Analysis of auditory functions in grades one, two, and three.

Thesis (Ed.M.)--Boston Universit

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

H₂azapa: a Versatile Acyclic Multifunctional Chelator for ⁶⁷Ga, ⁶⁴Cu, ¹¹¹In, and ¹⁷⁷Lu

Preliminary experiments with the novel acyclic triazole-containing bifunctional chelator H₂azapa and the radiometals ⁶⁴Cu, ⁶⁷Ga, ¹¹¹In, and ¹⁷⁷Lu have established its significant versatile potential as an alternative to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for metal-based radiopharmaceuticals. Unlike DOTA, H₂azapa radiolabels quantitatively with ⁶⁴Cu, ⁶⁷Ga, ¹¹¹In, and ¹⁷⁷Lu in 10 min at room temperature. In vitro competition experiments with human blood serum show that ⁶⁴Cu remained predominantly chelate-bound, with only 2% transchelated to serum proteins after 20 h. Biodistribution experiments with [⁶⁴Cu­(azapa)] in mice reveal uptake in various organs, particularly in the liver, lungs, heart, intestines, and kidneys. When compared to [⁶⁴Cu­(DOTA)]^2–, the lipophilic neutral [⁶⁴Cu­(azapa)] was cleared through the gastrointestinal tract and accumulated in the liver, which is common for lipophilic compounds or free ⁶⁴Cu. The chelator H₂azapa is a model complex for a click-based bifunctional chelating agent, and the lipophilic benzyl “place-holders” will be replaced by hydrophilic peptides to modulate the pharmacokinetics and direct activity away from the liver and gut. The solid-state molecular structure of [In­(azapa)­(H₂O)]­[ClO₄] reveals a very rare eight-coordinate distorted square antiprismatic geometry with one triazole arm bound, and the structure of [⁶⁴Cu­(azapa)] shows a distorted octahedral geometry. The present study demonstrates significant potential for bioconjugates of H₂azapa as alternatives to DOTA in copper-based radiopharmaceuticals, with the highly modular and “clickable” molecular scaffold of H₂azapa easily modified into a variety of bioconjugates. H₂azapa is a versatile addition to the “pa” family, joining the previously published H₂dedpa (^67/68Ga and ⁶⁴Cu), H₄octapa (¹¹¹In, ¹⁷⁷Lu, and ⁹⁰Y), and H₅decapa (²²⁵Ac) to cover a wide range of important nuclides

H₂azapa: a Versatile Acyclic Multifunctional Chelator for ⁶⁷Ga, ⁶⁴Cu, ¹¹¹In, and ¹⁷⁷Lu

Preliminary experiments with the novel acyclic triazole-containing bifunctional chelator H₂azapa and the radiometals ⁶⁴Cu, ⁶⁷Ga, ¹¹¹In, and ¹⁷⁷Lu have established its significant versatile potential as an alternative to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for metal-based radiopharmaceuticals. Unlike DOTA, H₂azapa radiolabels quantitatively with ⁶⁴Cu, ⁶⁷Ga, ¹¹¹In, and ¹⁷⁷Lu in 10 min at room temperature. In vitro competition experiments with human blood serum show that ⁶⁴Cu remained predominantly chelate-bound, with only 2% transchelated to serum proteins after 20 h. Biodistribution experiments with [⁶⁴Cu­(azapa)] in mice reveal uptake in various organs, particularly in the liver, lungs, heart, intestines, and kidneys. When compared to [⁶⁴Cu­(DOTA)]^2–, the lipophilic neutral [⁶⁴Cu­(azapa)] was cleared through the gastrointestinal tract and accumulated in the liver, which is common for lipophilic compounds or free ⁶⁴Cu. The chelator H₂azapa is a model complex for a click-based bifunctional chelating agent, and the lipophilic benzyl “place-holders” will be replaced by hydrophilic peptides to modulate the pharmacokinetics and direct activity away from the liver and gut. The solid-state molecular structure of [In­(azapa)­(H₂O)]­[ClO₄] reveals a very rare eight-coordinate distorted square antiprismatic geometry with one triazole arm bound, and the structure of [⁶⁴Cu­(azapa)] shows a distorted octahedral geometry. The present study demonstrates significant potential for bioconjugates of H₂azapa as alternatives to DOTA in copper-based radiopharmaceuticals, with the highly modular and “clickable” molecular scaffold of H₂azapa easily modified into a variety of bioconjugates. H₂azapa is a versatile addition to the “pa” family, joining the previously published H₂dedpa (^67/68Ga and ⁶⁴Cu), H₄octapa (¹¹¹In, ¹⁷⁷Lu, and ⁹⁰Y), and H₅decapa (²²⁵Ac) to cover a wide range of important nuclides