations, allocation of time for item writing and pairing new writers with experienced writers for mentorship could enhance writer engagement

National and rural-urban prevalence and determinants of early initiation of breastfeeding in India

Background: Early initiation of breastfeeding (EIBF) reduces the risk of neonatal mortality. Previous studies from India have documented some factors associated with EIBF. However, those studies used data with limited sample size that potentially affect the application of the evidence. Additionally, the effectiveness of national breastfeeding programmes requires up-to-date analysis of new and robust EIBF data. The present study aimed to investigate the prevalence and determinants of EIBF in India and determine to what extent these factors differ by a mother’s residence in the rural or urban area. Methods: This study used information from a total weighted sample of 94,401 mothers from the 2015–2016 India National Family Health Survey. Multivariate logistic regression was used to investigate the association between the study factors and EIBF in India and rural-urban populations, after adjusting for confounders and sampling weight. Results: Our analysis indicated that 41.5% (95% confidence interval (CI): 40.9–42.5, P < 0.001) of Indian mothers initiated breastfeeding within 1-h post-birth, with similar but significant different proportions estimated for those who resided in rural (41.0, 95% CI: 40.3–41.6, P < 0.001) and urban (42.9, 95% CI: 41.7–44.2, P < 0.001) areas. Mothers who had frequent health service contacts and those with higher educational attainment reported higher EIBF practice. Multivariate analyses revealed that higher educational achievement, frequent antenatal care visits and birthing in a health facility were associated with EIBF in India and rural populations (only health facility birthing for urban mothers). Similarly, residing in the North-Eastern, Southern, Eastern and Western regions were also associated with EIBF. Birthing through caesarean, receiving delivery assistance from non-health professionals and residing in rural areas of the Central region were associated with delayed EIBF in all populations. Conclusion: We estimated that more than half of Indian mothers delayed breastfeeding initiation, with different rural-urban prevalence. Key modifiable factors (higher maternal education and frequent health service contacts) were associated with EIBF in India, with notable difference in rural-urban populations. Our study suggests that targeted and well-coordinated infant feeding policies and interventions will improve EIBF for all Indian mothers

Threshold concept-based transition pedagogy in pathway programs supporting students' transition into allied health degrees

Student numbers continue to rise in higher education worldwide. As a result, increasing numbers of students entering first-year university are under-prepared for the significant challenges of post-school study, particularly students who have traditionally been under-represented in the higher education context. Universities have addressed this by developing sophisticated strategies to tackle retention and attrition rates. In an Australian context, however, it is not clear if attempts by universities to address attrition rates have succeeded as recent numbers indicate that rates continue to rise. This rise in attrition is a multi-dimensional global phenomenon. Students’ transition to university is an indication for the successful completion of a degree. The College, at Western Sydney University, provides pathway programs for students who enter with low high school scores. These pathway students’ transition into Allied Health university degrees. Transition pedagogy can support these students in the successful and sustainable transition to university. Transition pedagogy represents a curriculum-mediated approach intentionally designed to address the phase of ‘transition’

Using team-based learning in a problem-based learning medical course to improve transition from a pre-clinical to clinical learning environment

Many medical schools choose between using either a problem-based learning (PBL) or a team-based learning (TBL) approach to curriculum to teach pre-clinical students the foundational sciences needed to understand disease processes. This study explores whether it is possible to combine the strengths of both approaches to better prepare medical students for the transition from a pre-clinical to a clinical learning environment. While PBL allows students to identify gaps in learning and then apply new knowledge to an established problem, TBL gives students the opportunity to apply their learning to multiple new clinical problems thus providing opportunities for knowledge transfer. We used the Learning Activity Management System (LAMS) to run modified TBL sessions that were designed to fit within the normal lecture program. Iterative development of the intervention over five years based on staff and student feedback has delivered positive educational outcomes

