Enhanced laser-induced damage performance of all-glass metasurfaces for energetic pulsed laser applications.

To fabricate optical components with surface layers compatible with high-power laser applications that may operate as antireflective coatings, polarization rotators, or harness physical anisotropy for other uses, metasurfaces are becoming an appealing candidate. In this study, large-beam (1.05 cm diameter) 351-nm laser-induced damage testing was performed on an all-glass metasurface structure composed of cone-like features with a subwavelength spacing of adjacent features. These structures were fabricated on untreated fused silica glass and damage tested, as were structures that were fabricated on fused silica glass that experienced a preliminary etching process to remove the surface Beilby layer that is characteristic of polished fused silica. The laser-induced damage onset for structures on untreated fused silica glass was 19.3J⋅c m -2, while the sample that saw an initial pretreatment etch exhibited an improved damage onset of 20.4J⋅c m -2, only 6% short of the reference pretreated glass damage onset of 21.7J⋅c m -2. For perspective, the National Ignition Facility operational average fluence at this wavelength and pulse length is about 10J/c m 2. At a fluence of 25.5J⋅c m -2, the reference (pretreated) fused silica initiated 5.2 damage sites per m m 2, while the antireflective metasurface sample with a preliminary etching process treatment initiated 9.8 damage sites per m m 2. These findings demonstrate that substrate-engraved metasurfaces are compatible with high energy and power laser applications, further broadening their application space.

Wide-field probing of silica laser-induced damage precursors by photoluminescence photochemical quenching.

We describe a wide-field approach to probe transient changes in photoluminescence (PL) of defects on silica surfaces. This technique allows simultaneous capture of spatially resolved PL with spontaneous quenching behavior. We attribute the quenching of PL intensity to photochemical reactions of surface defects and/or subsurface fractures with ambient molecules. Such quenching curves can be accurately reproduced by our theoretical model using two quenchable defect populations with different reaction rates. The fitting parameters of our model are spatially correlated to fractures in silica where point defects and mechanical stresses are known to be present, potentially indicating regions prone to laser-induced damage growth. We believe that our approach allows rapid spatial resolved identification of damage prone morphology, providing a new pathway to fast, non-destructive predictions of laser-induced damage growth.

Pruritus epidemiology and quality of life.

The burden of chronic pruritus is increasingly recognized as significant worldwide. As wet-laboratory researchers investigate the pathophysiology of chronic pruritus, epidemiologists and health services researchers are quantifying the impact of pruritus by incidence, prevalence, and quality of life measures. Outcomes researchers are also investigating factors that may predict chronic pruritus incidence and severity. Such efforts will direct resources for research, public health intervention, and clinical care.

Model laser damage precursors for high quality optical materials.

Surface damage is known to occur at fluences well below the intrinsic limit of the fused silica. A native surface precursor can absorb sub band-gap light and initiate a process which leads to catastrophic damage many micrometers deep with prominent fracture networks. Previously, the absorption front model of damage initiation has been proposed to explain how this nano-scale absorption can lead to macro-scale damage. However, model precursor systems designed to study initiation experimentally have not been able to clearly reproduce these damage events. In our study, we create artificial absorbers on fused silica substrates to investigate precursor properties critical for native surface damage initiation. Thin optically absorbing films of different materials were deposited on silica surfaces and then damage tested and characterized. We demonstrated that strong interfacial adhesion strength between absorbers and silica is crucial for the launch of an absorption front and subsequent damage initiation. Simulations using the absorption-front model are performed and agree qualitatively with experimental results.

Growth model for laser-induced damage on the exit surface of fused silica under UV, ns laser irradiation.

We present a comprehensive statistical model which includes both the probability of growth and growth rate to describe the evolution of exit surface damage sites on fused silica optics over multiple laser shots spanning a wide range of fluences. We focus primarily on the parameterization of growth rate distributions versus site size and laser fluence using Weibull statistics and show how this model is consistent with established fracture mechanics concepts describing brittle materials. Key growth behaviors and prediction errors associated with the present model are also discussed.

Factors mediating the impact of chronic pruritus on quality of life.

