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1.
Clin Orthop Relat Res ; 482(2): 244-256, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37646744

ABSTRACT

BACKGROUND: The interpretation of patient-reported outcomes requires appropriate comparison data. Currently, no patient-specific reference data exist for the Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function (PF), Upper Extremity (UE), and Pain Interference (PI) scales for individuals 50 years and older. QUESTIONS/PURPOSES: (1) Can all PROMIS PF, UE, and PI items be used for valid cross-country comparisons in these domains among the United States, the United Kingdom, and Germany? (2) How are age, gender, and country related to PROMIS PF, PROMIS UE, and PROMIS PI scores? (3) What is the relationship of age, gender, and country across individuals with PROMIS PF, PROMIS UE, and PROMIS PI scores ranging from very low to very high? METHODS: We conducted telephone interviews to collect custom PROMIS PF (22 items), UE (eight items), and PI (eight items) short forms, as well as sociodemographic data (age, gender, work status, and education level), with participants randomly selected from the general population older than 50 years in the United States (n = 900), United Kingdom (n = 905), and Germany (n = 921). We focused on these individuals because of their higher prevalence of surgeries and lower physical functioning. Although response rates varied across countries (14% for the United Kingdom, 22% for Germany, and 12% for the United States), we used existing normative data to ensure demographic alignment with the overall populations of these countries. This helped mitigate potential nonresponder bias and enhance the representativeness and validity of our findings. We investigated differential item functioning to determine whether all items can be used for valid crosscultural comparisons. To answer our second research question, we compared age groups, gender, and countries using median regressions. Using imputation of plausible values and quantile regression, we modeled age-, gender-, and country-specific distributions of PROMIS scores to obtain patient-specific reference values and answer our third research question. RESULTS: All items from the PROMIS PF, UE, and PI measures were valid for across-country comparisons. We found clinically meaningful associations of age, gender, and country with PROMIS PF, UE, and PI scores. With age, PROMIS PF scores decreased (age ß Median = -0.35 [95% CI -0.40 to -0.31]), and PROMIS UE scores followed a similar trend (age ß Median = -0.38 [95% CI -0.45 to -0.32]). This means that a 10-year increase in age corresponded to a decline in approximately 3.5 points for the PROMIS PF score-a value that is approximately the minimum clinically important difference (MCID). Concurrently, we observed a modest increase in PROMIS PI scores with age, reaching half the MCID after 20 years. Women in all countries scored higher than men on the PROMIS PI and 1 MCID lower on the PROMIS PF and UE. Additionally, there were higher T-scores for the United States than for the United Kingdom across all domains. The difference in scores ranged from 1.21 points for the PROMIS PF to a more pronounced 3.83 points for the PROMIS UE. Participants from the United States exhibited up to half an MCID lower T-scores than their German counterparts for the PROMIS PF and PROMIS PI. In individuals with high levels of physical function, with each 10-year increase in age, there could be a decrease of up to 4 points in PROMIS PF scores. Across all levels of upper extremity function, women reported lower PROMIS UE scores than men by an average of 5 points. CONCLUSION: Our study provides age-, gender-, and country-specific reference values for PROMIS PF, UE, and PI scores, which can be used by clinicians, researchers, and healthcare policymakers to better interpret patient-reported outcomes and provide more personalized care. These findings are particularly relevant for those collecting patient-reported outcomes in their clinical routine and researchers conducting multinational studies. We provide an internet application ( www.common-metrics.org/PROMIS_PF_and_PI_Reference_scores.php ) for user-friendly accessibility in order to perform age, gender, and country conversions of PROMIS scores. Population reference values can also serve as comparators to data collected with other PROMIS short forms or computerized adaptive tests. LEVEL OF EVIDENCE: Level II, diagnostic study.