Generation of transparency and cellular organization in lens explants

The lens grows via the proliferation and differentiation of lens epithelial cells into lens fibres. This differentiation process, thought to be controlled by factors present in the vitreous fluid, generates tightly-packed, parallel-aligned fibre cells that confer transparency to the lens. Using lens epithelial-cell explants we examined how explant orientation and growth factor treatment can affect cellular arrangement and explant transparency. Fibre cell differentiation was induced in lens explants by culturing cells with fibroblast growth factor (FGF) or bovine vitreous. Cell shape and arrangement was investigated using confocal microscopy, electron microscopy, immunofluorescence and in situ hybridization. Explant transparency was measured using light microscopy. Confocal microscopy demonstrated that explant orientation determined cellular arrangement, irrespective of the differentiation stimuli used. In explants where epithelial cells were confined between their normal basement membrane (the lens capsule) and the base of the culture dish, the cells became elongated, thin and parallel-aligned. In contrast, in explants cultured with cells directly exposed to the culture media the cells appeared to be shorter, globular and haphazardly arranged. FGF initiated the differentiation of most lens epithelial cells; however, abnormal cellular morphologies developed with subsequent culture of the cells. As a result, the transparency of these explants decreased with prolonged culture. Interestingly, explants cultured with vitreous (i) did not develop abnormal cellular morphologies, (ii) contained two distinct cell types (retained epithelial cells and newly differentiated fibre cells) and (iii) remained transparent throughout the lengthy culture period. In summary, we have developed a culture system that generates a transparent tissue with a cellular arrangement resembling that of the lens in vivo. We have shown that while FGF and vitreous initiate differentiation within this system, better maintenance of fibre cell integrity, more appropriate regulation of molecular events, and better maintenance of explant transparency was achieved in the presence of vitreous. This system offers an opportunity to further investigate the process of lens fibre cell differentiation as well as a means of better identifying the factors that contribute to the development of tissue transparency in vitro

Transforming growth factor-β-induced epithelial-mesenchymal transition in the lens : a model for cataract formation

The vertebrate lens has a distinct polarity and structure that are regulated by growth factors resident in the ocular media. Fibroblast growth factors, in concert with other growth factors, are key regulators of lens fiber cell differentiation. While members of the transforming growth factor (TGFβ) superfamily have also been implicated to play a role in lens fiber differentiation, inappropriate TGFβ signaling in the anterior lens epithelial cells results in an epithelial-mesenchymal transition (EMT) that bears morphological and molecular resemblance to forms of human cataract, including anterior subcapsular (ASC) and posterior capsule opacification (PCO; also known as secondary cataract or after-cataract), which occurs after cataract surgery. Numerous in vitro and in vivo studies indicate that this TGFβ-induced EMT is part of a wound healing response in lens epithelial cells and is characterized by induced expression of numerous extracellular matrix proteins (laminin, collagens I, III, tenascin, fibronectin, proteoglycans), intermediate filaments (desmin, α-smooth muscle actin) and various integrins (α2, α5, α7B), as well as the loss of epithelial genes [Pax6, Cx43, CP49, α-crystallin, E-cadherin, zonula occludens-1 protein (ZO-1)]. The signaling pathways involved in initiating the EMT seem to primarily involve the Smad-dependent pathway, whereby TGFβ binding to specific high affinity cell surface receptors activates the receptor-Smad/Smad4 complex. Recent studies implicate other factors [such as fibroblast growth factor (FGFs), hepatocyte growth factor, integrins], present in the lens and ocular environment, in the pathogenesis of ASC and PCO. For example, FGF signaling can augment many of the effects of TGFβ, and integrin signaling, possibly via ILK, appears to mediate some of the morphological features of EMT initiated by TGFβ. Increasing attention is now being directed at the network of signaling pathways that effect the EMT in lens epithelial cells, with the aim of identifying potential therapeutic targets to inhibit cataract, particularly PCO, which remains a significant clinical problem in ophthalmology

Laminin-binding integrins in rat lens morphogenesis and their regulation during fibre differentiation

Mammalian lens development involves cell-cell and cell-ECM interactions. As integrins are a major family of cell adhesion molecules, we examined the expression patterns of several integrin subunits (α3A, α3B, α6A, α6B, β1 and β4) during rat lens development. RT-PCR, in situ hybridisation, immunofluorescence and immunoblotting were used to investigate expression of integrin subunits during lens development and differentiation. RT-PCR showed expression of α3A, α6A, α6B and β1A but not α3B or β4 subunits in postnatal rat lenses. Each subunit displayed distinct spatio-temporal expression patterns. β1 integrin was expressed in both epithelium and fibres. α3A subunit expression was restricted to the epithelium; expression ceased abruptly at the lens equator. Expression of the α6A subunit increased during fibre differentiation, whereas α6B expression was predominantly associated with epithelial cells during lens development. In lens epithelial explants, FGF induced some of the changes in integrin expression that are characteristic of fibre differentiation in vivo. One notable exception was the inability of FGF to reproduce the distinctive down-regulation of the α3 isoform that is associated with initiation of elongation in vivo. Interestingly, vitreous treatment was able to reproduce this shift in α3 expression indicating that another factor(s), in addition to FGF, may be required for full and complete transition from an epithelial cell to a fibre cell. Integrin subunit expression therefore appears to be highly regulated during lens development and fibre differentiation with evidence of major changes in α3 and α6 isoform expression. These results indicate that integrins may play important roles in development and growth of the lens. How specific integrin subunits influence the behaviour of cells in different developmental compartments of the lens remains to be determined

