Measuring earplug noise attenuation: A comparison of laboratory and field methods.

Hearing protection device (HPD) fit-testing is a recommended best practice for hearing conservation programs as it yields a metric of the amount of attenuation an individual achieves with an HPD. This metric, the personal attenuation rating (PAR), provides hearing health care, safety, and occupational health personnel the data needed to select the optimal hearing protection for the occupational environment in which the HPD will be worn. Although commercial-off-the-shelf equipment allows the professional to complete HPD fit tests in the field, a standard test methodology does not exist across HPD fit-test systems. The purpose of this study was to compare the amount of attenuation obtained using the "gold standard" laboratory test (i.e., real-ear attenuation at threshold [REAT]) and three commercially available HPD fit-test systems (i.e., Benson Computer Controlled Fit Test System [CCF-200] with narrowband noise stimuli, Benson CCF-200 with pure tone stimuli, and Michael and Associates FitCheck Solo). A total of 57 adults, aged 18 to 63, were enrolled in the study and tested up to seven earplugs each across all fit-test systems. Once fitted by a trained member of the research team, earplugs remained in the ear throughout testing across test systems. Results revealed a statistically significant difference in measured group noise attenuation between the laboratory and field HPD fit-test systems (p < .0001). The mean attenuation was statistically significantly different (Benson CCF-200 narrowband noise was +3.1 dB, Benson CCF-200 pure tone was +2.1 dB, and Michael and Associates FitCheck Solo was +2.5 dB) from the control laboratory method. However, the mean attenuation values across the three experimental HPD fit-test systems did not reach statistical significance and were within 1.0 dB of one another. These findings imply consistency across the evaluated HPD fit-test systems and agree with the control REAT test method. Therefore, the use of each is acceptable for obtaining individual PARs outside of a laboratory environment.

Personal attenuation ratings versus derated noise reduction ratings for hearing protection devices.

National and international regulatory and consensus standards setting bodies have previously proposed derating hearing protector ratings to provide a better match between ratings determined in a laboratory and the real-world measurements of attenuation for workers. The National Institute for Occupational Safety and Health has proposed a derating scheme that depends upon the type of protector. This paper examines four real-world studies where personal attenuation ratings (PARs) were measured at least twice, before and after an intervention in earplug fitting techniques. Results from these studies indicate that individualized earplug fitting training dramatically improves a worker's achieved PAR value. Additionally, derating schemes fail to accurately predict the majority of achieved PARs. Because hearing protector fit testing systems are now readily available for use in the workplace, personal attenuation ratings provide a better estimate of worker noise exposures and are able to identify those persons who need additional instruction in fitting hearing protection devices.

The Effect of Using an Active Earmuff on High Frequency Hearing in United States Marine Corps Weapons Instructors.

OBJECTIVES: To investigate the change in hearing and perceived comfort over 1 year related to using an active hearing protection device (HPD) among United States Marine Corps (USMC) personnel routinely exposed to hazardous noise. METHODS: USMC Weapons Instructors (n = 127) were issued an active earmuff that met military standards and was compatible with other protective equipment. These participants completed pre- and post-hearing tests and comfort surveys. A control cohort (n = 94) was also included to compare individual changes in high-frequency pure tone average (HF-PTA) over 1 year. RESULTS: The control group's HF-PTA was 3 dB worse than the intervention group after only 1 year. Survey responses revealed perceived improvements in the ability to hear and understand, situational awareness, and safety. CONCLUSIONS: Active HPDs can reduce hearing loss and improve hearing-related occupational tasks.

How hearing conservation training format impacts personal attenuation ratings in U.S. Marine Corps Training Recruits.

OBJECTIVE: The purpose of this fit-testing study in the field was to systematically compare three Hearing Protection Device (HPD) fit-training methods and determine whether they differ in the acquisition of HPD fitting skill and resulting amount of earplug attenuation. DESIGN: Subjects were randomly assigned to receive HPD fit-training using one of three training methods: current, experiential HPD (eHPD), and integrated. Personal Attenuation Ratings (PARs) were acquired via HPD fit-testing and used to verify attenuations pre- and post-training. STUDY SAMPLE: US Marine training recruits (n = 341) identified via HPD fit-testing for remedial HPD fit-training and assigned to three cohorts. RESULTS: The post-training HPD fit-test passing rate differed by training method, with pass rates ranging from 50% (current) to nearly 92% (eHPD). The difference between group delta PAR values were significantly higher (>9 dB) in both the eHPD and integrated methods compared to the current method. CONCLUSION: The HPD fit-training methods that teach "what right feels like" (eHPD and integrated) provided a greater number of trainees with the skill to achieve noise attenuation values required for impulse noise exposures encountered during basic training. The attenuation achieved by those methods was significantly greater than the current training method.