Subject(s)
Patient Reported Outcome Measures , Upper Extremity , Female , Humans , Male , Lower Extremity , Minimal Clinically Important Difference , Pain , Middle Aged
2.
Sci Rep ; 13(1): 22498, 2023 12 15.
Article in English | MEDLINE | ID: mdl-38110426

ABSTRACT

During the SARS-CoV-2 pandemic, the German healthcare system faced challenges of efficiently allocating testing resources. To address this, we developed an open-source personalized recommendation system (PRS) called "CovApp". The PRS utilized a questionnaire to estimate the risk of infection, provided personalized recommendations such as testing, self-isolation, or quarantine, and featured QR code data transmission to electronic health records. The PRS served up to 2.5 million monthly users and received 67,000 backlinks from 1800 domains. We clinically evaluated the PRS at the SARS-CoV-2 testing facility at Charité and observed a 21.7% increase in patient throughput per hour and a 22.5% increase in patients per day. Patients using the PRS were twice as likely to belong to the High Risk group eligible for testing (18.6% vs. 8.9%, p < 0.0001), indicating successful compliance with CovApp's recommendations. CovApp served as a digital bridge between the population and medical staff and significantly improved testing efficiency. As an open-source platform, CovApp can be readily customized to address emerging public health crises. Further, given the EHR interface, the app is of great utility for other applications in clinical settings.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/epidemiology , Electronic Health Records , COVID-19 Testing , Delivery of Health Care , Internet
3.
Qual Life Res ; 32(3): 749-758, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36617606

ABSTRACT

PURPOSE: The assessment of health-related quality of life (HRQOL) measured via patient-reported outcomes (PROs) is a key component in clinical trials and increasingly used in clinical routine worldwide. Two PRO measures (PROMs) that share the same definition of health and report outcomes on a comparable T-metric anchored to general population samples are the PROMIS-29 and the EORTC QLQ-C30. In this study, we investigate the empirical agreement of these underlying concepts. METHODS: We collected PROMIS-29 and EORTC QLQ-C30 data from 1,478 female patients at a breast cancer outpatient centre. We calculated descriptive statistics and correlations between the subscales of both instruments. We performed exploratory (EFA) and confirmatory factor analysis (CFA) in randomly split subsamples in order to assess the underlying psychometric structure of both instruments. RESULTS: The cohort (mean age = 47.4, ± 14.49) reported comparable mean HRQOL scores between the corresponding subscales of both instruments similar to general population reference values. Correlation between the corresponding subscales of both instruments ranged between 0.59 (Social Role) and 0.78 (Physical Functioning). Both an exploratory and a theoretically driven confirmatory factor analysis provided further support for conceptual agreement of the scales. CONCLUSION: EORTC QLQ-C30 and PROMIS-29 showed similar scores and satisfactory agreement in conceptional and statistical analysis. This suggests that the underlying conceptualization of health is reasonably close. Hence, the development of score transformation algorithms or calibration of both instruments on common scales could prospectively increase the comparability of clinical and research PRO data collected with either instrument.


Subject(s)
Breast Neoplasms , Quality of Life , Humans , Female , Quality of Life/psychology , Algorithms , Calibration , Factor Analysis, Statistical , Surveys and Questionnaires
4.
Geburtshilfe Frauenheilkd ; 82(7): 747-754, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35815101

ABSTRACT

Introduction The gathering of health and quality-of-life issues that matter most to patients over so-called patient-reported outcomes (PROs) is a key aspect of patient-centered healthcare. In obstetrics, this approach has the potential to expand the current understanding of what quality entails by including patient perspectives. The International Consortium for Health Outcome Measures (ICHOM), founded in 2012, is a global organization which aims to standardise the collection of PROs and make the results comparable worldwide. A PRO Set for obstetrics, "Pregnancy and Childbirth", was published in 2018. The aim of our work was to translate the instruments of this set that are not yet available in German into German. Methods The instruments were translated from English into German using the Functional Assessment of Chronic Illness Therapy (FACIT) translation method. The translated instruments consisted of the Breastfeeding Self-Efficacy Scale - Short Form (BSES-SF), the Mother-to-Infant Bonding Scale (MIBS), and the Birth Satisfaction Scale - Revised (BSS-R) as well as a number of individual questions (items). Results The final version of the German translations were found to be easily comprehensible by the target group. During the cognitive debriefing, it became clear that pregnant women and women who had just given birth often used a number of medically incorrect terms to refer to their symptoms or complaints. In the translations great care was taken to ensure that the wording was as close as possible to the general usage of the language while at the same time the terminology was medically correct. To achieve a precise but comprehensible translation, the response structure of the BSES-SF also had to be adapted. Conclusions The instruments of the ICHOM Standard Set "Pregnancy and Childbirth", which were not previously available in German, were successfully translated into German. This meant dealing with a few challenges such as adapting questions or response structures. The cultural and linguistic comprehensibility of the German translations were confirmed during the subsequent cognitive debriefing. The translations offer the possibility of implementing the complete ICHOM Set for Pregnancy and Childbirth. This would provide an opportunity to expand the existing understanding of quality by including the subjective experience of women during and after childbirth and, in future, to compare outcomes with those of other hospitals across the world.

