Statistical vs Clinical Significance in Product Testing: Can They Be Designed to Satisfy Equivalence?

Statistical issues associated with demonstrating significance between treatment groups (efficacy or superiority) and nonsignificance (equivalence) are presented and discussed. Methodologies for demonstrating efficacy of a product are proposed and contrasted, incorporating clinical and statistical criteria, with emphasis on situations in which placebo groups are precluded from the study design. Distinctions are drawn between study designs for demonstrating superiority and those for equivalence, including the determination of sample sizes needed for the different approaches. The "at least as good as" criterion is proposed as a reasonable alternative to that of equivalence in active control equivalence studies for demonstrating that dental product modifications or new products are efficacious.     

Hurricane Hugo blows down the broccoli: Preschoolers' post-disaster play and adjustment

This article reports highlights from over 200 parents' observations of their preschoolers' play and verbalizations in the year following Hurricane Hugo. Commonly reported activities included reenactment and discussion of the event in multiple mediums, personification of Hugo, and expression of fears related to storms. Precocious concern for others, insight, and vocabulary were also noted. In these intact, relatively high functioning families, parents seemed able to facilitate their youngsters' adjustment without outside intervention.Portions of this report were presented in earlier form at the 1991 Society for Research in Child Development meeting in Seattle, Washington.     

Characteristics of sex offenders who were sexually victimized as children

From a data bank of 479 sex offenders, a comparison was undertaken of those reporting any childhood sexual abuse versus those reporting none. A total of 201 men (42.0%) reported abuse, 261 (54.5%) did not and for 17 (3.5%), information was unavailable. The Abused and Nonabused Groups were compared on demographic information, the MMPI, Clarke Sex History Questionnaire and the Clarke Parent Child Relations Questionnaire. The Abused and Nonabused groups were similar in age, marital status, income, and criminal history, but the Abused Group had significantly less education. The Abused Group showed sexualization of their childhood, not only in the number of contacts with adults but also with age peers and siblings of both sexes. They tended to have wider ranging and more frequent sexual experiences as adults both with men and women. They more often raped. The Abused Group tended to show more emotional instability than the Nonabused Group in more frequent suicidal ideation and suicide attempts, as well as in elevated Mania Scale Scores on the MMPI. The family background of the Abused Group was more disturbed than the Nonabused Group's; especially father-son relations. They reported more alcohol use and abuse in their parents and more parent-child aggression than nonabused offenders did. Although it is unlikely that child sexual abuse causes sexual anomalies, the results of the present study suggest that childhood sexual victimization in the lives of adult sex offenders merits further investigation and has implications for treatment.     

Synergistic action of immunostimulatory DNA and fcgamma receptor IIB-crosslinking on B-cell phenotype and function

CpG DNA functions via the toll-like receptor-9 (TLR-9) receptor, inducing B cell proliferation and promoting immunoglobulin production. B cell responses to CpG DNA-containing immune complexes could be important in chronic autoimmunity and immune responses to bacterial components. Therefore, we investigated the potential synergy of CpG DNA-stimulation with FcgammaR clustering (CFR) on splenic B cell activity. CFR-induced splenocyte proliferation was significantly increased compared to treatment with CpG DNA alone. While the levels of interleukin-10 (IL-10) were increased in CpG DNA-treated splenocyte cultures, particularly following FcgammaRII/III-clustering, CFR treatment reduced IL-6 levels. B-cell maturation in culture was enhanced by CFR. Indeed, the frequency of IgG expressing cells after stimulation with CpG DNA was increased and was even higher after CFR stimulation. Furthermore, the frequency of plasma cell precursors was markedly increased by stimulation with CFR. Late splenic B cell subsets, transitional type 2 (T2) and mature (M) B cells, responded strongly to CpG DNA with proliferation and the response was enhanced by FcgammaR-clustering. Immature transitional type 1 (T1) B cells showed distinctly lower proliferative response to CpG DNA and very small effects of FcgammaR-clustering, despite similar expression of Fcgamma-receptors by all B cell subsets. In conclusion, these data show synergistic impact of CpG DNA and simultaneous FcgammaR-clustering on B cell proliferation and differentiation.     

Finite-element models of the human head

A review is presented of the existing finite-element (FE) models for the biomechanics of human head injury. Finite element analysis can be an important tool in describing the injury biomechanics of the human head. Complex geometric and material properties pose challenges to FE modelling. Various assumptions and simplifications are made in model development that require experimental validation. More recent models incorporate anatomic details with higher precision. The cervical vertebral column and spinal cord are included. Model results have been more qualitative than quantitative owing to the lack of adequate experimental validation. Advances include transient stress distribution in the brain tissue, frequency responses, effects of boundary conditions, pressure release mechanism of the foramen magnum and the spinal cord, verification of rotation and cavitation theories of brain injury, and protective effects of helmets. These theoretical results provide a basic understanding of the internal biomechanical responses of the head under various dynamic loading conditions. Basic experimental research is still needed to determine more accurate material properties and injury tolerance criteria, so that FE models can fully exercise their analytical and predictive power for the study and prevention of human head injury.     

