Interference fringes in a nonlinear Michelson interferometer based on spontaneous parametric down-conversion.

Quantum nonlinear interferometers (QNIs) can measure the infrared physical quantities of a sample by detecting visible photons. A QNI with Michelson geometry based on the spontaneous parametric down-conversion in a second-order nonlinear crystal is studied systematically. A simplified theoretical model of the QNI is presented. The interference visibility, coherence length, equal-inclination interference, and equal-thickness interference for the QNI are demonstrated theoretically and experimentally. As an application example of the QNI, the refractive index and the angle between two surfaces of a BBO crystal are measured using equal-inclination interference and equal-thickness interference.

Angular-spectrum-dependent interference.

Optical interference is not only a fundamental phenomenon that has enabled new theories of light to be derived but it has also been used in interferometry for the measurement of small displacements, refractive index changes, and surface irregularities. In a two-beam interferometer, variations in the interference fringes are used as a diagnostic for anything that causes the optical path difference (OPD) to change; therefore, for a specified OPD, greater variation in the fringes indicates better measurement sensitivity. Here, we introduce and experimentally validate an interesting optical interference phenomenon that uses photons with a structured frequency-angular spectrum, which are generated from a spontaneous parametric down-conversion process in a nonlinear crystal. This interference phenomenon is manifested as interference fringes that vary much more rapidly with increasing OPD than the corresponding fringes for equal-inclination interference; the phenomenon is parameterised using an equivalent wavelength, which under our experimental conditions is 29.38 nm or about 1/27 of the real wavelength. This phenomenon not only enriches the knowledge with regard to optical interference but also offers promise for applications in interferometry.

Fourth-harmonic generation of orbital angular momentum light with cascaded quasi-phase matching crystals.

Orbital angular momentum (OAM) light, combined with the nonlinear process to expand the frequency range, has drawn increasing research interest in recent years. Here, we implement the first, to the best of our knowledge, experimental fourth-harmonic generation of OAM light with two cascaded quasi-phase-matching crystals. A Laguerre-Gaussian beam was transmitted through a duplet crystals system and frequency-doubled twice by two separate second-harmonic generation processes, which transduced the frequency of the OAM beam from telecom band to visible band and then to ultraviolet (UV) band. The topological charge of the OAM beam was increased substantially in the cascaded frequency conversion processes. In this experiment, we verify the OAM conservation by utilizing a specially designed interferometer, and the results correspond well with the numerical simulation. This work provides an effective method for the generation of UV OAM beams with high topological charges.

Real-time quantum edge enhanced imaging.

With the development of optical information processing technology, image edge enhancement technology has rapidly received extensive attention, especially in the field of quantum imaging. However, quantum edge enhanced imaging faces challenges in terms of time-consuming acquisition processes and the complexity of the devices used, which limits practical applications in real-time usage scenarios. Here we introduce and experimentally demonstrate a real-time (0.5 Hz) quantum edge enhanced imaging method that combines the spiral phase contrast technique with heralded single-photon imaging. The edge enhancement results show high quality and background free from raw data. Compared with direct imaging, our configuration can improve the signal-to-noise ratio significantly using the tight time correlations between photon pairs. The method also offers competitive advantages over ghost imaging, including higher brightness and a compact optical fiber delay rather than a free space delay. Additionally, we explore curved edge enhancement for specific feature recognition and the oriented shadow effect. Overall, this efficient and versatile platform paves an alternative path toward real-time quantum edge detection in applications including nondestructive bio-imaging, night vision and covert monitoring.

High-quality versatile photonic sources for multiple quantum optical experiments.

Entangled sources are important components for quantum information science and technology (QIST). The ability to generate high-quality entangled sources will determine the extent of progress in this field. Unlike previous schemes, a thin quasi-phase matching nonlinear crystal and a dense-wave-division-multiplexing device are used here to build high-quality versatile photonic sources with a simple configuration that can be used to perform Hong-Ou-Mandel interference, time-energy entanglement and multi-channel polarization entanglement experiments. The measurement results from various quantum optical experiments show the high quality of these photonic sources. These multi-functional photonic sources will be very useful in a variety of QIST applications.

Comparisons of the clinical outcomes between early- and adult-onset bipolar disorders: A prospective cohort analysis.

