The purpose of this article is to examine how the field of mixed methods currently is being defined. The authors asked many of the current leaders in mixed methods research how they define mixed methods research. The authors provide the leaders' definitions and discuss the content found as they searched for the criteria of demarcation. The authors provide a current answer to the question, What is mixed methods research? They also briefly summarize the recent history of mixed methods and list several issues that need additional work as the field continues to advance. They argue that mixed methods research is one of the three major “research paradigms” (quantitative research, qualitative research, and mixed methods research). The authors hope this article will contribute to the ongoing dialogue about how mixed methods research is defined and conceptualized by its practitioners.

Effective delivery to the retina is presently one of the most challenging areas in drug development in ophthalmology, due to anatomical barriers preventing entry of therapeutic substances. Intraocular injection is presently the only route of administration for large protein therapeutics, including the anti-Vascular Endothelial Growth Factors Lucentis (ranibizumab) and Avastin (bevacizumab). Anti-VEGFs have revolutionised the management of age-related macular degeneration and have increasing indications for use as sight-saving therapies in diabetes and retinal vascular disease. Considerable resources have been allocated to develop non-invasive ocular drug delivery systems. It has been suggested that the anionic phospholipid binding protein annexin A5, may have a role in drug delivery. In the present study we demonstrate, using a combination of in vitro and in vivo assays, that the presence of annexin A5 can significantly enhance uptake and transcytosis of liposomal drug carrier systems across corneal epithelial barriers. This system is employed to deliver physiologically significant concentrations of Avastin to the posterior of the rat eye (127 ng/g) and rabbit retina (18 ng/g) after topical application. Our observations provide evidence to suggest annexin A5 mediated endocytosis can enhance the delivery of associated lipidic drug delivery vehicles across biological barriers, which may have therapeutic implications.

The authors empirically tested a theoretical model of mastery motivation with 169 4-year-old African American at-risk children and their parents. The authors hypothesized that (a) parent characteristics (exogenous variables of education, income, and global self-efficacy) would predict parenting beliefs and parent-child relationships, (b) parenting beliefs and parent-child relationships would predict children's mastery, and (c) children's mastery would predict academic gains from pretest to posttest. The results showed that parents' education predicted parenting beliefs, parents' global self-efficacy predicted parenting beliefs and parent-child relationships, parenting beliefs predicted parent-child relationships, parent-child relationships predicted children's mastery, and children's mastery predicted children's performance on achievement tests controlling for pretest differences. This research provides support for the contention that motivational patterns develop early as a function of family variables and have the potential to influence academic success.

Parkinson’s Disease (PD) is the second most common neurodegenerative disease worldwide, affecting 1 % of the population over 65 years of age. Dopaminergic cell death in the substantia nigra and accumulation of Lewy bodies are the defining neuropathological hallmarks of the disease. Neuronal death and dysfunction have been reported in other central nervous system regions, including the retina. Symptoms of PD typically manifest only when more than 70 % of dopaminergic cells are lost, and the definitive diagnosis of PD can only be made histologically at post-mortem, with few biomarkers available.In this study, a rotenone-induced rodent model of PD was employed to investigate retinal manifestations in PD and their usefulness in assessing the efficacy of a novel therapeutic intervention with a liposomal formulation of the PPAR-γ (Peroxisome proliferator-activated receptor gamma) agonist rosiglitazone.Retinal assessment was performed using longitudinal in vivo imaging with DARC (detection of apoptosing retinal cells) and OCT (optical coherence tomography) technologies and revealed increased RGCs (Retinal Ganglion Cells) apoptosis and a transient swelling of the retinal layers at day 20 of the rotenone insult. Follow-up of this model demonstrated characteristic histological neurodegenerative changes in the substantia nigra and striatum by day 60, suggesting that retinal changes precede the “traditional” pathological manifestations of PD. The therapeutic effect of systemic administration of different formulations of rosiglitazone was then evaluated, both in the retina and the brain. Of all treatment regimen tested, sustained release administration of liposome-encapsulated rosiglitazone proved to be the most potent therapeutic strategy, as evidenced by its significant neuroprotective effect on retinal neurons at day 20, and on nigrostriatal neurons at day 60, provided convincing evidence for its potential as a treatment for PD.Our results demonstrate significant retinal changes occurring in this model of PD. We show that rosiglitazone can efficiently protect retinal neurons from the rotenone insult, and that systemic administration of liposome-encapsulated rosiglitazone has an enhanced neuroprotective effect on the retina and CNS (Central Nervous System). To our knowledge, this is the first in vivo evidence of RGCs loss and early retinal thickness alterations in a PD model. Together, these findings suggest that retinal changes may be a good surrogate biomarker for PD, which may be used to assess new treatments both experimentally and clinically.