Exploring the need for and application of human factors and ergonomics in ambulance design: Overcoming the barriers with technical standards.

Ergonomic risk factors, such as excessive physical effort, awkward postures or repetitive movements, were the leading causes of injuries amongst EMS workers in the United States, of which 90% were attributed to lifting, carrying, or transferring a patient and/or equipment. Although the essential tasks of patient handling, transport, and care cannot be eliminated, the design of ambulances and associated equipment is modifiable. Our aims were to identify the extent of Human Factors and Ergonomic (HFE) considerations in existing ambulance design standards/regulations, and describe how HFE and the standards/regulations were applied in the EMS system. Through an extensive environmental scan of jurisdictionally relevant standards/regulations and key informant interviews, our findings demonstrated that existing standards/regulations had limited considerations for HFE. As a result, HFE principles continue to be considered reactively through retrofit rather than proactively in upstream design. We recommend that performance-based HFE requirements be integrated directly into ambulance design standards.

Frequency of KCNQ1 variants causing loss of methylation of Imprinting Centre 2 in Beckwith-Wiedemann syndrome.

BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder caused by disturbances of the chromosomal region 11p15.5. The most frequent molecular finding in BWS is loss of methylation (LOM) of the Imprinting Centre 2 (IC2) region on the maternal allele, which is localised in intron 10 of the KCNQ1 gene. In rare cases, LOM of IC2 has been reported in families with KCNQ1 germline variants which additionally cause long-QT syndrome (LQTS). Thus, a functional link between disrupted KCNQ1 transcripts and altered IC2 methylation has been suggested, resulting in the co-occurrence of LQTS and BWS in case of maternal inheritance. Whereas these cases were identified by chance or in patients with abnormal electrocardiograms, a systematic screen for KCNQ1 variants in IC2 LOM carriers has not yet been performed. RESULTS: We analysed 52 BWS patients with IC2 LOM to determine the frequency of germline variants in KCNQ1 by MLPA and an amplicon-based next generation sequencing approach. We identified one patient with a splice site variant causing premature transcription termination of KCNQ1. CONCLUSIONS: Our study strengthens the hypothesis that proper KCNQ1 transcription is required for the establishment of IC2 methylation, but that KCNQ1 variants cause IC2 LOM only in a small number of BWS patients.

POLR3A variants with striatal involvement and extrapyramidal movement disorder.

Biallelic variants in POLR3A cause 4H leukodystrophy, characterized by hypomyelination in combination with cerebellar and pyramidal signs and variable non-neurological manifestations. Basal ganglia are spared in 4H leukodystrophy, and dystonia is not prominent. Three patients with variants in POLR3A, an atypical presentation with dystonia, and MR involvement of putamen and caudate nucleus (striatum) and red nucleus have previously been reported. Genetic, clinical findings and 18 MRI scans from nine patients with homozygous or compound heterozygous POLR3A variants and predominant striatal changes were retrospectively reviewed in order to characterize the striatal variant of POLR3A-associated disease. Prominent extrapyramidal involvement was the predominant clinical sign in all patients. The three youngest children were severely affected with muscle hypotonia, impaired head control, and choreic movements. Presentation of the six older patients was milder. Two brothers diagnosed with juvenile parkinsonism were homozygous for the c.1771-6C > G variant in POLR3A; the other seven either carried c.1771-6C > G (n = 1) or c.1771-7C > G (n = 7) together with another variant (missense, synonymous, or intronic). Striatal T2-hyperintensity and atrophy together with involvement of the superior cerebellar peduncles were characteristic. Additional MRI findings were involvement of dentate nuclei, hila, or peridentate white matter (3, 6, and 4/9), inferior cerebellar peduncles (6/9), red nuclei (2/9), and abnormal myelination of pyramidal and visual tracts (6/9) but no frank hypomyelination. Clinical and MRI findings in patients with a striatal variant of POLR3A-related disease are distinct from 4H leukodystrophy and associated with one of two intronic variants, c.1771-6C > G or c.1771-7C > G, in combination with another POLR3A variant.

Defining Normal Balance for Army Aviators.