BACKGROUND: This study aimed to explore the impact of age-at-onset on clinical outcomes in bipolar-spectrum disorders, including the development of alcohol or substance use disorder, suicidality, and psychiatric hospitalization. METHODS: This population-based study enrolled newly-diagnosed bipolar-spectrum patients, including 4,367 patients with early-onset bipolar disorder (EOBD), 64,787 patients with adult-onset bipolar disorder (AOBD), and the same number of age-controlled comparison subjects without bipolar disorder, from Taiwan's National Health Insurance Research Database. Time-dependent covariate Cox regression models were used to estimate the effect of age-at-onset on clinical outcomes with adjustment for pre-existing psychiatric comorbid conditions and pharmacological treatment patterns. Sensitivity analyses using different definitions of study sample and age cutoffs were conducted. RESULTS: The average follow-up duration was 5.7 years. After adjustment with time-dependent covariates and chronological age, there were no significant differences in the risks for developing new-onset alcohol or substance use disorders and psychiatric hospitalization between EOBD and AOBD patients. Although EOBD patients had a higher risk of hospitalization for suicide and self-harm than did AOBD patients in primary analysis, this finding did not replicated in the sensitivity analyses. LIMITATIONS: The symptom profile and severity of bipolar disorder was not available in the NHIRD; therefore, surrogate indicators of clinical outcome might not be sensitive enough to detect the subtle differences. CONCLUSIONS: EOBD and AOBD patients had similar risks for developing alcohol or substance use disorders. Their risk of psychiatric hospitalization was similar. Whether EOBD patients might have a higher risk of hospitalization for suicide and self-harm warrants further investigations.

Attention Deficits in a Comorbidity-Free Sample of Euthymic Pediatric Bipolar Disorder.

Attention deficits are considered one of the potential endophenotypic markers of Bipolar Disorder (BD). Pediatric bipolar disorder (PBD) likely has stronger genetic underpinnings than adult onset BD; therefore, demonstrating attention deficits in PBD can be both strategic and convincing in attesting their status as one of the potential endophenotypic markers of BD. However, unlike adult literature, uncertainty exists regarding the magnitude of attention deficits in PBD. In this regard, one key unresolved question is the potential impact of attention deficit hyperactivity disorder (ADHD). The main goal of the study was to examine attention deficits in a comorbidity-free sample of euthymic PBD patients. Thirty (21 boys, 9 girls) remitted PBD patients without co-morbidity and thirty age (<17 years), sex, handedness, and Full-Scale IQ matched control subjects were compared on performance on attention tasks. Working memory (WM), which might potentially confound with the attention task performances, was also examined. Compared to controls, PBD patients performed poorly on various tests of attention, but not on any WM tasks. Further, it was found that observed attention deficits were independent of residual mood symptoms, medication effect or illness characteristics. Such attention deficits in this comorbidity-free PBD sample further endorses its status as an endophenotypic marker of bipolar disorders and establishes continuity with deficits found in adult bipolar patients.

SP1-induced up-regulation of lncRNA LUCAT1 promotes proliferation, migration and invasion of cervical cancer by sponging miR-181a.

Long noncoding RNA lung cancer associated transcript 1 (LUCAT1) has been shown to be a lncRNA that facilitates the development and progression of several tumours. However, the evidence of LUCAT1 modulating the growth and metastasis of cervical cancer (CC) were still lacking. The present study aimed to explore the expression pattern, biological function and potential mechanism of LUCAT1 in CC. In this study, we, first, confirmed that LUCAT1 acted as an up-regulated lncRNA by analyzing the data from GCTA dataset and RT-PCR in both CC tissues and cell lines. We also showed that TINCR overexpression is induced by nuclear transcription factor SP1. Then, clinical assays showed that LUCAT1 was associated with advanced clinical progression and poor prognosis of CC patients. Importantly, multivariate Cox model confirmed that LUCAT1 expression was an independent prognostic factor for both 5-year overall survival in CC. Then, lost-function assays revealed that knockdown of LUCAT1 significantly suppressed CC cells proliferation, colony formation, migration, invasion and EMT by a series of cells experiments. Mechanistically, Bioinformatic tools predicted that miR-181a may target LUCAT1, which was confirmed using luciferase reporter assay and RNA immunoprecipitation (RIP) assays. Overall, our findings showed that SP1-activated LUCAT1 exerts an oncogenic function in CC by binding to miR-181a, suggesting that miR-181a may be a ponderable and promising therapeutic target for CC.

