Echolalia from a transdiagnostic perspective.

Background & aims: Echolalia, the repetition of one's or others' utterances, is a behavior present in typical development, autism spectrum disorder, aphasias, Tourette's, and other clinical groups. Despite the broad range of conditions in which echolalia can occur, it is considered primarily through a disorder-specific lens, which limits a full understanding of the behavior. Method: Empirical and review papers on echolalia across disciplines and etiologies were considered for this narrative review. Literatures were condensed into three primary sections, including echolalia presentations, neural mechanisms, and treatment approaches. Main contribution: Echolalia, commonly observed in autism and other developmental conditions, is assessed, observed, and treated in a siloed fashion, which reduces our collective knowledge of this communication difference. Echolalia should be considered as a developmental, transdiagnostic, and communicative phenomenon. Echolalia is commonly considered as a communicative behavior, but little is known about its neural etiologies or efficacious treatments. Conclusions: This review is the first to synthesize echolalia from a transdiagnostic perspective, which allows for the direct comparisons across and within clinical groups to inform assessment, treatment, conceptualization, and research recommendations. Implications: Considering echolalia transdiagnostically highlights the lack of consensus on operationalization and measurement across and within disorders. Clinical and research future directions need to prioritize consistent definitions of echolalia, which can be used to derive accurate prevalence estimates. Echolalia should be considered as a communication strategy, used similarly across developmental and clinical groups, with recommended strategies of shaping to increase its effectiveness.

Neurogenesis in the neonatal rat hippocampus is regulated by sexually dimorphic epigenetic modifiers.

BACKGROUND: Neurogenesis in the hippocampus endures across the lifespan but is particularly prolific during the first postnatal week in the developing rodent brain. The majority of new born neurons are in the dentate gyrus (DG). The number of new neurons born during the first postnatal week in the DG of male rat pups is about double the number in females. In other systems, the rate of cell proliferation is controlled by epigenetic modifications in stem cells. We, therefore, explored the potential impact of DNA methylation and histone acetylation on cell genesis in the developing DG of male and female rats. METHODS: Cell genesis was assessed by quantification of BrdU + cells in the DG of neonatal rats following injections on multiple days. Methylation and acetylation were manipulated pharmacologically by injection of well vetted drugs. DNA methylation, histone acetylation and associated enzyme activity were measured using commercially available colorimetric assays. mRNA was quantified by PCR. Multiple group comparisons were made by one- or two-way ANOVA followed by post-hoc tests controlling for multiple comparisons. Two groups were compared by t test. RESULTS: We found higher levels of DNA methylation in male DG and treatment with the DNA methylating enzyme inhibitor zebularine reduced the methylation and correspondingly reduced cell genesis. The same treatment had no impact on either measure in females. By contrast, treatment with a histone deacetylase inhibitor, trichostatin-A, increased histone acetylation in the DG of both sexes but increased cell genesis only in females. Females had higher baseline histone deacetylase activity and greater inhibition in response to trichostatin-A treatment. The mRNA levels of the proproliferative gene brain-derived neurotrophic factor were greater in males and reduced by inhibiting both DNA methylation and histone deacetylation only in males. CONCLUSIONS: These data reveal a sexually dimorphic epigenetically based regulation of neurogenesis in the DG but the mechanisms establishing the distinct regulation involving DNA methylation in males and histone acetylation in females is unknown.

Artificial Coherent States of Light by Multiphoton Interference in a Single-Photon Stream.

Coherent optical states consist of a quantum superposition of different photon number (Fock) states, but because they do not form an orthogonal basis, no photon number states can be obtained from it by linear optics. Here we demonstrate the reverse, by manipulating a random continuous single-photon stream using quantum interference in an optical Sagnac loop, we create engineered quantum states of light with tunable photon statistics, including approximate weak coherent states. We demonstrate this experimentally using a true single-photon stream produced by a semiconductor quantum dot in an optical microcavity, and show that we can obtain light with g^{(2)}(0)→1 in agreement with our theory, which can only be explained by quantum interference of at least 3 photons. The produced artificial light states are, however, much more complex than coherent states, containing quantum entanglement of photons, making them a resource for multiphoton entanglement.

Age, but Not Sex, Modulates Foxp3 Expression in the Rat Brain across Development.