INTRODUCTION: One challenge clinicians face is determining when a military Service Member (SM) can return to duty after an injury that affects the postural control. The gold standard to measure postural control is the Sensory Organization Test (SOT). This test measures the amount of sway present in an individual's static stance that may be used to examine range of function and monitor recovery from injury. Normative values currently available were developed using a sample of clinically normal adults from the general population (i.e., civilian non-aviator). Previous research suggests that these values should not be used as a comparative cohort for high-performing populations in the military. However, normative values, specific to military SMs, do not exist. The aim of this study was to develop a normative clinical database for functional balance (i.e., the SOT) for military-trained aviators, an occupational specialty that may consist of high performers. MATERIALS AND METHODS: Forty-three U.S. Army trained aviators, between 23 and 40 years old with medical clearance for flight operations from the Fort Rucker, Alabama area community consented and participated in this study. The SOT was delivered using the NeuroCom SMART EquiTest Clinical Research System with the Data Acquisition Toolkit (version 9.3). RESULTS: A statistically significant (p < 0.01) difference between the study cohort of Army-trained aviators and the publically available general civilian normative values was found for the more challenging conditions, in which the force plate was not fixed (i.e., conditions four through six). The study cohort of Army-trained aviators were found to have a higher equilibrium score in each of these three conditions. Similarly, a significant difference (p < 0.01) between the two cohorts was found on the visual and vestibular sensory analysis ratios, and the visual preference scores (i.e., greater reliance upon visual information in the maintenance of balance). The study cohort were found to have a higher ratios (i.e., greater dependence upon these sensory cues) in each of these conditions. CONCLUSION: Army-trained aviators are high-functioning performers whose SOT scores differ from that of the general civilian population, particularly for the more challenging test conditions. New normative values were developed from this study population. Use of the developed normative values could be used as a comparative cohort in screening aviators who are recovering from injuries that affect postural stability.

Structural brain anomalies in patients with FOXG1 syndrome and in Foxg1+/- mice.

OBJECTIVE: FOXG1 syndrome is a rare neurodevelopmental disorder associated with heterozygous FOXG1 variants or chromosomal microaberrations in 14q12. The study aimed at assessing the scope of structural cerebral anomalies revealed by neuroimaging to delineate the genotype and neuroimaging phenotype associations. METHODS: We compiled 34 patients with a heterozygous (likely) pathogenic FOXG1 variant. Qualitative assessment of cerebral anomalies was performed by standardized re-analysis of all 34 MRI data sets. Statistical analysis of genetic, clinical and neuroimaging data were performed. We quantified clinical and neuroimaging phenotypes using severity scores. Telencephalic phenotypes of adult Foxg1+/- mice were examined using immunohistological stainings followed by quantitative evaluation of structural anomalies. RESULTS: Characteristic neuroimaging features included corpus callosum anomalies (82%), thickening of the fornix (74%), simplified gyral pattern (56%), enlargement of inner CSF spaces (44%), hypoplasia of basal ganglia (38%), and hypoplasia of frontal lobes (29%). We observed a marked, filiform thinning of the rostrum as recurrent highly typical pattern of corpus callosum anomaly in combination with distinct thickening of the fornix as a characteristic feature. Thickening of the fornices was not reported previously in FOXG1 syndrome. Simplified gyral pattern occurred significantly more frequently in patients with early truncating variants. Higher clinical severity scores were significantly associated with higher neuroimaging severity scores. Modeling of Foxg1 heterozygosity in mouse brain recapitulated the associated abnormal cerebral morphology phenotypes, including the striking enlargement of the fornix. INTERPRETATION: Combination of specific corpus callosum anomalies with simplified gyral pattern and hyperplasia of the fornices is highly characteristic for FOXG1 syndrome.

What do parents expect from a genetic diagnosis of their child with intellectual disability?

BACKGROUND: Caring for a child with intellectual disability (ID) has been associated with increased social and psychological burdens. Diagnostic and prognostic uncertainty may enhance emotional stress in families. METHOD: The present authors assessed the motivations, expectations, mental health, physical health and the quality of life of 194 parents whose children with intellectual disability were undergoing a genetic diagnostic workup. RESULTS: Most parents considered a diagnosis highly relevant for their own emotional relief, their child's therapies and education, or family planning. Parental mental health was significantly lower compared with the normative sample, but physical health was not different. The severity of the child's intellectual disability correlated negatively with their parents' mental and physical health, quality of life, and positively with parental anxiety. CONCLUSION: Healthcare providers should be aware of the disadvantages facing families with intellectually disabled children. Receiving practical, social and psychological support as well as genetic testing might be particularly relevant for families with severely disabled children.

FOXG1 syndrome: genotype-phenotype association in 83 patients with FOXG1 variants.