Nonlinear frequency conversion and manipulation of vector beams in a Sagnac loop.

Vector beams (VBs) are widely investigated for their special intensities and polarization distributions, which are useful in optical micromanipulation, optical microfabrication, optical communication, and single molecule imaging. To date, nonlinear frequency conversion (NFC) and manipulation of VBs remain challenging because of the polarization sensitivity of most nonlinear processes. Here we report an experimental realization of NFC and manipulation of VBs that can be used to expand the available frequency band. The main idea of our scheme is the introduction of a Sagnac loop to solve the polarization dependence problem of NFC in nonlinear crystals. Additionally, we find that a linearly polarized VB should be transformed into a hybrid-polarized VB in exponential form before performing NFC. The experimental results agree well with those of our theoretical model. The proposed method is also applicable to other wavebands and second-order nonlinear processes, and may be generalized to the quantum regime for single photons.

Quantum frequency conversion for multiplexed entangled states generated from micro-ring silicon chip.

Silicon-on-chip photonic circuits are among some very promising platforms for generating nonclassical photonic quantum state, because of its low loss, small footprint, and compatibility with complementary metal-oxide-semiconductor (CMOS) and telecommunications techniques. Dense wavelength division multiplexing (DWDM) is a leading technique for enhancing the transmission capacity of both classical and quantum communications. To bridge the frequency gap between silicon-chip and other quantum systems, such as quantum memories, a quantum interface is indispensable. Here, we demonstrate a quantum interface for multiplexed energy-time entanglement states, which are generated on a silicon micro-ring cavity that is based on frequency up-conversion. By switching the pump wavelength, energy-time entanglement from any channel can be selected at will after being up-converted. The high visibilities of two-photon interference over three channels after frequency up-conversion clearly prove that the entanglement is fully preserved during the quantum frequency conversion (QFC) process. Our work provides new perspectives regarding channel capacity enhancement in quantum communications and for quantum resources being transferred between two different quantum systems.

Revealing the Behavior of Photons in a Birefringent Interferometer.

The interferometer is one of the most important devices for revealing the nature of light and for precision optical metrology. Although many experiments were performed for probing photon behavior in various configurations, a complete study of photon behavior in a birefringent interferometer has not been performed, to our knowledge. By using an environmental turbulence immune Mach-Zehnder interferometer, we observe tunable photonic beatings by rotating a birefringent crystal versus the temperature of the crystal for both the single photon and two photons. Furthermore, the two-photon interference fringes beat 2 times faster than the single-photon interference fringes. This beating effect is used to determine the thermal dispersion coefficients of the two principal refractive axes with a single measurement: the two-photon interference shows superresolution and high sensitivity. Obvious differences between two-photon and single-photon interference are also revealed in unbalanced situations. In addition, the influence of the photon bandwidth on the beating behaviors that come from polarization-dependent decoherence is also investigated. Our findings will be important for better understanding the behavior of two-photon interference in a birefringent interferometer and for precision optical metrology with quantum enhancement.

Impacts of Electroconvulsive Therapy on 1-Year Outcomes in Patients With Schizophrenia: A Controlled, Population-Based Mirror-Image Study.

Objectives: Despite the decline in the use of electroconvulsive therapy (ECT) in patients with schizophrenia, ECT augmentation is still recommended for those with poor response to standard pharmacological intervention. However, the effectiveness of augmentation of antipsychotics with ECT on long-term clinical outcomes needs to be verified in an expanded sample. Methods: Patients who were hospitalized for schizophrenia and received ECT for the first time during that hospitalization were identified from the total population health insurance database in Taiwan between 2002 and 2011. A comparison group was randomly selected and matched by age, gender, calendar year of hospitalization, and duration of hospitalization. Using a mirror-image design, the changes in rates of psychiatric and overall hospitalization, length of hospital stay, number of emergency department visits, and direct medical costs across the 1-year pre- and post-treatment periods were examined. Results: A total of 2074 patients with the same number of comparison participants were included in the analysis. The rate of re-hospitalization decreased significantly in the ECT group during the 1-year post-treatment period, while there was no significant difference in the comparison group. Correspondingly, the total medical expenses increased significantly in the non-ECT group, but not in the ECT group. Notably, the reduction in the psychiatric re-hospitalization rate in the ECT group was more pronounced among those treated with clozapine or a medium-high average daily dose of antipsychotics. Conclusion: This 1-year mirror-image analysis indicated that augmentation of antipsychotics with ECT in schizophrenic patients was associated with a reduced rate of psychiatric re-hospitalization.

