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The adaptive response of the mandible and temporomandibular joint (TMJ) to altered occlusion in juvenile patients is presently unclear. To address this question, we established a mouse model in which all molars were extracted from the maxillary right quadrant in prepubertal, 3‐week‐old mice and analyzed morphological, tissue, cellular, and molecular changes in the mandible and condyle 3 weeks later. Unilateral loss of maxillary molars led to significant, robust, bilateral changes, primarily in condylar morphology, including anteroposterior narrowing of the condylar head and neck and increased convexity at the condylar surface, as determined by geometric morphometric analysis. Furthermore, both condyles in experimental mice exhibited a degenerative phenotype, which included decreased bone volume and increased mineral density near the condylar head surface compared to control mice. Changes in condylar morphology and mineralized tissue composition were associated with alterations in the cellular architecture of the mandibular condylar cartilage, including increased expression of markers for mature (Col2a1) and hypertrophic (Col10a1) chondrocytes, suggesting a shift toward differentiating chondrocytes. Our results show significant bilateral condylar morphological changes, alterations in tissue composition, cellular organization, and molecular expression, as well as degenerative disease, in response to the unilateral loss of teeth. Our study provides a relatively simple, tractable mouse tooth extraction system that will be of utility in uncovering the cellular and molecular mechanisms of condylar and mandibular adaptation in response to altered occlusion. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Summary: Invasive fungal disease (IFD) confers a substantial risk for morbidity and mortality to immunocompromised patients. Invasive aspergillosis (IA) is the most common IFD caused by moulds but the prevalence of other rare mould diseases, such as mucormycosis, hyalohyphomycosis and phaeohyphomycosis, may be increasing. Treatments are available for IA, but evidence to support efficacy and safety of antifungal agents for rare IFDs, or for IFDs in special patient populations, is limited or lacking. The VITAL trial was conducted to assess the efficacy and safety of isavuconazole for the treatment of patients with IA and renal impairment, or with IFDs caused by rare moulds, yeasts or dimorphic fungi. These patients stand to benefit most from a new treatment option but are unlikely to be included in a randomised, controlled trial. In this article, we review the challenges faced in the design and conduct of the VITAL trial. We also review the findings of VITAL, which included evidence of the efficacy and safety of isavuconazole. Finally, we consider the importance of trials such as VITAL to inform therapeutic decision making for clinicians faced with the challenge of treating patients with rare IFDs and as one paradigm of how to determine efficacy and safety of new drugs for rare and resistant infections without a suitable comparator. [ABSTRACT FROM AUTHOR]

Background Currently, treatment of latent tuberculosis infection (LTBI) in Australia consists most commonly of a 9-month course of isoniazid (9H). A 3-month course of weekly isoniazid and rifapentine (3HP) has been shown to be as effective as 9 months of daily isoniazid, and associated with less hepatotoxicity; however, rifapentine is not currently available in Australia. Introduction of this regimen would have apparent advantages for people with LTBI in Victoria by safely shortening duration of LTBI therapy. However, the cost benefit of this new therapeutic approach is uncertain. Aim Cost-analysis of standard and short-course therapy for LTBI in an Australian context. Methods Single-centre randomised controlled trial conducted between December 2013-March 2016. Participants underwent 1:1 randomisation to either a 9-month course of daily isoniazid or a 12-week course of weekly isoniazid and rifapentine. The primary outcome measure was total healthcare system costs (in Australian dollars; AUD) per completed course of LTBI therapy. Secondary cost analyses were performed to consider varying assumptions regarding commercial cost of rifapentine. Results Overall, 34 of 40 (85%) participants in the 9H group and 36/40 (90%) in the 3HR group completed therapy. One patient in the 3HP group was hospitalised for a febrile illness; no hospitalisations were recorded in the 9H group. The cost per completed course of 9H was 601 AUD, while that of 3HP was significantly lower at 511 AUD ( P < 0.01). Conclusions This study provides cost analysis evidence to support the use of 3HP for the treatment of LTBI in Australia. [ABSTRACT FROM AUTHOR]

