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"Gilbert, Jennifer"
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Reliability of a Complication Classification System for Orthopaedic Surgery
Background
Quality of health care and safety have been emphasized by various professional and governmental groups. However, no standardized method exists for grading and reporting complications in orthopaedic surgery. Conclusions regarding outcomes are incomplete without a standardized, objective complication grading scheme applied concurrently. The general surgery literature has the Clavien-Dindo classification that meets the above criteria.
Questions/purposes
We asked whether a previously reported classification would show high intraobserver and interobserver reliabilities when modified for orthopaedic surgery specifically looking at hip preservation surgery. We therefore determined the interreader and intrareader reliabilities of the adapted classification scheme as applied to hip preservation surgery.
Methods
We adapted the validated Clavien-Dindo complication classification system and tested its reliability for orthopaedic surgery, specifically hip preservation surgery. There are five grades based on the treatment required to manage the complication and the potential for long-term morbidity. Forty-four complication scenarios were created from a prospective multicenter database of hip preservation procedures and from the literature. Ten readers who perform hip surgery at eight centers in three countries graded the scenarios at two different times. Fleiss’ and Cohen’s κ statistics were performed for interobserver and intraobserver reliabilities, respectively.
Results
The overall Fleiss’ κ value for interobserver reliability was 0.887 (95% CI, 0.855–0.891). The weighted κ was 0.925 (95% CI, 0.894–0.956) for Grade I, 0.838 (95% CI, 0.807–0.869) for Grade II, 0.87 (95% CI, 0.835–0.866) for Grade III, and 0.898 (95% CI, 0.866–0.929) for Grade IV. The Cohen’s κ value for intraobserver reliability was 0.891 (95% CI, 0.857–0.925).
Conclusions
The adapted classification system shows high interobserver and intraobserver reliabilities for grading of complications when applied to orthopaedic surgery looking at complications of hip preservation surgery. This grading scheme may facilitate standardization of complication reporting and make outcome studies more comparable.
Journal Article
Vector-free intracellular delivery by reversible permeabilization
Despite advances in intracellular delivery technologies, efficient methods are still required that are vector-free, can address a wide range of cargo types and can be applied to cells that are difficult to transfect whilst maintaining cell viability. We have developed a novel vector-free method that uses reversible permeabilization to achieve rapid intracellular delivery of cargos with varying composition, properties and size. A permeabilizing delivery solution was developed that contains a low level of ethanol as the permeabilizing agent. Reversal of cell permeabilization is achieved by temporally and volumetrically controlling the contact of the target cells with this solution. Cells are seeded in conventional multi-well plates. Following removal of the supernatant, the cargo is mixed with the delivery solution and applied directly to the cells using an atomizer. After a short incubation period, permeabilization is halted by incubating the cells in a phosphate buffer saline solution that dilutes the ethanol and is non-toxic to the permeabilized cells. Normal culture medium is then added. The procedure lasts less than 5 min. With this method, proteins, mRNA, plasmid DNA and other molecules have been delivered to a variety of cell types, including primary cells, with low toxicity and cargo functionality has been confirmed in proof-of-principle studies. Co-delivery of different cargo types has also been demonstrated. Importantly, delivery occurs by diffusion directly into the cytoplasm in an endocytic-independent manner. Unlike some other vector-free methods, adherent cells are addressed in situ without the need for detachment from their substratum. The method has also been adapted to address suspension cells. This delivery method is gentle yet highly reproducible, compatible with high throughput and automated cell-based assays and has the potential to enable a broad range of research, drug discovery and clinical applications.
Journal Article
Evidence-Based Practices in a Changing World: Reconsidering the Counterfactual in Education Research
Experimental and quasi-experimental designs are used in educational research to establish causality and develop effective practices. These research designs rely on a counterfactual model that, in simple form, calls for a comparison between a treatment group and a control group. Developers of educational practices often assume that the population from which control groups are drawn is unchanging in its behavior or performance. This is not always the case. Populations and study samples can change over time—sometimes dramatically so. We illustrate this important point by presenting data from 5 randomized control trials of the efficacy of Kindergarten Peer-Assisted Learning Strategies, a supplemental, peer-mediated reading program. The studies were conducted across 9 years and involved 2,591 students. Findings demonstrate a dramatic increase in the performance of control students over time, and suggest the need for a more nuanced understanding of the counterfactual model and its role in establishing evidence-based practices.
