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Objective: To compare postoperative isometric quadriceps strength indices (QI%) and hamstring strength limb symmetry indices (HI%) between partial thickness quadriceps tendon (pQT), full thickness quadriceps tendon (fQT), and bone-patellar-tendon bone (BPTB) autograft anterior cruciate ligament reconstruction (ACLR)., Methods: Patients with primary ACLR with pQT, fQT, or BPTB autograft with the documentation of quantitative postoperative strength assessments between 2016 and 2021 were included. Isometric Biodex data, including QI% and HI% (calculated as the percentage of involved to uninvolved limb strength) were collected between 5 and 8 months and between 9 and 15 months postoperatively., Results: In total, 124 and 51 patients had 5-8- and 9-15-month follow-up strength data, respectively. No significant difference was detected between groups for sex. However, patients undergoing fQT were found to be older than those undergoing BPTB (24.6±7 vs 20.2±5; ​p = 0.01). There were no significant differences in the number of concomitant meniscus repairs between the groups (pQT vs. fQT vs. BPTB). No significant differences were detected in median (min-max) QI% between pQT, fQT, and BPTB 5-8 months [87 ​% (44%-130 ​%), 84 ​% (44%-110 ​%), 82 ​% (37%-110 ​%) or 9-15 months [89 ​% (50%-110 ​%), 89 ​% (67%-110 ​%), and 90 ​% (74%-140 ​%)] postoperatively. Similarly, no differences were detected in median HI% between the groups 5-8 months or 9-15 months postoperatively., Conclusion: The study was unable to detect differences in the recovery of quadriceps strength between patients undergoing ACLR with pQT, fQT, and BPTB autografts at 5-8 months and 9-15-months postoperatively., Level of Evidence: III., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Adverse local tissue reaction (ALTR) is a recognized complication of total hip arthroplasty (THA) with metal-on-polyethylene (MoP) bearing surface implants. Specific models of THA implants have been identified as having a higher incidence of ALTR. The purpose of this study is to determine if serum metal levels, patient symptoms, implant factors, and imaging findings can be predictive of ALTR within this high-risk population., Methods: We retrospectively reviewed an observational cohort of 474 patients who underwent MoP THA and were at increased risk of having ALTR. Patients were stratified based on the presence or absence of ALTR. Patient symptoms, serum metal ions, implant head offset, and imaging findings were compared., Results: Patients with ALTR were more likely to be symptomatic (52.9% vs 9.9%, P < .0001). The presence of ALTR was associated with significantly higher serum cobalt and chromium levels (6.2 ppb vs 3.6 ppb, P  < .0001; 2.3 ppb vs 1.2 ppb, P < .0001). Head offsets greater than 4 mm were associated with a higher prevalence of ALTR (53% vs 38%, P  = .05). On metal artifact reduction sequence magnetic resonance imaging, patients with ALTR had larger effusions (4.7 cm vs 2.1 cm, P < .001) and a higher incidence of trochanteric bursitis (47% vs 16%, P < .001)., Conclusions: In high-risk MoP implants, serum cobalt and chromium levels are elevated, even in patients without ALTR. A larger femoral head offset is a risk factor for the development of ALTR. Our study suggests that patients presenting with painful THA and elevated metal ions require risk stratification based on patient symptoms, metal artifact reduction sequence magnetic resonance imaging findings, and implant factors., (© 2021 The American Association of Hip and Knee Surgeons. Published by Elsevier Inc.)

