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Photoinduced phase transition is a central issue in the field of non-equilibrium quantum physics. Here, the authors demonstrate that a terahertz electric-field pulse changes a Mott insulator of an organic molecular compound to a macroscopically polarized charge-order state.

Familial hypertrophic cardiomyopathy (HCM) is a common but severe genetic disease. A pregnant woman with familial HCM was referred to our hospital as both the couple and their families were concerned that the baby would later develop HCM. Therefore, we determined the risk of HCM in the neonate. Using whole-exome sequencing, mutational analysis was performed on the patient, her family members (including her father, mother, sister, and husband), and the neonate. Sanger sequencing was also performed. We found that HCM in this family was caused by a mutation in the cardiac heavy chain β-myosin (MYH7) gene. Encouragingly, the neonate did not carry this MYH7 mutation as the father was also negative. We were able to determine that the neonate had no risk of familial HCM. Obstetricians should consider genetic screening if a pregnant woman has a severe risk of such familial complications. Content: We demonstrated absence of familial HCM in a neonate and suggest appropriate genetic screening in pregnant women with familial complications.

Introdução: A escassez de insumos tem sido uma grande limitação para o avanço da vacinação. O objetivo deste estudo foi avaliar a efetividade, imunogenicidade e segurança da meia dose da ChAdOx1 nCoV-19. Métodos: Ensaio clínico controlado não randomizado de fase III com grupos de comparação interna e externa (profissionais de saúde vacinados com dose plena). Moradores de Viana-ES, 18-49 anos, receberam duas meias doses da ChAdOx1 nCoV-19, com intervalo de 8 semanas. Foram estudados a incidência novos casos, número de mortes, internações e admissões em UTI, anticorpos neutralizantes por teste de neutralização em placa (PRNT) e quimioluminescência contra a porção RBD da fração S1 da proteína Spike, anticorpos totais IgG específico para SARS-Cov2, fatores solúveis sistêmicos, imunidade celular por estimulação antígeno-específica de células mononucleares do sangue periférico in vitro e investigação de Linfócitos T e B de memória e de citocinas intracitoplasmáticas. Eventos adversos foram monitorizados por diário, registro em plataforma digital, busca ativa por telefone, notificações no E-SUS notifica. Tempos de coleta: antes, 28 dias após 1ª.(D1) e 2ª. (D2) doses, e seguimento 3,6,12 meses pós D2. Resultados: Dos 27.000 elegíveis, 20.546 indivíduos receberam duas meias doses. Desses, 572 coletaram amostras biológicas. Após D2, a taxa de soroconversão entre soronegativos no baseline (n = 239) foi 99,8% semelhante à dose plena (DP) (n = 104, 100%). A média geométrica dos títulos de anticorpos (IC95%; UA/dL) foi 1.324 (1.148-1.527) com a MD e 3.727 (2.975-4.668) com DP (p < 0,001). No subgrupo com infecção natural prévia, os títulos foram semelhantes à dose padrão, mas houve queda dos títulos após D2 comparado com D1 nos dois grupos (MD = 9.569 (8.768-10.443) vs. 5.742 (3.195-6.347)), (DP = 9.533 (7.377-12.319) vs. 4.915 (3.767-6.412)). A frequência de eventos adversos foi semelhante, mas a duração dos sintomas foi menor no grupo MD. Não ocorreram eventos adversos graves. Taxas de casos confirmados após imunização completa foi semelhante à dose plena (20/248.830 vs. 28/419.248 casos/pessoas dia). Conclusão: Meia dose da ChAdOx1 nCoV-19 é segura, imunogênica e capaz de induzir anticorpos neutralizantes em 99,8%. Em pessoas que tiveram infecção natural, uma meia dose foi semelhante a dose plena, e suficiente para induzir altos títulos de anticorpos. Resultados de imunidade celular e efetividade estão sendo analisados. Apoio: ICEPi/SESA, MS, PNI, OPAS, HUCAM, UFES, EBSERH.

