Effects of Stimulus Type on 16-kHz Detection Thresholds.

OBJECTIVES: Audiometric testing typically does not include frequencies above 8 kHz. However, recent research suggests that extended high-frequency (EHF) sensitivity could affect hearing in natural communication environments. Clinical assessment of hearing often employs pure tones and frequency-modulated (FM) tones interchangeably regardless of frequency. The present study was designed to evaluate how the stimulus chosen to measure EHF thresholds affects estimates of hearing sensitivity. DESIGN: The first experiment used standard audiometric procedures to measure 8- and 16-kHz thresholds for 5- to 28-year olds with normal hearing in the standard audiometric range (250 to 8000 Hz). Stimuli were steady tones, pulsed tones, and FM tones. The second experiment tested 18- to 28-year olds with normal hearing in the standard audiometric range using psychophysical procedures to evaluate how changes in sensitivity as a function of frequency affect detection of stimuli that differ with respect to bandwidth, including bands of noise. Thresholds were measured using steady tones, pulsed tones, FM tones, narrow bands of noise, and one-third-octave bands of noise at a range of center frequencies in one ear. RESULTS: In experiment 1, thresholds improved with increasing age at 8 kHz and worsened with increasing age at 16 kHz. Thresholds for individual participants were relatively similar for steady, pulsed, and FM tones at 8 kHz. At 16 kHz, mean thresholds were approximately 5 dB lower for FM tones than for steady or pulsed tones. This stimulus effect did not differ as a function of age. Experiment 2 replicated this greater stimulus effect at 16 kHz than at 8 kHz and showed that the slope of the audibility curve accounted for these effects. CONCLUSIONS: Contrary to prior expectations, there was no evidence that the choice of stimulus type affected school-age children more than adults. For individual participants, audiometric thresholds at 16 kHz were as much as 20 dB lower for FM tones than for steady tones. Threshold differences across stimuli at 16 kHz were predicted by differences in audibility across frequency, which can vary markedly between listeners. These results highlight the importance of considering spectral width of the stimulus used to evaluate EHF thresholds.

The role of cryopreservation techniques in manufacturing, transport, and storage of Car-T therapy products.

Several clinical trials have proved the efficacy and safety of T-cells chimeric antigen receptor (CAR-T cells) in treatment of malignant lymphoma and the first products were registered in the European Union in 2018. The shelf-life of CAR-T cell products in the liquid state is short, so cryopreservation offers a significant benefit for logistics in manufacturing and patient management. Direct shipment of the cryopreserved CAR-T cell therapy products to the clinical department is feasible, nevertheless, intermediate storage in the hospital cryostorage facility gives significant advantage in planning of their administration to patients. Moreover, some manufacturers prefer transport of the starting material cryopreserved at the collection site. The cryopreservation protocol used for starting material by the authors is based on combining dimethyl sulphoxide (DMSO) with hydroxyethyl starch (HES) and slow controlled cooling in cryobags housed in metal cassettes. This achieves the mononuclear cell post-thaw viability of 98.8 ± 0.5 % and recovery of 72.8, ± 10.2 %. Transport of the starting material to the manufactures and return transport of the CAR-T therapy product is performed by authorized courier companies. Intermediate cryostorage of the final CAR-T cell therapy product is performed in a separate dry-storage liquid nitrogen container. On the day of infusion, the cryopreserved products are transported to the clinical department in a dry shipper. On the wards the product is removed from the cassette, inserted into a sterile plastic bag, thawed in a 37 degree C water bath followed by immediate intravenous administration. The authors discuss the adherence of the used technology to good manufacturing practice (GMP) principles and genetic safety assurance rules. Doi: 10.54680/fr23310110112.

Pressure-Mediated Reflection Spectroscopy Criterion Validity as a Biomarker of Fruit and Vegetable Intake: A 2-Site Cross-Sectional Study of 4 Racial or Ethnic Groups.