The interconnectivity between brain development and the immune system has become an area of interest for many neuroscientists. However, to date, a limited number of known immune mediators of the peripheral nervous system (PNS) have been found to influence the development of the central nervous system (CNS). FOXP3 is a well-established mediator of regulatory T-cells in the PNS. However, the expression pattern of FOXP3 in the CNS and the PNS throughout development is unknown. To fill this void, we have characterized, in several brain regions, the developmental profile of Foxp3 for both sexes using rats. We found different patterns of Foxp3 in the CNS and PNS. In the CNS, we found Foxp3 was ubiquitously expressed, with the levels of Foxp3 varying by brain region. We also found both Foxp3 mRNA and protein levels peak during embryonic development and then steadily decrease with a peak increase during adulthood. In adulthood, the protein but not mRNA increases to the equivalent levels found at the embryonic stage of life. In the PNS, Foxp3 protein levels were low embryonically and increased steadily over the life of the animal with maximal levels reached in adulthood. Patterns observed for both the PNS and CNS were similar in males and females across all developmental timepoints. Our novel findings have implications for understanding how the neural immune system impacts neurodevelopmental disorders such as autism and schizophrenia.

Molecular detection of Streptococcus equi subspecies equi in face flies (Musca autumnalis) collected during a strangles outbreak on a Thoroughbred farm.

The objective of this study was to detect Streptococcus equi subspecies equi (S. equi) (Lactobacillales: Streptococcaceae) using quantitative polymerase chain reaction (qPCR) in flies collected from a farm with a documented outbreak of strangles. A total of 1856 face flies [Musca autumnalis (Diptera: Muscidae)] were collected using conventional fly traps. The flies were processed for nucleic acid purification and tested for the presence of S. equi by qPCR. A total of 10/1856 flies (0.54%) tested qPCR-positive for S. equi. The results may implicate the presence of face flies as a risk factor for the transmission of S. equi and highlight the need to institute proper husbandry measures, biosecurity protocols and fly control in order to reduce the potential for infection in at-risk horses.

Direct detection of Coccidioides from Arizona soils using CocciENV, a highly sensitive and specific real-time PCR assay.

Coccidioides immitis and Coccidioides posadasii are soil fungi endemic to desert regions of the southwestern United States, and the causative agents of valley fever, or coccidioidomycosis. Studies have shown that the distribution of Coccidioides in soils is sporadic and cannot be explained by soil characteristics alone, suggesting that biotic and other abiotic factors should be examined. However, tools to reliably and robustly screen the large number of soils needed to investigate these potential associations have not been available. Thus, we developed a real-time polymerase chain reaction (PCR) assay for testing environmental samples by modifying CocciDx, an assay validated for testing clinical specimens to facilitate coccidioidomycosis diagnosis. For this study, we collected soil samples from previously established locations of C. posadasii in Arizona and new locations in fall 2013 and spring 2014, and screened the extracted DNA with the new assay known as CocciEnv. To verify the presence of Coccidioides in soil using an alternate method, we employed next generation amplicon sequencing targeting the ITS2 region. Results show our modified assay, CocciEnv, is a rapid and robust method for detecting Coccidioides DNA in complex environmental samples. The ability to test a large number of soils for the presence of Coccidioides is a much-needed tool in the understanding of the ecology of the organism and epidemiology of the disease and will greatly improve our understanding of this human pathogen.

Observation of the Unconventional Photon Blockade.

We observe the unconventional photon blockade effect in quantum dot cavity QED, which, in contrast to the conventional photon blockade, operates in the weak coupling regime. A single quantum dot transition is simultaneously coupled to two orthogonally polarized optical cavity modes, and by careful tuning of the input and output state of polarization, the unconventional photon blockade effect is observed. We find a minimum second-order correlation g^{(2)}(0)≈0.37, which corresponds to g^{(2)}(0)≈0.005 when corrected for detector jitter, and observe the expected polarization dependency and photon bunching and antibunching; close by in parameter space, which indicates the abrupt change from phase to amplitude squeezing.

Electro-optic polarization tuning of microcavities with a single quantum dot.

We present an oxide aperture microcavity with embedded quantum dots which utilizes a three-contact design to independently tune the quantum dot wavelength and birefringence of the cavity modes. A polarization splitting tuning of ∼5 GHz is observed. For a typical microcavity polarization splitting, the method can be used to achieve perfect polarization degeneracy that is required for many polarization-based implementations of photonic quantum gates. The embedded quantum dot wavelength can be tuned into resonance with the cavity, independent of the polarization tuning.

Forward bias operation of silicon photonic Mach Zehnder modulators for RF applications.

