Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-9 (of 9 Records) |
Query Trace: Davis RR[original query] |
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Immunofocusing humoral immunity potentiates the functional efficacy of the AnAPN1 malaria transmission-blocking vaccine antigen
Bender NG , Khare P , Martinez J , Tweedell RE , Nyasembe VO , López-Gutiérrez B , Tripathi A , Miller D , Hamerly T , Vela EM , Davis RR , Howard RF , Nsango S , Cobb RR , Harbers M , Dinglasan RR . NPJ Vaccines 2021 6 (1) 49 Malaria transmission-blocking vaccines (TBVs) prevent the completion of the developmental lifecycle of malarial parasites within the mosquito vector, effectively blocking subsequent infections. The mosquito midgut protein Anopheline alanyl aminopeptidase N (AnAPN1) is the leading, mosquito-based TBV antigen. Structure-function studies identified two Class II epitopes that can induce potent transmission-blocking (T-B) antibodies, informing the design of the next-generation AnAPN1. Here, we functionally screened new immunogens and down-selected to the UF6b construct that has two glycine-linked copies of the T-B epitopes. We then established a process for manufacturing UF6b and evaluated in outbred female CD1 mice the immunogenicity of the preclinical product with the human-safe adjuvant Glucopyranosyl Lipid Adjuvant in a liposomal formulation with saponin QS21 (GLA-LSQ). UF6b:GLA-LSQ effectively immunofocused the humoral response to one of the key T-B epitopes resulting in potent T-B activity, underscoring UF6b as a prime TBV candidate to aid in malaria elimination and eradication efforts. |
Scientific rigor required for a re-examination of exchange rate for occupational noise measurements Re: Dobie, R.A., & Clark, W.W. (2014) Exchange rates for intermittent and fluctuating occupational noise: a systematic review of studies of human permanent threshold shift, Ear Hear, 35, 86-96
Morata TC , Themann CL , Byrne DC , Davis RR , Murphy WJ , Stephenson MR . Ear Hear 2015 36 (4) 488-91 Dobie and Clark’s recent article “Exchange rates for intermittent and fluctuating occupational noise: A systematic review of studies of human permanent threshold shift” aimed to compare the suitability of a 3-dB versus 5-dB exchange rate (ER) in predicting hearing loss from non-impulsive intermittent or fluctuating noise exposures by reviewing studies of human noise-induced permanent threshold shift. The authors concluded that 3-dB ER systematically overestimates the risk of noise-induced hearing loss for intermittent or fluctuating noise. We contend that the authors did not arrive at their conclusions through an appropriate investigation. The article used flawed methodologies in the treatment and analysis of the data/studies and drew conclusions that were not substantiated by the cited data. | The authors indicated that their review did not aim to make recommendations for regulation of occupational noise, but suggested that their review provided evidence for a re-examination of recommendations in their concluding remarks. The National Institute for Occupational Safety and Health (NIOSH) maintains its recommendation of the 3-dB ER to provide sufficient protection for the many variations of continuous, intermittent and fluctuating noise exposure scenarios encountered in the workplace. In view of the advances in noise measurement and the studies’ other weaknesses, we question the suitability of revisiting a narrow segment of the human evidence (excluding robust animal studies and temporary threshold shift studies) based on outdated methodologies to address such an important issue. |
Noise exposure immediately activates cochlear mitogen-activated protein kinase signaling
Alagramam KN , Stepanyan R , Jamesdaniel S , Chen DH , Davis RR . Noise Health 2014 16 (73) 400-9 Noise-induced hearing loss (NIHL) is a major public health issue worldwide. Uncovering the early molecular events associated with NIHL would reveal mechanisms leading to the hearing loss. Our aim is to investigate the immediate molecular responses after different levels of noise exposure and identify the common and distinct pathways that mediate NIHL. Previous work showed mice exposed to 116 decibels sound pressure level (dB SPL) broadband noise for 1 h had greater threshold shifts than the mice exposed to 110 dB SPL broadband noise, hence we used these two noise levels in this study. Groups of 4-8-week-old CBA/CaJ mice were exposed to no noise (control) or to broadband noise for 1 h, followed by transcriptome analysis of total cochlear RNA isolated immediately after noise exposure. Previously identified and novel genes were found in all data sets. Following exposure to noise at 116 dB SPL, the earliest responses included up-regulation of 243 genes and down-regulation of 61 genes, while a similar exposure at 110 dB SPL up-regulated 155 genes and down-regulated 221 genes. Bioinformatics analysis indicated that mitogen-activated protein kinase (MAPK) signaling was the major pathway in both levels of noise exposure. Nevertheless, both qualitative and quantitative differences were noticed in some MAPK signaling genes, after exposure to different noise levels. Cacna1b , Cacna1g , and Pla2g6 , related to calcium signaling were down-regulated after 110 dB SPL exposure, while the fold increase in the expression of Fos was relatively lower than what was observed after 116 dB SPL exposure. These subtle variations provide insight on the factors that may contribute to the differences in NIHL despite the activation of a common pathway. |
