Dielectric collapse at the LaAlO3/SrTiO3 (001) heterointerface under applied electric field.

The fascinating interfacial transport properties at the LaAlO3/SrTiO3 heterointerface have led to intense investigations of this oxide system. Exploiting the large dielectric constant of SrTiO3 at low temperatures, tunability in the interfacial conductivity over a wide range has been demonstrated using a back-gate device geometry. In order to understand the effect of back-gating, it is crucial to assess the interface band structure and its evolution with external bias. In this study, we report measurements of the gate-bias dependent interface band alignment, especially the confining potential profile, at the conducting LaAlO3/SrTiO3 (001) heterointerface using soft and hard x-ray photoemission spectroscopy in conjunction with detailed model simulations. Depth-profiling analysis incorporating the electric field dependent dielectric constant in SrTiO3 reveals that a significant potential drop on the SrTiO3 side of the interface occurs within ~2 nm of the interface under negative gate-bias. These results demonstrate gate control of the collapse of the dielectric permittivity at the interface, and explain the dramatic loss of electron mobility with back-gate depletion.

Identification of serologic markers for school-aged children with congenital rubella syndrone

BACKGROUND: Congenital rubella syndrome (CRS) case identification is challenging in older children since laboratory markers of congenital rubella virus (RUBV) infection do not persist beyond age 12 months. METHODS: We enrolled children with CRS born between 1998 and 2003 and compared their immune responses to RUBV with those of their mothers and a group of similarly aged children without CRS. Demographic data and sera were collected. Sera were tested for anti-RUBV immunoglobulin G (IgG), IgG avidity, and IgG response to the 3 viral structural proteins (E1, E2, and C), reflected by immunoblot fluorescent signals. RESULTS: We enrolled 32 children with CRS, 31 mothers, and 62 children without CRS. The immunoblot signal strength to C and the ratio of the C signal to the RUBV-specific IgG concentration were higher (P < .029 for both) and the ratio of the E1 signal to the RUBV-specific IgG concentration lower (P = .001) in children with CRS, compared with their mothers. Compared with children without CRS, children with CRS had more RUBV-specific IgG (P < .001), a stronger C signal (P < .001), and a stronger E2 signal (P ≤ .001). Two classification rules for children with versus children without CRS gave 100% specificity with >65% sensitivity. CONCLUSIONS: This study was the first to establish classification rules for identifying CRS in school-aged children, using laboratory biomarkers. These biomarkers should allow improved burden of disease estimates and monitoring of CRS control programs. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Titanium dxy ferromagnetism at the LaAlO3/SrTiO3 interface.

A number of recent transport and magnetization studies have shown signs of ferromagnetism in the LaAlO3/SrTiO3 heterostructure, an unexpected property with no bulk analogue in the constituent materials. However, no experiment thus far has provided direct information on the host of the magnetism. Here we report spectroscopic investigations of the magnetism using element-specific techniques, including X-ray magnetic circular dichroism and X-ray absorption spectroscopy, along with corresponding model calculations. We find direct evidence for in-plane ferromagnetic order at the interface, with Ti(3+) character in the dxy orbital of the anisotropic t2g band. These findings establish a striking example of emergent phenomena at oxide interfaces.

Surto de Doença Meningocócica no Município de Estrela D’Oeste, SP, Setembro de 2006: da / investigação ao controle / Meningitis Outbreak in the city of Estrela D’Oeste/SP, September, 2006: from investigation to

A doença meningocócica (DM) é uma moléstia infecciosa aguda de expressiva relevância em saúde pública, devido ao seu potencial epidêmico, a elevada morbi-mortalidade e ao percentual significativo de seqüelas. Em setembro de 2006, o Município de Estrela D’Oeste/São Paulo confirmou a ocorrência de 3 casos de DM e letalidade de 66,7%. Os casos foram sorogrupados e todos identificados como meningococo do sorogrupo C. O objetivo da investigação foi caracterizar e confirmar a ocorrência do surto da doença na região. A investigação dos casos foi realizada a partir da análise de bancos de dados, de fichas epidemiológicas de notificação/investigação, de fichas de atendimento hospitalar e dos exames processados e de entrevistas com os médicos, casos suspeitos, contatos e familiares. Para inclusão no presente surto foram utilizadas as seguintes definições de casos: caso suspeito: todo paciente com sinais e/ou sintomas de meningite aguda, isto é, febre alta, vômitos, cefaléia intensa, rigidez de nuca ou abaulamento de fontanela; com ou sem toxemia (sonolência e/ou torpor e/ou irritação) e lesões cutâneas (petéquias ou púrpuras) residente ou que se deslocou para o Município de Estrela D’Oeste, no mês de setembro de 2006. Caso confirmado: caso suspeito com critério de confirmação laboratorial e/ou necropsia. Na ocasião, foi confirmado um surto de DM no Município de Estrela D’Oeste, com três casos e dois óbitos, desenvolvido em curso rápido e progressivo e com identificação do meningococo sorogrupo C nos três casos, o que está de acordo com a atual prevalência do sorogrupo C no Estado de São Paulo. As medidas de controle, quimioprofilaxia e vacinação, foram realizadas de forma criteriosa e oportuna. A investigação permitiu a descrição clínica e epidemiológica dos casos, com a confirmação de surto e a efetivação oportuna das ações de prevenção e controle.