In this paper, we demonstrate that forward bias (+0.9V) of a high-speed silicon (Si) optical Mach-Zehnder modulator (MZM) increases the radio-frequency (RF) link gain by 30 dB when compared to reverse bias operation (-8V). RF applications require tunable, narrowband electro-optic conversion with high gain to mitigate noise of the optical receiver and realize high RF spur-free dynamic range. Compared to reverse bias, the forward bias gain rolls off more rapidly but offers higher RF link gain improvement of more than 13.2 dB at 20 GHz. Furthermore, forward bias is shown to result in comparable spurious-free dynamic range (SFDR: 104.5 dB.Hz2/3). We demonstrate through an analytical dc transfer curve the existence of simultaneous high gain and OIP3 and verify the theoretical results with measurement under forward bias at a bias point of around +0.9 V.

Epidemiologic Investigation of Highly Pathogenic H5N2 Avian Influenza Among Upper Midwest U.S. Turkey Farms, 2015.

In 2015, an outbreak of H5N2 highly pathogenic avian influenza (HPAI) occurred in the United States, severely impacting the turkey industry in the upper midwestern United States. Industry, government, and academic partners worked together to conduct a case-control investigation of the outbreak on turkey farms in the Upper Midwest. Case farms were confirmed to have HPAI-infected flocks, and control farms were farms with noninfected turkey flocks at a similar stage of production. Both case and control farms were affiliated with a large integrated turkey company. A questionnaire administered to farm managers and supervisors assessed farm biosecurity, litter handling, dead bird disposal, farm visitor and worker practices, and presence of wild birds on operations during the 2 wk prior to HPAI confirmation on case premises and the corresponding time frame for control premises. Sixty-three farms, including 37 case farms and 26 control farms were included in the analysis. We identified several factors significantly associated with the odds of H5N2 case farm status and that may have contributed to H5N2 transmission to and from operations. Factors associated with increased risk included close proximity to other turkey operations, soil disruption (e.g., tilling) in a nearby field within 14 days prior to the outbreak, and rendering of dead birds. Observation of wild mammals near turkey barns was associated with reduced risk. When analyses focused on farms identified with H5N2 infection before April 22 (Period 1), associations with H5N2-positive farm status included soil disruption in a nearby field within 14 days prior to the outbreak and a high level of visitor biosecurity. High level of worker biosecurity had a protective effect. During the study period after April 22 (Period 2), factors associated with HPAI-positive farm status included nonasphalt roads leading to the farm and use of a vehicle wash station or spray area. Presence of wild birds near dead bird disposal areas was associated with reduced risk. Study results indicated that the initial introduction and spread of H5N2 virus likely occurred by both environmental and between-farm pathways. Transmission dynamics appeared to change with progression of the outbreak. Despite enhanced biosecurity protocols, H5N2 transmission continued, highlighting the need to review geographic/topologic factors such as farm proximity and potential dust or air transmission associated with soil disruption. It is likely that biosecurity improvements will reduce the extent and speed of spread of future outbreaks, but our results suggest that environmental factors may also play a significant role in farms becoming infected with HPAI.

Effects of ambient exposure, refrigeration, and icing on Vibrio vulnificus and Vibrio parahaemolyticus abundances in oysters.

Vibrio vulnificus (Vv) and V. parahaemolyticus (Vp) illnesses are typically acquired through the consumption of raw molluscan shellfish, particularly oysters. As Vibrio spp. are naturally-occurring bacteria, one means of mitigation of illness is achieved by limiting post-harvest growth. In this study, effects of ambient air storage, refrigeration, and icing of oysters on Vibrio spp. abundances were examined at two sites in Alabama (AL) [Dog River (DR) and Cedar Point (CP)] and one site in Delaware Bay, New Jersey (NJ). As the United States shellfish program recommendations include testing for total these organisms and gene targets, Vv and total (tlh) and pathogenic (tdh+ and trh+) Vp were enumerated from samples using MPN-real-time-PCR approaches. Mean Vv and Vp abundances in oysters from AL-DR were lowest in immediately iced samples (2.3 and -0.1 log MPN/g, respectively) and highest in the 5h ambient then refrigerated samples (3.4 and 0.5 log MPN/g, respectively). Similarly, in AL-CP Vv and Vp mean levels in oysters were lowest in immediately iced samples (3.6 and 1.2 log MPN/g, respectively) and highest in 5h ambient then refrigerated samples (5.1 and 3.2 log MPN/g, respectively). Mean levels of pathogenic Vp from AL sites were frequently below the limit of detection (<0.3 MPN/g). In NJ, Vv and Vp mean abundances in oysters were highest in samples which were held for 7h in the shade (5.3 and 4.8 log MPN/g, respectively). Mean pathogenic Vp levels in oysters at initial harvest were also highest in oysters 7h in the shade (2.1 and 2.2 log MPN/g for tdh+ and trh+ Vp). Regardless of sampling location, Vibrio spp. levels were generally significantly (p<0.05) greater in oysters exposed to 5h of air storage compared to the initially harvested samples. In addition, the data demonstrated that the use of layered ice resulted in lower Vibrio spp. levels in oysters, compared to those that were refrigerated post-harvest. These results suggest vibriosis risk can be mitigated by shorter storage times and more rapid cooling of oysters, providing data regulatory authorities can use to evaluate Vibrio spp. control plans.