BACKGROUND: Valid biomarkers of fruit and vegetable (FV) intake are needed for field-based nutrition research. OBJECTIVES: To examine criterion-related validity of pressure-mediated reflection spectroscopy as a proxy measure of FV intake, using plasma carotenoids and self-reported FV and carotenoid intake as primary and secondary criterion measures, respectively. METHODS: Healthy adults 18-65 y of age, self-identifying as African American/black (n = 61), Asian (n = 53), white (n = 70), or Hispanic (n = 29), in North Carolina and Minnesota were recruited. Skin carotenoids were assessed via pressure-mediated reflection spectroscopy (Veggie Meter), skin melanin via spectrophotometer, and total plasma carotenoid concentration by HPLC-photodiode array detection. Self-reported carotenoid and FV intake was assessed using a semiquantitative FFQ. Relations between skin carotenoids, plasma carotenoids, FV, and carotenoid intake, with differences by race or ethnicity, age, sex, weight status, cholesterol, and melanin index, were examined by bivariate correlations and adjusted multivariate linear regressions. RESULTS: The overall unadjusted correlation between skin and total plasma carotenoids was r = 0.71 and ranged from 0.64 (non-Hispanic black) to 0.80 (Hispanic). Correlations between skin carotenoids and self-reported FV intake ranged from 0.24 (non-Hispanic black) to 0.53 (non-Hispanic white), with an overall correlation of r = 0.35. In models adjusted for age, sex, racial or ethnic group, and BMI, skin carotenoids were associated with plasma carotenoids (R2 = 0.55), FV (R2 = 0.17), and carotenoid intake (R2 = 0.20). For both plasma carotenoid and FV measures, associations with skin carotenoids did not vary by race, but these relations did differ by skin melanin-those with lower melanin had a lower correlation between skin and plasma carotenoids. CONCLUSIONS: Reflection spectroscopy-assessed skin carotenoids may be a reasonable alternative to measurement of plasma carotenoids, a biomarker used to approximate FV intake.

Binaural Frequency Modulation Detection in School-Age Children, Young Adults, and Older Adults: Effects of Interaural Modulator Phase.

OBJECTIVES: The purpose of this study was to measure low-rate binaural frequency modulation (FM) detection across the lifespan as a gauge of temporal fine structure processing. Children and older adults were expected to perform more poorly than young adults but for different reasons. DESIGN: Detection of 2-Hz FM carried by a 500-Hz pure tone was measured for modulators that were either in-phase or out-of-phase across ears. Thresholds were measured in quiet and in noise. Participants were school-age children (n = 44), young adults (n = 11), and older adults (n = 17) with normal or near-normal hearing. RESULTS: Thresholds were lower for out-of-phase than in-phase modulators among all listening groups. Detection thresholds improved with child age, with larger effects of age for dichotic than diotic FM. Introduction of masking noise tended to elevate thresholds; this effect was larger for the dichotic condition than the diotic condition, and larger for older adults than young adults. In noise, young adults received the greatest dichotic benefit, followed by older adults, then young children. The relative effects of noise on dichotic benefit did not differ for young adults compared to young children and older adults; however, young children saw greater reduction in benefit due to noise than older adults. CONCLUSION: The difference in dichotic benefit between children and young adults is consistent with maturation of central auditory processing. Differences in the effect of noise on dichotic benefit in young children and older adults support the idea that different factors or combinations of factors limit performance in these two groups. Although dichotic FM detection appears to be more sensitive to the effects of development and aging than diotic FM detection, the positive correlation between diotic and dichotic FM detection thresholds for all listeners suggests contribution of one or more factors common to both conditions.

Evaluation of the first U.S. staple foods ordinance: impact on nutritional quality of food store offerings, customer purchases and home food environments.