Antimicrobial agents play a central role in modern health care, especially in the hospital setting. This article describes the currently available information on the volumes of antimicrobial use in Australian hospitals, the appropriateness of that use, and the levels of compliance with nationally or locally endorsed prescribing guidelines. The data presented here come from the 2014 National Antimicrobial Utilisation Surveillance Program report and the 2013 and 2014 National Antimicrobial Prescribing Survey reports and are based on voluntary participation in the two programs. While the results can be considered indicative only, they show that Australia has high volumes of prescribing in hospitals, and that in certain circumstances and conditions these are inappropriate and/or not compliant with national or local prescribing guidelines. In 2014, the national aggregate use rate for antimicrobials was 936 defined daily doses per 1000 occupied bed days. In the same year, the overall rate of appropriate prescribing was 72%, and compliance with guidelines was 74% where this was assessable. The rate of surgical antimicrobial prophylaxis exceeding the benchmark of 24 hours was high (36%), as was the inappropriate prescribing for infective exacerbations of chronic obstructive pulmonary disease (38%). The findings indicate that there is room for improvement in antimicrobial prescribing in Australian hospitals, and provides insights into where the efforts for improvement might be directed. [ABSTRACT FROM AUTHOR]

Researchers have demonstrated qualitative differences in witness verbal reports made in the presence and absence of misinformation. The present study examined changes in linguistic markers present in verbal reports in the context of a repeated-retrieval misinformation study. After witnessing an event, an immediate retrieval group engaged in a free-recall test associated with the event. The delayed retrieval group completed a filler task. Following, all participants were presented with a post-event narrative that included neutral, consistent, and misleading details. Both groups then took two free-recall tests. We found that hesitations were more likely to accompany correctly remembered details if those details were altered in the narrative, than if there was consistency between the original event and narrative. We also found that retrieval prior to misinformation positively influenced the inclusion of hesitations in free-recall reports that immediately followed the narrative.Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Survivin is a microtubule-associated protein believed to be involved in preserving cell viability and regulating tumor cell mitosis, and it is overexpressed in many primary tumor types, including melanoma. YM155 is a first-in-class survivin suppressant. The purpose of this Phase 2 study was to evaluate the 6-month progression-free survival ( PFS) rate in patients with unresectable Stage III or IV melanoma receiving a combination of YM155 plus docetaxel. The study had two parts: Part 1 established the dose of docetaxel that was tolerable in combination with YM155, and Part 2 evaluated the tolerable docetaxel dose (75 mg/m2) in combination with YM155 (5 mg/m2 per day continuous infusion over 168 h every 3 weeks). The primary endpoint was 6-month PFS rate. Secondary endpoints were objective response rate (ORR), 1-year overall survival ( OS) rate, time from first response to progression, clinical benefit rate (CBR), and safety. Sixty-four patients with metastatic melanoma were treated with docetaxel and YM155. Eight patients received an initial docetaxel dose of 100 mg/m2 and 56 patients received 75 mg/m2 of docetaxel. Six-month PFS rate per Independent Review Committee ( IRC) was 34.8% ( n = 64; 95% CI, 21.3-48.6%), and per Investigator was 31.3% ( n = 64; 95% CI, 19.5-43.9%). The best ORR (complete response [ CR] + partial response [ PR]) per IRC was 12.5% (8/64). The stable disease ( SD) rate was 51.6% (33/64), leading to a CBR ( CR + PR + SD) of 64.1% (41/64). Estimated probability of 1-year survival was 56.3%. YM155 is a novel agent showing modest activity when combined with docetaxel for treating patients with melanoma. YM155 was generally well tolerated, but the predetermined primary efficacy endpoint (i.e., 6-month PFS rate ≥20%) was not achieved. [ABSTRACT FROM AUTHOR]

Predicting sand parameters such as D[sub r] , K[sub 0] , and OCR from CPT measurements is an important and challenging task for the geotechnical engineer. In the present study, a system of neural networks is developed for predicting these parameters based on CPT measurements. The proposed system uses backpropagation neural networks for function approximation and probabilistic neural networks for classification. By strategically combining both types of networks, the proposed system is able to predict accurately D[sub r] , K[sub 0] , and OCR of sands from CPT measurements and other soil parameters. Details on the development of the proposed system are presented, along with comparisons of the results obtained by this system with existing methods. [ABSTRACT FROM AUTHOR]

This article presents various artificial neural network (ANN) models for evaluating liquefaction resistance and potential of sandy soils. Various issues concerning ANN modeling such as data preprocessing, training algorithms, and implementation are discussed. The desired ANN is trained and tested with a large historical database of liquefaction performance at sites where cone penetration test (CPT) measurements are available. The ANN models are found to be effective in predicting liquefaction resistance and potential. The developed ANN models are ported to a spreadsheet for ease of use. A simple procedure for conducting uncertainty analysis to address the issue of parameter and model uncertainties is also presented using the ANN-based spreadsheet model. This uncertainty analysis is carried out using @Risk, which is an add-in macro that works well with popular spreadsheet programs such as Microsoft Excel and Lotus 1-2-3. The results of the present study show that the developed ANN model has potential as a practical design tool for assessing liquefaction resistance of sandy soils. [ABSTRACT FROM AUTHOR]