5.
RSC Adv ; 12(13): 7996-8002, 2022 Mar 08.
Article in English | MEDLINE | ID: mdl-35424741

ABSTRACT

Combinatorial material science crucially depends on robust, high-throughput characterization methods. While X-ray photoelectron spectroscopy (XPS) may provide detailed information about chemical and electronic properties, it is a time-consuming technique and, therefore, is not viewed as a high-throughput method. Here we present preliminary XPS data of 169 measurement spots on a combinatorial 72 × 72 cm2 Cu x Ni1-x O y compositional library to explore how characterization and evaluation routines can be optimized to improve throughput in XPS for combinatorial studies. In particular, two quantification approaches are compared. We find that a simple integration (of XPS peak regions) approach is suited for fast evaluation of, in the example system, the [Cu]/([Cu] + [Ni]) ratio. Complementary to that, the time-consuming (XPS peak-) fit approach provides additional insights into chemical speciation and oxidation state changes, without a large deviation of the [Cu]/([Cu] + [Ni]) ratio. This insight suggests exploiting the fast integration approach for 'real time' analysis during XPS data collection, paving the way for an 'on-the-fly' selection of points of interest (i.e., areas on the sample where sudden composition changes have been identified) for detailed XPS characterization. Together with the envisioned improvements when going from laboratory to synchrotron-based excitation sources, this will shorten the analysis time sufficiently for XPS to become a realistic characterization option for combinatorial material science.

6.
ACS Appl Mater Interfaces ; 14(7): 9676-9684, 2022 Feb 23.
Article in English | MEDLINE | ID: mdl-35134299

ABSTRACT

Copper indium disulfide (CuInS2) grown under Cu-rich conditions exhibits high optical quality but suffers predominantly from charge carrier interface recombination, resulting in poor solar cell performance. An unfavorable "cliff"-like conduction band alignment at the buffer/CuInS2 interface could be a possible cause of enhanced interface recombination in the device. In this work, we exploit direct and inverse photoelectron spectroscopy together with electrical characterization to investigate the cause of interface recombination in chemical bath-deposited Zn(O,S)/co-evaporated CuInS2-based devices. Temperature-dependent current-voltage analyses indeed reveal an activation energy of the dominant charge carrier recombination path, considerably smaller than the absorber bulk band gap, confirming the dominant recombination channel to be present at the Zn(O,S)/CuInS2 interface. However, photoelectron spectroscopy measurements indicate a small (0.1 eV) "spike"-like conduction band offset at the Zn(O,S)/CuInS2 interface, excluding an unfavorable energy-level alignment to be the prominent cause for strong interface recombination. The observed band bending upon interface formation also suggests Fermi-level pinning not to be the main reason, leaving near-interface defects (as recently observed in Cu-rich CuInSe2) as the likely reason for the performance-limiting interface recombination.

7.
Angew Chem Int Ed Engl ; 60(39): 21583-21591, 2021 Sep 20.
Article in English | MEDLINE | ID: mdl-34228886

ABSTRACT

Tin is the frontrunner for substituting toxic lead in perovskite solar cells. However, tin suffers the detrimental oxidation of SnII to SnIV . Most of reported strategies employ SnF2 in the perovskite precursor solution to prevent SnIV formation. Nevertheless, the working mechanism of this additive remains debated. To further elucidate it, we investigate the fluoride chemistry in tin halide perovskites by complementary analytical tools. NMR analysis of the precursor solution discloses a strong preferential affinity of fluoride anions for SnIV over SnII , selectively complexing it as SnF4 . Hard X-ray photoelectron spectroscopy on films shows the lower tendency of SnF4 than SnI4 to get included in the perovskite structure, hence preventing the inclusion of SnIV in the film. Finally, small-angle X-ray scattering reveals the strong influence of fluoride on the colloidal chemistry of precursor dispersions, directly affecting perovskite crystallization.