BACKGROUND: Many lower-income and racially diverse communities in the U.S. have limited access to healthy foods, with few supermarkets and many small convenience stores, which tend to stock limited quantities and varieties of healthy foods. To address food access, in 2015 the Minneapolis Staple Foods Ordinance became the first policy requiring food stores to stock minimum quantities and varieties of 10 categories of healthy foods/beverages, including fruits, vegetables, whole grains and other staples, through licensing. This study examined whether: (a) stores complied, (b) overall healthfulness of store environments improved, (c) healthy customer purchases increased, and (d) healthfulness of home food environments improved among frequent small store shoppers. METHODS: Data for this natural (or quasi) experiment were collected at four times: pre-policy (2014), implementation only (no enforcement, 2015), enforcement initiation (2016) and continued monitoring (2017). In-person store assessments were conducted to evaluate food availability, price, quality, marketing and placement in randomly sampled food retailers in Minneapolis (n = 84) and compared to those in a nearby control city, St. Paul, Minnesota (n = 71). Stores were excluded that were: supermarkets, authorized through WIC (Special Supplemental Nutrition Program for Women, Infants, and Children), and specialty stores (e.g., spice shops). Customer intercept interviews were conducted with 3,039 customers exiting stores. Home visits, including administration of home food inventories, were conducted with a sub-sample of frequent shoppers (n = 88). RESULTS: Overall, findings indicated significant improvements in healthy food offerings by retailers over time in both Minneapolis and St. Paul, with no significant differences in change between the two cities. Compliance was low; in 2017 only 10% of Minneapolis retailers in the sample were fully compliant, and 51% of participating Minneapolis retailers met at least 8 of the 10 required standards. Few changes were observed in the healthfulness of customer purchases or the healthfulness of home food environments among frequent shoppers, and changes were not different between cities. CONCLUSIONS: This study is the first evaluation a local staple foods ordinance in the U.S. and reflects the challenges and time required for implementing such policies. TRIAL REGISTRATION: NCT02774330 .

Characterizing the orthodontic patient's purchase decision: A novel approach using netnography.

INTRODUCTION: A deeper and more thorough characterization of why patients do or do not seek orthodontic treatment is needed for effective shared decision making about receiving treatment. Previous orthodontic qualitative research has identified important dimensions that influence treatment decisions, but our understanding of patients' decisions and how they interpret benefits and barriers of treatment are lacking. The objectives of this study were to expand our current list of decision-making dimensions and to create a conceptual framework to describe the decision-making process. METHODS: Discussion boards, rich in orthodontic decision-making data, were identified and analyzed with qualitative methods. An iterative process of data collection, dimension identification, and dimension refinement were performed to saturation. A conceptual framework was created to describe the decision-making process. RESULTS: Fifty-four dimensions captured the ideas discussed in regard to a patient's decision to receive orthodontic treatment. Ten domains were identified: function, esthetics, psychosocial benefits, diagnosis, finances, inconveniences, risks of treatment, individual aspects, societal attitudes, and child-specific influences, each containing specific descriptive and conceptual dimensions. A person's desires, self-perceptions, and viewpoints, the public's views on esthetics and orthodontics, and parenting philosophies impacted perceptions of benefits and barriers associated with orthodontic treatment. CONCLUSIONS: We identified an expanded list of dimensions, created a conceptual framework describing the orthodontic patient's decision-making process, and identified dimensions associated with yes and no decisions, giving doctors a better understanding of patient attitudes and expectations.

Results of a 2-year randomized, controlled obesity prevention trial: Effects on diet, activity and sleep behaviors in an at-risk young adult population.

Excess weight gain tends to occur in young adulthood. However, research examining effective weight-related interventions for this age group has been limited. As one of seven trials in the EARLY Trials consortium (Early Adult Reduction of weight through LifestYle intervention), the CHOICES Study (Choosing Healthy Options in College Environments and Settings) tested effects of a technology-integrated, young adult weight gain prevention intervention. It was a randomized controlled trial with assessments at baseline (2011) and 4-, 12- and 24-months post-intervention initiation and included 441 participants (ages 18-35) who were students at three Minnesota community colleges. The 24-month intervention included a 1-credit academic course and social networking and support online intervention. This analysis examined effects on 12 secondary behavioral outcomes across three domains: diet (fast food, sugary beverages, breakfast, at-home meal preparation), physical activity/screen time (minutes and energy expenditure in leisure time physical activity, television viewing, leisure time computer use) and sleep (hours of sleep, time required to fall asleep, days not getting enough rest, difficulty staying awake). The intervention resulted in significant reductions in fast food (p=0.007) but increases in difficulty staying awake (p=0.015). There was limited evidence of other behavior changes at 4months (0.05

Recruiting and retaining young adults in a weight gain prevention trial: Lessons learned from the CHOICES study.

