The Value of p-Value in Biomedical Research

Significance tests and the corresponding p-values play a crucial role in decision making. In this commentary the meaning, interpretation and misinterpretation of p-values is presented. Alternatives for evaluating the reported evidence are also discussed

The Analysis of Association Between Traits When Differences Between Trait States Matter

Because of their elementary significance in almost all fields of science, measures of association between two variables or traits are abundant and multiform. One aspect of association that is of considerable interest, especially in population genetics and ecology, seems to be widely ignored. This aspect concerns association between complex traits that show variable and arbitrarily defined state differences. Among such traits are genetic characters controlled by many and potentially polyploid loci, species characteristics, and environmental variables, all of which may be mutually and asymmetrically associated. A concept of directed association of one trait with another is developed here that relies solely on difference measures between the states of a trait. Associations are considered at three levels: between individual states of two variables, between an individual state of one variable and the totality of the other variable, and between two variables. Relations to known concepts of association are identified. In particular, measures at the latter two levels turn out to be interpretable as measures of differentiation. Examples are given for areas of application (search for functional relationships, distribution of variation over populations, genomic associations, spatiogenetic structure)

Behaviour sequelae following acute Kawasaki disease.

BACKGROUND: Kawasaki disease is a systemic vasculitis and may affect cerebral function acutely. The aim of the present study was to measure a number of behaviour and social parameters within a cohort of Kawasaki disease patients. METHODS: Parents of children with past diagnosis of Kawasaki disease were recruited to complete several behaviour screening questionnaires. Sixty five sets of questionnaires relating to the patient cohort received were eligible for inclusion. Two control groups were used, a hospital (HC) control and a sibling control (SC) group. RESULTS: 40% of the Kawasaki disease group showed elevated internalising scores in the clinical or borderline-clinical range. This compared with 18% of hospital controls and 13% of sibling controls. Additionally, the Kawasaki disease (KD) group were shown to be experiencing greater overall total difficulties when compared with the controls (KD 13.7, HC 8.6, SC 8.9). The KD group attained higher behavioural scores within the internalising sub-categories of somatic problems (KD 61, HC 57, SC 54) and withdrawn traits (KD 56, HC 53, SC 51). The KD group were also shown to be suffering more thought problems (KD 57, HC 53, SC 50) compared with the controls. Further difficulties relating to conduct (KD 3.3, HC 1.4) and social interactions (KD 6.7, HC 8.3) are also highlighted for the KD group compared with hospital controls. Positron emission tomograms were performed on nine patients to investigate severe behavioural problems. Three showed minor changes, possibly a resolving cerebral vasculopathy. CONCLUSION: Kawasaki disease can be associated with significant behavioural sequelae. This is an important consideration in the long-term follow up and referral to a clinical psychologist may be necessary in selected patients

Radiographic manifestations of experimental aluminum toxicity in growing bone

To evaluate the effect of aluminum on growing bone in the presence of normal renal function, the following experiment was performed. Eight littermate pair-fed pigs (5 weeks old) were randomly assigned to one of two study groups: control C, n =4, or aluminum treated Al, n =4. Daily intravenous injections of either aluminum 1.5 mg/kg/day (Al group) or vehicle only (C group) were given during the 8-week duration of the study. The radiographic findings which appeared in the aluminum-treated group and not in the controls consisted of areas of sclerosis in the submetaphyseal regions and the periphery of epiphyses. In addition there was separation of the anterior tibial tubercle. The growth plates did not increase in width despite the presence of osteomalacia and histologic evidence of extensive deposition of aluminum in bone. The area of sclerosis visualized in the radiographs correlated histologically with thickened bony trabeculae. The increased width of these trabeculae is attributable to an increase in primary spongiosum and broadened seams of osteoid.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46782/1/256_2004_Article_BF00356955.pd

Circumstellar disks and planets. Science cases for next-generation optical/infrared long-baseline interferometers

We present a review of the interplay between the evolution of circumstellar disks and the formation of planets, both from the perspective of theoretical models and dedicated observations. Based on this, we identify and discuss fundamental questions concerning the formation and evolution of circumstellar disks and planets which can be addressed in the near future with optical and infrared long-baseline interferometers. Furthermore, the importance of complementary observations with long-baseline (sub)millimeter interferometers and high-sensitivity infrared observatories is outlined.Comment: 83 pages; Accepted for publication in "Astronomy and Astrophysics Review"; The final publication is available at http://www.springerlink.co

