Correlation between composition, microstructure, and emission properties in Nd-doped Si-rich Si oxynitride films: investigation into the nature of the sensitizer.

Rare earth (RE) ions doped in Si-based materials, compatible with Si technology, are promising compounds with regards to optical communication and energy conversion. In this article, we show the emission properties of Nd-doped Si-rich Si oxynitride (Nd-SRSON) films, and their dependence on the dangling bond density and the nature of the sensitizer. These films were prepared by reactive magnetron sputtering and post-annealing. The film composition, microstructure, and emission properties were investigated as a function of deposition parameters and annealing temperatures. Both Fourier transform infrared (FTIR) and ellipsometry spectroscopy measurements have confirmed that the sample composition (Si/N ratio) can be carefully tuned by varying the ratio of reactive nitrogen to argon in the sputtering plasma. Moreover, FTIR and x-ray photoelectron spectroscopy measurements demonstrate the existence of both nitrogen and oxygen dangling bonds (N· and O·) in as-deposited samples. These dangling bonds were passivated during annealing. Under non-resonant excitation at 488 nm, the films exhibit a significant photoluminescence (PL) signal from Nd3+ ions demonstrating the occurrence of an effective sensitization of Nd3+ ions in the host matrix. Both PL excitation and ellipsometry results (the energy band gap from new amorphous model) exclude the sensitization by an exciton with energy over the band gap, whereas the presence of Si agglomerates, at the atomic scale, have been identified as effective sensitizers towards Nd3+ ions. This work not only provides knowledge to optimize Si-based materials for favorable emission properties, but also, presents a universal methodology to investigate the nature of sensitizers for RE emitters. This allows one to find correlations between composition, microstructure, and emission properties.

Efficacy, Immunogenicity, and Safety of a 9-Valent Human Papillomavirus Vaccine: Subgroup Analysis of Participants From Asian Countries.

Background: A 9-valent human papillomavirus-6/11/16/18/31/33/45/52/58 (9vHPV) vaccine extends coverage to 5 next most common oncogenic types (31/33/45/52/58) in cervical cancer versus quadrivalent HPV (qHPV) vaccine. We describe efficacy, immunogenicity, and safety in Asian participants (India, Hong Kong, South Korea, Japan, Taiwan, and Thailand) from 2 international studies: a randomized, double-blinded, qHPV vaccine-controlled efficacy study (young women aged 16-26 years; NCT00543543; Study 001); and an immunogenicity study (girls and boys aged 9-15 years; NCT00943722; Study 002). Methods: Participants (N = 2519) were vaccinated at day 1 and months 2 and 6. Gynecological samples (Study 001 only) and serum were collected for HPV DNA and antibody assessments, respectively. Injection-site and systemic adverse events (AEs) were monitored. Data were analyzed by country and vaccination group. Results: 9vHPV vaccine prevented HPV-31/33/45/52/58-related persistent infection with 90.4%-100% efficacy across included countries. At month 7, ≥97.9% of participants seroconverted for each HPV type. Injection-site AEs occurred in 77.7%-83.1% and 81.9%-87.5% of qHPV and 9vHPV vaccine recipients in Study 001, respectively, and 62.4%-85.7% of girls/boys in Study 002; most were mild to moderate. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Asian participants. Data support 9vHPV vaccination programs in Asia. Clinical Trials Registration: NCT00543543; NCT00943722.

Spin-Orbital-Angular-Momentum Coupled Bose-Einstein Condensates.

We demonstrate coupling between the atomic spin- and orbital-angular momentum (OAM) of the atom's center-of-mass motion in a Bose-Einstein condensate (BEC). The coupling is induced by Raman-dressing lasers with a Laguerre-Gaussian beam and creates coreless vortices in an F=1 ^{87}Rb spinor BEC. We observe correlations between spin and OAM in the dressed state and characterize the spin texture; the result is in good agreement with the theory. In the presence of the Raman field, our dressed state is stable for 0.1 s or longer, and it decays due to collision-induced relaxation. As we turn off the Raman beams, the vortex cores in the bare spin |m_{F}=1⟩ and |-1⟩ split. These spin-OAM coupled systems with the Raman-dressing approach have great potential for exploring new topological textures and quantum states.

