Early onset preeclampsia is characterized by altered placental lipid metabolism and a premature increase in circulating FABP4

Preeclampsia is a pregnancy-associated disorder that manifests as a sudden increase in maternal blood pressure accompanied by proteinuria. Because the placenta is a key organ in preeclampsia, we used proteomic and lipidomic analyses to compare placentae from preeclamptic and gestational age matched control pregnancies. Fatty acid binding protein 4 (FABP4), enoyl-CoA dehydrogenase and delta-3,5-delta-2,4-dienoyl-CoA isomerase had altered abundance in preeclamptic placentae compared to controls. FABP4 placental protein and RNA and plasma levels were all increased in early-onset preeclampsia (prior to 28 weeks gestation) compared to controls (6-fold, 3.3-fold and 3.5-fold respectively). After 28 weeks, FABP4 protein in control placenta and plasma increased to the same concentrations as in preeclampsia. Total tetracosapentaenoic acid in preeclamptic placentae was decreased to 0.6 of control levels before 28 weeks. The data indicate a disruption of fatty acid transport and metabolism in the placenta in early onset preeclampsia that is reflected in the maternal plasma

Impact of meningitis on intelligence and development: A systematic review and meta-analysis

BACKGROUND: We undertook a systematic review and meta-analysis to address the question "what is the impact of meningitis on IQ and development." METHODS: Search: conducted using standardized search terms across Medline, PsychInfo and EMBASE to 06/2014. Eligibility: human studies of any infectious aetiology of meningitis reporting IQ or infant developmental age or stage outcomes. Quality: Centre for Evidence Based Medicine, Oxford, quality tools. Analysis: random effects meta-analysis by organism. RESULTS: 39 studies were included in the review, 34 providing data on IQ (2015 subjects) and 12 on developmental delay (382 subjects). Across all bacterial organisms, meningitis survivors had a mean IQ 5.50 (95% CI: -7.19, -3.80; I2 = 47%, p = 0.02) points lower than controls. IQ was significantly lower than controls for Neisseria meningitides (NM: 5 points) and Haemophilus influenzae b (Hib: 6 points) but not in viral meningitis, with only single studies included for Streptococcus pneumoniae (SP) and group B streptococcus (GBS). The pooled relative risk (RR) for low IQ (IQ<70) in survivors of bacterial meningitis compared with controls was 4.99 (95% CI: 3.17, 7.86) with no significant heterogeneity (I2 = 49%, p = 0.07). Developmental delay of approximately 0.5SD was reported in studies of bacterial meningitis but no delay in the only study of viral meningitis. CONCLUSIONS: We found moderate evidence that surviving bacterial meningitis has a deleterious impact on IQ and development but no evidence that viral meningitis had meaningful cognitive impacts. Survivors of bacterial meningitis should be routinely offered screening for cognitive deficits and developmental delay in addition to hearing loss

Viral respiratory infections at the Hajj: comparison between UK and Saudi pilgrims

ABSTRACTA high incidence of respiratory infection, including influenza, has been reported at the Hajj in Mecca, Saudi Arabia. Reported rates of influenza have been higher among UK than among domestic pilgrims, but this could be explained by methodological differences among studies. Accordingly, the present study compared the frequencies of respiratory viruses among UK and Saudi pilgrims using the same study design. Pilgrims with upper respiratory tract symptoms were recruited from Mecca and the neighbouring valley Mina during the Hajj 2006. Nasal swabs were used for point-of-care influenza testing and real-time RT-PCR (rtRT-PCR) tests for influenza virus, rhinovirus, parainfluenza virus, adenovirus, human metapneumovirus and respiratory syncytial virus. Of 260 pilgrims investigated, 150 were from the UK and 110 were Saudi; of these, 38 (25%) UK pilgrims and 14 (13%) Saudi pilgrims had respiratory infections detectable by rtRT-PCR (p 0.01). In the UK group, there were 19 (13%) cases of rhinovirus infection, 15 (10%) cases of influenza virus infection, two (1%) cases of dual infections with influenza virus and rhinovirus, one (3%) case of parainfluenza virus infection, and one (1%) case of respiratory syncytial virus infection. Fifty-six (37%) UK pilgrims had been vaccinated against influenza virus, with the rates of influenza in the vaccinated and unvaccinated group being 7% and 14%, respectively (p 0.19). In the Saudi group, there were three (3%) cases of rhinovirus infection and 11 (10%) cases of influenza. Only four (4%) Saudi pilgrims had been vaccinated against influenza virus, and none of these was infected with influenza virus. Overall, a significantly higher proportion of the UK pilgrims had detectable respiratory infections (25% vs. 13%, p 0.01). Influenza rates were similar in both groups, but the reported rates of influenza vaccination differed