IMPORTANCE: Chronic pruritus is a common problem with a deleterious effect on quality of life. The factors mediating the relationship between chronic pruritus and quality of life are poorly understood. OBJECTIVE: To determine the factors that mediate the impact of chronic pruritus on quality of life. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study based on a nationwide telephone survey of US military veterans sampled from the Veterans Hospital Patient Database. Participants were veterans who agreed to participate and were found to have chronic pruritus. MAIN OUTCOMES AND MEASURES: Statistical significance of predictor variables (characteristics of patients and their chronic pruritus) in multivariate analysis using ItchyQoL scores as response variables. RESULTS: Of 6000 veterans telephoned, 1075 consented to participate; 405 of these had chronic pruritus. Factors that mediated the impact of chronic pruritus on quality of life were demographic characteristics (age [P = .007], race [P = .05], marital status [P = .04]), personality (extroversion [P = .03], neuroticism [P = .01]), pruritus characteristics (severity [P < .001], duration [P = .01], frequency [P < .001], location [P = .005]), and possible etiology (cutaneous vs systemic [P = .03]). Notable factors not found significant include sex (P = .98) and socioeconomic variables (education level [P > .99], employment status [P = .53], income [P = .62]). CONCLUSIONS AND RELEVANCE: The multitude of factors that significantly influence the impact of chronic pruritus on quality of life demonstrates the complex nature of this relationship. A better appreciation of these factors will improve the clinical evaluation and treatment of chronic pruritus.

FOXP1 mutations cause intellectual disability and a recognizable phenotype.

Mutations in FOXP1, located at 3p13, have been reported in patients with global developmental delay (GDD), intellectual disability (ID), and speech defects. Mutations in FOXP2, located at 7q31, are well known to cause developmental speech and language disorders, particularly developmental verbal dyspraxia (DVD). FOXP2 has been shown to work co-operatively with FOXP1 in mouse development. An overlap in FOXP1 and FOXP2 expression, both in the songbird and human fetal brain, has suggested that FOXP1 may also have a role in speech and language disorders. We report on a male child with a 0.19 MB intragenic deletion that is predicted to result in haploinsufficiency of FOXP1. Review of our patient and others reported in the literature reveals an emerging phenotype of GDD/ID with moderate to severe speech delay where expressive speech is most severely affected. DVD appears not to be a distinct feature in this group. Facial features include a broad forehead, downslanting palpebral fissures, a short nose with broad tip, relative or true macrocephaly, a frontal hair upsweep and prominent digit pads. Autistic traits and other behavioral problems are likely to be associated with haploinsufficiency of FOXP1. Congenital malformations may be associated.

Predictive modeling techniques for nanosecond-laser damage growth in fused silica optics.

Empirical numerical descriptions of the growth of laser-induced damage have been previously developed. In this work, Monte-Carlo techniques use these descriptions to model the evolution of a population of damage sites. The accuracy of the model is compared against laser damage growth observations. In addition, a machine learning (classification) technique independently predicts site evolution from patterns extracted directly from the data. The results show that both the Monte-Carlo simulation and machine learning classification algorithm can accurately reproduce the growth of a population of damage sites for at least 10 shots, which is extremely valuable for modeling optics lifetime in operating high-energy laser systems. Furthermore, we have also found that machine learning can be used as an important tool to explore and increase our understanding of the growth process.

Probability of growth of small damage sites on the exit surface of fused silica optics.

Growth of laser damage on fused silica optical components depends on several key parameters including laser fluence, wavelength, pulse duration, and site size. Here we investigate the growth behavior of small damage sites on the exit surface of SiO2 optics under exposure to tightly controlled laser pulses. Results demonstrate that the onset of damage growth is not governed by a threshold, but is probabilistic in nature and depends both on the current size of a damage site and the laser fluence to which it is exposed. We also develop models for use in growth prediction. In addition, we show that laser exposure history also influences the behavior of individual sites.

Exploration of the multiparameter space of nanosecond-laser damage growth in fused silica optics.