Mesothelin-specific cell-based vaccine generates antigen-specific immunity and potent antitumor effects by combining with IL-12 immunomodulator.

Ovarian cancer is a gynecologic malignancy with a high mortality rate. In the present study, we developed a novel cell-based vaccine, Meso-VAX, to generate mesothelin antigen-specific immune responses and immunotherapy against ovarian cancer. Mesothelin, a secreted protein anchored at the cell membrane, has recently been identified as a potential new tumor antigen for ovarian cancer. In this study, mice vaccinated with Meso-VAX and adeno-associated virus (AAV)-IL-12 exhibited dramatic increases in the number of mesothelin-specific CD4(+) helper and CD8(+) cytotoxic T-cell precursors, higher titers of anti-mesothelin Abs and in vitro tumor killing activity, and all of these mice were tumor-free after 60 days of tumor challenge. In addition, a significant reduction in peritoneal tumors and longer survival were noted in the mice vaccinated with Meso-VAX combined with AAV-IL-12. CD4(+) helper and CD8(+) cytotoxic T lymphocytes were essential for the antitumor effect generated by Meso-VAX combined with AAV-IL-12. The post-vaccination sera of the mice vaccinated with Meso-VAX and AAV-IL-12 also showed mesothelin-specific complement-dependent cell-mediated cytotoxicity. Our results suggest that a Meso-VAX cell-based vaccine combined with AAV-IL-12 can generate antigen-specific immunological responses and antitumor effects on ovarian cancer.

Continuous positive airway pressure-associated cutaneous amoebiasis in an immunosuppressed patient.

Organisms of the genus Acanthamoeba are environmentally ubiquitous and colonizers of the oral mucosa in humans. While largely asymptomatic in healthy persons, Acanthamoeba infection can cause disseminated disease with poor prognosis in immunosuppressed populations. Here we report a unique case of cutaneous amoebiasis associated with continuous positive airway pressure use in an immunosuppressed patient.

Microdeletions/duplications involving TBX1 gene in fetuses with conotruncal heart defects which are negative for 22q11.2 deletion on fluorescence in-situ hybridization.

OBJECTIVES: Conotruncal heart defects (CTD) are associated with del22q11.2 syndrome, which is often diagnosed by fluorescence in-situ hybridization (FISH). However, in those negative for del22q11.2 on FISH, the etiology is usually obscure. We aimed to use high-resolution array comparative genomic hybridization (array CGH) to clarify the underlying genetic causes in these cases. METHODS: In this retrospective study, fetal samples of amniocytes or fibroblasts, taken either for prenatal diagnosis by amniocentesis or for postnatal survey after termination of pregnancy, were obtained from 45 fetuses with CTD and were investigated by cytogenetic analysis including karyotyping and FISH for del22q11.2 syndrome. Eight fetuses with no findings on karyotyping and FISH were investigated further by array CGH, real-time quantitative polymerase chain reaction (qPCR) and Sanger sequencing of TBX1. RESULTS: Array CGH revealed that three of the eight fetuses carried submicroscopic genomic imbalances. Of these, two cases showed similar small microdeletions/duplications in 22q11.2 (one 0.85 kb microdeletion and one 8.51 kb microduplication). The minimal shared region spanned exon 2 of TBX1, a candidate gene responsible for cardiovascular defects in del22q11.2 syndrome. In all eight cases, the array CGH results were confirmed by qPCR, and Sanger sequencing did not detect other molecular pathologies. CONCLUSION: Our findings indicate an association between TBX1 variations and fetal CTD. The results also demonstrate the power of array CGH to further scrutinize the critical gene(s) of del22q11.2 syndrome responsible for heart defects. Array CGH apparently has diagnostic sensitivity superior to that of FISH in fetuses with CTD associated with del22q11.2 (and dup22q11.2) syndrome.

Genome-wide normalized score: a novel algorithm to detect fetal trisomy 21 during non-invasive prenatal testing.