8.
Clin Microbiol Infect ; 26(12): 1685.e7-1685.e12, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32827715

ABSTRACT

OBJECTIVE: In Berlin, the first public severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing site started 1 day after the first case in the city occurred. We describe epidemiological and clinical characteristics and aim at identifying risk factors for SARS-CoV-2 detection during the first 6 weeks of operation. METHODS: Testing followed national recommendations, but was also based on the physician's discretion. We related patient characteristics to SARS-CoV-2 test positivity for exploratory analyses using a cross-sectional, observational study design. RESULTS: Between 3 March and 13 April 2020, 5179 individuals attended the site (median age 34 years; interquartile range 26-47 years). The median time since disease onset was 4 days (interquartile range 2-7 days). Among 4333 persons tested, 333 (7.7%) were positive. Test positivity increased up to 10.3% (96/929) during the first 3 weeks and then declined, paralleling Germany's lock-down and the course of the epidemic in Berlin. Strict adherence to testing guidelines resulted in 10.4% (262/2530) test positivity, compared with 3.9% (71/1803) among individuals tested for other indications. A nightclub was a transmission hotspot; 27.7% (26/94) of one night's visitors were found positive. Smell and/or taste dysfunction indicated coronavirus disease 2019 (COVID-19) with 85.6% specificity (95% CI 82.1%-88.1%). Four per cent (14/333) of those infected were asymptomatic. Risk factors for detection of SARS-CoV-2 infection were recent contact with a positive case (second week after contact, OR 3.42; 95% CI 2.48-4.71), travel to regions of high pandemic activity (e.g. Austria, OR 4.16; 95% CI 2.48-6.99), recent onset of symptoms (second week, OR 3.61; 95% CI 1.87-6.98) and an impaired sense of smell/taste (4.08; 95% CI 2.36-7.03). CONCLUSIONS: In this young population, early-onset presentation of COVID-19 resembled flu-like symptoms, except for smell and/or taste dysfunction. Risk factors for SARS-CoV-2 detection were return from regions with high incidence and contact with confirmed SARS-CoV-2 cases, particularly when tests were administered within the first 2 weeks after contact and/or onset of symptoms.


Subject(s)
COVID-19 Testing/statistics & numerical data , COVID-19/epidemiology , Carrier State/epidemiology , Adult , Berlin/epidemiology , COVID-19/diagnosis , COVID-19/physiopathology , COVID-19 Testing/methods , Carrier State/diagnosis , Carrier State/virology , Cross-Sectional Studies , Female , Humans , Incidence , Male , Mass Screening/statistics & numerical data , Middle Aged , Olfaction Disorders/epidemiology , Olfaction Disorders/virology , Pandemics/statistics & numerical data , Risk Factors , Sensitivity and Specificity , Taste Disorders/epidemiology , Taste Disorders/virology
9.
ACS Appl Mater Interfaces ; 12(31): 34941-34948, 2020 Aug 05.
Article in English | MEDLINE | ID: mdl-32633119

ABSTRACT

The underlying beneficial mechanism of heavy alkali postdeposition treatment (PDT) of Cu(In,Ga)Se2 thin-film solar cell absorbers that led to new record efficiencies in recent years is studied using photoelectron spectroscopy. Excitation energies between 40.8 eV and 6 keV were used to examine the near-surface region of Cu(In,Ga)Se2 thin-film solar cell absorbers that underwent NaF and combined NaF/RbF PDT. The already Cu-deficient surface region after NaF PDT, which is modeled as a Cu:(In + Ga):Se = 1:5:8 phase, shows further depletion after NaF/RbF PDT and seems to incorporate some Rb. Additionally, we have found strong indications for the NaF/RbF PDT-induced formation of a Rb-In-Se-type compound with a 1:1:2 stoichiometry partially covering the absorber surface. The electronic Cu(In,Ga)Se2 structure is modified due to the RbF treatment, with a pronounced shift in the valence band maximum away from the Fermi level in the immediate vicinity of the surface.