Fully integrated microwave frequency synthesizer on heterogeneous silicon-III/V.

We demonstrate a photonic microwave generator on the heterogeneous silicon-InP platform. Waveguide photodiodes with a 3 dB bandwidth of 65 GHz and 0.4 A/W responsivity are integrated with lasers that tune over 42 nm with less than 150 kHz linewidth. Microwave signal generation from 1 to 112 GHz is achieved.

A multi-wavelength, high-contrast contact radiography system for the study of low-density aerogel foams.

A multi-wavelength, high contrast contact radiography system has been developed to characterize density variations in ultra-low density aerogel foams. These foams are used to generate a ramped pressure drive in materials strength experiments at the National Ignition Facility and require precision characterization in order to reduce errors in measurements. The system was used to characterize density variations in carbon and silicon based aerogels to ∼10.3% accuracy with ∼30 µm spatial resolution. The system description, performance, and measurement results collected using a 17.8 mg/cc carbon based JX-6 (C20H30) aerogel are discussed in this manuscript.

Purification of a single-photon nonlinearity.

Single photon nonlinearities based on a semiconductor quantum dot in an optical microcavity are a promising candidate for integrated optical quantum information processing nodes. In practice, however, the finite quantum dot lifetime and cavity-quantum dot coupling lead to reduced fidelity. Here we show that, with a nearly polarization degenerate microcavity in the weak coupling regime, polarization pre- and postselection can be used to restore high fidelity. The two orthogonally polarized transmission amplitudes interfere at the output polarizer; for special polarization angles, which depend only on the device cooperativity, this enables cancellation of light that did not interact with the quantum dot. With this, we can transform incident coherent light into a stream of strongly correlated photons with a second-order correlation value up to 40, larger than previous experimental results, even in the strong-coupling regime. This purification technique might also be useful to improve the fidelity of quantum dot based logic gates.

Effects of Intertidal Harvest Practices on Levels of Vibrio parahaemolyticus and Vibrio vulnificus Bacteria in Oysters.

UNLABELLED: Vibrio parahaemolyticus and Vibrio vulnificus can grow rapidly in shellfish subjected to ambient air conditions, such as during intertidal exposure. In this study, levels of total and pathogenic (tdh(+) and/or trh(+)) V. parahaemolyticus and total V. vulnificus were determined in oysters collected from two study locations where intertidal harvest practices are common. Samples were collected directly off intertidal flats, after exposure (ambient air [Washington State] or refrigerated [New Jersey]), and after reimmersion by natural tidal cycles. Samples were processed using a most-probable-number (MPN) real-time PCR method for total and pathogenic V. parahaemolyticus or V. vulnificus In Washington State, the mean levels of V. parahaemolyticus increased 1.38 log MPN/g following intertidal exposure and dropped 1.41 log MPN/g after reimmersion for 1 day, but the levels were dependent upon the container type utilized. Pathogenic V. parahaemolyticus levels followed a similar trend. However, V. vulnificus levels increased 0.10 log MPN/g during intertidal exposure in Washington but decreased by >1 log MPN/g after reimmersion. In New Jersey, initial levels of all vibrios studied were not significantly altered during the refrigerated sorting and containerizing process. However, there was an increase in levels after the first day of reimmersion by 0.79, 0.72, 0.92, and 0.71 log MPN/g for total, tdh(+) and trh(+) V. parahaemolyticus, and V. vulnificus, respectively. The levels of all targets decreased to those similar to background after a second day of reimmersion. These data indicate that the intertidal harvest and handling practices for oysters that were studied in Washington and New Jersey do not increase the risk of illness from V. parahaemolyticus or V. vulnificus IMPORTANCE: Vibrio parahaemolyticus and Vibrio vulnificus are the leading causes of seafood-associated infectious morbidity and mortality in the United States. Vibrio spp. can grow rapidly in shellfish subjected to ambient air conditions, such as during periods of intertidal exposure. When oysters are submersed with the incoming tide, the vibrios can be purged. However, data on the rates of increase and purging during intertidal harvest are scarce, which limits the accuracy of risk assessments. The objective of this study was to help fill these data gaps by determining the levels of total and pathogenic (tdh(+) and/or trh(+)) V. parahaemolyticus and V. vulnificus in oysters from two locations where intertidal harvest practices are common, using the current industry practices. The data generated provide insight into the responses of Vibrio spp. to relevant practices of the industry and public health, which can be incorporated into risk management decisions.