OBJECTIVES: Non-invasive prenatal testing for fetal trisomy 21 (T21) by massively parallel shotgun sequencing (MPSS) is available for clinical use but its efficacy is limited by several factors, e.g. the proportion of cell-free fetal DNA in maternal plasma and sequencing depth. Existing algorithms discard DNA reads from the chromosomes for which testing is not being performed (i.e. those other than chromosome 21) and are thus more susceptible to diluted fetal DNA and limited sequencing depth. We aimed to describe and evaluate a novel algorithm for aneuploidy detection (genome-wide normalized score (GWNS)), which normalizes read counts by the proportions of DNA fragments from chromosome 21 in normal controls. METHODS: We assessed the GWNS approach by comparison with two existing algorithms, i.e. Z-score and normalized chromosome value (NCV), using theoretical approximations and computer simulations in a set of 86 cases (64 euploid and 22 T21 cases). We then validated GWNS by studying an expanded set of clinical samples (n = 208). Finally, dilution experiments were undertaken to compare performance of the three algorithms (Z-score, NCV, GWNS) when fetal DNA concentration was low. RESULTS: At fixed levels of significance and power, GWNS required a smaller fetal DNA proportion and fewer total MPSS reads compared to Z-score or NCV. In dilution experiments, GWNS also outperformed the other two methods by reaching the correct diagnosis with the lowest range of fetal DNA concentrations (GWNS, 3.83-4.75%; Z-score, 4.75-5.22%; NCV, 6.47-8.58%). CONCLUSION: Our results demonstrate that GWNS is comparable to Z-score and NCV methods regarding the performance of detecting fetal T21. Dilution experiments suggest that GWNS may perform better than the other methods when fetal fraction is low.

Cardiac iron measurement and iron chelation therapy in patients with ß thalassaemia major: experience from Taiwan.

BACKGROUND: The aims of our study were to evaluate (i) the relationship between cardiac T2* values and cardiac complications in Asian ß-thalassaemia major (TM) patients, and (ii) the association between cardiac T2* values and other parameters currently used to predict cardiac complications as a result of transfusion iron overload. METHODS: We examined the myocardial iron loads of 88 TM patients from Taiwan with cardiac T2* magnetic resonance imaging (MRI) and assessed the correlation between cardiac T2* values and serum ferritin levels, liver iron concentration and left ventricular ejection fraction (LVEF). We also determined the predictive value of these measurements for the development of arrhythmia. RESULTS AND CONCLUSION: In our group of Taiwanese patients, the relative risk for arrhythmia was 10·36 when cardiac T2* values were less than 10 ms (compared with ≥10 ms) and 1·98 when serum ferritin levels increased >2500 ng mL(-1) (compared with ≤2500 ng mL(-1) ). Serum ferritin levels correlated with cardiac T2* values in patients with abnormal myocardial iron loads (T2* < 20 ms, r = -0·48, P = 0·004, n = 34), but LVEF (measured by echocardiography) gave no indication of excess myocardial iron deposition (r = -0·07, P = 0·52) or of the risk of developing arrhythmia.

Decadal stability in coral cover could mask hidden changes on reefs in the East Asian Seas.

Coral reefs in the Central Indo-Pacific region comprise some of the most diverse and yet threatened marine habitats. While reef monitoring has grown throughout the region in recent years, studies of coral reef benthic cover remain limited in spatial and temporal scales. Here, we analysed 24,365 reef surveys performed over 37 years at 1972 sites throughout East Asia by the Global Coral Reef Monitoring Network using Bayesian approaches. Our results show that overall coral cover at surveyed reefs has not declined as suggested in previous studies and compared to reef regions like the Caribbean. Concurrently, macroalgal cover has not increased, with no indications of phase shifts from coral to macroalgal dominance on reefs. Yet, models incorporating socio-economic and environmental variables reveal negative associations of coral cover with coastal urbanisation and sea surface temperature. The diversity of reef assemblages may have mitigated cover declines thus far, but climate change could threaten reef resilience. We recommend prioritisation of regionally coordinated, locally collaborative long-term studies for better contextualisation of monitoring data and analyses, which are essential for achieving reef conservation goals.

