Publications by authors named "Stephanie Karch"

14 Publications

  • Page 1 of 1

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

Int J Audiol 2021 Feb 14;60(2):151-159. Epub 2020 Sep 14.

Naval Hospital Beaufort, BHC, MCRD, Parris Island, SC, USA.

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: , (eHPD), and . 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 ( = 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14992027.2020.1811407DOI Listing
February 2021

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

Appl Ergon 2020 Oct 22;88:103144. Epub 2020 May 22.

Canadian Institute for Safety, Wellness, and Performance, School of Business, Conestoga College Institute of Technology and Advanced Learning, Kitchener, ON, Canada; Centre of Research Expertise for the Prevention of Musculoskeletal Disorders, Waterloo, ON, Canada; School of Public Health and Health Systems, University of Waterloo, ON, Canada; School of Geography and Earth Sciences, McMaster University, Hamilton, ON, Canada. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.apergo.2020.103144DOI Listing
October 2020

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

Clin Epigenetics 2020 05 11;12(1):63. Epub 2020 May 11.

Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13148-020-00856-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216698PMC
May 2020

POLR3A variants with striatal involvement and extrapyramidal movement disorder.

Neurogenetics 2020 04 15;21(2):121-133. Epub 2020 Jan 15.

Department of Child Neurology, Center for Childhood White Matter Diseases, Emma Children's Hospital, Vrije Universiteit, and Amsterdam Neuroscience, Amsterdam University Medical Centers, Amsterdam, The Netherlands.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-019-00602-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064625PMC
April 2020

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

Ann Clin Transl Neurol 2019 Apr 3;6(4):655-668. Epub 2019 Mar 3.

Institut für Medizinische Genetik und angewandte Genomik Universitätsklinikum Tübingen Tübingen Germany.

Objective: FOXG1 syndrome is a rare neurodevelopmental disorder associated with heterozygous 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 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 +/- 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 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acn3.735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469254PMC
April 2019

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

J Appl Res Intellect Disabil 2019 Sep 15;32(5):1129-1137. Epub 2019 Apr 15.

Section for Neuropediatrics and Inborn Errors of Metabolism, University Children's Hospital, Clinic I, Heidelberg, Germany.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jar.12602DOI Listing
September 2019

Defining Normal Balance for Army Aviators.

Mil Med 2019 07;184(7-8):e296-e300

U.S. Army Aeromedical Research Laboratory, 6901 Farrel Rd, Ft Rucker, AL.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/milmed/usz064DOI Listing
July 2019

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

Genet Med 2018 01 29;20(1):98-108. Epub 2017 Jun 29.

CeGaT, Tübingen, Germany.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/gim.2017.75DOI Listing
January 2018

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

Am J Med Genet A 2017 Jul 10;173(7):1878-1886. Epub 2017 May 10.

Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.

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 patientś 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.38252DOI Listing
July 2017

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

Am J Med Genet A 2017 May 29;173(5):1369-1373. Epub 2017 Mar 29.

Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.38164DOI Listing
May 2017

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

US Army Med Dep J 2016 Oct-Dec(3-16):52-63

US Army Aeromedical Research Laboratory, Fort Rucker, Alabama.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
April 2017

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

Am J Med Genet A 2016 06 26;170(6):1502-9. Epub 2016 Mar 26.

Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.37632DOI Listing
June 2016

Oligoclonal bands predict multiple sclerosis in children with optic neuritis.

Ann Neurol 2015 Jun 11;77(6):1076-82. Epub 2015 May 11.

Department of Neurology, University of Würzburg, Würzburg, Germany.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.24409DOI Listing
June 2015

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

Am J Med Genet A 2014 Dec 24;164A(12):3061-8. Epub 2014 Sep 24.

Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.36761DOI Listing
December 2014