Introdução: A escassez de insumos tem limitado o avanço da vacinação contra a Covid-19, no mundo. A vacinação com meia dose da ChAdOx1 nCOv-19 foi comparada à dose padrão no Estudo Viana. O objetivo deste estudo foi avaliar e monitorar os eventos adversos com meia dose e comparar com dose padrão. Métodos: Ensaio clínico de fase III que testou meia dose da ChAdOx1 nCoV-19 (AZD1222) em adultos de 18 a 49 anos da cidade de Viana - Espírito Santo. Os eventos adversos foram avaliados por meio de registros no sistema e-SUS notifica, busca ativa e estudos de casos de eventos adversos pós-vacina (EAVP) e eventos adversos de interesse especial (EAIE), telefone celular e 0800 disponível aos participantes, questionário eletrônico 7 e 30 dias após a primeira e segunda dose, busca ativa SAC Fiocruz e disque intoxicações, busca ativa de rumores no CIEVS, vigilância de todos os óbitos do município. Em uma subamostra, os eventos adversos foram avaliados por diário auto-aplicável e entrevista aos participantes, 28 dias após a primeira (D1) e a segunda dose (D2). O mesmo questionário foi aplicado numa coorte de trabalhadores da saúde, ajustado por idade, que recebeu 2 doses de dose padrão. Resultados: Foram incluídos 20.546 participantes. Desses, 572 foram convidados a responder um diário de eventos adversos. Dessa subamostra, 501 e 381 devolveram os diários pós D1 e D2. Não houve reações graves. Os sintomas mais frequentes foram (84% e 52%, p

In organic molecular compounds, intramolecular vibration is sometimes coupled with intermolecular charge transfer (CT). In such materials, vibrational excitation by a midinfrared (MIR) pulse causes collective intermolecular CTs that can be a route to an electronic-state conversion. Here, we report that an ionic-to-neutral (IN) conversion in tetrathiafulvalene-p-chloranil (TTF-CA) can be driven by a strong vibrational excitation induced by an MIR pulse. Using MIR-pump subcycle-reflectivity-probe and second-harmonic-generation-probe measurements, we discuss the coherent electron and lattice dynamics during and after the IN conversion, which are distinct from the dynamics of the photoinduced transition by electronic excitation alone.

Sjögren’s syndrome (SS) is an autoimmune disease affecting the salivary and lacrimal glands. Symptoms range from dryness to severe extra-glandular disease involving manifestations in the skin, lungs, nervous system, and kidney. Fatigue occurs in 70% of patients, characterizing primary SS (pSS) and significantly impacting the patient’s quality of life. There are some generic and specific instruments used to measure fatigue in SS. The mechanisms involved with fatigue in SS are still poorly understood, but it appears fatigue signaling pathways are more associated with cell protection and defense than with pro-inflammatory pathways. There are no established pharmacological treatment options for fatigue in pSS. So far, exercise and neuromodulation techniques have shown positive effects on fatigue in pSS. This study briefly reviews fatigue in pSS, with special attention to outcome measures, biomarkers, and possible treatment options.

Immunotherapy drugs have recently been approved by the Food and Drug Administration for the treatment of several genitourinary malignancies, including bladder cancer, renal cancer, and prostate cancer. Preclinical data and early clinical trial results suggest that immune checkpoint inhibitors can act synergistically with radiation therapy to enhance tumor cell killing at local irradiated sites and in some cases at distant sites through an abscopal effect. Because radiation therapy is commonly used in the treatment of genitourinary malignancies, there is great interest in testing the combination of immunotherapy with radiation therapy in these cancers to further improve treatment efficacy. In this review, we discuss the current evidence and biological rationale for combining immunotherapy with radiation therapy, as well as emerging data from ongoing and planned clinical trials testing the efficacy and tolerability of this combination in the treatment of genitourinary malignancies. We also outline outstanding questions regarding sequencing, dose fractionation, and biomarkers that remain to be addressed for the optimal delivery of this promising treatment approach.