Responses of immature permanent teeth with infected necrotic pulp tissue and apical periodontitis/abscess to revascularization procedures.

AIM: To report several types of response of immature permanent teeth with infected necrotic pulp tissue and either apical periodontitis or abscess to revascularization procedures. METHODOLOGY: Twenty immature permanent teeth with infected necrotic pulp tissue and either apical periodontitis or abscesses from 20 patients were included. The teeth were isolated with rubber dam, and pulp chambers was accessed through the crowns. The canals were gently irrigated with 5.25% sodium hypochlorite with minimal mechanical debridement. Calcium hydroxide was used as an inter-appointment intracanal medicament and placed into the coronal half of the canal space. After resolution of clinical signs and symptoms, bleeding was induced into the canal space from the periapical tissues using K-files. The coronal canal space was sealed with a mixture of mineral trioxide aggregate (MTA) and saline solution. The access cavity was filled with composite resin. These immature permanent teeth with infected necrotic pulp tissue and apical periodontitis/abscesses were followed up from 6 to 26 months. RESULTS: Five types of responses of these immature permanent teeth with infected necrotic pulp tissue and apical periodontitis/abscess to revascularization procedures were observed: type 1, increased thickening of the canal walls and continued root maturation; type 2, no significant continuation of root development with the root apex becoming blunt and closed; type 3, continued root development with the apical foramen remaining open; type 4, severe calcification (obliteration) of the canal space; type 5, a hard tissue barrier formed in the canal between the coronal MTA plug and the root apex. CONCLUSIONS: Based on this case series, the outcome of continued root development was not as predictable as increased thickening of the canal walls in human immature permanent teeth with infected necrotic pulp tissue and apical periodontitis/abscess after revascularization procedures. Continued root development of revascularized immature permanent necrotic teeth depends on whether the Hertwig's epithelial root sheath survives in case of apical periodontitis/abscess. Severe pulp canal calcification (obliteration) by hard tissue formation might be a complication of internal replacement resorption or union between the intracanal hard tissue and the apical bone (ankylosis) in revascularized immature permanent necrotic teeth.

Risk of gynaecological malignancies in cytologically atypical glandular cells: follow-up study of a nationwide screening population.

OBJECTIVE: To investigate the relationship between screening status, clinical characteristics and risk of gynaecological malignancies in women with a cytological diagnosis of atypical glandular cells (AGC). DESIGN: Prospective study of a screened population. POPULATION: Case series from nationwide screening population. METHODS: The 8281 women who were diagnosed with cytological AGC for the first time were divided into screened (5386 women) and unscreened (2895 cases) groups according to their screening status. Follow-up histological reports were analysed. MAIN OUTCOME MEASURES: Diagnosis of cervical, uterine, or ovarian cancers. RESULTS: Of the 323 women who developed gynaecological malignancies, 271 had invasive cervical cancers, 40 had uterine cancers and 12 had ovarian cancers, with a mean follow up of 1.9 years and 50 740 person-years. Previous screening status was a strong risk predictor of gynaecological malignancies (hazard ratio 1.69, P = 0.0027). Compared with the general screening population, women with a first diagnosis of cytological AGC had significantly increased ratios of developing gynaecological malignancies (17.85-fold for cervical cancer, 5.68-fold for uterine cancer, and 2.04-fold for ovarian cancer, P < 0.05). When compared with women aged <35 years, those in other age groups had a significantly higher risk of developing gynaecological cancers (age ≥60 years, hazard ratio 1.99, 95% CI 1.20-2.37, P = 0.016). CONCLUSIONS: Comprehensive evaluation for women with cytological AGC, including pelvic examination, ultrasonography, colposcopy, endocervical curettage, cervical biopsy and endometrial biopsy needs to be considered, especially for those with risk factors (i.e. >60 years old, lower educational status, previous Papanicolaou smear interval longer than 2 years, or no previous Papanicolaou smear).

Brain metastasis as a late manifestation of ovarian carcinoma.