Influenza and respiratory syncytial virus infections in British Hajj pilgrims

Viral respiratory infections including influenza and respiratory syncytial virus (RSV) have been reported during the Hajj among international pilgrims. To help establish the burden of these infections at the Hajj, we set up a study to confirm these diagnoses in symptomatic British pilgrims who attended the 2005 Hajj. UK pilgrims with symptoms of upper respiratory tract infection (URTI) were invited to participate; after taking medical history, nasal swabs were collected for point-of-care testing (PoCT) of influenza and for subsequent PCR analysis for influenza and RSV. Of the 205 patients recruited, 37 (18%) were positive for either influenza or RSV. Influenza A (H3) accounted for 54% (20/37) of the virus-positive samples, followed by RSV 24% (9/37), influenza B 19% (7/37), and influenza A (H1) 3% (1/37). Of the influenza-positive cases, 29% (8/28) had recently had a flu immunisation. Influenza was more common in those who gave a history of contact with a pilgrim with a respiratory illness than those who did not (17 versus 9%). The overall rate of RSV was 4% (9/202). This study confirms that influenza and RSV cause acute respiratory infections in British Hajj pilgrims. Continuing surveillance and a programme of interventions to contain the spread of infection are needed at the Hajj, particularly when the world is preparing for an influenza pandemic

Modelling the Interfacial Flow of Two Immiscible Liquids in Mixing Processes

This paper presents an interface tracking method for modelling the flow of immiscible metallic liquids in mixing processes. The methodology can provide an insight into mixing processes for studying the fundamental morphology development mechanisms for immiscible interfaces. The volume-of-fluid (VOF) method is adopted in the present study, following a review of various modelling approaches for immiscible fluid systems. The VOF method employed here utilises the piecewise linear for interface construction scheme as well as the continuum surface force algorithm for surface force modelling. A model coupling numerical and experimental data is established. The main flow features in the mixing process are investigated. It is observed that the mixing of immiscible metallic liquids is strongly influenced by the viscosity of the system, shear forces and turbulence. The numerical results show good qualitative agreement with experimental results, and are useful for optimisating the design of mixing casting processes

The Seroepidemiology of Haemophilus influenzae Type B Prior to Introduction of an Immunization Programme in Kathmandu, Nepal.

Haemophilus influenzae type b (Hib) is now recognized as an important pathogen in Asia. To evaluate disease susceptibility, and as a marker of Hib transmission before routine immunization was introduced in Kathmandu, 71 participants aged 7 months-77 years were recruited and 15 cord blood samples were collected for analysis of anti-polyribosylribitol phosphate antibody levels by enzyme-linked immunosorbent assay. Only 20% of children under 5 years old had levels considered protective (>0.15 µg/ml), rising to 83% of 15-54 year-olds. Prior to introduction of Hib vaccine in Kathmandu, the majority of young children were susceptible to disease

Heterologous prime-boost vaccination using an ASO3B-adjuvanted influenza A(H5N1) vaccine in infants and children <3 years of age

Presented in part: Options for the Control of Influenza VIII Conference, Cape Town, South Africa, 5–10 September 2013BACKGROUND: Protecting young children from pandemic influenza should also reduce transmission to susceptible adults, including pregnant women. METHODS: An open study assessed immunogenicity and reactogenicity of a heterologous booster dose of A/turkey/Turkey/1/2005(H5N1)-AS03B (AS03B is an Adjuvant System containing α-tocopherol and squalene in an oil-in-water emulsion [5.93 mg tocopherol]) in infants and children aged 6 to <36 months that was given 6 months following 2-dose primary vaccination with A/Indonesia/05/2005(H5N1)-AS03B. Vaccines contained 1.9 µg of hemagglutinin antigen and AS03B. Hemagglutinin inhibition (HI) responses, microneutralization titers, and antineuraminidase antibody levels were assessed for 6 months following the booster vaccination. RESULTS: For each age stratum (defined on the basis of the subject's age at first vaccination as 6 to <12 months, 12 to <24 months, and 24 to <36 months) and overall (n=113), European influenza vaccine licensure criteria were fulfilled for responses to A/turkey/Turkey/1/2005(H5N1) 10 days following the booster vaccination. Local pain and fever increased with consecutive doses. Anamnestic immune responses were demonstrated for HI, neutralizing, and antineuraminidase antibodies against vaccine-homologous/heterologous strains. Antibody responses to vaccine-homologous/heterologous strains persisted in all children 6 months following the booster vaccination. CONCLUSIONS: Prevaccination of young children with a clade 2 strain influenza A(H5N1) AS03-adjuvanted vaccine followed by heterologous booster vaccination boosted immune responses to the homologous strain and a related clade, with persistence for at least 6 months. The results support a prime-boost vaccination approach in young children for pandemic influenza preparedness. CLINICAL TRIALS REGISTRATION: NCT01323946.Terry Nolan, Patricia Izurieta, Bee-Wah Lee, Poh Chong Chan, Helen Marshall, Robert Booy, Mamadou Drame, and David W. Vaugh

