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Our aim was to develop a brief cognitive behavioural therapy (CBT) protocol to augment treatment for social anxiety disorder (SAD). This protocol focused specifically upon fear of positive evaluation (FPE). To our knowledge, this is the first protocol that has been designed to systematically target FPE.
To test the feasibility of a brief (two-session) CBT protocol for FPE and report proof-of-principle data in the form of effect sizes.
Seven patients with a principal diagnosis of SAD were recruited to participate. Following a pre-treatment assessment, patients were randomized to either (a) an immediate CBT condition (n = 3), or (b) a comparable wait-list (WL) period (2 weeks; n = 4). Two WL patients also completed the CBT protocol following the WL period (delayed CBT condition). Patients completed follow-up assessments 1 week after completing the protocol.
A total of five patients completed the brief, FPE-specific CBT protocol (two of the seven patients were wait-listed only and did not complete delayed CBT). All five patients completed the protocol and provided 1-week follow-up data. CBT patients demonstrated large reductions in FPE-related concerns as well as overall social anxiety symptoms, whereas WL patients demonstrated an increase in FPE-related concerns.
Our brief FPE-specific CBT protocol is feasible to use and was associated with large FPE-specific and social anxiety symptom reductions. To our knowledge, this is the first treatment report that has focused on systematic treatment of FPE in patients with SAD. Our protocol warrants further controlled evaluation.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
Childhood early life stress (ELS) increases risk of adulthood major depressive disorder (MDD) and is associated with altered brain structure and function. It is unclear whether specific ELSs affect depression risk, cognitive function and brain structure.
This cross-sectional study included 64 antidepressant-free depressed and 65 never-depressed individuals. Both groups reported a range of ELSs on the Early Life Stress Questionnaire, completed neuropsychological testing and 3T magnetic resonance imaging (MRI). Neuropsychological testing assessed domains of episodic memory, working memory, processing speed and executive function. MRI measures included cortical thickness and regional gray matter volumes, with a priori focus on the cingulate cortex, orbitofrontal cortex (OFC), amygdala, caudate and hippocampus.
Of 19 ELSs, only emotional abuse, sexual abuse and severe family conflict independently predicted adulthood MDD diagnosis. The effect of total ELS score differed between groups. Greater ELS exposure was associated with slower processing speed and smaller OFC volumes in depressed subjects, but faster speed and larger volumes in non-depressed subjects. In contrast, exposure to ELSs predictive of depression had similar effects in both diagnostic groups. Individuals reporting predictive ELSs exhibited poorer processing speed and working memory performance, smaller volumes of the lateral OFC and caudate, and decreased cortical thickness in multiple areas including the insula bilaterally. Predictive ELS exposure was also associated with smaller left hippocampal volume in depressed subjects.
Findings suggest an association between childhood trauma exposure and adulthood cognitive function and brain structure. These relationships appear to differ between individuals who do and do not develop depression.
To develop a candidate definition for central line–associated bloodstream infection (CLABSI) in neonates with presumed mucosal barrier injury due to gastrointestinal (MBI-GI) conditions and to evaluate epidemiology and microbiology of MBI-GI CLABSI in infants
Multicenter retrospective cohort study.
Neonatal intensive care units from 14 US children’s hospitals and pediatric facilities.
A multidisciplinary focus group developed a candidate MBI-GI CLABSI definition based on presence of an MBI-GI condition, parenteral nutrition (PN) exposure, and an eligible enteric organism. CLABSI surveillance data from participating hospitals were supplemented by chart review to identify MBI-GI conditions and PN exposure.
