Disentangling the Impact of Point Defect Density and Carrier Localization-Enhanced Auger Recombination on Efficiency Droop in (In,Ga)N/GaN Quantum Wells.

The internal quantum efficiency of (In,Ga)N/GaN quantum wells can surpass 90% for blue-emitting structures at moderate drive current densities but decreases significantly for longer emission wavelengths and at higher excitation rates. This latter effect is known as efficiency "droop" and limits the brightness of light-emitting diodes (LEDs) based on such quantum wells. Several mechanisms have been proposed to explain efficiency droop including Auger recombination, both intrinsic and defect-assisted, carrier escape, and the saturation of localized states. However, it remains unclear which of these mechanisms is most important because it has proven difficult to reconcile theoretical calculations of droop with measurements. Here, we first present experimental photoluminescence measurements extending over three orders of magnitude of excitation for three samples grown at different temperatures that indicate that droop behavior is not dependent on the point defect density in the quantum wells studied. Second, we use an atomistic tight-binding electronic structure model to calculate localization-enhanced radiative and Auger rates and show that both the corresponding carrier density-dependent internal quantum efficiency and the carrier density decay dynamics are in excellent agreement with our experimental measurements. Moreover, we show that point defect density, Auger recombination, and the effect of the polarization field on recombination rates only limit the peak internal quantum efficiency to about 70% in the resonantly excited green-emitting quantum wells studied. This suggests that factors external to the quantum wells, such as carrier injection efficiency and homogeneity, contribute appreciably to the significantly lower peak external quantum efficiency of green LEDs.

BAOMS QOMS: findings from the pilot phase and lessons learned in the feasibility evaluation of a national quality improvement initiative.

The BAOMS QOMS pilot was developed and run in six England OMFS units between December 2019 - April 2020. The aims of this pilot project were: to evaluate feasibility of the questionnaires developed for the audit and how effective they were with regards to quality improvement, to test the processes associated with the data collection system and finally, to provide baseline data to support patient data collection without the requirement of prospective consent. The pilot included a series of six audits (oral and dentoalveolar [ODA], oncology, orthognathic, reconstruction, trauma, and skin). Data entry was clinician-led in five OMFS units and in one unit (EKHU), it was additionally supported by members of the clinical coding team. One hundred and twenty-eight REDCap account user details were issued and of these, 45 (35%) completed registration and 22 (17%) were active users who participated in the pilot data entry. Disproportionate focus on individual audits within QOMS was seen, though not all units offered the full range of service audited. Users suggest the skin and ODA audits were sufficiently clear, but improvement is required in the oncology and reconstruction questionnaire particularly. The pilot was successful in aiding the project team identify areas of weaknesses and strength in the design of the REDCap registry and implementation of the next phase of the initiative. The information and experience gained has to date enabled a successful application for section 251 approval from the HRA and progress for the next phase of national data collection.

Risk for Heterosexual HIV Transmission Among Non-Injecting Female Partners of Injection Drug Users in Estonia.

The HIV epidemic in Estonia, as with other eastern European countries, is currently concentrated among injection drug users (IDUs). Non-IDUs who have IDU sex partners could serve as a potential bridge in an expanding epidemic. We applied HIV transmission modelling to data collected from non-IDU/IDU heterosexual couples in Kohtla-Järve, Estonia to estimate HIV risk from IDUs to their sex partners based on self-reported sexual behaviors shared by the couple. IDUs and their current main non-injecting sex partners were recruited for an interviewer-administered survey and HIV testing. Bernoulli modelling techniques were applied to estimate the risk of HIV transmission (incidence) among HIV negative non-injecting female partners of male IDUs. The estimated HIV incidence in this population of non-injecting women with only main sexual partners in the last 6 months ranged from 3.24 to 4.94 HIV seroconversions per 100 person years depending on the value used in the models for the per act transmission rate during acute stage infection. Non-IDUs who have IDU sex partners are at high risk for HIV and could serve as a potential bridge to a more generalized epidemic. Whether this might lead to an expansion of the HIV epidemic beyond core groups in Estonia or other Eastern European countries warrants closer study.

Increased expression of ER stress- and hypoxia-associated molecules in grey matter lesions in multiple sclerosis.