Red blood cell alloimmunization during pregnancy causes hemolytic disease of the fetus and newborn. While alloimmunization in pregnancy is treatable with anti-D antibodies, management with other antibodies has not been studied. A 32-year-old woman had anti-E antibodies detected during pregnancy, but the titer was < 1 : 2. Her newborn was admitted to hospital because direct Coombs tests were positive. Low titers of maternal anti-E antibodies were found in the newborn. We performed phototherapy and administered intravenous immunoglobulin because the newborn showed early jaundice and hyperkalemia, which suggested hemolytic disease. After being discharged at 6 days of age, the baby was readmitted to hospital at 9 days because of recurrent jaundice and underwent phototherapy. The baby was later discharged without recurrence of jaundice. Low anti-E antibody titers in pregnancy can cause alloimmunization, which can be treated successfully. The potential risk of hemolytic disease should be considered in cases with such low titers.

We report a high performance mid-infrared pump visible probe measurement system, which can measure phase-sensitive responses to a mid-infrared pulse along the oscillating electromagnetic field. In this system, the pump light is a phase-locked mid-infrared pulse with a temporal width of 100 fs, which is produced via difference frequency generation (DFG) from two idler pulses of two optical parametric amplifiers (OPAs) that are excited by the same Ti:sapphire regenerative amplifier. The probe pulse is a visible pulse with a temporal width of 9 fs and is generated from a custom-built non-collinear OPA. By measuring the electric-field waveforms of mid-infrared pump pulses with electro-optic sampling and evaluating their carrier envelope phase (CEP) and the temporal positions of their envelopes relative to ultrashort visible probe pulses, we are able to perform double feedback corrections that eliminate both the following sources of drift. The CEP drift in mid-infrared pulses originating from fluctuations in the difference of optical-path lengths of the two idler pulses before the DFG is corrected by inserting a wedge plate in one idler path, and the drift in pump–probe delay times due to fluctuations in the difference of the overall optical-path lengths of the pump and probe pulses is corrected with mechanical delay lines. In this double feedback system, the absolute carrier phase of mid-infrared pulses can be fixed within 200 mrad and errors in the measurement of phase-sensitive responses can be reduced to within 1 fs over a few tens of hours.

Understanding the dynamics of cuprates following photoexcitation can provide insights into the complex coupling mechanisms that underlie their exotic equilibrium behaviour. Here the authors use pump-probe reflection spectroscopy to investigate the nonequilibrium spin dynamics of Mott-insulating Nd2CuO4.

Abstract We present possible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals, and study the capability of the network to determine the sky location of the source. We report our findings for gravitational-wave transients, with particular focus on gravitational-wave signals from the inspiral of binary neutron star systems, which are the most promising targets for multi-messenger astronomy. The ability to localize the sources of the detected signals depends on the geographical distribution of the detectors and their relative sensitivity, and $$90\%$$ 90% credible regions can be as large as thousands of square degrees when only two sensitive detectors are operational. Determining the sky position of a significant fraction of detected signals to areas of 5–$$20~\mathrm {deg}^2$$ 20deg2 requires at least three detectors of sensitivity within a factor of $$\sim 2$$ ∼2 of each other and with a broad frequency bandwidth. When all detectors, including KAGRA and the third LIGO detector in India, reach design sensitivity, a significant fraction of gravitational-wave signals will be localized to a few square degrees by gravitational-wave observations alone.

Objectives: To provide safety and efficacy data on infants implanted below 12 months of age. Methods: With the wide application of newborn hearing screening programs, infants with deafness are being identified at birth. When a hearing aid trial fails, cochlear implantation is the only option to restore hearing. Mounting evidence suggests that age at implantation is a strong predictor of language outcomes. Using the minimally invasive surgical technique we have employed for nearly two decades, a limited clinical trial was initiated in the year 2000 because this age limitation fell outside of FDA guidelines. The infants were initially assessed using the preferential listening paradigm to confirm that they could learn associations between speech sounds and objects. Sufficient time was allowed to pass to administer more traditional language measures. Results: No surgical or anesthetic complications occurred in this group of infants. The pattern of listening skill development mirrored that seen in normal hearing infants. Long-term language assessments using the Peabody Picture Vocabulary Test (PPVT) and other measures have demonstrated that many of infants achieved age appropriate language skills. Conclusion: Cochlear implantation in children less than 12 months of age is safe and efficacious as demonstrated by long-term PPVT language data. Keywords: Infants, Cochlear implantation, Treatment outcome

The current FDA-approved whole blood stabilization method for circulating tumor cell (CTC) isolation suffers from RNA degradation. Here the authors combine hypothermic preservation and antiplatelet strategies to stabilize whole blood up to 72 h without compromising CTC yield and RNA integrity.