Historically, the rate at which laser-induced damage sites grow on the exit surface of SiO2 optics under subsequent illumination with nanosecond-laser pulses of any wavelength was believed to depend solely on laser fluence. We demonstrate here that much of the scatter in previous growth observations was due to additional parameters that were not previously known to affect growth rate, namely the temporal pulse shape and the size of a site. Furthermore, the remaining variability observed in the rate at which sites grow is well described in terms of Weibull statistics. The effects of site size and laser fluence may both be expressed orthogonally in terms of Weibull coefficients. In addition, we employ a clustering algorithm to explore the multiparameter growth space and expose average growth trends. Conversely, this analysis approach also identifies sites likely to exhibit growth rates outside the norm. The ability to identify which sites are likely to grow abnormally fast in advance of the manifestation of such behavior will significantly enhance the accuracy of predictive models over those based on average growth behaviors.

Analysis of 1ω bulk laser damage in KDP.

The influence of laser parameters on laser-induced damage in the bulk of KDP is difficult to determine because the damage manifests as discrete sites a few micrometers in diameter distributed throughout a relatively large volume of material. Here, we present a method to directly measure the size and location of many thousands of such sites and correlate them to the laser conditions that produced them. This technique is used to characterize the effects of pulse duration on damage initiated by 1053 nm light in the bulk of KDP crystals. We find that the density of damage sites produced by 1053 nm light is less sensitive to pulse duration than was previously reported for 526 nm and 351 nm light. In addition, the effect of pulse duration on the size of the damage sites produced appears insensitive to wavelength.

5q14.3 neurocutaneous syndrome: a novel continguous gene syndrome caused by simultaneous deletion of RASA1 and MEF2C.

Haploinsufficiency of RASA1, located on chromosome 5q14.3, has been identified as the etiology underlying the disorder capillary malformation-arteriovenous malformation (CM-AVM). Recently, haploinsufficiency of MEF2C, located 1.33 Mb distal to RASA1 on chromosome 5q14.3, has been implicated as the genetic etiology underlying a complex array of deficits including mental retardation, hypotonia, absent speech, seizures, and brain anomalies. Here we report a patient who is haploinsufficient in both RASA1 and MEF2C who presents with dermatologic and neurologic abnormalities that constitute a 5q14.3 neurocutaneous syndrome. This finding highlights the need to assess for CM-AVM in patients with neurologic features consistent with MEF2C haploinsufficiency, and vice versa.

Large contiguous gene deletions in Sjögren-Larsson syndrome.

Sjögren-Larsson syndrome (SLS) is an autosomal recessive disorder characterized by ichthyosis, mental retardation, spasticity and mutations in the ALDH3A2 gene for fatty aldehyde dehydrogenase, an enzyme that catalyzes the oxidation of fatty aldehyde to fatty acid. More than 70 mutations have been identified in SLS patients, including small deletions or insertions, missense mutations, splicing defects and complex nucleotide changes. We now describe 2 SLS patients whose disease is caused by large contiguous gene deletions of the ALDH3A2 locus on 17p11.2. The deletions were defined using long distance inverse PCR and microarray-based comparative genomic hybridization. A 24-year-old SLS female was homozygous for a 352-kb deletion involving ALDH3A2 and 4 contiguous genes including ALDH3A1, which codes for the major soluble protein in cornea. Although lacking corneal disease, she showed severe symptoms of SLS with uncommon deterioration in oral motor function and loss of ambulation. The other 19-month-old female patient was a compound heterozygote for a 1.44-Mb contiguous gene deletion and a missense mutation (c.407C>T, P136L) in ALDH3A2. These studies suggest that large gene deletions may account for up to 5% of the mutant alleles in SLS. Geneticists should consider the possibility of compound heterozygosity for large deletions in patients with SLS and other inborn errors of metabolism, which has implications for carrier testing and prenatal diagnosis.

Growth behavior of laser-induced damage on fused silica optics under UV, ns laser irradiation.

The growth behavior of laser-induced damage sites is affected by a large number of laser parameters as well as site morphology. Here we investigate the effects of pulse duration on the growth rate of damage sites located on the exit surface of fused silica optics. Results demonstrate a significant dependence of the growth parameters on laser pulse duration at 351 nm from 1 ns to 15 ns, including the observation of a dominant exponential versus linear, multiple-shot growth behavior for long and short pulses, respectively. These salient behaviors are tied to the damage morphology and suggest a shift in the fundamental growth mechanisms for pulses in the 1-5 ns range.