This paper aims to evaluate the clinical characteristics of ovarian cancer patients with cerebral metastases. Ten ovarian cancer patients with brain metastases were retrospectively identified from a total of 539 ovarian cancer patients. Their characteristics before and at the time of diagnosis of cerebral metastases were analysed. The survival of them was also measured. Ten (1.9%) of the 539 ovarian cancer patients had brain metastases in the study period. Nine had stage III or IV tumours with either moderate or poor histological differentiation. The mean time from diagnosis of ovarian cancer to documentation of central nervous system metastasis was 24.3 months, which was 11.1 months if other sites of metastasis were involved before cerebral relapse. All of the patients with intra-cranial tumours suffered from associated neurological defects and relived by treatments. The median survival time after diagnosis of central nervous system involvement was 3 months. In this study, all ovarian cancer patients with cerebral metastases had clinical neurological symptoms. Physicians should pay more attention to ovarian cancer patients with neurological defects and arrange brain imaging studies for the early diagnosis of brain metastases and prompt management to improve quality of life.

Cost-effectiveness analysis of human papillomavirus DNA testing and Pap smear for cervical cancer screening in a publicly financed health-care system.

OBJECTIVE: to evaluate the long-term cost-effectiveness of different strategies for human papillomavirus (HPV) DNA testing combined with Pap smear for cervical cancer screening in Taiwan. METHODS: this study adopts a perspective of Department of Health in cost-effectiveness analysis to compare a no-screening strategy with nine different screening strategies. These strategies comprise three screening tools (Pap smear alone, HPV DNA testing followed by Pap smear triage, and HPV DNA testing combined with Pap smear), and three screening intervals (annually, every 3 years, and every 5 years). Outcomes are life expectancy, quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs). Probabilistic sensitivity analyses (PSAs) were conducted to assess parameter uncertainty. RESULTS: when three times gross domestic product per capita is used as the decision threshold, all nine screening strategies were cost-effective compared with the no-screening strategy. Compared with the current screening strategy (an annual Pap smear), HPV DNA testing followed by Pap smear triage every 5 years and every 3 years were cost-effective. Results of PSA also indicated that a HPV DNA testing followed by Pap smear triage every 5 or every 3 years achieved the highest expected net benefits. CONCLUSIONS: possible economic advantages are associated with extending the cervical cancer screening interval from one Pap smear annually to HPV DNA testing followed by Pap smear triage every 5 years with an ICER $1 247 000 per QALY gained, especially in a country with a publicly financed health-care system.

Characterization and enhanced field emission properties of IrO2-coated carbon nanotube bundle arrays.

Low operating electric field and stable emission current have been achieved in IrO(2) nanocrystal-coated carbon nanotube bundle arrays (CNTBAs). Patterned vertically aligned CNTBAs were synthesized using thermal chemical vapor deposition followed by the deposition of IrO(2) nanocrystals by reactive radio-frequency magnetron sputtering using an Ir target. The structural and spectroscopic properties were characterized by field emission scanning and transmission electron microscopy, and Raman spectroscopy. The current density versus electric field measurements yielded a low turn-on field of 0.7 V microm(-1) at a current density of 0.1 microA cm(-2), a low threshold field of 2.3 V microm(-1) at a current density of 1 mA cm(-2) and a high field enhancement factor of 1 x 10(4) for the IrO(2)-coated CNTBAs. Long-term stability was also demonstrated. The enhancement of field emission characteristics is attributed to the combined effects of the geometrical structure of the IrO(2)-coated CNTBAs, and the natural conducting and enhanced resistance to oxidation properties of IrO(2).

Morphine-sparing effect by COX-1 inhibitor sustains analgesic function without compromising antigen-specific immunity and antitumor effect of naked DNA vaccine.