10.
ACS Appl Mater Interfaces ; 12(10): 12353-12361, 2020 Mar 11.
Article in English | MEDLINE | ID: mdl-32045207

ABSTRACT

We report on the chemical and electronic structure of cesium tin bromide (CsSnBr3) and how it is impacted by the addition of 20 mol % tin fluoride (SnF2) to the precursor solution, using both surface-sensitive lab-based soft X-ray photoelectron spectroscopy (XPS) and near-surface bulk-sensitive synchrotron-based hard XPS (HAXPES). To determine the reproducibility and reliability of conclusions, several (nominally identically prepared) sample sets were investigated. The effects of deposition reproducibility, handling, and transport are found to cause significant changes in the measured properties of the films. Variations in the HAXPES-derived compositions between individual sample sets were observed, but in general, they confirm that the addition of 20 mol % SnF2 improves coverage of the titanium dioxide substrate by CsSnBr3 and decreases the oxidation of SnII to SnIV while also suppressing formation of secondary Br and Cs species. Furthermore, the (surface) composition is found to be Cs-deficient and Sn-rich compared to the nominal stoichiometry. The valence band (VB) shows a SnF2-induced redistribution of Sn 5s-derived density of states, reflecting the changing SnII/SnIV ratio. Notwithstanding some variability in the data, we conclude that SnF2 addition decreases the energy difference between the VB maximum of CsSnBr3 and the Fermi level, which we explain by defect chemistry considerations.

11.
J Am Chem Soc ; 142(5): 2364-2374, 2020 Feb 05.
Article in English | MEDLINE | ID: mdl-31917562

ABSTRACT

Halide perovskites are a strong candidate for the next generation of photovoltaics. Chemical doping of halide perovskites is an established strategy to prepare the highest efficiency and most stable perovskite-based solar cells. In this study, we unveil the doping mechanism of halide perovskites using a series of alkaline earth metals. We find that low doping levels enable the incorporation of the dopant within the perovskite lattice, whereas high doping concentrations induce surface segregation. The threshold from low to high doping regime correlates to the size of the doping element. We show that the low doping regime results in a more n-type material, while the high doping regime induces a less n-type doping character. Our work provides a comprehensive picture of the unique doping mechanism of halide perovskites, which differs from classical semiconductors. We proved the effectiveness of the low doping regime for the first time, demonstrating highly efficient methylammonium lead iodide based solar cells in both n-i-p and p-i-n architectures.

13.
ACS Omega ; 4(6): 10985-10990, 2019 Jun 30.
Article in English | MEDLINE | ID: mdl-31460196

ABSTRACT

The chemical and electronic structure of MoO3 thin films is monitored by synchrotron-based hard X-ray photoelectron spectroscopy while annealing from room temperature to 310 °C. Color-coded 2D intensity maps of the Mo 3d and O 1s and valence band maximum (VBM) spectra show the evolution of the annealing-induced changes. Broadening of the Mo 3d and O 1s spectra indicate the reduction of MoO3. At moderate temperatures (120-200 °C), we find spectral evidence for the formation of Mo5+ and at higher temperatures (>165 °C) also of Mo4+ states. These states can be related to the spectral intensity above the VBM attributed to O vacancy induced gap states caused by partial filling of initially unoccupied Mo 4d-derived states. A clear relation between annealing temperature and the induced changes in the chemical and electronic structure suggests this approach as a route for deliberate tuning of MoO3 thin-film properties.

14.
JMIR Cancer ; 4(2): e11373, 2018 Dec 20.
Article in English | MEDLINE | ID: mdl-30573450

ABSTRACT

BACKGROUND: Collecting patient-reported outcome (PRO) data systematically enables objective evaluation of treatment and its related outcomes. Using disease-specific questionnaires developed by the International Consortium for Health Outcome Measurement (ICHOM) allows for comparison between physicians, hospitals, and even different countries. OBJECTIVE: This pilot project aimed to establish a digital system to measure PROs for new patients with breast cancer who attended the Charité Breast Center This approach should serve as a blueprint to further expand the PRO measurement to other disease entities and departments. METHODS: In November 2016, we implemented a Web-based system to collect PRO data at Charité Breast Center using the ICHOM dataset. All new patients at the Breast Center were enrolled and answered a predefined set of questions using a tablet computer. Once they started their treatment at Charité, automated emails were sent to the patients at predefined treatment points. Those emails contained a Web-based link through which they could access and answer questionnaires. RESULTS: By now, 541 patients have been enrolled and 2470 questionnaires initiated. Overall, 9.4% (51/541) of the patients were under the age of 40 years, 49.7% (269/541) between 40 and 60 years, 39.6% (214/541) between 60 and 80 years, and 1.3% (7/541) over the age of 80 years. The average return rate of questionnaires was 67.0%. When asked about the preference regarding paper versus Web-based questionnaires, 6.0% (8/134) of the patients between 50 and 60 years, 6.0% (9/150) between 60 and 70 years, and 12.7% (9/71) over the age of 70 years preferred paper versions. CONCLUSIONS: Measuring PRO in patients with breast cancer in an automated electronic version is possible across all age ranges while simultaneously achieving a high return rate.

