Exact distributions of intraclass correlation and Cronbach's alpha with Gaussian data and general covariance

Intraclass correlation and Cronbach’s alpha are widely used to describe reliability of tests and measurements. Even with Gaussian data, exact distributions are known only for compound symmetric covariance (equal variances and equal correlations). Recently, large sample Gaussian approximations were derived for the distribution functions

Study of the piezoresistivity of doped nanocrystalline silicon thin films

The piezoresistive response of n- and p-type hydrogenated nanocrystalline silicon thin films, deposited by hot-wire (HW) and plasma-enhanced chemical vapor deposition (PECVD) on thermally oxidized silicon wafers, has been studied using four-point bending tests. The piezoresistive gauge factor (GF) was measured on patterned thin-film micro-resistors rotated by an angle θ with respect to the principal strain axis. Both longitudinal (GFL) and transverse (GFT) GFs, corresponding to θ = 0° and 90°, respectively, are negative for n-type and positive for p-type films. For other values of θ (30°, 45°, 120°, and 135°) GFs have the same signal as GFL and GFT and their value is proportional to the normal strain associated with planes rotated by θ relative to the principal strain axis. It is concluded that the films are isotropic in the growth plane since the GF values follow a Mohr’s circle with the principal axes coinciding with those of the strain tensor. The strongest p-type pirezoresistive response (GFL = 41.0, GFT = 2.84) was found in a film deposited by PECVD at a substrate temperature of 250 °C and working pressure of 0.250 Torr, with dark conductivity 1.6 Ω−1cm−1. The strongest n-type response (GFL =− 28.1, GFT =− 5.60) was found in a film deposited by PECVD at 150 °C and working pressure of 3 Torr, with dark conductivity 9.7 Ω−1cm−1. A model for the piezoresistivity of nc-Si is proposed, based on a mean-field approximation for the conductivity of an ensemble of randomly oriented crystallites and neglecting grain boundary effects. The model is able to reproduce the measured GFL values for both n- and p-type films. It fails, however, to explain the transversal GFT data. Both experimental and theoretical data show that nanocrystalline silicon can have an isotropic piezoresistive effect of the order of 40% of the maximum response of crystalline silicon.Fundação para a Ciência e a Tecnologia (FCT) - PTDC/CTM/66558/2006, bolsa de investigação SFRH/BSAB/883/200

H5N1 Whole-Virus Vaccine Induces Neutralizing Antibodies in Humans Which Are Protective in a Mouse Passive Transfer Model

BACKGROUND: Vero cell culture-derived whole-virus H5N1 vaccines have been extensively tested in clinical trials and consistently demonstrated to be safe and immunogenic; however, clinical efficacy is difficult to evaluate in the absence of wide-spread human disease. A lethal mouse model has been utilized which allows investigation of the protective efficacy of active vaccination or passive transfer of vaccine induced sera following lethal H5N1 challenge. METHODS: We used passive transfer of immune sera to investigate antibody-mediated protection elicited by a Vero cell-derived, non-adjuvanted inactivated whole-virus H5N1 vaccine. Mice were injected intravenously with H5N1 vaccine-induced rodent or human immune sera and subsequently challenged with a lethal dose of wild-type H5N1 virus. RESULTS: Passive transfer of H5N1 vaccine-induced mouse, guinea pig and human immune sera provided dose-dependent protection of recipient mice against lethal challenge with wild-type H5N1 virus. Protective dose fifty values for serum H5N1 neutralizing antibody titers were calculated to be ≤1∶11 for all immune sera, independently of source species. CONCLUSIONS: These data underpin the confidence that the Vero cell culture-derived, whole-virus H5N1 vaccine will be effective in a pandemic situation and support the use of neutralizing serum antibody titers as a correlate of protection for H5N1 vaccines

Influenza D virus: Serological evidence in the Italian population from 2005 to 2017

Influenza D virus is a novel influenza virus, which was first isolated from an ailing swine in 2011 and later detected in cattle, suggesting that these animals may be a primary natural reservoir. To date, few studies have been performed on human samples and there is no conclusive evidence on the ability of the virus to infect humans. The aim of this serological study was to assess the prevalence of antibodies against influenza D virus in human serum samples collected in Italy from 2005 to 2017. Serum samples were analysed by haemagglutination inhibition and virus neutralization assays. The results showed that the prevalence of antibodies against the virus increased in the human population in Italy from 2005 to 2017, with a trend characterized by a sharp increase in some years, followed by a decline in subsequent years. The virus showed the ability to infect and elicit an immune response in humans. However, prevalence peaks in humans appear to follow epidemics in animals and not to persist in the human population

Measurements of polarized photo-pion production on longitudinally polarized HD and Implications for Convergence of the GDH Integral

