To quantify the effect of datalogging on speech recognition scores and time to achievement for a "benchmark" level of performance within the first year, and to provide a data-driven recommendation ...for minimum daily cochlear implant (CI) device usage to better guide patient counseling and future outcomes.
Retrospective cohort.
Tertiary referral center.
Three hundred thirty-seven adult CI patients with data logging and speech recognition outcome data who were implanted between August 2015 and August 2020.
Processor datalogging, speech recognition scores, achievement of "benchmark speech recognition performance" defined as 80% of the median score for speech recognition outcomes at our institution.
The 1-month datalogging measure correlated positively with word and sentences scores at 1, 3, 6, and 12 months postactivation. Compared with age, sex, and preoperative performance, datalogging was the largest predictive factor of benchmark achievement on multivariate analysis. Each hour/day increase of device usage at 1 month resulted in a higher likelihood of achieving benchmark consonant-nucleus-consonant and AzBio scores within the first year (odds ratio = 1.21, p < 0.001) as well as earlier benchmark achievement. Receiver operating characteristic curve analysis identified the optimal data logging threshold at an average of 12 hours/day.
Early CI device usage, as measured by 1-month datalogging, predicts benchmark speech recognition achievement in adults. Datalogging is an important predictor of CI performance within the first year postimplantation. These data support the recommended daily CI processor utilization of at least 12 hours/day to achieve optimal speech recognition performance for most patients.
IL-17-dependent cellular immune responses to the α1 chain of collagen type V are associated with development of bronchiolitis obliterans syndrome after lung transplantation, and with idiopathic ...pulmonary fibrosis and coronary artery disease, primary indications for lung or heart transplantation, respectively.
We found that 30% of the patients awaiting lung transplantation exhibited a strong cell-mediated immune response to col(V). Of these, 53% expressed HLA-DR15, compared to a 28% HLA-DR15 frequency in col(V) low-responders (p=0.02). After transplantation, patients with HLA-DR1 and -DR17, not -DR15, developed anti-col(V) responses most frequently (p=0.04 and 0.01 vs. controls, respectively). However, recipients of a lung from an HLA-DR15(+)donor were at significantly elevated risk of developing anti-col(V) responses (p=0.02) and BOS (p=0.03). To determine the molecular basis of this unusual pattern of DR allele bias, a peptide library comprising the collagenous region of the α1(V) protein was screened for binding to HLA-DR0101, -DR1501, -DR0301 (DR17) or to HLA-DQ2 (DQA1*0501: DQB1*0201; in linkage disequilibrium with -DR17) and -DQ6 (DQA1*0102: DQB1*0602; linked to -DR15). Eight 15-mer peptides, six DR-binding and two DQ-binding, were identified. HLA-DR15 binding to two peptides yielded the highest binding scores: 650 (where 100 = positive control) for p799 (GIRGLKGTKGEKGED), and 193 for p1439 (LRGIPGPVGEQGLPG). These peptides, which also bound weakly to HLA-DR1, elicited responses in both HLA-DR1(+) and -DR15(+) col(V) reactive hosts, whereas binding and immunoreactivity of p1049 (KDGPPGLRGFPGDRG) was DR15-specific. Remarkably, a col(V)-reactive HLA-DR1(+)DR15(neg) lung transplant patient, whose donor was HLA-DR15(+), responded not only to p799 and p1439, but also to p1049.
HLA-DR15 and IPF disease were independently associated with pre-transplant col(V) autoimmunity. The increased risk of de novo immunity to col(V) and BOS, associated with receiving a lung transplant from an HLA-DR15(+) donor, may result from presentation by donor-derived HLA- DR15, of novel self-peptides to recipient T cells.
Considerable evidence shows atherosclerosis to be a chronic inflammatory disease in which immunity to self-antigens contributes to disease progression. We recently identified the collagen type V ...col(V) α1(V) chain as a key autoantigen driving the Th17-dependent cellular immunity underlying another chronic inflammatory disease, obliterative bronchiolitis. Because specific induction of α1(V) chains has previously been reported in human atheromas, we postulated involvement of col(V) autoimmunity in atherosclerosis.
To determine whether col(V) autoimmunity may be involved in the pathogenesis of atherosclerosis.
Here, we demonstrate Th17-dependent anti-col(V) immunity to be characteristic of atherosclerosis in human coronary artery disease (CAD) patients and in apolipoprotein E-null (ApoE(-/-)) atherosclerotic mice. Responses were α1(V)-specific in CAD with variable Th1 pathway involvement. In early atherosclerosis in ApoE(-/-) mice, anti-col(V) immunity was tempered by an interleukin (IL)-10-dependent mechanism. In support of a causal role for col(V) autoimmunity in the pathogenesis of atherosclerosis, col(V) sensitization of ApoE(-/-) mice on a regular chow diet overcame IL-10-mediated inhibition of col(V) autoimmunity, leading to increased atherosclerotic burden in these mice and local accumulation of IL-17-producing cells, particularly in the col(V)-rich adventitia subjacent to the atheromas.
These findings establish col(V) as an autoantigen in human CAD and show col(V) autoimmunity to be a consistent feature in atherosclerosis in humans and mice. Furthermore, data are consistent with a causative role for col(V) in the pathogenesis of atherosclerosis.