Coherent frequency bridge between visible and telecommunications band for vortex light.

In quantum communications, vortex photons can encode higher-dimensional quantum states and build high-dimensional communication networks (HDCNs). The interfaces that connect different wavelengths are significant in HDCNs. We construct a coherent orbital angular momentum (OAM) frequency bridge via difference frequency conversion in a nonlinear bulk crystal for HDCNs. Using a single resonant cavity, maximum quantum conversion efficiencies from visible to infrared are 36%, 15%, and 7.8% for topological charges of 0,1, and 2, respectively. The average fidelity obtained using quantum state tomography for the down-converted infrared OAM-state of topological charge 1 is 96.51%. We also prove that the OAM is conserved in this process by measuring visible and infrared interference patterns. This coherent OAM frequency-down conversion bridge represents a basis for an interface between two high-dimensional quantum systems operating with different spectra.

Seizure Risk Associated With Antidepressant Treatment Among Patients With Depressive Disorders: A Population-Based Case-Crossover Study.

OBJECTIVE: To assess the risk of seizure associated with antidepressant use among patients with depressive disorders. METHODS: Individuals visiting the emergency department or hospitalized because of new-onset seizure (ICD-9-CM diagnostic code 345 or 780.3; our primary study outcome) after receiving antidepressants for depressive disorders, were identified from a Taiwanese total population health insurance database. Using a case-crossover study design, relative risk of antidepressant-related seizure was estimated by comparing the rates of antidepressant exposure during the case periods vs control periods. The effects of class and dose of antidepressant on seizure risk were explored, using a conditional logistic regression model adjusting for concomitant medications. Several sensitivity analyses were conducted to attest the results of primary analyses. RESULTS: A total of 10,002 patients were included between 2002 and 2012. Overall, antidepressant exposure was positively associated with increased seizure risk (OR = 1.48, 95% CI, 1.33-1.64). Among the antidepressants, the increases in seizure risk of bupropion (OR = 2.23, 95% CI, 1.58-3.16), selective serotonin reuptake inhibitors (OR = 1.76, 95% CI, 1.55-2.00), serotonin and norepinephrine reuptake inhibitors (OR = 1.40, 95% CI, 1.10-1.78), and mirtazapine (OR = 1.38, 95% CI, 1.08-1.77) showed clear dose-response effects. Furthermore, the seizure risk was highest among patients aged between 10 and 24 years and patients with major depression. The results of sensitivity analyses largely confirmed those from the primary analyses. CONCLUSIONS: The seizure-inducing propensity and dose-response relationship pattern, as well as potential risk factors, associated with individual antidepressants should be taken into consideration when choosing antidepressants during clinical practice.

Comparative risk of seizure with use of first- and second-generation antipsychotics in patients with schizophrenia and mood disorders.

OBJECTIVE: To compare the risk of antipsychotic-related seizure (ARS) by identifying seizures first diagnosed within 12 months after starting new antipsychotics, using a 12-year total population health claims database from Taiwan. METHODS: Seizure events were identified through emergency department visits or hospitalization with a diagnosis of convulsion (ICD-9-CM: 780.3) or epilepsy (ICD-9-CM: 345). Subjects had an ICD-9-CM diagnosis of schizophrenia, bipolar disorders, or major depressive disorders. Incidence rates of ARS were calculated by person-years of exposure. The ARS risk, adjusted for patient characteristics and medical conditions, of individual antipsychotics versus risperidone was examined by high-dimensional propensity score stratification analyses, followed by sensitivity analyses. RESULTS: The overall 1-year incidence rate of ARS was 9.6 (95% CI, 8.8-10.4) per 1,000 person-years (550 ARS events among 288,397 new antipsychotic users). First-generation antipsychotics were marginally associated with a higher ARS risk than second-generation antipsychotics (adjusted hazard ratio [aHR] = 1.34; 95% CI, 0.99-1.81; P = .061). Most antipsychotics, first- or second-generation, had comparable ARS risks versus risperidone. Notably, clozapine (aHR = 3.06; 95% CI, 1.40-6.71), thioridazine (aHR = 2.90; 95% CI, 1.65-5.10), chlorprothixene (aHR = 2.60; 95% CI, 1.04-6.49), and haloperidol (aHR = 2.34; 95% CI, 1.48-3.71) had higher ARS risks than risperidone, whereas aripiprazole (aHR = 0.41; 95% CI, 0.17-1.00; P = .050) had a marginally lower ARS risk. Sensitivity analyses largely confirmed such findings. CONCLUSIONS: Higher vigilance for ARS is warranted during use of clozapine, chlorprothixene, thioridazine, and haloperidol. The possible lower ARS risk associated with aripiprazole can be clinically significant but needs to be confirmed by larger-scale systematic studies. The comparative ARS risks of antipsychotics supplement empirical knowledge for making judicious choices in prescribing antipsychotics.