We report new measurements of inclusive pion production from frozen-spin HD for polarized photon beams covering the Delta(1232) resonance. These provide data simultaneously on both H and D with nearly complete angular distributions of the spin-difference cross sections entering the Gerasimov-Drell-Hearn (GDH) sum rule. Recent results from Mainz and Bonn exceed the GDH prediction for the proton by 22 microbarns, suggesting as yet unmeasured high-energy components. Our pi0 data reveal a different angular dependence than assumed in Mainz analyses and integrate to a value that is 18 microbarns lower, suggesting a more rapid convergence. Our results for deuterium are somewhat lower than published data, considerably more precise and generally lower than available calculations.Comment: 4 pages, 4 figures. Submitted for publication in Physical Review Letter

Production of Inactivated Influenza H5N1 Vaccines from MDCK Cells in Serum-Free Medium

BACKGROUND: Highly pathogenic influenza viruses pose a constant threat which could lead to a global pandemic. Vaccination remains the principal measure to reduce morbidity and mortality from such pandemics. The availability and surging demand for pandemic vaccines needs to be addressed in the preparedness plans. This study presents an improved high-yield manufacturing process for the inactivated influenza H5N1 vaccines using Madin-Darby canine kidney (MDCK) cells grown in a serum-free (SF) medium microcarrier cell culture system. PRINCIPAL FINDING: The current study has evaluated the performance of cell adaptation switched from serum-containing (SC) medium to several commercial SF media. The selected SF medium was further evaluated in various bioreactor culture systems for process scale-up evaluation. No significant difference was found in the cell growth in different sizes of bioreactors studied. In the 7.5 L bioreactor runs, the cell concentration reached to 2.3 × 10(6) cells/mL after 5 days. The maximum virus titers of 1024 Hemagglutinin (HA) units/50 µL and 7.1 ± 0.3 × 10(8) pfu/mL were obtained after 3 days infection. The concentration of HA antigen as determined by SRID was found to be 14.1 µg/mL which was higher than those obtained from the SC medium. A mouse immunogenicity study showed that the formalin-inactivated purified SF vaccine candidate formulated with alum adjuvant could induce protective level of virus neutralization titers similar to those obtained from the SC medium. In addition, the H5N1 viruses produced from either SC or SF media showed the same antigenic reactivity with the NIBRG14 standard antisera. CONCLUSIONS: The advantages of this SF cell-based manufacturing process could reduce the animal serum contamination, the cost and lot-to-lot variation of SC medium production. This study provides useful information to manufacturers that are planning to use SF medium for cell-based influenza vaccine production

Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study.

Ulcerative colitis is a chronic inflammatory disease of the colon that presents as diarrhea and gastrointestinal bleeding. We performed a genome-wide association study using DNA samples from 1,052 individuals with ulcerative colitis and preexisting data from 2,571 controls, all of European ancestry. In an analysis that controlled for gender and population structure, ulcerative colitis loci attaining genome-wide significance and subsequent replication in two independent populations were identified on chromosomes 1p36 (rs6426833, combined P = 5.1 x 10(-13), combined odds ratio OR = 0.73) and 12q15 (rs1558744, combined P = 2.5 x 10(-12), combined OR = 1.35). In addition, combined genome-wide significant evidence for association was found in a region spanning BTNL2 to HLA-DQB1 on chromosome 6p21 (rs2395185, combined P = 1.0 x 10(-16), combined OR = 0.66) and at the IL23R locus on chromosome 1p31 (rs11209026, combined P = 1.3 x 10(-8), combined OR = 0.56; rs10889677, combined P = 1.3 x 10(-8), combined OR = 1.29)

A Whole Virus Pandemic Influenza H1N1 Vaccine Is Highly Immunogenic and Protective in Active Immunization and Passive Protection Mouse Models

The recent emergence and rapid spread of a novel swine-derived H1N1 influenza virus has resulted in the first influenza pandemic of this century. Monovalent vaccines have undergone preclinical and clinical development prior to initiation of mass immunization campaigns. We have carried out a series of immunogenicity and protection studies following active immunization of mice, which indicate that a whole virus, nonadjuvanted vaccine is immunogenic at low doses and protects against live virus challenge. The immunogenicity in this model was comparable to that of a whole virus H5N1 vaccine, which had previously been demonstrated to induce high levels of seroprotection in clinical studies. The efficacy of the H1N1 pandemic vaccine in protecting against live virus challenge was also seen to be equivalent to that of the H5N1 vaccine. The protective efficacy of the H1N1 vaccine was also confirmed using a severe combined immunodeficient (SCID) mouse model. It was demonstrated that mouse and guinea pig immune sera elicited following active H1N1 vaccination resulted in 100% protection of SCID mice following passive transfer of immune sera and lethal challenge. The immune responses to a whole virus pandemic H1N1 and a split seasonal H1N1 vaccine were also compared in this study. It was demonstrated that the whole virus vaccine induced a balanced Th-1 and Th-2 response in mice, whereas the split vaccine induced mainly a Th-2 response and only minimal levels of Th-1 responses. These data supported the initiation of clinical studies with the same low doses of whole virus vaccine that had previously been demonstrated to be immunogenic in clinical studies with a whole virus H5N1 vaccine