Introduction: Bone is the most common distant site of breast cancer metastasis. Skeletal lesions can cause significant morbidity due to pain, pathologic fracture, and electrolyte abnormalities. Current treatment for patients with bone metastases (BoM) from breast cancer is highly personalized and often involves a multidisciplinary approach with chemotherapy, hormone therapy, bone-targeted antiresorptive agents, radiation therapy, and surgery. We have retrospectively collected clinical data from a series of patients with bone metastases to evaluate the clinical characteristics, prognostic factors, and survival patterns of patients with breast cancer BoM receiving standard multimodal therapy., Methods: A consecutive series of 167 patients with breast cancer BoM treated at a single institution between August 2013 and March 2020 were identified. Clinical information was obtained from the medical record and survival analyses were performed to evaluate patient outcomes and identify prognostic factors., Results: Thirty-seven patients (22%) presented with de novo BoM - bone metastases at the time of breast cancer diagnosis - and were 2.6 times more likely to die within the study period than those with asynchronous BoM (HR = 2.62, p = <0.0001). Patients who received bone-targeted medical therapy were 61% less likely to die after BoM diagnosis than those who did not (HR = 0.39, p = 0.001). Operative stabilization of BoM was more frequently employed in patients with lytic (p = 0.02) or mixed (p = 0.02) tumors than it was for those with blastic lesions. Patients treated with surgery had a lower overall bone metastasis survival than those treated without (p < 0.03)., Discussion: These findings reflect the current patterns in metastatic breast cancer treatment and associated outcomes. In a series of 167 consecutive patients, we demonstrate the natural history of breast cancer with BoM being treated with modern multimodal therapy. Understanding these treatment patterns and prognostic factors enhances the provider's ability to counsel patients and direct appropriate treatments., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Lucas reports other from Amgen, other from Bayer/Loxo, outside the submitted work. Dr. Puhalla reports personal fees from Abbvie, personal fees from Medimmune, personal fees from Puma, personal fees from Pfizer, grants and personal fees from Astra Zeneca, personal fees from Esai, personal fees from Nanostring, grants and non-financial support from Abbvie, grants from Pfizer, grants from Lilly, grants from Novartis, grants from Incyte, grants from Covance-Bayer, grants from Astra-zeneca, grants from Genentech, grants from Medivation, outside the submitted work. All other authors certify that he or she has no commercial associations that might pose a conflict of interest to this submitted article., (© 2021 The Authors.)

Background: Health care providers are unprepared to meet the health needs of patients who have disabilities. Disability training is needed, yet there is little agreement about what should be taught., Objective: Establish a national consensus on what healthcare providers across disciplines need to know to provide quality care to patients with all types of disabilities (e.g., mobility, sensory, developmental, mental health)., Methods: People with disabilities, disability advocates, family members of people with disabilities, disability and health professionals, and inter-disciplinary health educators systematically evaluated and provided feedback on a draft set of disability competencies. Based on this feedback, competencies were iteratively refined., Results: After two waves of feedback, six competencies, 49 sub-competencies, and 10 principles and values emerged that addressed topics such as respect, person-centered care, and awareness of physical, attitudinal, and communication health care barriers. An overwhelming majority (89%) agreed or strongly agreed that the disability competencies reflected the core understandings needed to provide quality care for patients with disabilities, were relevant across disability types (85%), and across health care disciplines (96%). Averaging evaluative feedback across competencies, participants reported that the competencies were important (98%) and clear (96%)., Conclusions: This consensus on what to teach is an important milestone in preparing a disability competent health care workforce. Future directions for research, training, and policy are discussed. When disability is included in health care education, the health care workforce will be prepared to deliver accessible, patient-centered, quality health care to patients with disabilities., Competing Interests: Declaration of competing interest The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention or the Department of Health and Human Services., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Physicians report discomfort when interacting with patients with disabilities, which can negatively impact the quality of healthcare they provide., Objective/hypothesis: An intervention structured around a formative clinical encounter was assessed for its effectiveness in changing comfort towards treating patients with disabilities. It was predicted that this encounter would have a positive short- and long-term impact on medical students., Method: During the 2017-2018 academic year, 169 third-year medical students conducted a patient encounter with a person who had a disability. Students met individually with the "patient" and completed a brief social and medical history as if they were meeting a new patient to establish care. A measure of perceived comfort caring for patients with disabilities was administered to students before and after the encounter. One year after the patient encounter, 59 students were surveyed about their satisfaction and the impact of the patient encounter., Results: The impact of encountering people with disabilities in a clinical setting was positive, with statistically significant improvements across all items on the measure of perceived comfort. Students were highly satisfied with the experience and anticipated feeling more confident, more comfortable, less awkward, and more skilled and efficacious when encountering a person with a disability in their future practice. A thematic analysis of the one year