The connection between perceived risk of homeland security incidents and homeland security preparedness has received considerable support in policing literature. From a contingency theory ...perspective, organizations rationally respond to risks in their external environments by taking steps to prepare for homeland security incidents. In past studies examining homeland security preparedness levels, risk has typically been measured using agency executives’ perceived likelihood of specific homeland security incidents occurring within their jurisdiction within a specified time range, and has largely ignored objective risk factors. In other disciplines, researchers and government organizations consider three dimensions when assessing risk: threat, vulnerability, and consequences. In the present study, the objective risk factors of social vulnerability, experience with past hazards, and built environment vulnerability not only fail to predict risk perceptions but are also not associated with preparedness measures. However, consistent with prior research, subjective risk perceptions remain a significant predictor of preparedness levels.
Within the tragedy of the Virginia Tech shooting was praise for the campus and community police departments based on their prior coordination and collaboration. After-action reports frequently ...credited the actions of the agencies with preventing an even greater loss of life thereby focusing attention on the presumed importance of close inter-agency relationships. This paper examines the level of agreement between officials representing campus public safety agencies and their neighboring local law enforcement departments on a range of issues related to campus critical incident preparedness. Data were collected from a national sample of both campus safety departments and a matched sample of adjacent law enforcement organizations. Results are based on agreement analysis of responses from 116 agency pairs. Overall findings suggest only modest agreement, at best, on issues related to campus safety including history of critical incidents, perceived risk of future incidents, mutual assistance, and preparedness activities, suggesting that agency officials may not share common understandings of important issues. In addition to reporting empirical findings, the research demonstrates the value of concordance measures as a means of examining agreement between law enforcement leaders and others.
Contingency theory, with regard to risk of homeland security incidents and homeland security preparedness, has received considerable empirical support. In past research, risk has been measured ...subjectively as agency executives' perceived risk of specific homeland security incidents occurring within their jurisdictions. This study examines actual risk, using the objective risk factors of experience with past natural hazards, social vulnerability, and urbanization. These risk factors, used in combination, have been significantly associated with terrorism-related homeland security incidents in the United States, and are used in risk assessment models of natural hazards. Contrary to expectations, the results of this study indicate that objective risk factors were not associated with either perceived risk or preparedness. Policy implications and directions for future research are discussed.
Background IL-17-dependent cellular immune responses to the alpha 1 chain of collagen type V are associated with development of bronchiolitis obliterans syndrome after lung transplantation, and with ...idiopathic pulmonary fibrosis and coronary artery disease, primary indications for lung or heart transplantation, respectively. Methodology/Principal Findings We found that 30% of the patients awaiting lung transplantation exhibited a strong cell-mediated immune response to col(V). Of these, 53% expressed HLA-DR15, compared to a 28% HLA-DR15 frequency in col(V) low-responders (p=0.02). After transplantation, patients with HLA-DR1 and -DR17, not -DR15, developed anti-col(V) responses most frequently (p=0.04 and 0.01 vs. controls, respectively). However, recipients of a lung from an HLA-DR15+ donor were at significantly elevated risk of developing anti-col(V) responses (p=0.02) and BOS (p=0.03). To determine the molecular basis of this unusual pattern of DR allele bias, a peptide library comprising the collagenous region of the alpha 1(V) protein was screened for binding to HLA-DR0101, -DR1501, -DR0301 (DR17) or to HLA-DQ2 (DQA1*0501: DQB1*0201; in linkage disequilibrium with -DR17) and -DQ6 (DQA1*0102: DQB1*0602; linked to -DR15). Eight 15-mer peptides, six DR-binding and two DQ-binding, were identified. HLA-DR15 binding to two peptides yielded the highest binding scores: 650 (where 100 = positive control) for p799 (GIRGLKGTKGEKGED), and 193 for p1439 (LRGIPGPVGEQGLPG). These peptides, which also bound weakly to HLA-DR1, elicited responses in both HLA-DR1+ and -DR15+ col(V) reactive hosts, whereas binding and immunoreactivity of p1049 (KDGPPGLRGFPGDRG) was DR15-specific. Remarkably, a col(V)-reactive HLA-DR1+DR15neg lung transplant patient, whose donor was HLA-DR15+, responded not only to p799 and p1439, but also to p1049. Conclusions/Significance HLA-DR15 and IPF disease were independently associated with pre-transplant col(V) autoimmunity. The increased risk of de novo immunity to col(V) and BOS, associated with receiving a lung transplant from an HLA-DR15+ donor, may result from presentation by donor-derived HLA- DR15, of novel self-peptides to recipient T cells.
Metabolism alterations are hallmarks of cancer, but the involvement of lipid metabolism in disease progression is unclear. We investigated the role of lipid metabolism in prostate cancer using tissue ...from patients with prostate cancer and patient-derived xenograft mouse models. We showed that fatty acid uptake was increased in human prostate cancer and that these fatty acids were directed toward biomass production. These changes were mediated, at least partly, by the fatty acid transporter CD36, which was associated with aggressive disease. Deleting
in the prostate of cancer-susceptible
mice reduced fatty acid uptake and the abundance of oncogenic signaling lipids and slowed cancer progression. Moreover, CD36 antibody therapy reduced cancer severity in patient-derived xenografts. We further demonstrated cross-talk between fatty acid uptake and de novo lipogenesis and found that dual targeting of these pathways more potently inhibited proliferation of human cancer-derived organoids compared to the single treatments. These findings identify a critical role for CD36-mediated fatty acid uptake in prostate cancer and suggest that targeting fatty acid uptake might be an effective strategy for treating prostate cancer.
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