BACKGROUND: The endoplasmic reticulum (ER) stress pathway may play a role in the pathogenesis multiple sclerosis (MS), and while ER stress-associated molecules have been demonstrated in white matter (WM) lesions, these have not been analysed in grey matter (GM) demyelination. OBJECTIVE: The objective was to characterise the type and frequency of GM lesions and establish expression profiles of ER stress- and hypoxia-associated markers. METHODS: Sections from 16 MS cases and 12 non-MS controls were stained for ER stress molecules (BiP and CHOP) and hypoxia-associated D110 antigen. RESULTS: Of the GM lesions analysed, 24% were type 1 (continuous between GM and WM), 22% were type 2 (entirely within GM) and the majority (54%) were type 3 (extending from pia mater). Comparison of GM lesions, MS normal-appearing grey matter (NAGM) and non-MS control tissue showed that NAGM, type 1 and type 3 lesions all had significantly increased levels of CHOP compared to controls. According to morphological and dual-labelling criteria, the majority of CHOP-positive cells were microglia. Approximately 50% of GM lesions contained D110-positive cells. CONCLUSION: These data suggest that ER stress plays an important role in GM lesion development and may be critical in activation of microglia in pre-lesional NAGM. The high number of lesions containing D110-positive cells suggests a role for hypoxic-like insult in GM lesion development.

De novo SCN1A mutations in migrating partial seizures of infancy.

OBJECTIVE: To determine the genetic etiology of the severe early infantile onset syndrome of malignant migrating partial seizures of infancy (MPSI). METHODS: Fifteen unrelated children with MPSI were screened for mutations in genes associated with infantile epileptic encephalopathies: SCN1A, CDKL5, STXBP1, PCDH19, and POLG. Microarray studies were performed to identify copy number variations. RESULTS: One patient had a de novo SCN1A missense mutation p.R862G that affects the voltage sensor segment of SCN1A. A second patient had a de novo 11.06 Mb deletion of chromosome 2q24.2q31.1 encompassing more than 40 genes that included SCN1A. Screening of CDKL5 (13/15 patients), STXBP1 (13/15), PCDH19 (9/11 females), and the 3 common European mutations of POLG (11/15) was negative. Pathogenic copy number variations were not detected in 11/12 cases. CONCLUSION: Epilepsies associated with SCN1A mutations range in severity from febrile seizures to severe epileptic encephalopathies including Dravet syndrome and severe infantile multifocal epilepsy. MPSI is now the most severe SCN1A phenotype described to date. While not a common cause of MPSI, SCN1A screening should now be considered in patients with this devastating epileptic encephalopathy.

Emergent properties of HIV risk among injection drug users in Tallinn, Estonia: synthesis of individual and neighbourhood-level factors.

OBJECTIVES: HIV/AIDS risk is embodied within multiple levels including structural and social levels. The aim of this study was to assess the effects of neighbourhood characteristics on HIV prevalence among injection drug users (IDU) residing in the area of Tallinn, Estonia in 2007. METHODS: A cross-sectional, multilevel design collecting individual-level data--a behaviour survey including data on self-reported residency and HIV antibody testing among 350 IDU and neighbourhood-level data--aggregate measures on socio-demo-economic residential characteristics from the 2000 Estonian census. Geocoding and multilevel modelling analysis was employed. RESULTS: Among the 350 IDU recruited, earlier age at first injection, fentanyl as the main injection drug, receptive syringe sharing, main income source other than legal employment and ever attended a syringe exchange programme remained significantly associated with increased odds of anti-HIV positivity in the multivariable analysis involving individual effects with no predictors at the neighbourhood level. In the multilevel model, individual (earlier at IDU initiation AOR 1.86, 95% CI 1.01 to 3.44; injecting opioids AOR 4.43, 95% CI 2.74 to 7.18; receptive syringe sharing AOR 2.51, 95% CI 1.86 to 3.37; main income source other than work AOR 2.04, 95% CI 1.32 to 3.14; ever attended a syringe exchange programme AOR 2.58, 95% CI 1.83 to 3.61) and neighbourhood level (higher unemployment rate AOR 5.95, 95% CI 2.47 to 14.31; greater residential change AOR 1.89, 95% CI 1.09 to 3.26) emerged as significant predictors of individual HIV-positive status. CONCLUSIONS: Our results indicate that both individual-level and emergent neighbourhood-level factors contribute to HIV risk among IDU and are amenable for preventive interventions.