Low-loss arrayed waveguide grating at 760 nm.

An arrayed waveguide grating (AWG) at 760 nm is demonstrated with an insertion loss smaller than 0.5 dB. Interface roughness and waveguide length errors contribute much more to scattering loss and phase errors at 760 nm than at longer wavelengths, thus requiring improved design and fabrication. This Letter details how this is achieved by minimizing interfacial scattering, grating side-order excitation, and phase errors in the AWG. With silicon nitride core and silicon dioxide clad waveguides on silicon, this AWG is compatible with heterogeneously integrated lasers for on-chip spectral beam combining.

Spatio-temporal optical random number generator.

We present a first random number generator (RNG) which simultaneously uses independent spatial and temporal quantum randomness contained in an optical system. Availability of the two independent sources of entropy makes the RNG resilient to hardware failure and signal injection attacks. We show that the deviation from randomness of the generated numbers can be estimated quickly from simple measurements thus eliminating the need for usual time-consuming statistical testing of the output data. As a confirmation it is demonstrated that generated numbers pass NIST Statistical test suite.

Fully integrated hybrid silicon two dimensional beam scanner.

In this work we present the first fully-integrated free-space beam-steering chip using the hybrid silicon platform. The photonic integrated circuit (PIC) consists of 164 optical components including lasers, amplifiers, photodiodes, phase tuners, grating couplers, splitters, and a photonic crystal lens. The PIC exhibited steering over 23° x 3.6° with beam widths of 1° x 0.6°.

Heterogeneous lasers and coupling to Si3N4 near 1060 nm.

A III-V/Si3N4 platform on silicon is presented capable of broad-spectral performance with initial heterogeneous lasers near 1060 nm. Continuous wave Fabry-Perot laser results for heterogeneous InGaAs/GaAs multiple quantum well (MQW) laser with output power approaching 0.25 mW on Si is demonstrated. Taper transmission loss measurements from III-V to Si3N4 are measured to be 2.5±0.75 dB.

Androgen modulation of Foxp1 and Foxp2 in the developing rat brain: impact on sex specific vocalization.

Sex differences in vocal communication are prevalent in both the animals and humans. The mechanism(s) mediating gender differences in human language are unknown, although, sex hormones, principally androgens, play a central role in the development of vocalizations in a wide variety of animal species. The discovery of FOXP2 has added an additional avenue for exploring the origins of language and animal communication. The FOXP2 gene is a member of the forkhead box P (FOXP) family of transcription factors. Prior to the prenatal androgen surge in male fetuses, we observed no sex difference for Foxp2 protein levels in cultured cells. In contrast, 24 hours after the onset of the androgen surge, we found a sex difference for Foxp2 protein levels in cultured cortical cells with males having higher levels than females. Furthermore, we observed the potent nonaromatizable androgen dihydrotestosterone altered not only Foxp2 mRNA and protein levels but also Foxp1. Androgen effects on both Foxp2 and Foxp1 were found to occur in the striatum, cerebellar vermis, and cortex. Immunofluorescence microscopy and coimmunoprecipitation demonstrate Foxp2 and the androgen receptor protein interact. Databases for transcription factor binding sites predict a consensus binding motif for androgen receptor on the Foxp2 promoter regions. We also observed a sex difference in rat pup vocalization with males vocalizing more than females and treatment of females with dihydrotestosterone eliminated the sex difference. We propose that androgens might be an upstream regulator of both Foxp2 and Foxp1 expression and signaling. This has important implications for language and communication as well as neuropsychiatric developmental disorders involving impairments in communication.