Melancholic features in inpatients with major depressive disorder associate with differential clinical characteristics and treatment outcomes.

To determine whether the presence of melancholic features in hospitalized patients with major depressive disorder (MDD) was associated with specific clinical characteristics and treatment outcomes, supporting melancholic depression as a distinct subtype within MDD. 126 acutely ill inpatients with MDD were enrolled in an open, 6-week trial with fixed-dose fluoxetine 20mg daily. Symptom severity was assessed regularly, using the 17-item Hamilton Depression Rating Scale (HAMD-17) and Clinical Global Impression of Severity (CGI-S). Melancholic features were defined according to the DSM-IV criteria. Clinical variables were compared between patients with and without melancholic features. Generalized estimating equations method was used to explore the differences in HAMD-17 and CGI-S scores between the 2 groups over time. Clinical response was defined as having a 50% or greater reduction in HAMD-17 scores. 96 (76.2%) of the 126 patients with at least one post-baseline assessment met the criteria for melancholic depression. Melancholic depression differed from non-melancholic depression in clinical characteristics and predicted a better response to fluoxetine treatment. The differentiation between melancholic and non-melancholic depression within MDD hence is clinically significant and valid.

Thrombomodulin promotes diabetic wound healing by regulating toll-like receptor 4 expression.

Keratinocyte-expressed thrombomodulin (TM) and the released soluble TM (sTM) have been demonstrated to promote wound healing. However, the effects of high glucose on TM expression in keratinocytes and the role of TM in diabetic ulcer remain unclear. In this study, we demonstrated that expressions of TM and Toll-like receptor 4 (TLR4) were both downregulated in high-glucose cultured human keratinocytes and in skin keratinocytes of diabetic patients. In addition, the wound-triggered upregulation of TM and sTM production was abolished in both high-glucose cultured human keratinocytes and streptozotocin-induced diabetic mouse skin. Furthermore, supplementation of recombinant sTM could increase TLR4 expression and promote cutaneous wound healing in both high-glucose cultured human keratinocytes and diabetic mice. However, in Tlr4-deleted mice, which exhibited delayed wound healing, the therapeutic benefit of recombinant sTM was abrogated. Moreover, our results showed that tumor necrosis factor-α (TNF-α) expression in keratinocytes was dose-dependently upregulated by glucose, and TNF-α treatment downregulated the expression of TM and TLR4. Taken together, high-glucose environment reduces the expression of TM and TLR4 in keratinocytes possibly through the action of TNF-α, and recombinant sTM can increase the TLR4 expression and promote wound healing under diabetic condition.

Clozapine use reduced psychiatric hospitalization and emergency room visits in patients with bipolar disorder independent of improved treatment regularity in a three-year follow-up period.