During 2009–2012, 410 CLABSIs occurred in 376 infants. MBI-GI conditions and PN exposure occurred in 149 (40%) and 324 (86%) of these 376 neonates, respectively. The distribution of pathogens was similar among neonates with versus without MBI-GI conditions and PN exposure. Fifty-nine (16%) of the 376 initial CLABSI episodes met the candidate MBI-GI CLABSI definition. Subsequent versus initial CLABSIs were more likely to be caused by an enteric organism (22 of 34 [65%] vs 151 of 376 [40%]; P = .009) and to meet the candidate MBI-GI CLABSI definition (19 of 34 [56%] vs 59 of 376 [16%]; P < .01).
While MBI-GI conditions and PN exposure were common, only 16% of initial CLABSIs met the candidate definition of MBI-GI CLABSI. The high proportion of MBI-GI CLABSIs among subsequent infections suggests that infants with MBI-GI CLABSI should be a population targeted for further surveillance and interventional research.
Infect Control Hosp Epidemiol 2014;35(11):1391–1399
Bulk structures of un-stabilized ZrO2-x with x in the 0 ≤ x ≤ 0.44 range under ambient pressure exist in three different structures (monoclinic, tetragonal and cubic). At ambient temperature and elevated pressures above 3.5 GPa, zirconia, at these compositions, a fourth phase is found, the orthorhombic structure. A dilute sol-gel method was used to produce nanoscale zirconia particles containing the unstabilized orthorhombic cotunnite structure for use in this project. Extensive characterization of this material indicates that the critical factor in determining the synthesized structures appears to be the number and placement of oxygen vacancies. These results also indicate that surface energy alone is not the controlling factor in determining the crystal structure synthesized.
We present a brief description of the Berkeley Visible Imaging Tube (BVIT) detector system, which is a user instrument on the 10-m Southern African Large Telescope (SALT), and include some preliminary observational results gained in mid-2011. The data show that BVIT is capable of revealing emission features occurring on time-scales of < 0.1 sec, thus opening up for the general user a window of high time-resolution astronomy at visible wavelengths.
Inactivated vaccines prepared from influenza virus strains obtained by the recombination of A/PR/8/34 (H1N1) or A/FM/1/47 (H1N1) viruses with A/Victoria/3/75 (H3N2) virus, were tested for their antigenicity in hamsters. The parental origin of the genes of each cloned recombinant virus was determined by polyacrylamide gel electrophoresis, and vaccines prepared from each strain by concentration, purification on sucrose density gradients and inactivation with formalin. All the recombinant strains used in these studies possessed surface haemagglutinin and neuraminidase antigens derived from the A/Victoria/75 parent strain.
On inoculation into hamsters, at equivalent concentrations, these vaccines varied in their ability to induce haemagglutination-inhibiting (HI) antibodies in the serum. This variation was not dependent on concentration and was observed using neutralization and single radial haemolysis, as well as HI. The possible reasons for the findings are discussed.
Three different types of bivalent influenza virus vaccine, a whole virus, an aqueous-surface-antigen vaccine and an adsorbed-surface-antigen vaccine were tested at three dosage levels in volunteers primed with respect to only one of the haemagglutinin antigens present in the vaccines.
The local and systemic reactions to all three vaccine types were mild in nature and, following first immunization, the aqueous-surface-antigen vaccine was the least reactogenic. The serum haemagglutination-inhibiting antibody response to the A/Victoria/75 component of the vaccines, to which the volunteer population was primed, was greatest following immunization with the aqueous-surface-antigen vaccine; the greatest antibody response to the A/New Jersey/76 component of the vaccines was observed following immunization with whole virus vaccine.
The serum antibody responses and 50% protective levels (PL50) of antibody were determined, using the SRH test, at one and twelve months post-vaccination in a group of student volunteers immunized with one of three dosages of a trivalent surface-antigen influenza virus vaccine, or with placebo.
It was found that, for the H3, H1 and B haemagglutinin components present in the vaccine, a dose of 6 μg HA elicited high serum antibody responses at one month post-immunization. High mean antibody levels and a high incidence of volunteers with PL50 values of antibody against each of the HA components of the vaccine remained in the volunteer group twelve months later. The results are discussed in relation to the vaccine dosage used and the nature of the population immunized.