Equation of state for polymer liquid crystals: theory and experiment

The first part of this paper develops a theory for the free energy of lyotropic polymer nematic liquid crystals. We use a continuum model with macroscopic elastic moduli for a polymer nematic phase. By evaluating the partition function, considering only harmonic fluctuations, we derive an expression for the free energy of the system. We find that the configurational entropic part of the free energy enhances the effective repulsive interactions between the chains. This configurational contribution goes as the fourth root of the direct interactions. Enhancement originates from the coupling between bending fluctuations and the compressibility of the nematic array normal to the average director. In the second part of the paper we use osmotic stress to measure the equation of state for DNA liquid crystals in 0.1M to 1M NaCl solutions. These measurements cover 5 orders of magnitude in DNA osmotic pressure. At high osmotic pressures the equation of state, dominated by exponentially decaying hydration repulsion, is independent of the ionic strength. At lower pressures the equation of state is dominated by fluctuation enhanced electrostatic double layer repulsion. The measured equation of state for DNA fits well with our theory for all salt concentrations. We are able to extract the strength of the direct electrostatic double layer repulsion. This is a new and alternative way of measuring effective charge densities along semiflexible polyelectrolytes.Comment: text + 5 figures. Submitted to PR

Causes and clinical features of childhood encephalitis: a multicenter, prospective cohort study

BACKGROUND:We aimed to determine the contemporary causes, clinical features, and short-term outcome of encephalitis in Australian children. METHODS:We prospectively identified children (≤14 years of age) admitted with suspected encephalitis at 5 major pediatric hospitals nationally between May 2013 and December 2016 using the Paediatric Active Enhanced Disease Surveillance (PAEDS) Network. A multidisciplinary expert panel reviewed cases and categorized them using published definitions. Confirmed encephalitis cases were categorized into etiologic subgroups. RESULTS:From 526 cases of suspected encephalitis, 287 children met criteria for confirmed encephalitis: 57% (95% confidence interval [CI], 52%-63%) had infectious causes, 10% enterovirus, 10% parechovirus, 8% bacterial meningoencephalitis, 6% influenza, 6% herpes simplex virus (HSV), and 6% Mycoplasma pneumoniae; 25% (95% CI, 20%-30%) had immune-mediated encephalitis, 18% acute disseminated encephalomyelitis, and 6% anti-N-methyl-d-aspartate receptor encephalitis; and 17% (95% CI, 13%-21%) had an unknown cause. Infectious encephalitis occurred in younger children (median age, 1.7 years [interquartile range {IQR}, 0.1-6.9]) compared with immune-mediated encephalitis (median age, 7.6 years [IQR, 4.6-12.4]). Varicella zoster virus encephalitis was infrequent following high vaccination coverage since 2007. Thirteen children (5%) died: 11 with infectious causes (2 influenza; 2 human herpesvirus 6; 2 group B Streptococcus; 2 Streptococcus pneumoniae; 1 HSV; 1 parechovirus; 1 enterovirus) and 2 with no cause identified. Twenty-seven percent (95% CI, 21%-31%) of children showed moderate to severe neurological sequelae at discharge. CONCLUSIONS:Epidemic viral infections predominated as causes of childhood encephalitis in Australia. The leading causes include vaccine-preventable diseases. There were significant differences in age, clinical features, and outcome among leading causes. Mortality or short-term neurological morbidity occurred in one-third of cases.Philip N Britton, Russell C Dale, Christopher C Blyth, Julia E Clark, Nigel Crawford, Helen Marshall ... et al

Efficacy of a trivalent influenza vaccine against seasonal strains and against 2009 pandemic H1N1: a randomized, placebo-controlled trial

Background: Before pandemic H1N1 vaccines were available, the potential benefit of existing seasonal trivalent inactivated influenza vaccines (IIV3s) against influenza due to the 2009 pandemic H1N1 influenza strain was investigated, with conflicting results. This study assessed the efficacy of seasonal IIV3s against influenza due to 2008 and 2009 seasonal influenza strains and against the 2009 pandemic H1N1 strain. Methods: This observer-blind, randomized, placebo-controlled study enrolled adults aged 18–64 years during 2008 and 2009 in Australia and New Zealand. Participants were randomized 2:1 to receive IIV3 or placebo. The primary objective was to demonstrate the efficacy of IIV3 against laboratory-confirmed influenza. Participants reporting an influenza-like illness during the period from 14 days after vaccination until 30 November of each study year were tested for influenza by real-time reverse transcription polymerase chain reaction. Results: Over a study period of 2 years, 15,044 participants were enrolled (mean age ± standard deviation: 35.5 ± 14.7 years; 54.4% female). Vaccine efficacy of the 2008 and 2009 IIV3s against influenza due to any strain was 42% (95% confidence interval [CI]: 30%, 52%), whereas vaccine efficacy against influenza due to the vaccine-matched strains was 60% (95% CI: 44%, 72%). Vaccine efficacy of the 2009 IIV3 against influenza due to the 2009 pandemic H1N1 strain was 38% (95% CI: 19%, 53%). No vaccine-related deaths or serious adverse events were reported. Solicited local and systemic adverse events were more frequent in IIV3 recipients than placebo recipients (local: IIV3 74.6% vs placebo 20.4%, p < 0.001; systemic: IIV3 46.6% vs placebo 39.1%, p < 0.001). Conclusions: The 2008 and 2009 IIV3s were efficacious against influenza due to seasonal influenza strains and the 2009 IIV3 demonstrated moderate efficacy against influenza due to the 2009 pandemic H1N1 strain