The Formation of the First Massive Black Holes

Supermassive black holes (SMBHs) are common in local galactic nuclei, and SMBHs as massive as several billion solar masses already exist at redshift z=6. These earliest SMBHs may grow by the combination of radiation-pressure-limited accretion and mergers of stellar-mass seed BHs, left behind by the first generation of metal-free stars, or may be formed by more rapid direct collapse of gas in rare special environments where dense gas can accumulate without first fragmenting into stars. This chapter offers a review of these two competing scenarios, as well as some more exotic alternative ideas. It also briefly discusses how the different models may be distinguished in the future by observations with JWST, (e)LISA and other instruments.Comment: 47 pages with 306 references; this review is a chapter in "The First Galaxies - Theoretical Predictions and Observational Clues", Springer Astrophysics and Space Science Library, Eds. T. Wiklind, V. Bromm & B. Mobasher, in pres

Early adversity predicts adoptees’ enduring emotional and behavioral problems in childhood

Children adopted from the public care system are likely to experience a cluster of inter-related risk factors that place them on a trajectory of mental health problems that persist across the life course. However, the specific effects of putative risk factors on children’s mental health post-placement are not well understood. We conducted a prospective, longitudinal study of children placed for adoption between 2014 and 2015 (N = 96). Adoptive parents completed questionnaires at approximately 5-, 21-, 36-, and 48 months post-placement. We used time series analysis to examine the impact of pre-adoptive risk factors (adverse childhood experiences [ACEs], number of moves, days with birth parents and in care) on children’s internalizing and externalizing problems, and prosocial behaviour over four years post-placement. Adoptees’ internalizing and externalizing problems remained consistently high over the four-year study period but more ACEs predicted increases in internalizing and externalizing problems. Contrary to expectations, more pre-placement moves and time in care predicted fewer problems over time, but exploratory analyses of interactive effects revealed this was only the case in rare circumstances. We identify pre- and post-removal factors that may incur benefits or have a deleterious impact on adoptees’ outcomes in post-adoptive family life. Our findings provide knowledge for front-line professionals in the support of adoptive families and underscore the vital need for effective early intervention

A Viral Vectored Prime-Boost Immunization Regime Targeting the Malaria Pfs25 Antigen Induces Transmission-Blocking Activity

The ookinete surface protein Pfs25 is a macrogamete-to-ookinete/ookinete stage antigen of Plasmodium falciparum, capable of exerting high-level anti-malarial transmission-blocking activity following immunization with recombinant protein-in-adjuvant formulations. Here, this antigen was expressed in recombinant chimpanzee adenovirus 63 (ChAd63), human adenovirus serotype 5 (AdHu5) and modified vaccinia virus Ankara (MVA) viral vectored vaccines. Two immunizations were administered to mice in a heterologous prime-boost regime. Immunization of mice with AdHu5 Pfs25 at week 0 and MVA Pfs25 at week 10 (Ad-MVA Pfs25) resulted in high anti-Pfs25 IgG titers, consisting of predominantly isotypes IgG1 and IgG2a. A single priming immunization with ChAd63 Pfs25 was as effective as AdHu5 Pfs25 with respect to ELISA titers at 8 weeks post-immunization. Sera from Ad-MVA Pfs25 immunized mice inhibited the transmission of P. falciparum to the mosquito both ex vivo and in vivo. In a standard membrane-feeding assay using NF54 strain P. falciparum, oocyst intensity in Anopheles stephensi mosquitoes was significantly reduced in an IgG concentration-dependent manner when compared to control feeds (96% reduction of intensity, 78% reduction in prevalence at a 1 in 5 dilution of sera). In addition, an in vivo transmission-blocking effect was also demonstrated by direct feeding of immunized mice infected with Pfs25DR3, a chimeric P. berghei line expressing Pfs25 in place of endogenous Pbs25. In this assay the density of Pfs25DR3 oocysts was significantly reduced when mosquitoes were fed on vaccinated as compared to control mice (67% reduction of intensity, 28% reduction in prevalence) and specific IgG titer correlated with efficacy. These data confirm the utility of the adenovirus-MVA vaccine platform for the induction of antibodies with transmission-blocking activity, and support the continued development of this alternative approach to transmission-blocking malaria subunit vaccines