Antibody determinations against H3N2 and H1N1 type A influenza viruses were carried out on paired sera obtained from volunteers taking part in influenza virus vaccine studies, using both the haemagglutination-inhibition (HI) and single radial haemolysis (SRH) test. Good correlation between the HI and SRH test was found for both H3N2 and H1N1 antibody and the zone area increases corresponding to significant SRH antibody rises determined for both virus strains. In both H3N2 and H1N1 vaccine studies, intranasal infection of the volunteers with live attenuated viruses was involved and by the measurement of HI and SRH antibodies prior to and following infection, levels of antibody equating with protection against the infecting viruses could be estimated. For the HI test the antibody titres associated with 50% protection were 42 for H1N1, and 44 for H3N2 viruses; for the SRH test, 50% protection was associated with zone areas of 20·0–25·0 mm2 for both H1N1 and H3N2 viruses.
Previous studies of boys at Christ's Hospital school have indicated that annual immunization with influenza virus vaccines did not significantly reduce the total incidence of influenza infection compared to unimmunized subjects. In view of the implications of this result, a similar study was conducted in ferrets to clarify these findings. Groups of ferrets were immunized or infected with a series of influenza A (H3N2) viruses over an 18-month period, and the immunity to subsequent live virus challenge was measured after each virus or vaccine exposure. The results indicated that live virus infection gave a more solid immunity than immunization with inactivated vaccine; and the serum haemagglutination-inhibiting antibody response was greater following immunization than following infection. In addition, differences in immunity could not be explained by measurements of cross-reacting and specific antibody, since the incidence of these antibodies was similar in both infected and immunized animals. The results do not suggest an explanation for the different levels of immunity induced following infection or immunization or the results obtained from the Christ's Hospital study. However, the relative contribution of various immune responses to virus or virus antigen is discussed, and it is suggested that the difference in immunity may lie in the ability of live virus infection to stimulate local antibody.
One hundred and nineteen volunteers were divided into five groups, and each volunteer inoculated subcutaneously with an aqueous subunit B/Hong Kong/73 vaccine containing 40, 20, 10, or 5 μg of HA or saline alone in a 0·5 ml volume. The incidence of reactions was recorded 24 h after inoculation. One month following immunization the serum HI antibody to B/Hong Kong/73 virus was measured; each volunteer was inoculated intranasally with live, attenuated influenza B (RB77) virus; and the incidence of infection by the challenge virus was determined by HI antibody response.
The results showed that the incidence of reactions to all doses of vaccine were relatively low, the severity mild, and the duration short. However, the incidence of reactions was highest for those given 40 μg HA and least for those given 5 μg HA. The serum HI antibody responses to vaccine showed a dose-response relationship. For volunteers given 40 μg HA, 22 (96%) showed a fourfold rise in antibody titre and all volunteers had antibody titres of > 40 following immunization: for volunteers given 5 μg HA the g.m.t. increased from 16·6 to 86·1; and for those given 10 and 20 μg HA the response was intermediate. Following challenge, the lowest incidence of infection was seen in volunteers given the highest dose of vaccine. However, all doses of vaccine induced some protection against challenge virus infection, and the incidence of infection was directly related to the serum antibody titre at the time of challenge. The 50% protection titre of serum HI antibody was estimated as 15 to 20.
Ferrets infected with influenza virus A2/Hong Kong/3/68 responded with a febrile reaction; the temperature was elevated by 1·0°C. or greater to a level of 40°C. or more. In addition, relatively high titres of virus were recovered from nasal washings taken 3 days after virus infection, serum antibody was produced, increased nasal protein was detected and nasal washings contained both HI and neutralizing antibody. Of four ferrets immunized with 400 CCA units of inactivated influenza virus A2/Aichi/2/68 in saline, only one produced detectable serum HI antibody, and none produced detectable nasal antibody. These ferrets were subsequently found to be susceptible to intranasal infection with influenza virus A2/Hong Kong/3/68. Thus, the temperature response, the titre of virus recovered from nasal washings and the serum HI antibody response found after virus infection was similar to that found after infection of non-immunized ferrets. However, the increase in protein concentration and the titre of HI and neutralizing antibody found in nasal washings after virus infection was detectably less than that found after virus infection of non-immunized ferrets.