Chiari I malformation, delayed gross motor skills, severe speech delay, and epileptiform discharges in a child with FOXP1 haploinsufficiency.

Human FOXP2 deficiency has been identified as a cause of hereditary developmental verbal dyspraxia. Another member of the same gene family, FOXP1, has expression patterns that overlap with FOXP2 in some areas of the brain, and FOXP1 and FOXP2 have the ability to form heterodimers. These findings suggest the possibility that FOXP1 may also contribute to proper speech development. However, no such role of FOXP1 has been established to date. Recently, a child was reported who presented with a 3p13-14.1 deletion of four genes, including FOXP1, and a constellation of deficits that included speech delay. In this study, we report the case of a patient with a single deletion of FOXP1. This patient presented with speech and motor developmental delays, a Chiari I malformation, and epileptiform discharges. The nature of the speech deficit is different from the primary oromotor verbal dyspraxia found in patients with FOXP2 deficiency. The patient's developmental deficits may support a role for FOXP1 in the development of verbal and motor skills.

Genome-wide linkage scan maps ETINPH gene to chromosome 19q12-13.31.

OBJECTIVE: Essential tremor (ET), one of the most common neurological disorders, comprises uncontrollable tremor, usually in the upper extremities. Idiopathic normal pressure hydrocephalus (iNPH) features ventricular enlargement in the absence of elevated intracranial pressure; its three cardinal symptoms are gait impairment, incontinence, and dementia. iNPH is among the most common medical problems in the older population. To date, the genetic etiologies of ET and iNPH remain largely elusive. METHODS: We previously identified a large kindred in which the affected members developed ET in adolescence or young adulthood and iNPH when elderly, in that case called ETINPH. Employing two different genotyping microarrays and two- or multipoint linkage analysis strategies, genome-wide linkage scans were performed. RESULTS: We mapped the ETINPH locus to chromosome 19q12-13.31. Fine-mapping in this region revealed a maximum two-point lod score of 2.8 at rs2023865 and a maximum multipoint lod score of 17.9 at rs9304878. By haplotype construction, a (conservatively) approximately 17-cM critical region from SNP rs11084582 to SNP rs7258420 was defined. This region contains several neuronal genes that constitute tantalizing etiological candidates for ETINPH. CONCLUSION: The importance of uncovering the genetic etiology of this disorder is irrefutable, as such a discovery could offer valuable insights into ET, iNPH, and related neurological conditions.

Van den Ende-Gupta syndrome: laryngeal abnormalities in two siblings.

In 1992, van den Ende et al. first reported an autosomal recessive multiple congenital anomaly syndrome characterized by blepharophimosis, arachnodactyly, and congenital contractures in a Brazilian girl born to consanguineous parents. Since then, nine total patients have been reported with van den Ende-Gupta syndrome (VDEGS), and the syndrome's phenotype has been found to also include additional dysmorphic facial features, palatal abnormalities, and slender skeletal features. We present two African-American sisters born to nonconsanguineous parents who have been diagnosed with VDEGS. Both sisters developed stridor and were found to have an unusual malformation characterized by large, globular cuneiform cartilages, shortened aryepiglottic folds, a tightly coiled epiglottis, and laryngomalacia. Both patients underwent supraglottoplasty with a successful outcome. A review of the literature reveals that airway problems have been reported in a previous patient. However, no specific airway anomaly has been reported. We suggest that all patients with VDEGS and stridor undergo direct laryngoscopy with consideration for surgical correction.

Laser-induced defect reactions governing damage initiation in DKDP crystals.

We investigate the interaction of high-power nanosecond-laser pulses at different frequencies with damage initiating defect structures in bulk KD(x)H(2-x)PO(4) (DKDP) crystals in order to enhance the understanding of a) the nature and behavior of the defects involved and b) the laser-induced defect reactions leading to improvement to the material performance. The experimental results indicate that there is more than one type of defect structure giving rise to damage initiation over two different spectral ranges. Moreover, within one set of defects we observe two different damage behaviors depending on the pre-irradiation parameters, pointing to more than one defect reaction pathway.