PurposeThe study aimed at widening the clinical and genetic spectrum and assessing genotype-phenotype associations in FOXG1 syndrome due to FOXG1 variants.MethodsWe compiled 30 new and 53 reported patients with a heterozygous pathogenic or likely pathogenic variant in FOXG1. We grouped patients according to type and location of the variant. Statistical analysis of molecular and clinical data was performed using Fisher's exact test and a nonparametric multivariate test.ResultsAmong the 30 new patients, we identified 19 novel FOXG1 variants. Among the total group of 83 patients, there were 54 variants: 20 frameshift (37%), 17 missense (31%), 15 nonsense (28%), and 2 in-frame variants (4%). Frameshift and nonsense variants are distributed over all FOXG1 protein domains; missense variants cluster within the conserved forkhead domain. We found a higher phenotypic variability than previously described. Genotype-phenotype association revealed significant differences in psychomotor development and neurological features between FOXG1 genotype groups. More severe phenotypes were associated with truncating FOXG1 variants in the N-terminal domain and the forkhead domain (except conserved site 1) and milder phenotypes with missense variants in the forkhead conserved site 1.ConclusionsThese data may serve for improved interpretation of new FOXG1 sequence variants and well-founded genetic counseling.

Diagnosis of CoPAN by whole exome sequencing: Waking up a sleeping tiger's eye.

Neurodegeneration with brain iron accumulation (NBIA) is a group of neurodegenerative disorders characterized by iron accumulation in the basal ganglia. Recently, mutations in CoA synthase (COASY) have been identified as a cause of a novel NBIA subtype (COASY Protein-Associated Neurodegeneration, CoPAN) in two patients with dystonic paraparesis, parkinsonian features, cognitive impairment, behavior abnormalities, and axonal neuropathy. COASY encodes an enzyme required for Coenzyme A (CoA) biosynthesis. Using whole exome sequencing (WES) we identified compound heterozygous COASY mutations in two siblings with intellectual disability, ataxic gait, progressive spasticity, and obsessive-compulsive behavior. The "eye-of-the tiger-sign," a characteristic hypointense spot within the hyperintense globi pallidi on MRI found in the most common subtype of NBIA (Pantothenate Kinase-Associated Neurodegeneration, PKAN), was not present. Instead, bilateral hyperintensity and swelling of caudate nucleus, putamen, and thalamus were found. In addition, our patients showed a small corpus callosum and frontotemporal and parietal white matter changes, expanding the brain phenotype of patients with CoPAN. Metabolic investigations showed increased free carnitine and decreased acylcarnitines in the patients dried blood samples. Carnitine palmitoyl transferase 1 (CPT1) deficiency was excluded by further enzymatic and metabolic investigations. As CoA and its derivate Acetyl-CoA play an essential role in fatty acid metabolism, we assume that abnormal acylcarnitine profiles are a result of the COASY mutations. This report not only illustrates that WES is a powerful tool to elucidate the etiology of rare genetic diseases, but also identifies unique neuroimaging and metabolic findings that may be key features for an early diagnosis of CoPAN.

DDX3X mutations in two girls with a phenotype overlapping Toriello-Carey syndrome.

Recently, de novo heterozygous variants in DDX3X have been reported in about 1.5% of 2659 females with previously unexplained intellectual disability (ID). We report on the identification of DDX3X variants in two unrelated girls with clinical features of Toriello-Carey Syndrome (T-CS). In patient 1, the recurrent variant c.1703C>T; p.(P568L) was identified when reconsidering X-linked de novo heterozygous variants in exome sequencing data. In patient 2, the DDX3X variant c.1600C>G; p.(R534G) was also detected by exome sequencing. Based on these data, de novo heterozygous DDX3X variants should be considered not only in females with unexplained ID, but also in individuals with a clinical diagnosis of T-CS.

Hearing Loss and Tinnitus in Military Personnel with Deployment-Related Mild Traumatic Brain Injury.

The objective of this study was to analyze differences in incidence and epidemiologic risk factors for significant threshold shift (STS) and tinnitus in deployed military personnel diagnosed with mild traumatic brain injury (mTBI) due to either a blast exposure or nonblast head injury. A retrospective longitudinal cohort study of electronic health records of 500 military personnel (456 met inclusion criteria) diagnosed with deployment-related mTBI was completed. Chi-square tests and STS incidence rates were calculated to assess differences between blast-exposed and nonblast groups; relative risks and adjusted odds ratios of developing STS or tinnitus were calculated for risk factors. Risk factors included such characteristics as mechanism of injury, age, race, military occupational specialty, concurrent diagnosis of posttraumatic stress disorder (PTSD), and nicotine use. Among blast-exposed and nonblast patients, 67% and 58%, respectively, developed STS, (P=.06); 59% and 40%, respectively, developed tinnitus (P<.001). Incidence of STS was 24% higher in the blast-exposed than nonblast group. Infantry service was associated with STS; Marine Corps service, PTSD, and zolpidem use were associated with tinnitus. Unprotected noise exposure was associated with both STS and tinnitus. This study highlights potential risk factors for STS and tinnitus among blast-exposed and nonblast mTBI patient groups.