Rayleigh anomaly-surface plasmon polariton resonances in palladium and gold subwavelength hole arrays.

Surface plasmon polaritons (SPPs) and Rayleigh anomalies (RAs) are two characteristic phenomena exhibited by periodic grating structures made of plasmonic materials. For Au subwavelength hole arrays, SPPs and RAs from opposite sides of the film can interact under certain conditions to produce highly intense, narrow spectral features called RA-SPP resonances. This paper reports how RA-SPP effects can be achieved in subwavelength hole arrays of Pd, a weak plasmonic material. Well-defined resonances are observed in measured and simulated optical transmission spectra with RASPP peaks as narrow as 45 nm (FWHM). Dispersion diagrams compiled from angle-resolved spectra show that RA-SPP resonances in Pd hole arrays shift in wavelength but do not decrease significantly in amplitude as the excitation angle is increased, in contrast with RA-SPP peaks in Au hole arrays. The apparent generality of the RA-SPP effect enables a novel route to optimize resonances in non-traditional plasmonic media.

Periventricular heterotopia, mental retardation, and epilepsy associated with 5q14.3-q15 deletion.

BACKGROUND: Periventricular heterotopia (PH) is an etiologically heterogeneous disorder characterized by nodules of neurons ectopically placed along the lateral ventricles. Most affected patients have seizures and their cognitive level varies from normal to severely impaired. At present, two genes have been identified to cause PH when mutated. Mutations in FLNA (Xq28) and ARFGEF2 (20q13) are responsible for X-linked bilateral PH and a rare autosomal recessive form of PH with microcephaly. Chromosomal rearrangements involving the 1p36, 5p15, and 7q11 regions have also been reported in association with PH but the genes implicated remain unknown. Fourteen additional distinct anatomoclinical PH syndromes have been described, but no genetic insights into their causes have been gleaned. METHODS: We report the clinical and imaging features of three unrelated patients with epilepsy, mental retardation, and bilateral PH in the walls of the temporal horns of the lateral ventricles, associated with a de novo deletion of the 5q14.3-15 region. We used microarray-based comparative genomic hybridization to define the boundaries of the deletions. RESULTS: The three patients shared a common deleted region spanning 5.8 Mb and containing 14 candidate genes. CONCLUSION: We identified a new syndrome featuring bilateral periventricular heterotopia (PH), mental retardation, and epilepsy, mapping to chromosome 5q14.3-q15. This observation reinforces the extreme clinical and genetic heterogeneity of PH. Array comparative genomic hybridization is a powerful diagnostic tool for characterizing causative chromosomal rearrangements of limited size, identifying potential candidate genes for, and improving genetic counseling in, malformations of cortical development.

Increased nicotinamide nucleotide transhydrogenase levels predispose to insulin hypersecretion in a mouse strain susceptible to diabetes.

AIMS/HYPOTHESIS: Insulin hypersecretion may be an independent predictor of progression to type 2 diabetes. Identifying genes affecting insulin hypersecretion are important in understanding disease progression. We have previously shown that diabetes-susceptible DBA/2 mice congenitally display high insulin secretion. We studied this model to map and identify the gene(s) responsible for this trait. METHODS: Intravenous glucose tolerance tests followed by a genome-wide scan were performed on 171 (C57BL/6 x DBA/2) x C57BL/6 backcross mice. RESULTS: A quantitative trait locus, designated hyperinsulin production-1 (Hip1), was mapped with a logarithm of odds score of 7.7 to a region on chromosome 13. Production of congenic mice confirmed that Hip1 influenced the insulin hypersecretion trait. By studying appropriate recombinant inbred mouse strains, the Hip1 locus was further localised to a 2 Mb interval, which contained only nine genes. Expression analysis showed that the only gene differentially expressed in islets isolated from the parental strains was Nnt, which encodes the mitochondrial proton pump, nicotinamide nucleotide transhydrogenase (NNT). We also found in five mouse strains a positive correlation (r2 = 0.90, p < 0.01) between NNT activity and first-phase insulin secretion, emphasising the importance of this enzyme in beta cell function. Furthermore, of these five strains, only those with high NNT activity are known to exhibit severe diabetes after becoming obese. CONCLUSIONS/INTERPRETATION: Insulin hypersecretion is associated with increased Nnt expression. We suggest that NNT must play an important role in beta cell function and that its effect on the high insulin secretory capacity of the DBA/2 mouse may predispose beta cells of these mice to failure.