Early prognosis of noise-induced hearing loss: prioritising prevention over prediction
Themann CL , Byrne DC , Davis RR , Morata TC , Murphy WJ , Stephenson MR . Occup Environ Med 2014 72 (2) 83-4 Moshammer and colleagues (1) have recommended routine implementation of a temporary threshold shift (TTS) screening test to identify workers particularly at risk of developing noise-induced hearing loss (NIHL) from occupational exposure to hazardous noise. Their work addresses an important occupational health problem. NIHL ranks among the most common work-related injuries in many countries, with an estimated global annual incidence of 1.6 million cases and accounting for approximately 16% of disabling adult hearing losses worldwide (2,3). Individuals vary in their susceptibility to the damaging effects of noise and no suitable method currently exists to predict the susceptibility of a particular worker. | In their study, Moshammer et al. measured TTS in newly-hired employees following exposure to a 20-minute, high intensity, low frequency experimental noise. They then followed the workers over time to see who ultimately developed a permanent threshold shift (PTS). The authors report that a TTS of 14 dB or more measured 2.5 minutes after the experimental exposure identifies workers at greater risk for PTS. They recommend routinely using this procedure to screen for susceptibility to noise in workplace hearing loss prevention programs. | However, this recommendation is premature in view of the study results. The TTS measure had a sensitivity of 82%, meaning that 18% of those who developed PTS were not identified by the TTS screening – a high false negative rate, particularly as we already know how to prevent PTS through reduction of noise exposures and consistent use of properly-fit hearing protection. Specificity was 70% at best, corresponding to a false positive rate 30%. If this procedure were implemented, approximately a third of the workers would be told that they are particularly at risk for NIHL when they aren’t, raising unnecessary alarm and opening the door to potential discrimination in work assignments, promotions, etc. |
Do hearing protectors protect hearing?
Groenewold MR , Masterson EA , Themann CL , Davis RR . Am J Ind Med 2014 57 (9) 1001-10 BACKGROUND: We examined the association between self-reported hearing protection use at work and incidence of hearing shifts over a 5-year period. METHODS: Audiometric data from 19,911 workers were analyzed. Two hearing shift measures-OSHA standard threshold shift (OSTS) and high-frequency threshold shift (HFTS)-were used to identify incident shifts in hearing between workers' 2005 and 2009 audiograms. Adjusted odds ratios were generated using multivariable logistic regression with multi-level modeling. RESULTS: The odds ratio for hearing shift for workers who reported never versus always wearing hearing protection was nonsignificant for OSTS (OR 1.23, 95% CI 0.92-1.64) and marginally significant for HFTS (OR 1.26, 95% CI 1.00-1.59). A significant linear trend towards increased risk of HFTS with decreased use of hearing protection was observed (P = 0.02). CONCLUSION: The study raises concern about the effectiveness of hearing protection as a substitute for noise control to prevent noise-induced hearing loss in the workplace. |
Acceptance of a semi-custom hearing protector by manufacturing workers
Davis RR , Murphy WJ , Byrne DC , Shaw PB . J Occup Environ Hyg 2011 8 (12) D125-30 Workers complain about wearing hearing protection for two primary reasons: comfort and communication.(1) Employers are concerned about hearing protection costs. Recent advances in hearing protector technology seemed to address those issues through a semi-custom earplug. This new device was designed to prevent overprotection by incorporating only enough attenuation to bring the worker down into the safe exposure zone. Although initially more expensive than disposable hearing protection devices (HPDs), the semi-custom hearing protector would be expected to last several years. | The Hearing Loss Prevention Team of the National Institute for Occupational Safety and Health (NIOSH) was invited by a major auto manufacturing company and the union (UAW) to supervise a longitudinal trial of a semi-custom hearing protector (SonoCustom by Sonomax Technologies, Inc.,Montreal, Canada). This protectorwas advertised as (1) being more comfortable since each plug was custom molded for each worker, and (2) more effective because each plug’s noise reduction rating was tuned to that worker’s particular job. The company’s hearing conservation contractor partnered with NIOSH by recruiting volunteers for the study and providing follow-up usage reports. The study was conducted over the course of 1 year with NIOSH site visits at the start, at 1 month, at 4 months, and at 1-year time intervals. The goal of this trial was to determine worker acceptance of the semi-custom earplug. | Compared with the non-custom earplugs used in this study, the SonoCustom ear plugs were relatively new to the market and have not been extensively investigated in the literature. Initial studies have focused on a new way to measure and model the acoustical performance.(2–4) Wagoner et al.(5) studied speech intelligibility and attenuation while subjects wore the SonoCustom earplugs or two other non-custom, commercially available hearing protectors in laboratory tests and in the field. In the laboratory they were not able to find any statistically significant difference, between the three earplugs, for speech intelligibility or attenuation. Regarding comfort issues, they briefly mentioned that the two non-custom HPDs were judged by the workers to be more comfortable and easier to use than the SonoCustom earplug. |