This study explored the differential effects of strategy training on German and American elementaryschool children and assessed the role of parents in the development of their children's strategic behavior and metacognition. 184 German and 161 American children were pretested on memory and metamemory tasks. Children were then assigned to either an organizational strategy training condition or a control condition. All children were tested on the maintenance and far-transfer of the strategy and task-related metamemory 1 week following training. Parents completed questionnaires about strategy instruction in the home. Strategy maintenance and metacognition were reassessed 6 months following training. German children were more strategic than American children. Instructed children performed better than control children. German parents reported more instruction of strategies in the home. These data suggest that formal education is responsible for aspects of cognitive development that have sometimes been viewed as a function of age.

The amyloid beta (Aβ) pathway is strongly implicated in neurodegenerative conditions such as Alzheimer's disease and more recently, glaucoma. Here, we identify the α2 adrenergic receptor agonists (α2ARA) used to lower intraocular pressure can prevent retinal ganglion cell (RGC) death via the non-amyloidogenic Aβ-pathway. Neuroprotective effects were confirmed in vivo and in vitro in different glaucoma-related models using α2ARAs brimonidine (BMD), clonidine (Clo) and dexmedetomidine. α2ARA treatment significantly reduced RGC apoptosis in experimental-glaucoma models by 97.7% and 92.8% (BMD, P<0.01) and 98% and 92.3% (Clo, P<0.01)) at 3 and 8 weeks, respectively. A reduction was seen in an experimental Aβ-induced neurotoxicity model (67% BMD and 88.6% Clo, both P<0.01, respectively), and in vitro, where α2ARAs significantly (P<0.05) prevented cell death, under both hypoxic (CoCl2) and stress (UV) conditions. In experimental-glaucoma, BMD induced ninefold and 25-fold and 36-fold and fourfold reductions in Aβ and amyloid precursor protein (APP) levels at 3 and 8 weeks, respectively, in the RGC layer, with similar results with Clo, and in vitro with all three α2ARAs. BMD significantly increased soluble APPα (sAPPα) levels at 3 and 8 weeks (2.1 and 1.6-fold) in vivo and in vitro with the CoCl2 and UV-light insults. Furthermore, treatment of UV-insulted cells with an sAPPα antibody significantly reduced cell viability compared with BMD-treated control (52%), co-treatment (33%) and untreated control (27%). Finally, we show that α2ARAs modulate levels of laminin and MMP-9 in RGCs, potentially linked to changes in Aβ through APP processing. Together, these results provide new evidence that α2ARAs are neuroprotective through their effects on the Aβ pathway and sAPPα, which to our knowledge, is the first description. Studies have identified the need for α-secretase activators and sAPPα-mimetics in neurodegeneration; α2ARAs, already clinically available, present a promising therapy, with applications not only to reducing RGC death in glaucoma but also other neurodegenerative processes involving Aβ.

This study examined the efficacy of a brief (four session) intimate partner violence (IPV) prevention program (Building a Lasting Love, Langhinrichsen-Rohling et al. 2005) that was designed to reduce the relationship violence of predominantly African American inner-city adolescent girls (n = 72) who were receiving teen pregnancy services. These high-risk girls were randomly assigned to the prevention program (n = 39) or waitlist control (n = 33) conditions. Implementation fidelity was documented. As predicted, girls who successfully completed the program (n = 24) reported significant reductions in their perpetration of psychological abuse toward their baby's father as compared to the control (n = 23) participants. They also reported experiencing significantly less severe IPV victimization over the course of the program. Preliminary analyses indicated that avoidant attachment to one's partner may be associated with less program-related change. These findings support the contention that brief IPV prevention programs can be targeted to selected groups of high-risk adolescents.

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