BACKGROUND/AIMS: Young adults are at risk of weight gain, but little is known about designing effective weight control trials for young adults or how to recruit and retain participants in these programs. The Choosing Healthy Options in College Environments and Settings (CHOICES) study evaluated the effectiveness of a weight gain prevention intervention for 2-year college students. We describe the methods used to recruit and retain the colleges and their students, describe the sample and discuss recommendations for future studies. METHODS: Students were recruited into a 24-month trial of a weight control intervention with assessment periods at baseline, 4-, 12- and 24-month follow-up. RESULTS: We successfully recruited 441 students through partnerships with three 2-year colleges through a variety of campus-based methods. Ultimately, 83.4% of the randomized cohort participated in the 24-month assessment period. Those retained more often were White (p = 0.03) compared to those who dropped out or were lost to follow-up; no other socio-demographic factor (e.g. gender, ethnicity and education), body mass index, body fat, waist circumference or weight status was observed to differ between randomly assigned groups. CONCLUSION: Two-year colleges and their students are interested in participating in weight-related trials and partnering with universities for research. Researchers must work closely with administrators to identify benefits to their institutions and to resolve student-level barriers to recruitment and retention. Our experiences from the Choosing Healthy Options in College Environments and Settings study should be useful in identifying effective recruitment and retention methods for weight gain prevention trials among young adults.

A 2-year young adult obesity prevention trial in the US: Process evaluation results.

Our objective was to conduct a process evaluation of the CHOICES (Choosing Healthy Options in College Environments and Settings) study, a large, randomized, controlled trial designed to prevent unhealthy weight gain in young adults (aged 18-35) attending 2-year community colleges in the USA. The 24-month intervention consisted of participation in an academic course and a social networking and support website. Among intervention participants, completion rates for most course activities were >80%, reflecting a high level of dose received. Course retention and participant satisfaction were also high. Engagement results, however, were mixed with less than half of participants in the online and hybrid sections of the course reporting that they interacted with course materials ≥3 h/week, but 50-75% reporting that they completed required lessons 'all/very thoroughly'. Engagement in the website activities was also mixed with more than half of intervention participants logging onto the website during the first month, but then declining to 25-40% during the following 23 months of the intervention. Intervention engagement is a challenge of online interventions and a challenge of working with the young adult age group in general. Additional research is needed to explore strategies to support engagement among this population, particularly for relatively long intervention durations.

Guidelines for the use of cell lines in biomedical research.

Cell-line misidentification and contamination with microorganisms, such as mycoplasma, together with instability, both genetic and phenotypic, are among the problems that continue to affect cell culture. Many of these problems are avoidable with the necessary foresight, and these Guidelines have been prepared to provide those new to the field and others engaged in teaching and instruction with the information necessary to increase their awareness of the problems and to enable them to deal with them effectively. The Guidelines cover areas such as development, acquisition, authentication, cryopreservation, transfer of cell lines between laboratories, microbial contamination, characterisation, instability and misidentification. Advice is also given on complying with current legal and ethical requirements when deriving cell lines from human and animal tissues, the selection and maintenance of equipment and how to deal with problems that may arise.

Training support staff to modify fluids to appropriate safe consistencies for adults with intellectual disabilities and dysphagia: an efficacy study.