Morphine and ketorolac, two analgesics with different mechanisms, have been widely used in controlling cancer pain and postoperative pain in surgery. Our previous study revealed that morphine could suppress the anti-tumor effect of antigen-specific DNA vaccine. In this study, we further evaluated and compared another analgesic drug, ketorolac, with morphine for its analgesic functions and the antitumor immunities of antigen-specific DNA vaccine. We first observed that ketorolac-treated mice did not enhance tumorigenesis nor suppress the anti-tumor effects of antigen-specific (calreticulin linked to HPV16 E7) CRT/E7 DNA vaccine. We then demonstrated that ketorolac was less potent in inducing apoptosis of T lymphocytes and the generation of reactive oxygen species, in reducing mitochondrial membrane potentials, and leading to the activation of caspases 3 and 7 in T lymphocytes than morphine. When CRT/E7 DNA vaccinated mice treated with ketorolac, the declines of frequencies of E7-specific IFN-gamma-secreting CD8+ T cell precursors were slower in the morphine-treated group. CRT/E7 DNA vaccinated mice, treated with a mixture of morphine and ketorolac, could maintain the analgesic function without experiencing a decrease in the anti-tumor effects. CRT/E7 DNA vaccine with the opioid-sparing effect of ketorolac could provide potent anti-tumor effects and good analgesic function.

Noncarrier naked antigen-specific DNA vaccine generates potent antigen-specific immunologic responses and antitumor effects.

Genetic immunization strategies have largely focused on the use of plasmid DNA with a gene gun. However, there remains a clear need to further improve the efficiency, safety, and cost of potential DNA vaccines. The gold particle-coated DNA format delivered through a gene gun is expensive, time and process consuming, and raises aseptic safety concerns. This study aims to determine whether a low-pressured gene gun can deliver noncarrier naked DNA vaccine without any particle coating, and generate similarly strong antigen-specific immunologic responses and potent antitumor effects compared with gold particle-coated DNA vaccine. Our results show that mice vaccinated with noncarrier naked chimeric CRT/E7 DNA lead to dramatic increases in the numbers of E7-specific CD8+ T-cell precursors and markedly raised titers of E7-specific antibodies. Furthermore, noncarrier naked CRT/E7 DNA vaccine generated potent antitumor effects against subcutaneous E7-expressing tumors and pre-established E7-expressing metastatic pulmonary tumors. In addition, mice immunized with noncarrier naked CRT/E7 DNA vaccine had significantly less burning effects on the skin compared with those vaccinated with gold particle-coated CRT/E7 DNA vaccine. We conclude that noncarrier naked CRT/E7 DNA vaccine delivered with a low-pressured gene gun can generate similarly potent immunologic responses and effective antitumor effects has fewer side effects, and is more convenient than conventional gold particle-coated DNA vaccine.

High mesothelin correlates with chemoresistance and poor survival in epithelial ovarian carcinoma.

The objective of this paper is to investigate the mesothelin expression level to the clinicopathological features, chemoresponse, and to the outcome of patients with epithelial ovarian carcinoma (EOC). Mesothelin mRNA was detected by real-time quantitative reverse-transcription PCR in 139 EOC patients. Clinical characteristics, histopathological items, responses to chemotherapy, progression-free survival (PFS), and overall survival (OS) were recorded. Tumours with advanced stages had higher mesothelin than those with early stages. The chemoresistant patients showed significantly higher mesothelin than did chemosensitive patients (2.81 vs 0.43, P<0.001), irrespective of optimal or suboptimal surgery in those with advanced stages. Highly expressed levels of mesothelin were an independent but poor prognostic factor in the PFS (2.03 (1.23-3.37) P=0.006) and OS (3.72 (1.64-8.45), P=0.002) of the 139 EOC patients in multivariate analysis. In addition, patients in advanced stages with highly expressed mesothelin also had significantly worse OS, regardless of whether they had undergone optimal (13.85 (1.76-125.60), P=0.013) or suboptimal (4.47 (1.83-10.88), P=0.001) debulking surgery in multivariate analysis. Out results provide new evidence that mesothelin expression is associated with chemoresistance and with shorter disease-free survival and worse OS of patients with EOC.

Effectiveness of national cervical cancer screening programme in Taiwan: 12-year experiences.

BACKGROUND: We examined cervical cancer incidence before and after nationwide cervical cancer screening was initiated in Taiwan in mid-1995. RESULTS: The invasive cancer incidence decreased by 47.8% during 1995-2006. The carcinoma in situ incidence increased 1.7-fold during 1995-2000, and decreased by 19.6% during 2000-2006. CONCLUSION: The Taiwan national programme has significantly decreased invasive cervical cancer.