Journal Article
Performance variations across reading comprehension assessments: Examining the unique contributions of text, activity, and reader
These studies examined the contribution of text, activity, and reader to variance in reading comprehension test scores. Study 1 focused on multiple-choice and open-ended item responses, whereas Study 2 examined retell. Both studies included 79 fourth-grade students (age M = 9.72; SD = .34). Each student read six passages from the Qualitative Reading Inventory-Fifth Edition (QRI-5) and completed comprehension assessments of varying response format (open-ended questions, multiple choice, and retell). Measures of cognitive capacity, language knowledge, learning motivation, and word reading fluency were also administered. In Study 1, item-response crossed random effects models revealed statistically significant differences between open-ended question and multiple-choice response formats, and three covariates significantly predicted reading comprehension test scores: (a) attentive behavior, (b) language knowledge, and (c) working memory. Further exploratory analyses identified two-way interactions: (a) Response Format × Attentive Behavior, and (b) Response Format × Language Knowledge. In Study 2, crossed random effects models revealed two statistically significant predictors of retell scores: (a) text genre, and (b) language knowledge. Findings suggest different response format activities may contribute to variance in reading comprehension tests scores, and this test property may further interact with text as well as reader abilities.
Journal Article
Cost-Effectiveness of Community-Based TB/HIV Screening and Linkage to Care in Rural South Africa
South Africa has one of the highest burdens of TB worldwide, driven by the country's widespread prevalence of HIV, and further complicated by drug resistance. Active case finding within the community, particularly in rural areas where healthcare access is limited, can significantly improve diagnosis and treatment coverage in high-incidence settings. We evaluated the potential health and economic consequences of implementing community-based TB/HIV screening and linkage to care. Using a dynamic model of TB and HIV transmission over a time horizon of 10 years, we compared status quo TB/HIV control to community-based TB/HIV screening at frequencies of once every two years, one year, and six months. We also considered the impact of extending IPT from 36 months for TST positive and 12 months for TST negative or unknown patients (36/12) to lifetime use for all HIV-infected patients. We conducted a probabilistic sensitivity analysis to assess the effect of parameter uncertainty on the cost-effectiveness results. We identified four strategies that saved the most life years for a given outlay: status quo TB/HIV control with 36/12 months of IPT and TB/HIV screening strategies at frequencies of once every two years, one year, and six months with lifetime IPT. All of these strategies were very cost-effective at a threshold of $6,618 per life year saved (the per capita GDP of South Africa). Community-based TB/HIV screening with linkage to care is therefore very cost-effective in rural South Africa.
Journal Article
Hippocampal Leptin Signaling Reduces Food Intake and Modulates Food-Related Memory Processing
The increase in obesity prevalence highlights the need for a more comprehensive understanding of the neural systems controlling food intake; one that extends beyond food intake driven by metabolic need and considers that driven by higher-order cognitive factors. The hippocampus, a brain structure involved in learning and memory function, has recently been linked with food intake control. Here we examine whether administration of the adiposity hormone leptin to the dorsal and ventral sub-regions of the hippocampus influences food intake and memory for food. Leptin (0.1 μg) delivered bilaterally to the ventral hippocampus suppressed food intake and body weight measured 24 h after administration; a higher dose (0.4 μg) was needed to suppress intake following dorsal hippocampal delivery. Leptin administration to the ventral but not dorsal hippocampus blocked the expression of a conditioned place preference for food and increased the latency to run for food in an operant runway paradigm. Additionally, ventral but not dorsal hippocampal leptin delivery suppressed memory consolidation for the spatial location of food, whereas hippocampal leptin delivery had no effect on memory consolidation in a non-spatial appetitive response paradigm. Collectively these findings indicate that ventral hippocampal leptin signaling contributes to the inhibition of food-related memories elicited by contextual stimuli. To conclude, the results support a role for hippocampal leptin signaling in the control of food intake and food-related memory processing.