Exome sequencing reveals a novel CWF19L1 mutation associated with intellectual disability and cerebellar atrophy.

Intellectual disability (ID) with cerebellar ataxia comprises a genetically heterogeneous group of neurodevelopmental disorders. We identified a homozygous frameshift mutation in CWF19L1 (c.467delC; p.(P156Hfs*33)) by a combination of linkage analysis and Whole Exome Sequencing in a consanguineous Turkish family with a 9-year-old boy affected by early onset cerebellar ataxia and mild ID. Serial MRI showed mildly progressive cerebellar atrophy. Absent C19L1 protein expression in lymphoblastoid cell lines strongly suggested that c.467delC is a disease-causing alteration. One further pregnancy of the mother had been terminated at 22 weeks of gestation because of a small cerebellum and agenesis of corpus callosum. The homozygous CWF19L1 variant was also present in the fetus. Postmortem examination of the fetus in addition showed unilateral hexadactyly and vertebral malformations. These features have not been reported and may represent an expansion of the CWF19L1-related phenotypic spectrum, but could also be due to another, possibly autosomal recessive disorder. The exact function of the evolutionarily highly conserved C19L1 protein is unknown. So far, homozygous or compound heterozygous mutations in CWF19L1 have been identified in two Turkish siblings and a Dutch girl, respectively, affected by cerebellar ataxia and ID. A zebrafish model showed that CWF19L1 loss-of-function mutations result in abnormal cerebellar morphology and movement disorders. Our report corroborates that loss-of-function mutations in CWF19Ll lead to early onset cerebellar ataxia and (progressive) cerebellar atrophy. © 2016 Wiley Periodicals, Inc.

Oligoclonal bands predict multiple sclerosis in children with optic neuritis.

We retrospectively evaluated predictors of conversion to multiple sclerosis (MS) in 357 children with isolated optic neuritis (ON) as a first demyelinating event who had a median follow-up of 4.0 years. Multiple Cox proportional-hazards regressions revealed abnormal cranial magnet resonance imaging (cMRI; hazard ratio [HR] = 5.94, 95% confidence interval [CI] = 3.39-10.39, p < 0.001), presence of cerebrospinal fluid immunoglobulin G oligoclonal bands (OCB; HR = 3.69, 95% CI = 2.32-5.86, p < 0.001), and age (HR = 1.08 per year of age, 95% CI = 1.02-1.13, p = 0.003) as independent predictors of conversion, whereas sex and laterality (unilateral vs bilateral) had no influence. Combined cMRI and OCB positivity indicated a 26.84-fold higher HR for developing MS compared to double negativity (95% CI = 12.26-58.74, p < 0.001). Accordingly, cerebrospinal fluid analysis may supplement cMRI to determine the risk of MS in children with isolated ON.

3p25.3 microdeletion of GABA transporters SLC6A1 and SLC6A11 results in intellectual disability, epilepsy and stereotypic behavior.

Small interstitial deletions affecting chromosome region 3p25.3 have been reported in only five patients so far, four of them with overlapping telomeric microdeletions 3p25.3 and variable features of 3p- syndrome, and one patient with a small proximal microdeletion and a distinct phenotype with intellectual disability (ID) and multiple congenital anomalies. Here we report on three novel patients with overlapping proximal microdeletions 3p25.3 of 1.1-1.5 Mb in size showing a consistent non-3p- phenotype with ID, epilepsy/EEG abnormalities, poor speech, ataxia and stereotypic hand movements. The smallest region of overlap contains two genes encoding sodium- and chloride-dependent GABA transporters which have not been associated with this disease phenotype in humans so far. The protein function, the phenotype in transporter deficient animal models and the effects of specific pharmacological transporter inhibition in mice and humans provide evidence that these GABA transporters are plausible candidates for seizures/EEG abnormalities, ataxia and ID in this novel group of patients. A fourth novel patient deleted for a 3.16 Mb region, both telomeric and centromeric to 3p25.3, confirms that the telomeric segment is critical for the 3p- syndrome phenotype. Finally, a region of 643 kb is suggested to harbor one or more genes causative for polydactyly which is part of the 3p- syndrome.