Severe myoclonic epilepsy of infancy (Dravet syndrome): recognition and diagnosis in adults.

Establishing an etiologic diagnosis in adults with refractory epilepsy and intellectual disability is challenging. We analyzed the phenotype of 14 adults with severe myoclonic epilepsy of infancy. This phenotype comprised heterogeneous seizure types with nocturnal generalized tonic-clonic seizures predominating, mild to severe intellectual disability, and variable motor abnormalities. The diagnosis was suggested by a characteristic evolution of clinical findings in the first years of life. Ten had mutations in SCN1A and one in GABRG2.

A new molecular mechanism for severe myoclonic epilepsy of infancy: exonic deletions in SCN1A.

We examined cases of severe myoclonic epilepsy of infancy (SMEI) for exon deletions or duplications within the sodium channel SCN1A gene by multiplex ligation-dependent probe amplification. Two of 13 patients (15%) who fulfilled the strict clinical definition of SMEI but without SCN1A coding or splicing mutations had exonic deletions of SCN1A.

Gene transfer into rat mesenchymal stem cells: a comparative study of viral and nonviral vectors.

Mesenchymal stem cells (MSCs) have been proposed for use in combinatorial gene and cell therapy protocols for the treatment of disease and promotion of repair. The efficacy of such a therapeutic approach depends on determination of which vectors give maximal transgene expression with minimal cell death. The study was carried out on bone-marrow derived rat MSCs, and a range of vectors was tested on the same stem cell preparation. Adenovirus, adeno-associated virus (AAV; serotypes 1, 2, 4, 5, and 6), lentivirus, and nonviral vectors were compared. Lentivirus proved to be most effective with transduction efficiencies of up to 95%, concurrent with low levels of cell toxicity. Adenovirus also proved effective, but a significant increase in cell death was seen with increasing viral titer. Rat MSCs remained refractory to transduction by all AAV serotypes, in contrast to rabbit MSCs tested at the same time. Lipofection of plasmid DNA gave moderate transfection levels but was also accompanied by cell death. Electroporative gene transfer proved ineffective at the parameters tested and resulted in high cell death. High and moderate levels of cell transduction using lentivirus vectors did not affect the ability of the cells to differentiate down the adipogenic pathway.

Failure to confirm association of a polymorphism in ABCB1 with multidrug-resistant epilepsy.

Alteration of ATP-binding cassette subfamily B member 1 transporter (ABCB1) can plausibly cause drug-resistant epilepsy as it influences brain penetration of drugs. The CC genotype at the ABCB1 C3435T polymorphism was reported to be associated with multidrug resistance. A replication study in 401 drug-resistant and 208 drug-responsive subjects with epilepsy showed no significant association between the CC genotype and drug-resistant epilepsy. The authors suggest the initial association may have arisen by chance.

LGI1 mutations in temporal lobe epilepsies.

BACKGROUND AND OBJECTIVES: A number of familial temporal lobe epilepsies (TLE) have been recently recognized. Mutations in LGI1 (leucine-rich, glioma-inactivated 1 gene) have been found in a few families with the syndrome of autosomal dominant partial epilepsy with auditory features (ADPEAF). The authors aimed to determine the spectrum of TLE phenotypes with LGI1 mutations, to study the frequency of mutations in ADPEAF, and to examine the role of LGI1 paralogs in ADPEAF without LGI1 mutations. METHODS: The authors performed a clinical and molecular analysis on 75 pedigrees comprising 54 with a variety of familial epilepsies associated with TLE and 21 sporadic TLE cases. All were studied for mutations in LGI1. ADPEAF families negative for LGI1 mutations were screened for mutations in LGI2, LGI3, and LGI4. RESULTS: Four families had ADPEAF, 22 had mesial TLE, 11 had TLE with febrile seizures, two had TLE with developmental abnormalities, and 15 had various other TLE syndromes. LGI1 mutations were found in two of four ADPEAF families, but in none of the other 50 families nor in the 21 individuals with sporadic TLE. The mutations were novel missense mutations in exons 1 (c.124T-->G; C42G) and 8 (c.1418C-->T; S473L). No mutations in LGI2, LGI3, or LGI4 were found in the other two ADPEAF families. CONCLUSION: In TLE, mutations in LGI1 are specific for ADPEAF but do not occur in all families. ADPEAF is genetically heterogeneous, but mutations in LGI2, LGI3, or LGI4 did not account for families without LGI1 mutations.