BACKGROUND: Modifying the consistency of food and drink is a strategy commonly used in the management of dysphagia for people with intellectual disabilities (ID). People with ID often depend on others for the preparation of food and drink and therefore depend on those caregivers achieving the correct consistency to keep them safe and avoid discomfort during mealtimes. Clinical experience and prior research have demonstrated that although training can improve modification, carers often find modification difficult and potentially stressful and recommend additional support for carers. Fluid consistency is often modified through the addition of powdered thickener. This study investigates the efficacy of typical training and use of consistency guides, the Thickness Indicator Model (TIM) tubes, in helping carers to modify fluids accurately. METHOD: A 3 × 3 pre-post experimental design with a control group was employed to compare the observed accuracy of modification across three groups and at three time points (pre-intervention baseline, immediately post-training intervention and 3-10 months post-training). Sixty-two paid carers who supported people with ID were recruited to participate in the study and each was randomly allocated to one of the three groups: a control group given written guidance only, a group who received typical training and written guidance and a group who received training, written guidance and the TIM tubes. RESULTS & CONCLUSIONS: Typical training resulted in significantly greater carer accuracy in modifying fluid consistencies when compared with written guidance alone. Use of the TIM tubes also significantly improved accuracy in the modification of drinks compared with the group who modified with the aid of written guidance alone. At 3-10-month follow-up only the group who received typical training alongside the TIM tubes were significantly more accurate than the Written Guidance group. Further research is warranted to ascertain the effectiveness of the training and the utility of the TIM tubes in improving accuracy over a longer time scale and in individuals' usual living environments.

A genomic basis of vocal rhythm in birds.

Vocal rhythm plays a fundamental role in sexual selection and species recognition in birds, but little is known of its genetic basis due to the confounding effect of vocal learning in model systems. Uncovering its genetic basis could facilitate identifying genes potentially important in speciation. Here we investigate the genomic underpinnings of rhythm in vocal non-learning Pogoniulus tinkerbirds using 135 individual whole genomes distributed across a southern African hybrid zone. We find rhythm speed is associated with two genes that are also known to affect human speech, Neurexin-1 and Coenzyme Q8A. Models leveraging ancestry reveal these candidate loci also impact rhythmic stability, a trait linked with motor performance which is an indicator of quality. Character displacement in rhythmic stability suggests possible reinforcement against hybridization, supported by evidence of asymmetric assortative mating in the species producing faster, more stable rhythms. Because rhythm is omnipresent in animal communication, candidate genes identified here may shape vocal rhythm across birds and other vertebrates.

Prospects for Biological Control of Macadamia Felted Coccid in Hawaii with Metaphycus macadamiae Polaszek & Noyes, a New Encyrtid Wasp Native to New South Wales, Australia.

Macadamia felted coccid (MFC), Acanthococcus ironsidei (Williams) (Hemiptera: Eriococcidae), was first discovered in 2005 on the Island of Hawaii. Host plants are restricted to Macadamia species, with Macadamia integrifolia Maiden & Betche (Proteaceae) being grown in Hawaii for nut production. Approximately 6839 hectares macadamia nuts are harvested in Hawaii with an estimated farm value of USD 48.8 million (2019-2020 records). Exploration in Australia started in November 2013 for the evaluation of potential parasitoids being host specific for introduction into Hawaii. A dominant solitary endoparasitoid of MFC from New South Wales was discovered and described as Metaphycus macadamiae Polaszek & Noyes sp. n (Hymenoptera: Encyrtidae: Encyrtinae). Biology and host specificity testing were conducted at the Hawaii Department of Agriculture, Insect Containment Facility, on nine hemipteran and three lepidopteran eggs. Results indicated that M. macadamiae is host specific to MFC. There has been no evidence of parasitism or host feeding on any of the non-target insect hosts that were tested. Parasitoid emergence from the control (MFC) averaged 30.2% compared to 0% on non-target hosts. A low rate of parasitoid emergence in the laboratory (average 30.2%) and an increased rate of MFC nymphal mortality was due to adult feeding. Field parasitism reached up to 32.7% emergence in Alstonville, New South Wales, Australia. We report on the parasitoid performance in native Australia, rearing biology, host specificity testing, and the extant natural enemies associated with MFC in Hawaii. A petition to release this parasitoid for the biocontrol of MFC in Hawaii is pending. Once permitted for release, the colony will be shared with South African Mac Nut Association for their biocontrol program of this invasive pest. They will conduct their own testing before approval for release.