The effects of yellow fever immunization (17DD) inadvertently used in early pregnancy during a mass campaign in Brazil.

BACKGROUND: This study describes the consequences of the inadvertent immunization of pregnant women during a mass vaccination campaign in the Campinas region of the state of São Paulo, Brazil, in February and March 2000. The study was carried out by the Women's Comprehensive Healthcare Center (CAISM), at the State University of Campinas (UNICAMP). The objective of the study was to evaluate the possible effects of the vaccine on pregnancy and conceptus, and to assess congenital infection resulting from immunization. METHODS: Pregnant women who received the YF vaccine were identified at primary health clinics and referred to the study site, a public reference, high-risk clinic, serving 42 towns in a region with a population of 3,000,000. A 12-month serological follow-up for newborns (PRNT), and an examination to detect congenital abnormalities was offered to pregnant women, who signed a consent form. In a sub-sample of women who were delivered at the study site, additional exams were proposed: neonatal fontanel ultrasound, funduscopy, audiometry, neuro-pediatric follow-up until 12 months of age, and IgM detection at birth. Fifteen blood samples from placentas and umbilical cords were tested for PCR. FINDINGS: A total of 480 pregnant, immunized women were identified, who had received the vaccine at a mean of 5.7 weeks (95% CI 5.2-6.2) of gestation. The great majority of women were unaware of their pregnancy at the time they were vaccinated, and only 46.7% were counseled to avoid immunization if pregnant. After a minimum 6-week interval, 98.2% pregnant women were IgG positive. A total of 19.6% of women reported mild adverse events (headache, fever or myalgia). No IgM antibodies were detected at birth and no placental or umbilical cord blood was positive according to PCR. The frequency of malformations (2.3% or 7/304 babies), miscarriages (2.5% or 11/441 pregnancies), stillbirths (0.7%) and premature delivery (7.8%) was similar to that found in the general population. At 12 months follow-up, 7% of samples were reactive to PRNT. However, after 12 months, only one child was seropositive. INTERPRETATION: Contrary to a previous study, maternal seroconversion was very high when immunization was carried out in early pregnancy. Vaccine applied during the first trimester does not appear to cause malformations, complications to the central nervous system, nor adverse perinatal results as represented by premature deliveries or perinatal deaths. The 12-month serological follow-up is inconclusive and should be extended to 24 months. Evaluation of the risk of miscarriage was hindered by late presentation at the study clinic.

Risk of fatal adverse events associated with 17DD yellow fever vaccine.

Yellow fever (YF), an acute infectious disease, is endemic in the north and central-west of Brazil. This disease can be prevented by the use of a vaccine. In Brazil, four fatal adverse events have been associated with the YF vaccine used in the country (17DD vaccine). We briefly describe the last two fatalities, and estimate the risk of 17DD-associated fatal adverse events under different epidemiological scenarios. Controversies regarding the appropriate denominator that enters the estimation of risk serve as a motivation for each proposed scenario. The statistical procedures used show optimum behaviour when assessing the risk of rare events. Risk estimates vary from 0.043 (95 % CI 0.017-0.110) to 2.131 (95 % CI 0.109-12.071) fatalities per million doses administered. The robust estimates of the risk of fatal adverse events we present constitute an important element in future risk-benefit analysis and point to the need for good quality vaccine coverage and adverse-events surveillance data to assess the risk of vaccination. Although vaccination of YF endemic regions is necessary to maintain low disease prevalence, preventive administration of YF vaccine to the entire population should be cautiously analysed.