Relationship between comfort and attenuation measurements for two types of earplugs
Byrne DC , Davis RR , Shaw PB , Specht BM , Holland AN . Noise Health 2011 13 (51) 86-92 Noise-induced hearing loss is almost always preventable if properly fitted hearing protectors are worn to reduce exposure. Many individuals choose not to wear hearing protection because it may interfere with effective communication in the workplace or it may be uncomfortable. Hearing protector comfort has not received the same amount of attention as noise reduction capability. The present study was conducted to evaluate the comfort level of two different types of insert earplugs as well as the attenuation levels achieved by the earplugs. Attenuation levels were obtained with a commercially available earplug fit-test system, and the comfort ratings were obtained by questionnaire. The primary research objective was to determine whether hearing protector comfort was related to measured attenuation values. A linear mixed effects model provided evidence for an inverse relationship between comfort and attenuation. |
Heat and humidity buildup under earmuff-type hearing protectors
Davis RR , Shaw PB . Noise Health 2011 13 (51) 93-8 A major barrier to effective wear of hearing protection is comfort. This study examined several comfort indicators in the earmuff-type hearing protectors. Twenty subjects wore hearing protectors instrumented with two different temperature/humidity measurement systems (Omega and iButton) while walking a corridor for about 25 min. The instruments recorded the temperature and humidity every 10 s and their results were compared. In addition, skin surface pH was measured at the ear canal entrance before and after the task. Finally, the subject indicated earmuff comfort at the beginning and end of the session. Earmuff comfort decreased significantly over the course of the walking task. Ear canal pH became slightly less acidic, but the change was not statistically significant. The two temperature/humidity systems provided comparable results. Heat increased at about 0.3 degrees F while humidity built up at about 0.5%/min. However, the study found some limitations on the instrumentation. The complexity of the electrical connections and equipment in the Omega probe system led to loss of three subject's data. The iButton device was more robust, but provided only 256 gradations of temperature and relative humidity. Even with its limitations, the iButton device would be a valuable tool for field studies. The present study showed that the buildup of heat and humidity can be modeled using linear equations. The present study demonstrates that relatively inexpensive tools and a low-exertion task can provide important information about the under-earmuff environment, which can inform assumptions about comfort during use. |
Introduction to the special issue: Hearing protection state of the art
Davis RR . Noise Health 2011 13 (51) 85 It appears that the hearing protection device (HPD) will be a fixture of hearing loss prevention programs for the foreseeable future. The perception in industry is that it is more cost-effective to place workers in hearing loss prevention programs wearing hearing protection devices than to quiet the environment to safe levels. This issue describes the state of the art for research in hearing protection devices and hearing loss prevention programs. | The barriers to workers accepting and wearing hearing protection include comfort and communication. Byrne et al. describe a simple study where subjects wearing a foam plug in one ear and a wax plug in the other report on comfort. Davis and Shaw characterize heat and humidity buildup under an earmuff both in terms of physical and comfort measures. Another barrier is the ability to hear safety signals. Alali and Casali report some new research on detection and localization of backup alarms while wearing different types of hearing protection. | Training workers to more effectively use their hearing protection is fundamental to the hearing loss prevention program. Two companion papers by Stephenson et al. demonstrate how health communication can significantly influence attitudes, beliefs, and behavioral intentions about hearing protector use. Murphy et al. provide information on the effectiveness of video training versus professional training of HPD insertion techniques for workers. Their results seem to indicate that human contact is still needed for good hearing protection device placement. Ehlers and Graydon present a case study of their work on "training the trainers" to propagate the hearing loss prevention message to the agricultural community - an underserved population. | The goal of hearing protector use is to reduce exposure of the ear to noise and thus hearing loss. A number of tools are emerging to help the hearing loss professional with that task, including individual fit-testing and under-the-protector monitoring. |
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