Youth substance use and body composition: does risk in one area predict risk in the other?

Both substance use and obesity are prevalent among youth. As youth age, substance use rates increase and over the past three decades, obesity rates among youth have tripled. While these two factors have both short- and long-term health impacts, little research has explored how substance use and obesity among youth may be related. This study explores the bi-directional longitudinal relationships between substance use and body composition. Participants (N = 704; 50.7% female) were mostly white (86.4%) with a baseline mean age of 14.7 years. Objectively measured body composition was used to calculate body mass index z-scores (BMI z-score) and percent body fat. Cross-lagged structural equation models, accounting for clustering at the school level, were run to determine the longitudinal association between body composition and self-reported substance use (alcohol, cigarette, and marijuana), adjusting for socio-demographic characteristics, pubertal status, and weight satisfaction. Baseline alcohol use predicted decreased BMI z-score at follow-up and a similar association with percent body fat approached significance. Baseline cigarette use predicted increased percent body fat. No longitudinal associations were seen between baseline body composition and future substance use. Our results suggest that substance use contributes to subsequent body composition; however, body composition does not contribute to subsequent substance use. Continued research that explores these relationships longitudinally is greatly needed.

Longitudinal bi-directional relationships between sleep and youth substance use.

Despite the known deficits in sleep that occur during adolescence and the high prevalence of substance use behaviors among this group, relatively little research has explored how sleep and substance use may be causally related. The purpose of this study was to explore the longitudinal bi-directional relationships between sleep duration, sleep patterns and youth substance use behaviors. Participants included 704 mostly white (86.4 %) youth, 51 % female, with a baseline mean age of 14.7 years. Self-reported substance use behaviors included past month alcohol, cigarette, and marijuana use. Sleep measures included sleep duration on weekends and weekdays, total sleep, weekend oversleep, and weekend sleep delay. Cross-lagged structural equation models, accounting for clustering at the school level, were run to determine the longitudinal association between sleep and substance use adjusting for socio-demographic characteristics, pubertal status, body mass index z-score, and depressive symptoms. Cigarette use and weekend sleep were bi-directionally related as were marijuana use and total sleep. No other bi-directional associations were identified. However, alcohol use predicted shorter weekend oversleep and marijuana use predicted increased weekend sleep and weekend oversleep. Sleep patterns and duration also predicted adolescents' cigarette, alcohol, and marijuana use. Sleep, both patterns and duration, and substance use among youth are intertwined. Future research is needed to explore these bi-directional relationships, as well as other important contextual factors that may moderate these associations.

Situational characteristics of young adults' eating occasions: a real-time data collection using Personal Digital Assistants.

OBJECTIVE: To examine (i) situational characteristics of young adults' eating occasions, including away-from-home eating, social influences and multi-tasking, and (ii) how these characteristics are associated with specific foods/beverages consumed. DESIGN: Participants logged numerous characteristics of eating occasions (n 1237) in real time over 7 d. SETTING: Minneapolis/St. Paul metropolitan area (Minnesota, USA). SUBJECTS: Forty-eight participants, aged 18-23 years. RESULTS: Half of all eating occasions (46 %) occurred alone, 26 % occurred while watching television and 36 % involved other multi-tasking. Most participants (63 %) did not think about their food choices in advance of eating occasions. Eating that occurred in the absence of television viewing and/or other multi-tasking was less likely to include sweetened beverages and more likely to include items like water, fruit, vegetables, cereal, grains and entrées. Eating occasions occurring alone, and/or those occurring at home, were more likely to include snack foods that required little preparation (e.g. cookies, baked goods) and less likely to include more traditional meal items (e.g. fruits, vegetables, entrée items). CONCLUSIONS: Overall, a large proportion of young adults' eating occasions occurred alone, while engaging in other activities and with little advanced planning. Although many young adults' eating occasions consist of a wide range of highly processed, energy-dense, convenience products, more traditional meal settings (i.e. eating at home with others in the absence of multi-tasking) may result in more structured mealtimes and better food choices, such as more fruits and vegetables. Effective behavioural strategies promoting positive eating patterns, including home meal preparation, are urgently needed among young adults.