Genomic analysis distinguishes phases of early development of the mouse atrio-ventricular canal

Valve formation during embryonic heart development involves a complex interplay of regional specification, cell transformations, and remodeling events. While many studies have addressed the role of specific genes during this process, a global understanding of the genetic basis for the regional specification and development of the heart valves is incomplete. We have undertaken genome-wide transcriptional profiling of the developing heart valves in the mouse. Four Serial Analysis of Gene Expression libraries were generated and analyzed from the mouse atrio-ventricular canal (AVC) at embryonic days 9.5-12.5, covering the stages from initiation of endothelial to mesenchymal transition (EMT) through to the beginning of endocardial cushion remodeling. We identified 14 distinct temporal patterns of gene expression during AVC development. These were associated with specific functions and signaling pathway members. We defined the temporal distribution of mesenchyme genes during the EMT process and of specific Notch and transforming growth factor-β targets. This work provides the first comprehensive temporal dataset during the formation of heart valves. These results identify molecular signatures that distinguish different phases of early heart valve formation allowing gene expression and function to be further investigated

Rictor and integrin-linked kinase interact and regulate Akt phosphorylation and cancer cell survival

An unbiased proteomic screen to identify integrin-linked kinase (ILK) interactors revealed rictor as an ILK-binding protein. This finding was interesting because rictor, originally identified as a regulator of cytoskeletal dynamics, is also a component of mammalian target of rapamycin complex 2 (mTORC2), a complex implicated in Akt phosphorylation. These functions overlap with known ILK functions. Coimmunoprecipitation analyses confirmed this interaction, and ILK and rictor colocalized in membrane ruffles and leading edges of cancer cells. Yeast two-hybrid assays showed a direct interaction between the NH2- and COOH-terminal domains of rictor and the ILK kinase domain. Depletion of ILK and rictor in breast and prostate cancer cell lines resulted in inhibition of Akt Ser473 phosphorylation and induction of apoptosis, whereas, in several cell lines, depletion of mTOR increased Akt phosphorylation. Akt and Ser473P-Akt were detected in ILK immunoprecipitates and small interfering RNA-mediated depletion of rictor, but not mTOR, inhibited the amount of Ser473P-Akt in the ILK complex. Expression of the NH2-terminal (1-398 amino acids) rictor domain also resulted in the inhibition of ILK-associated Akt Ser473 phosphorylation. These data show that rictor regulates the ability of ILK to promote Akt phosphorylation and cancer cell survival

Preferential dependence of breast cancer cells versus normal cells on integrin-linked kinase for protein kinase B/Akt activation and cell survival

The emerging paradigm of "oncogene addiction" has been called an Achilles' heel of cancer that can be exploited therapeutically. Here, we show that integrin-linked kinase (ILK), which is either activated or overexpressed in many types of cancers, is a critical regulator of breast cancer cell survival through the protein kinase B (PKB)/Akt pathway but is largely dispensable for the survival of normal breast epithelial cells and mesenchymal cells. We show that inhibition of ILK activity with a pharmacologic ILK inhibitor, QLT-0267, results in the inhibition of PKB/Akt Ser473 phosphorylation, stimulation of apoptosis, and a decrease in mammalian target of rapamycin (mTOR) expression in human breast cancer cells. In contrast, QLT-0267 treatment has no effect on PKB/Akt Ser473 phosphorylation or apoptosis in normal human breast epithelial, mouse fibroblast, or vascular smooth muscle cells. The inhibition of PKB/Akt Ser473 phosphorylation by QLT-0267 in breast cancer cells was rescued by a kinase-active ILK mutant but not by a kinase-dead ILK mutant. Furthermore, a dominant-negative ILK mutant increased apoptosis in the MDA-MB-231 breast cancer cell line but not in normal human breast epithelial cells. The inhibitor was active against ILK isolated from all cell types but did not have any effect on cell attachment and spreading. Our data point to an "ILK addiction" of breast cancer cells whereby they become dependent on ILK for cell survival through the mTOR-PKB/Akt signaling pathway and show that ILK is a promising target for the treatment of breast cancer