Semiautomated analytical image correlation.

Machine vision refers to computer programs consisting of a collection of pattern recognition and digital image processing algorithms (Fabel, G. Motion Control 2000, 53-54). A version of machine vision has been applied to correlating digital images generated by optical microscopy and secondary ion mass spectrometry (SIMS). By suitable application of image processing algorithms, semiautomated correlation between optical and secondary ion images is possible. For correlation of minor constituents evident in secondary ion images but invisible in optical images, correlation is performed by reference to the relative position of minor to major constituents. Precise coordinates of features apparent in one analytical image can be translated into the corresponding coordinates of an analytical image obtained by a different method. In principle, this capability yields a semiautomated system to combine complementary features of disparate imaging methods, such as secondary ion and optical microscopy.

Optimisation of electrotransfer of plasmid into skeletal muscle by pretreatment with hyaluronidase -- increased expression with reduced muscle damage.

The efficiency of plasmid gene transfer to skeletal muscle can be significantly improved by the application of an electrical field to the muscle following injection of plasmid DNA. However, this electrotransfer is associated with significant muscle damage which may result in substantial loss of transfected muscle fibres. Reduction of the voltage used in the technique can result in a decrease in muscle damage, with a concomitant reduction in expression, but without a significant decrease in the number of transfected fibres. Pre-treatment of the muscle with a solution of bovine hyaluronidase greatly increases the efficiency of plasmid gene transfer when used in conjunction with electrotransfer, but not when used alone. This combination treatment results in greatly enhanced levels of transfected muscle fibres without the increases in muscle damage associated with the electrotransfer process.

Continuous-wave and passively Q-switched cladding-pumped planar waveguide lasers.

Greater than 12 W of average output power has been generated from a diode-pumped Yb:YAG cladding-pumped planar waveguide laser. The laser radiation developed is linearly polarized and diffraction limited in the guiding dimension. A slope efficiency of 0.5 W/W with a peak optical-optical conversion efficiency of 0.31 W/W is achieved. In a related structure, greater than 8 W of Q -switched average output power has been generated from a Nd:YAG cladding-pumped planar waveguide laser by incorporation of a Cr(4+): YAG passive Q switch monolithically into the waveguide structure. Pulse widths of 3 ns and pulse-repetition frequencies as high as 80 kHz have been demonstrated. A slope efficiency of 0.28 W/W with a peak optical-optical conversion efficiency of 0.21 W/W is achieved.

Secondary ion images of the rodent brain.

Sections of biologic tissue obtained from laboratory rodents are prepared and analyzed by secondary ion mass spectrometry. The intensity of phosphocholine secondary ions is used to identify anatomical features of the brain from secondary ion images and to evaluate the effectiveness of procedures developed. Secondary ion emission of phosphocholine (m/z 184), is found to be abundant and its intensity is heterogeneous. Effects of sample thickness are addressed. Correspondence between conventional optical images of stained tissue and secondary ion images shows that successive ion images may be used to produce a three-dimensional map of the brain, i.e., an atlas.

Colonic spasm and pseudo-obstruction in an elongated colon secondary to physical exertion: diagnosis by stress barium enema.

Anatomic and functional abnormalities of the colon are known to cause a variety of abdominal complaints, including constipation, diarrhea, and pain. We describe a patient with dolichocolon (elongated colon) with transient spasm (pseudo-obstruction) associated with exertion. The diagnosis in this case rested with a novel approach and less invasive evaluation of the colon.