Four ferrets were immunized with 400 CCA units of inactivated A2/Aichi/2/68 virus in adjuvant 65, and these ferrets produced relatively high titres of serum HI antibody but no detectable nasal antibody. After subsequent virus infection with influenza virus A2/Hong Kong/3/68, these ferrets showed a modified temperature response, reduced titres of virus in nasal washings compared to that found in nasal washings from non-immunized ferrets, no increase in nasal protein and no detectable nasal HI antibody. Thus, immunization with inactivated virus in adjuvant 65 resulted in a significant modification of the response of ferrets to challenge virus; however, the immunity was not complete, and appreciably less than that found after infection with live homologous virus.
The inactivation kinetics of CELO virus were studied in the presence of 1/4000 formaldehyde. Inactivation of the virus by formaldehyde at 4° C. was not complete after 14 days incubation. Formaldehyde inactivation at 36° C., however, was rapid and no virus was detected after 24 hr. incubation.
Neutralizing antibody to CELO virus was detected in 20–88% of sera tested from five flocks of hens. This suggested dissemination of the virus in England and Scotland. However, no CELO virus neutralizing antibody at a serum dilution of 1/8 was detected in 142 normal human sera or in 229 sera from persons who had been immunized with egg grown, inactivated influenza virus vaccine.
We would like to thank Professor C. H. Stuart-Harris and Drs J. E. Wilson, D. A. Martin and D. Breeze for their help and their criticisms of the manuscript.
Dr G. C. Schild kindly supplied a number of the human sera used in the study. The study was financed in part by the National Fund for Research in Poliomyelitis and other Crippling Diseases and by the British Empire Cancer Campaign.
The anti-haemagglutinin antibody response in adult human volunteers to inactivated whole virus or tween ether split influenza A/Victoria/75 (H3N2) and A/Scotland/74 (H3N2) virus vaccines was investigated using antibody adsorption and single-radial-haemolysis (SRH) techniques. The concentrations of haemagglutinin (HA), nucleoprotein (NP) and matrix (M) antigens measured by single radial diffusion (SRD) and rocket immunoelectrophoresis were similar for both the whole virus and split vaccines. Whole virus and split vaccines induced cross-reactive (CR) antibody in 87% of vaccinees. Strain specific (SS) antibody to A/Hong Kong/1/68 or the homologous virus was induced less frequently than CR antibody. Higher anti-haemagglutinin antibody titres were detected in persons receiving the split virus vaccines than in those receiving the whole virus vaccines. No antibody to the type-specific matrix protein was detectable, but 33% of volunteers developed an antibody rise to type-specific nucleoprotein antigen.
The specificity of the anti-haemagglutinin antibody response in human adults to natural infection with A/Port Chalmers/73 (H3N2) virus was similar to that induced by inactivated vaccines in that a high proportion of subjects developed CR anti-haemagglutinin antibody, which reacted with A/Hong Kong/68 virus and the homologous A/Port Chalmers/73 virus, and SS antibody for A/Hong Kong/68 virus but SS antibody for A/Port Chalmers/73 virus was infrequently stimulated by natural infection.