16.
J Phys Chem Lett ; 9(8): 1852-1858, 2018 Apr 19.
Article in English | MEDLINE | ID: mdl-29569928

ABSTRACT

In a combined theoretical and experimental work, we investigate X-ray absorption near-edge structure spectroscopy of the I L3 and the Pb M5 edges of the methylammonium lead iodide (MAPbI3) hybrid inorganic-organic perovskite and its binary phase PbI2. The absorption onsets are dominated by bound excitons with sizable binding energies of a few hundred millielectronvolts and pronounced anisotropy. The spectra of both materials exhibit remarkable similarities, suggesting that the fingerprints of core excitations in MAPbI3 are essentially given by its inorganic component, with negligible influence from the organic groups. The theoretical analysis complementing experimental observations provides the conceptual insights required for a full characterization of this complex material.

17.
Am J Med Genet A ; 170(3): 728-33, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26640080

ABSTRACT

Using whole-exome sequencing, we identified a homozygous acceptor splice-site mutation in intron 6 of the KATNB1 gene in a patient from a consanguineous Turkish family who presented with congenital microcephaly, lissencephaly, short stature, polysyndactyly, and dental abnormalities. cDNA analysis revealed complete loss of the natural acceptor splice-site resulting either in the usage of an alternative, exonic acceptor splice-site inducing a frame-shift and premature protein truncation or, to a minor extent, in complete skipping of exon 7. Both effects most likely lead to complete loss of KATNB1 function. Homozygous and compound heterozygous mutations in KATNB1 have very recently been described as a cause of microcephaly with brain malformations and seizures. We extend the KATNB1 associated phenotype by describing a syndrome characterized by primordial dwarfism, lissencephaly, polysyndactyly, and dental anomalies, which is caused by a homozygous truncating KATNB1 mutation.


Subject(s)
Dwarfism/genetics , Homozygote , Lissencephaly/genetics , Microcephaly/genetics , Mutation , Syndactyly/genetics , Child, Preschool , DNA Mutational Analysis , Dwarfism/diagnosis , Exome , Female , Gene Order , Genetic Loci , High-Throughput Nucleotide Sequencing , Humans , Lissencephaly/diagnosis , Magnetic Resonance Imaging , Microcephaly/diagnosis , Pedigree , Phenotype , Syndactyly/diagnosis , Syndrome
18.
Opt Express ; 21(7): 7858-67, 2013 Apr 08.
Article in English | MEDLINE | ID: mdl-23571876

ABSTRACT

This study presents a novel numerical model for laser ablation and laser damage in glass including beam propagation and nonlinear absorption of multiple incident ultrashort laser pulses. The laser ablation and damage in the glass cutting process with a picosecond pulsed laser was studied. The numerical results were in good agreement with our experimental observations, thereby revealing the damage mechanism induced by laser ablation. Beam propagation effects such as interference, diffraction and refraction, play a major role in the evolution of the crater structure and the damage region. There are three different damage regions, a thin layer and two different kinds of spikes. Moreover, the electronic damage mechanism was verified and distinguished from heat modification using the experimental results with different pulse spatial overlaps.


Subject(s)
Glass/chemistry , Glass/radiation effects , Lasers , Models, Chemical , Computer Simulation , Radiation Dosage , Scattering, Radiation
19.
JIMD Rep ; 10: 17-22, 2013.
Article in English | MEDLINE | ID: mdl-23430795

ABSTRACT

With over 1,000 nuclear genes that could potentially cause a mitochondrial disorder, the current diagnostic approach requires targeted molecular analysis, guided by a combination of clinical and biochemical features. However, the expanding molecular and clinical spectrum means that this approach does not always yield a result. Here we report the unusual clinical presentation of "Progressive External Ophthalmoplegia (PEO) plus" Leigh syndrome in three children from a consanguineous family where exome sequencing identified mutations in NDUFS8. NDUFS8 is a nuclear-encoded structural core protein of complex I, and mutations are expected to cause infantile onset and severe disease. Our patients had a later onset, milder and a clinically distinct phenotype, and this gene would not normally be considered in this context. Being untargeted to specific genes, whole exome analysis has the potential to re-write the phenotype and reveal an unexpected molecular aetiology, as illustrated by this family.

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