Circulating tumour cells contribute to metastatic spread. Here the authors find that beta-chain of haemoglobin is overexpressed in those cells and protects them from oxidative stress, prolonging their survival in circulation and thereby increasing the likelihood of metastasis formation.

Circulating tumor cells (CTCs) are shed from primary tumors into the bloodstream, mediating the hematogenous spread of cancer to distant organs. To define their composition, we compared genome-wide expression profiles of CTCs with matched primary tumors in a mouse model of pancreatic cancer, isolating individual CTCs using epitope-independent microfluidic capture, followed by single-cell RNA sequencing. CTCs clustered separately from primary tumors and tumor-derived cell lines, showing low-proliferative signatures, enrichment for the stem-cell-associated gene Aldh1a2, biphenotypic expression of epithelial and mesenchymal markers, and expression of Igfbp5, a gene transcript enriched at the epithelial-stromal interface. Mouse as well as human pancreatic CTCs exhibit a very high expression of stromal-derived extracellular matrix (ECM) proteins, including SPARC, whose knockdown in cancer cells suppresses cell migration and invasiveness. The aberrant expression by CTCs of stromal ECM genes points to their contribution of microenvironmental signals for the spread of cancer to distant organs.

The genetic variation among nine soybean-originating isolates of Colletotrichum truncatum from different Brazilian states was studied. Nitrate non-utilizing (nit) mutants were obtained with potassium chlorate and used to characterize vegetative compatibility reactions, heterokaryosis and RAPD profile. Based on pairings of nit mutants from the different isolates, five vegetative complementation groups (VCG) were identified, and barriers to the formation of heterokaryons were observed among isolates derived from the same geographic area. No complementation was observed among any of the nit mutants recovered from the isolate A, which was designed heterokaryon-self-incompatible. Based on RAPD analysis, a polymorphism was detected among the wild isolate C and their nit1 and NitM mutants. RAPD amplification, with five different primers, also showed polymorphic profiles among Brazilian C. truncatum isolates. Dendrogram analysis resulted in a similarity degree ranging between 0.331 and 0.882 among isolates and identified three RAPD groups. Despite the lack of a correlation between the RAPD analysis and the vegetative compatibility grouping, results demonstrated the potential of VCG analysis to differentiate C. truncatum isolates genotypically similar when compared by RAPD.

BACKGROUND: It is not known whether the addition of chemotherapy to radiation therapy improves outcomes in primary vaginal cancer. Here, we review clinical outcomes in patients with primary vaginal cancer treated with radiation therapy (RT) or concurrent chemoradiation therapy (CRT). METHODS: Seventy-one patients with primary vaginal cancer treated with definitive RT with or without concurrent chemotherapy at a single institution were identified and their records reviewed. A total of 51 patients were treated with RT alone; 20 patients were treated with CRT. Recurrences were analyzed. Overall survival (OS) and disease-free survival (DFS) rates were estimated using the Kaplan-Meier method. Cox regression analysis was performed. RESULTS: The median age at diagnosis was 61 years (range, 18-92 years) and the median follow-up time among survivors was 3.0 years. Kaplan-Meier estimates for OS and DFS differed significantly between the RT and CRT groups (3-yr OS = 56% vs. 79%, log-rank p = 0.037; 3-yr DFS = 43% vs. 73%, log-rank p = 0.011). Twenty-three patients (45%) in the RT group had a relapse at any site compared to 3 (15%) in the CRT group (p = 0.027). With regard to the sites of first relapse, 10 patients (14%) had local only, 4 (6%) had local and regional, 9 (13%) had regional only, 1 (1%) had regional and distant, and 2 (3%) had distant only relapse. On univariate analysis, the use of concurrent chemotherapy, FIGO stage, tumor size, and date of diagnosis were significant predictors of DFS. On multivariate analysis, the use of concurrent chemotherapy remained a significant predictor of DFS (hazard ratio 0.31 (95% CI, 0.10-0.97; p = 0.04)). CONCLUSIONS: Vaginal cancer results in poor outcomes. Adequate radiation dose is essential to ensure curative management. Concurrent chemotherapy should be considered for vaginal cancer patients.