Groups of student volunteers were immunized with one of five different inactivated influenza virus vaccines. The concentration of virus in the various vaccines differed by both the international unitage test and by the concentration of haemagglutinin, as measured by the single radial diffusion test; the results of the two methods of standardization showed no correlation. The serum HI response to immunization was variable; volunteers given A/England/72 showed a 16·6-fold increase in homologous serum antibody titre whilst volunteers given A/Hong Kong/68 vaccine showed a 4·2-fold increase. The variable response of volunteers to immunization could not be explained by the varied concentration of virus in the vaccines, as measured by either test, the titres of serum HI antibody present before immunization, or a combination of these two factors.
The ability to infect volunteers with WRL 105 virus 4 weeks after immunization with heterologous, inactivated virus vaccine was directly related to the degree of cross-reactivity between the haemagglutinins of this vaccine virus and WRL 105 virus. Thus, the greatest number of infections by the challenge virus were seen in volunteers given A/Hong Kong/68 vaccine, less were observed in volunteers given A/England/72 vaccine, and least were found in groups given A/Port Chalmers/73 or A/Scotland/74 vaccine. However, compared with the incidence of infection in volunteers given B/Hong Kong/73 vaccine, all the heterologous influenza A vaccine gave some immunity to challenge infection.
Volunteers were inoculated with vaccine made from the 30c mutant, A/Port Chalmers/73 or B/Hong/8/73. Preliminary experiments showed that the 30c strain was antigenically quite close to A/HK/8/68. Volunteers given 30c developed haemagglutination inhibiting antibodies against the ‘current’ 1973 serotypes (as well as to the vaccine virus) but the titres were less than those after the A/PC/73 vaccine. Volunteers were then challenged with a live attenuated virus, WRL 105, with A/Finland/4/74 antigens, by intranasal inoculation. The rates of infection were 43% after B/Hong Kong/8/73, 20% after 30c and 5% after A/PC/73. This indicated that the 30c gave some protection but the vaccine prepared from the current strain gave more.
A group of 23 volunteers were each inoculated with 600 CCA of a new form of influenza virus A/England/42/72 vaccine; this vaccine consisted of purified haemagglutinin and neuraminidase antigens adsorbed to alhydrogel. No significant reactions to the vaccine were reported. Twenty-two volunteers produced increased titres of serum HI antibody, and all showed increased titres of NI antibody after immunization. Thus, for volunteers with no pre-immunization serum HI antibody, the geometric mean titre of serum antibody increased from 1/5 to 1/196 after immunization. Ten volunteers developed local neutralizing antibody after immunization; this antibody response was detected most frequently in volunteers who showed the greater serum antibody response to immunization, and in nasal washings with the higher concentrations of protein and IgA. Ten weeks after immunization, the vaccinees and a group of matched controls were inoculated intranasally with attenuated A/England/42/72 virus. Evidence of infection with the challenge virus was found in 14 of the control subjects and in one of the vaccinees. The results indicate that the surface-antigen-adsorbed vaccine induced high titres of serum antibody, and gave significant protection against challenge infection.
The haemagglutinin of influenza virus A 2/Hong Kong/1/68 was shown to be markedly different from that of previously isolated A 2 virus strains. No haemagglutination-inhibiting (HI) antibody to A 2/Hong Kong/1/68 virus was detected in serum specimens collected in 1966 from persons aged 60 years or less. In contrast, HI antibody tests with 270 sera collected in 1968 indicated that 9·6% had demonstrable HI antibody at low titres, and 35·2% of 454 postepidemic (1969) sera had demonstrable HI antibody at relatively high titres. Most sera from persons aged 80 years and more collected in 1968 and 1969 had demonstrable HI anti-body to influenza virus A 2/Hong Kong/1/68. No HI antibody to the Hong Kong virus was detected in pre-epidemic sera from children aged 6 months to 3 years, whereas 32 % of postepidemic sera had HI antibody. The acquisition of HI antibody to A 2/Hong Kong/1/68 was not accompanied by an increase hi the incidence or titres of HI antibody to heterotypic A 2 influenza viruses. For sera from children aged 4–11 years, an increase of HI titre to heterotypic A 2 influenza was found.