Prevalence of antibodies to human herpesvirus-8 in populations with and without risk for infection in São Paulo State

Human herpesvirus 8 (HHV-8) is a newly described herpesvirus that is etiologically associated with all forms of Kaposi's sarcoma (KS). Seroepidemiological studies have shown high prevalence rates of HHV-8 antibodies among men who have sex with men (MSM) and AIDS patients, African children, Brazilian Amerindians, and elderly individuals in certain regions of Europe. The aim of the present study was to determine the prevalence of HHV-8 antibodies in healthy children and young adults from different cities in São Paulo State, and in a population at high risk for HHV-8 infection: HIV-negative MSM, and AIDS patients with and without KS. Antibodies to HHV-8 latency-associated nuclear antigen and lytic-phase antigens were detected by immunofluorescence assays. In 643 healthy children and young adults from the general population attending a vaccination program for yellow fever in ten different cities in São Paulo State, the prevalence of HHV-8 antibodies detected by the presence of latent or lytic antigens ranged from 1.0 to 4.1 percent in the different age groups (mean = 2.5 percent). In the MSM group, the prevalence was 31/95 (32.6 percent). In the group of patients with AIDS, the prevalence was 39.2 percent (51/130) for non-KS patients and 98.7 percent (77/78) for AIDS patients with the diagnosis of KS confirmed by histopathological examination. We conclude that HHV-8 has a restricted circulation among healthy children and young adults in the general population of São Paulo State and a high prevalence among MSM and AIDS patients.

Prevalence of antibodies to human herpesvirus-8 in populations with and without risk for infection in São Paulo State.

Human herpesvirus 8 (HHV-8) is a newly described herpesvirus that is etiologically associated with all forms of Kaposi's sarcoma (KS). Seroepidemiological studies have shown high prevalence rates of HHV-8 antibodies among men who have sex with men (MSM) and AIDS patients, African children, Brazilian Amerindians, and elderly individuals in certain regions of Europe. The aim of the present study was to determine the prevalence of HHV-8 antibodies in healthy children and young adults from different cities in São Paulo State, and in a population at high risk for HHV-8 infection: HIV-negative MSM, and AIDS patients with and without KS. Antibodies to HHV-8 latency-associated nuclear antigen and lytic-phase antigens were detected by immunofluorescence assays. In 643 healthy children and young adults from the general population attending a vaccination program for yellow fever in ten different cities in São Paulo State, the prevalence of HHV-8 antibodies detected by the presence of latent or lytic antigens ranged from 1.0 to 4.1% in the different age groups (mean=2.5%). In the MSM group, the prevalence was 31/95 (32.6%). In the group of patients with AIDS, the prevalence was 39.2% (51/130) for non-KS patients and 98.7% (77/78) for AIDS patients with the diagnosis of KS confirmed by histopathological examination. We conclude that HHV-8 has a restricted circulation among healthy children and young adults in the general population of São Paulo State and a high prevalence among MSM and AIDS patients.

Hepatitis B vaccine in infants: a randomized controlled trial comparing gluteal versus anterolateral thigh muscle administration.

A significantly diminished antibody response to hepatitis B vaccine has been demonstrated in adults when the buttock is used as the injection site. However, in Brazil, the buttock continues to be recommended as site of injection for intramuscular administration of vaccines in infants. In this age group, there are no controlled studies evaluating the immunogenicity of the hepatitis B vaccine when administered at this site. In the present study, 258 infants were randomized to receive the hepatitis B vaccine either in the buttock (n = 123) or in the anterolateral thigh muscle (n = 135). The immunization schedule consisted of three doses of hepatitis B vaccine (Engerix Bregister mark or target, 10 microg) at 2, 4 and 9 months of age. There were no significant differences in the proportion of seroconversion (99.3% x 99.2%), or in the geometric mean titer of ELISA anti-HBs (1,862.1 x 1,229.0 mIU/mL) between the two groups. This study demonstrates that a satisfactory serological response can be obtained when the hepatitis B vaccine is administered intramuscularly into the buttock.

Serious adverse events associated with yellow fever 17DD vaccine in Brazil: a report of two cases.

BACKGROUND: The yellow fever vaccine is regarded as one of the safest attenuated virus vaccines, with few side-effects or adverse events. We report the occurrence of two fatal cases of haemorrhagic fever associated with yellow fever 17DD substrain vaccine in Brazil. METHODS: We obtained epidemiological, serological, virological, pathological, immunocytochemical, and molecular biological data on the two cases to determine the cause of the illnesses. FINDINGS: The first case, in a 5-year-old white girl, was characterised by sudden onset of fever accompanied by headache, malaise, and vomiting 3 days after receiving yellow fever and measles-mumps-rubella vaccines. Afterwards she decompensated with icterus and haemorrhagic signs and died after a 5-day illness. The second patient-a 22-year-old black woman-developed a sore throat and fever accompanied by headache, myalgia, nausea, and vomiting 4 days after yellow fever vaccination. She then developed icterus, renal failure, and haemorrhagic diathesis, and died after 6 days of illness. Yellow fever virus was recovered in suckling mice and C6/36 cells from blood in both cases, as well as from fragments of liver, spleen, skin, and heart from the first case and from these and other viscera fragments in case 2. RNA of yellow fever virus was identical to that previously described for 17D genomic sequences. IgM ELISA tests for yellow fever virus were negative in case 1 and positive in case 2; similar tests for dengue, hantaviruses, arenaviruses, Leptospira, and hepatitis viruses A-D were negative. Tissue injuries from both patients were typical of wild-type yellow fever. INTERPRETATION: These serious and hitherto unknown complications of yellow fever vaccination are extremely rare, but the safety of yellow fever 17DD vaccine needs to be reviewed. Host factors, probably idiosyncratic reactions, might have had a substantial contributed to the unexpected outcome.