BACKGROUND: Prolonged wound-discharge following total hip arthroplasty (THA) is associated with an increased risk of infection. However, the potential role of hypertension in prolonging the duration of wound healing in this population has not yet been investigated. The aim of the present study was to compare healing in this population that has not yet been investigated. The aim of the present study was to compare hypertensive and normotensive THA patients in terms of the length of time required to achieve a dry wound and the length of stay in the hospital. METHODS: One hundred and twenty primary THA patients were evaluated. Pre-operative clinical history and physical examination revealed that 29 were hypertensive and 91 were normotensive. The two groups were statistically matched using optimal propensity score matching. The outcomes of interest were the number of days until a dry wound was observed and the duration of hospital stay. RESULTS: The average systolic blood pressures were 150.1 mmHg and 120.3 mmHg for the hypertensive and normotensive groups, respectively. The mean number of days until the wound was dry was 3.79 for the hypertensive group and 2.03 for the normotensive group. Hypertensive patients required more days for their wounds to dry than normotensive patients (odds ratio = 1.65, p

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The N-geneous method is a recently developed method for determination of low-density lipoprotein cholesterol (LDL-C) in human serum. In the present study, we attempted to adapt this method to bovine serum. The values of LDL-C obtained using the N-geneous method were highly correlated with those from the method using ultracentrifugation and heparin sepharose affinity chromatography (r = 0.934, p < 0.001). The reproducibility of this method was acceptable (intra-assay CV 4.2%, inter-assay CV 7.6%) for clinical use. Using the N-geneous method, serum LDL-C was evaluated in cows around parturition, and in cows with fatty liver induced by fasting. The concentration of LDL-C decreased significantly in cows close to parturition. A reduced concentration of LDL-C was also observed in cows with fatty liver. In both cases, the changes of LDL-C were similar to those of apolipoprotein B (apoB)-100, and the values of LDL-C were highly correlated (r = 0.876, p < 0.001) with those of apoB-100. These results suggest that the concentration of LDL-C reflects the level of apoB-100. The N-geneous method is simple and rapid, and might to be a useful tool to elucidate the clinical significance of LDL-C in bovine serum. [ABSTRACT FROM AUTHOR]

OBJECTIVES:: With the application of universal newborn hearing screening programs, a large pool of newly identified deaf infants has been identified. The benefits of early intervention with cochlear implants (CI) is being explored. Mounting evidence suggests that age at implantation is a strong predictor of language outcomes. However, new behavioral procedures are needed to measure speech and language skills during infancy. Also, procedures are needed to analyze the speech input to young CI recipients.STUDY DESIGN:: Cohort-sequential.METHODS:: Thirteen infants with profound hearing loss who were implanted between the ages of 6 to 12 months of age participated in this study. Eight participated in two new behavioral methodologies: 1) the visual habituation procedure to assess their discrimination of speech sounds; 2) the preferential looking paradigm to assess their ability to learn associations between speech sounds and objects. Older implanted infants and normal-hearing infants were also tested for comparison. The pitch of mothersʼ speech to infants was analyzed.RESULTS:: Patterns of looking times for the very early implanted infants were similar to those of normal hearing infants. Mothersʼ speech to infants with CIs was similar in pitch to normal-hearing infants who had the same duration of experience with sounds.CONCLUSIONS:: No surgical or anesthetic complications occurred in this group of infants, and the pattern of listening skill development mirrors that seen in normal-hearing infants. Mothers adjust their speech to suit the listening experience of their infants. [ABSTRACT FROM AUTHOR]