OBJECTIVES: The efficacy of clozapine in bipolar disorder remains to be systemically examined. In the current study, we sought to disentangle the effect of clozapine from that of improved treatment regularity and to compare the effect of clozapine with the effect of regular treatment for bipolar disorder by exploring the complete 10-year clozapine prescription data from a Taiwanese total population health claims database. METHODS: In the period between 2000 and 2009, 3,874 (3.3%) out of the 117,785 patients identified as having bipolar disorder in a Taiwanese total population health claims database were ever prescribed clozapine. Among them, 920 patients with bipolar disorder who had good pre-clozapine medication compliance and received at least two clozapine prescriptions were further categorized according to their clozapine medication possession ratio (MPR) as regular users (MPR ≥ 0.8; n = 476) and irregular users (MPR < 0.8; n = 444). Using a mirror-image design, we compared the numbers of emergency room (ER) visits, hospitalizations and hospital days, and the average durations of a single hospitalization during the pre- and post-clozapine mirror periods with a follow-up time of up to three years, controlling for time-variant course confounders. RESULTS: The patterns of change in outcome indices from the pre-clozapine period to the post-clozapine period differed significantly between the two clozapine-user groups. Clinical outcome indices improved only in regular users, while they deteriorated in irregular users. Over the three-year follow-up period, the irregular users consistently had a higher adjusted risk for increased numbers of ER visits [odds ratio (OR): 2.06-2.43], hospitalizations (OR: 2.52-3.22), and total hospital days (OR: 2.42-2.91) when compared to the regular users. Thus, effects of clozapine were consistently demonstrated in one- to three-year mirror comparison periods. CONCLUSIONS: Clozapine, when used with high treatment regularity (MPR > 0.8), was effective in reducing the numbers of ER visits, hospitalizations, and total hospital days in patients with bipolar disorder with previous frequent hospitalizations and ER visits despite regular pre-clozapine treatment for bipolar disorder. However, high early attrition and suboptimal treatment compliance need to be rectified in order to optimize the outcome of clozapine treatment in bipolar disorders.

Egg consumption is associated with increased risk of ovarian cancer: Evidence from a meta-analysis of observational studies.

BACKGROUND: The findings of epidemiologic studies on the association between egg consumption and ovarian cancer risk remain conflicting. The aim of this meta-analysis was to investigate whether an association exists between egg intake and ovarian cancer risk in epidemiologic studies. METHODS: A literature search was carried out using PUBMED, EMBASE, and Cochrane Library Central database for all medical literature published in English-language journals up to August 2013. Before meta-analysis, between-study heterogeneity and publication bias were assessed using adequate statistical tests. Fixed-effect and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Subgroup analyses and sensitivity analysis were also performed. RESULTS: A total of 12 eligible studies (six case-control studies and six cohort studies) were included, involving 629,453 subjects and 3728 ovarian cancer cases. We found that high egg intake (comparing the highest with the lowest category) was associated with a significant increased risk of ovarian cancer (RR = 1.21, 95% CI [1.06, 1.38]). When we examined whether the associations differed by study type, statistically significant effect of egg intake on ovarian cancer was observed among case-control studies (RR = 1.22, 95% CI [1.03, 1.43]), but not among cohort studies (RR = 1.20, 95% CI [0.97, 1.48]). CONCLUSIONS: Our findings suggest that egg consumption may increase ovarian cancer risk. Additional studies, especially large prospective cohort studies, are warranted to confirm the findings.

RHBDL2 is a critical membrane protease for anoikis resistance in human malignant epithelial cells.

Anoikis resistance allows metastatic tumor cells to survive in a homeless environment. Activation of epithelial growth factor receptor (EGFR) signaling is one of the key mechanisms for metastatic tumor cells to resist anoikis, yet the regulation mechanisms of homeless-triggered EGFR activation in metastatic tumor cells remain unclear. Rhomboid-like-2 (RHBDL2), an evolutionally conserved intramembrane serine protease, can cleave the EGF ligand and thus trigger EGFR activation. Herein, we demonstrated that RHBDL2 overexpression in human epithelial cells resulted in promotion of cell proliferation, reduction of cell adhesion, and suppression of anoikis. During long-term suspension cultures, increased RHBDL2 was only detected in aggressive tumor cell lines. Treatment with the rhomboid protease inhibitor or RHBDL2 shRNA increased cleaved caspase 3, a marker of apoptosis. Finally, inhibition of EGFR activation increased the cleaved caspase 3 and attenuated the detachment-induced focal adhesion kinase phosphorylation. Taken together, these findings provide evidence for the first time that RHBDL2 is a critical molecule in anoikis resistance of malignant epithelial cells, possibly through the EGFR-mediated signaling. Our study demonstrates RHBDL2 as a new therapeutic target for cancer metastasis.