Journal Article
Prevention: Necessary But Insufficient? A 2-Year Follow-Up of an Effective First-Grade Mathematics Intervention
We present first-grade, second-grade, and third-grade impacts for a first-grade intervention targeting the conceptual and procedural bases that support arithmetic. At-risk students (average age at pretest = 6.5) were randomly assigned to three conditions: a control group (n = 224) and two variants of the intervention (same conceptual instruction but different forms of practice: speeded [n = 211] vs. nonspeeded [n = 204]). Impacts on all first-grade content outcomes were significant and positive, but no follow-up impacts were significant. Many intervention children achieved average mathematics achievement at the end of third grade, and prior math and reading assessment performance predicted which students will require sustained intervention. Finally, projecting impacts 2 years later based on nonexperimental estimates of effects of first-grade math skills overestimates long-term intervention effects.
Journal Article
Endocrine cell type sorting and mature architecture in the islets of Langerhans require expression of Roundabout receptors in β cells
Pancreatic islets of Langerhans display characteristic spatial architecture of their endocrine cell types. This architecture is critical for cell-cell communication and coordinated hormone secretion. Islet architecture is disrupted in type-2 diabetes. Moreover, the generation of architecturally correct islets
in vitro
remains a challenge in regenerative approaches to type-1 diabetes. Although the characteristic islet architecture is well documented, the mechanisms controlling its formation remain obscure. Here, we report that correct endocrine cell type sorting and the formation of mature islet architecture require the expression of Roundabout (Robo) receptors in β cells. Mice with whole-body deletion of
Robo1
and conditional deletion of
Robo2
either in all endocrine cells or selectively in β cells show complete loss of endocrine cell type sorting, highlighting the importance of β cells as the primary organizer of islet architecture. Conditional deletion of
Robo
in mature β cells subsequent to islet formation results in a similar phenotype. Finally, we provide evidence to suggest that the loss of islet architecture in
Robo KO
mice is not due to β cell transdifferentiation, cell death or loss of β cell differentiation or maturation.
Journal Article
Determinants of Human African Trypanosomiasis Elimination via Paratransgenesis
Human African trypanosomiasis (HAT), transmitted by tsetse flies, has historically infected hundreds of thousands of individuals annually in sub-Saharan Africa. Over the last decade, concerted control efforts have reduced reported cases to below 10,000 annually, bringing complete elimination within reach. A potential technology to eliminate HAT involves rendering the flies resistant to trypanosome infection. This approach can be achieved through the introduction of transgenic Sodalis symbiotic bacteria that have been modified to produce a trypanocide, and propagated via Wolbachia symbionts, which confer a reproductive advantage to the paratransgenic tsetse. However, the population dynamics of these symbionts within tsetse flies have not yet been evaluated. Specifically, the key factors that determine the effectiveness of paratransgenesis have yet to be quantified. To identify the impact of these determinants on T.b. gambiense and T.b. rhodesiense transmission, we developed a mathematical model of trypanosome transmission that incorporates tsetse and symbiont population dynamics. We found that fecundity and mortality penalties associated with Wolbachia or recombinant Sodalis colonization, probabilities of vertical transmission, and tsetse migration rates are fundamental to the feasibility of HAT elimination. For example, we determined that HAT elimination could be sustained over 25 years when Wolbachia colonization minimally impacted fecundity or mortality, and when the probability of recombinant Sodalis vertical transmission exceeded 99.9%. We also found that for a narrow range of recombinant Sodalis vertical transmission probability (99.9-90.6% for T.b. gambiense and 99.9-85.8% for T.b. rhodesiense), cumulative HAT incidence was reduced between 30% and 1% for T.b. gambiense and between 21% and 3% for T.b. rhodesiense, although elimination was not predicted. Our findings indicate that fitness and mortality penalties associated with paratransgenic symbionts, as well as tsetse migration rates, are instrumental to HAT elimination, and should be a key focus in the development of paratransgenic symbionts.
Journal Article