follow-up data suggest that students valued the encounter and desired more content on disability throughout their education., Conclusions: Medical education should include dedicated exposure to persons with disabilities and a simulated patient experience allowing for a safe environment to gain skills and confidence., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: People with disabilities disproportionately use tobacco and suffer associated negative health consequences. Research is needed to explore tobacco cessation programming for people with disabilities to counter these health disparities., Objective: We evaluated the impact of Living Independent From Tobacco on tobacco use, knowledge and attitudes about tobacco use, coping skills, and perceived health status among people with disabilities. We also assessed participants' subjective impressions at post-test., Methods: Living Independent From Tobacco was evaluated via train the trainer model at three Midwestern sites serving people with disabilities. Outcomes were assessed at four time points: pre- and post-test (n = 30), and again at 1-month (n = 26) and 6-months (n = 13)., Results: Long-term tobacco users with disabilities significantly reduced tobacco use from pre-test to post-test (p = 0.003), and, compared to baseline, this reduction continued to be significant 1-month after the intervention (p = 0.02). From pre-test to post-test, perceived health status significantly improved (p = 0.0001). No significant changes were observed across time points for knowledge and attitudes about tobacco use nor for coping skills. Qualitative data revealed the importance of coping skills to mitigate the negative effects of nicotine withdrawal. Peer accountability was also noted as an important source of motivation for tobacco cessation., Conclusions: Data from the present study provide evidence for the short-term effectiveness of Living Independent From Tobacco to reduce tobacco use and improve health status among people with disabilities. Qualitative data revealed the importance of coping skills and peer accountability to support tobacco cessation. Implications for tobacco cessation programming for people with disabilities are discussed., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Tyrosinase is the rate-limiting enzyme for the production of melanin pigmentation. In the mouse and other animals, homozygous null mutations in the Tyrosinase gene (Tyr) result in the absence of pigmentation, i.e. albinism. Here we used the CRISPR/Cas9 system to generate mono- and bi-allelic null mutations in the Tyr locus by zygote injection of two single-guide and Cas9 RNAs. Injection into C57BL/6N wild-type embryos resulted in one completely albino founder carrying two different Tyr mutations. In addition, three pigmentation mosaics and fully pigmented littermates were obtained that transmitted new mutant Tyr alleles to progeny in test crosses with albinos. Injection into Tyr heterozygous (B6CBAF1/J×FVB/NJ) zygotes resulted in the generation of numerous albinos and also mice with a graded range of albino mosaicism. Deep sequencing revealed that the majority of the albinos and the mosaics had more than two new mutant alleles. These visual phenotypes and molecular genotypes highlight the somatic mosaicism and allele complexity in founders that occurs for targeted genes during CRISPR/Cas9-mediated mutagenesis by zygote injection in mice., (Copyright © 2014. Published by Elsevier Inc.)

A mathematical model is presented that simulates the annually averaged transport of radionuclides, originating from the BNFL reprocessing plant at Sellafield, throughout the Irish Sea. The model, CUMBRIA77, represents the processes of radionuclide transport and dispersion in the marine environment and allows predictions of radionuclide concentration in various environmental media, including biota, to be made throughout the whole of the Irish Sea. In this paper we describe the use of the model to reconstruct the historical activity concentrations of 137Cs and 239+240Pu in a variety of environmental media in the western Irish Sea and along the Irish east coast back to 1950. This reconstruction exercise is of interest because only limited measurements of 137Cs and 239+240Pu activity are available prior to the 1980s. The predictions were compared to the available measured data to validate their accuracy. The results of the reconstruction indicate that activity concentrations of 137Cs in the western Irish Sea follow a similar, though slightly delayed and smoothed, profile to the discharges from the Sellafield site, with concentrations at the time of peak discharge (the mid-1970s) being around an order of magnitude higher than those measured in the 1980s and 1990s. By contrast, the concentrations of 239+240Pu at the time of peak discharges were similar to those presently measured. These differences reflect the distinct marine chemistries of the two nuclides, in particular the higher propensity of plutonium to bind to sediments leading to extended transport times. Despite these differences in behaviour the doses to Irish seafood consumers from 137Cs remain significantly higher than those from 239+240Pu.

Aminophylline and theophylline are commonly used to treat asthma. We studied theophylline pharmacokinetics in the pregnant and nonpregnant rabbit as well as in the intrauterine and extrauterine fetus. The t1/2 was increased (p less than 0.05) and the clearance was decreased (p less than 0.05) in the pregnant compared to the nonpregnant rabbit. The t1/2 of theophylline in the newborn rabbit was 43.5 +/- 12.0 hr, approximately 15 times longer than in the nonpregnant rabbit. Twenty-four hours after a 20 min maternal aminophylline infusion, both the intrauterine fetus and maternal serum theophylline concentrations were very similar. The transplacental transfer from the maternal to fetal circulation occurred in less than 1 hr. The maternal to fetal serum ratios for theophylline were similar after a 5-day maternal aminophylline infusion (ratio 1.22 +/- 0.20) or after a 20 min infusion (ratio 1.24 +/- 0.20). Our findings indicate that the newborn rabbit eliminates theophylline very slowly, and maternal aminophylline or theophylline therapy that would result in high peak serum concentrations in the fetus, particularly just before birth, should be avoided.