Speech-in-Speech Recognition and Spatially Selective Attention in Children and Adults.

Purpose Knowing target location can improve adults' speech-in-speech recognition in complex auditory environments, but it is unknown whether young children listen selectively in space. This study evaluated masked word recognition with and without a pretrial cue to location to characterize the influence of listener age and masker type on the benefit of spatial cues. Method Participants were children (5-13 years of age) and adults with normal hearing. Testing occurred in a 180° arc of 11 loudspeakers. Targets were spondees produced by a female talker and presented from a randomly selected loudspeaker; that location was either known, based on a pretrial cue, or unknown. Maskers were two sequences comprising spondees or speech-shaped noise bursts, each presented from a random loudspeaker. Speech maskers were produced by one male talker or by three talkers, two male and one female. Results Children and adults benefited from the pretrial cue to target location with the three-voice masker, and the magnitude of benefit increased with increasing child age. There was no benefit of location cues in the one-voice or noise-burst maskers. Incorrect responses in the three-voice masker tended to correspond to masker words produced by the female talker, and in the location-known condition, those masker intrusions were more likely near the cued loudspeaker for both age groups. Conclusions Increasing benefit of the location cue with increasing child age in the three-voice masker suggests maturation of spatially selective attention, but error patterns do not support this idea. Differences in performance in the location-unknown condition could play a role in the differential benefit of the location cue.

Evaluation of cell substrates for the production of biologicals: Revision of WHO recommendations. Report of the WHO Study Group on Cell Substrates for the Production of Biologicals, 22-23 April 2009, Bethesda, USA.

Evaluating cell substrates for producing vaccines and other biologicals is one of the critical aspects in assuring quality and safety of these products. As part of its mission in setting standards for biological products, WHO provides recommendations for manufacturing and evaluating biologicals. Regular updates of the guidance documents are important to manufacturers and regulators worldwide. WHO Expert Committee on Biological Standardization (ECBS) identified a need for revising the requirements for cell substrates (WHO TRS 878, annex 1). In response, WHO established a Study Group (SG) in 2006 that prepared an updated set of recommendations for using cell substrates for the production of biologicals. A summary of the proposed changes that the SG made in 2007 is available at WHO web site (http://www.who.int/biologicals/publications/meetings/areas/vaccines/cells/en/index.html). Draft revised recommendations were circulated to regulators, manufacturers and other experts for comments in April 2009. The SG held its third meeting on 22-23 April 2009 to review progress in the revision and to propose further improvements. In addition, the experts discussed the need for reference preparations, reference cell banks, and standardization of testing methodologies. The SG proposed clarifications of the rationale for in vivo testing as well as the potential for applying new methods for in vitro testing for detecting microbial agents. In line with this, WHO should conduct review of the current manufacturers' practice in using tests for microbial agents and interpreting these results. Additionally, WHO should take a lead in developing an International Standard for nucleic acid amplification test (NAT) for detecting mycoplasma contamination in cell substrates. WHO Collaborating Centers will lead this initiative, involving other relevant institutions in this area. Finally, advice on the replacement of the WHO Vero reference cell bank 10-87 with respect to the source of cells and re-characterization of the bank was provided. The intended use of the replacement cell bank would be the same as for the current cell bank, which is to serve as a source of well-characterized cells for establishing master cell banks for the production of biologicals. The SG will report outcomes of its discussion to the ECBS at its next meeting in October 2009 for further considerations and advice regarding the proposed course of action.

Impact of Therapeutic Music Listening on Intensive Care Unit Patients: A Pilot Study.

This pilot study investigated the association between patient-specific, therapeutic music listening as a nursing intervention for mechanically ventilated patients, and the proportion of time those patients were considered to have intensive care unit delirium. The pilot study used the person-centered nursing framework as its theoretic foundation. Findings from an intimate prospective cohort design encourage an expanded look at potential benefits of therapeutic music listening in large, multisite, randomized clinical trials. Research and practice implications are discussed.