[Measles seroprevalence among pediatricians in a teaching hospital]. / Soroprevalência de sarampo entre pediatras de um hospital-escola.

OBJECTIVE: A measles outbreak occurred in S. Paulo state, during 1996 and 1997, resulting in 20,921 cases. Forty seven percent of the cases occurred in people between 20 and 29 years of age, and one of the control strategies of the Department of Health was the vaccination of health care workers. The prevalence of antibodies against measles among the hospital pediatricians was investigated. METHODS: One hundred and fifty samples were taken from volunteer pediatricians to test for measles antibodies using ELISA. A questionnaire about their having had measles and the vaccine was filled out. RESULTS: Of the 150 doctors, 122 (81.4%) were female and 28 (18.6%) male, of between 23 and 46 years of age (mean and median 27 years). The majority (98%-147/150) had protective levels of antibodies against measles (>100 UI/ml); 118 (80.3%-118/147) without and 29 (19.7%-29/147) with a history of measles. Only 3 pediatricians (2%-3/150), had negative serology, 2 without and 1 with a history of measles. Out of the 118 without history of measles, 79 (67%-39/118) in spite of the protective level of antibodies against measles, did not know if they, had been vaccinated. Out of the 79 vaccinated pediatricians, 64 (81%-64/79), had been vaccinated 25 years before, and still maintained protective levels of antibodies. Of the 3 doctors with negative serologies only one declared that he had been vaccinated. CONCLUSIONS: Measles seroprevalence among pediatricians of this hospital is high, especially due to preceding vaccination. On the other hand, the 2% of pediatricians with negative serology, in an epidemic situation could constitute a significant population for the acquisition and dissemination of the disease.

Recent immunization against measles does not interfere with the sero-response to yellow fever vaccine.

In order to determine whether previous measles vaccination interferes with the sero-response to yellow fever vaccine, 294 children at nine months of age were randomly assigned to immunization with yellow fever vaccine at different time intervals after measles vaccination. The seroconversion rate (SCR) and the log10 geometric mean titer (GMT) for 17 DD yellow fever vaccine at different intervals after Schwarz measles vaccination were: 1-6 days: SCR = 44/57 = 77%; GMT = 4.57; 7-13 days: SCR = 36/53 = 68%; GMT = 4.46; 14-21 days: SCR = 55/65 = 85%; GMT = 4.46; 22-27 days: SCR = 41/54 = 76%; GMT = 4.41 and >28 days: SCR = 52/65 = 80%; GMT = 4.24 (p > 0.05). We conclude that recent immunization against measles does not interfere with the sero-response to yellow fever vaccine.

Mycobacterium bovis dissemination (BCG strain) among immunodeficient Brazilian infants.

This study reports Mycobacterium bovis (BCG strain) dissemination in four primary immunodeficient (PID) patients. Their diagnoses were: chemotaxis defect, cellular immunodeficiency, combined immunodeficiency and chronic granulomatous disease (CGD). Patients were vaccinated with BCG (Moreau strain) between 17 days and 4 months of age. Identification of the BCG strain was performed in many sites, such as bone marrow, ganglionic mass, cerebrospinal fluid and in the site of vaccination. The first therapeutic schedule included rifampicin, isoniazid and ethambutol; no uniform treatment could be used for these patients. Therapy was adjusted as required on the basis of BCG sensitivity results. This study shows that PID patients are susceptible to BCG dissemination and demonstrates the importance of an early diagnosis for their prognosis.

[Serological evaluation of immunization against measles with 2 doses administered at 6 and 11 months of age: a prospective study]. / Avaliação sorológica de imunização contra o sarampo com duas doses administradas aos 6 e 11 meses de idade: estudo prospectivo.

A prospective study was designed to evaluate the serologic efficacy of a two dose measles vaccination schedule, at 6 months and 11 months of age. Infants were given a further attenuated measles virus vaccine (BIKEN CAM 70, Fundação Oswaldo Cruz) and serum samples were tested for measles antibodies using the indirect immunofluorescence technique (IFA) and ELISA. Seroconversion rates 6 to 12 months (mean of 8.0 +/- 1.7 months) following the second dose of measles vaccine were 88.5% (85/96) by IFA and 96.8% (93/96) by ELISA. No measles cases were reported during the study period. In regions where a significant proportion of measles cases occurs before nine months of age, vaccination with a two doses schedule, at 6 and 11 months of age, may represent an alternative for measles control.