Spatial EEG Synchronisation Over Sensorimotor Hand Areas in Brisk and Slow Self-Paced Index Finger Movements

The changes of spatial EEG synchronisation during brisk and slow voluntary self-paced movements of the right and left index finger were analysed in 12 right-handed and 11 left-handed subjects. EEG was recorded from the left and right sensorimotor area using 24 closely spaced electrodes. A novel measure of spatial EEG synchronisation, -complexity, was computed separately for the left and right sensorimotor area in 64 overlapping one-second epochs representing 4.5 s of the pre-movement and 3.5 s of the post-movement period. -complexity was higher, hence spatial synchronisation was lower, in slow than in brisk movements, especially in the right-handed. A sustained increase of -complexity was observed during execution of a slow movement. A decrease of -complexity which was often associated with a brief burst of spatially synchronised 10-Hz oscillations occurred at the onset of extensor muscle contraction. We suggest that increased spatial EEG synchronisation at movement onset may prevent spillover of excitation from the sensorimotor hand area to other cortical regions. During movement, the cortical neuronal assemblies subserve distinct, specialised functions manifesting in increased -complexity.     

Measurement of functional ability and health status in the arthritic patient

Chronic arthritis may have great impact on the patient but also on his or her family, relatives and friends. The assessment of the consequences of chronic arthritis and the effect of therapy not only in terms of physical, but also psychological and social dimensions deserves more attention. Functional ability and health status can be measured using a questionnaire or ‘instrument’, high-lighting important aspects not quantified with more traditional measurements. In this paper, arguments to apply such instruments more frequently are given. Health status instruments can be used not only to assess beneficial but also deleterious (side-)effects of therapeutic interventions. The properties are summarized of the most frequently used instruments assessing functional ability and health status. Many of these instruments have been evaluated sufficiently for validity and reliability; their sensitivity to detect change seems to be satisfactory. Therefore it is advisable to choose an internationally accepted, frequently used instrument, reflecting the area of interest.     

Host response toBothrops asper snake venom

As part of the characterization of the host reactivity to the venom ofBothrops asper, we investigated the inflammatory responses in the mouse footpad model. The subcutaneously injected venom induced a rapid increase of serum IL-6 concentration, which peaked between 3 and 6 h and returned to normal values at 12 h. In contrast, serum TNF- and IL-1 were not detectable at any time point studied. A myotoxic phospholipase A₂ isoform purified from this venom, myotoxin II, was also able to induce a systemic IL-6 release when injected into the footpad. Both venom and myotoxin induced local edema and a leukocyte infiltrate accumulating in the muscle and subdermal tissue within 6 h. The infiltrate consisted predominantly of neutrophils at 6 and 24 h, but at later times, mononuclear cells also appeared. The edema, leukocyte infiltration, and IL-6 responses did not depend on the hemorrhagic activity of venom, since all three effects were seen after injection of (1) preneutralized venom, devoid of hemorrhagic activity, and (2) purified myotoxin II. Circulating platelet numbers were significantly decreased 30 min after venom injection and returned to normal after 12 h. The venom also induced a rapid inversion in the ratio of neutrophils to lymphocytes in peripheral blood, which did not normalize until 12 h later. The present observations suggest that venom, besides its cytotoxic properties, induces early hematologic and immunologic alterations. These findings may be of relevance in future treatment modalities.     

Long-term outcomes using vascular grafts sealed with fragmented autologous adipose tissue for aortoiliac occlusive disease

The aim of this study was to test the safety and efficacy of fragmented autologous adipose tissue (FAT) grafts for revascularization in aortoiliac occlusive disease. Twenty-seven patients with atherosclerotic aortoiliac occlusive disease underwent surgical treatment using FAT grafts. A piece of adipose connective tissue was obtained from the operative wound, cut into small pieces, and pressed into the wall of a fabric vascular prosthesis. Cumulative primary patency rates were 92% at 1 year, 92% at 3 years, and 86% at 6 years. Cumulative secondary patency rates were 96%, 96%, and 90% for the same intervals. In this clinical study, the FAT grafts demonstrated good long-term patency rates and no particular problems. This is the first clinical report of long-term outcomes using FAT grafts for aortofemoral or aortoiliac bypasses. FAT grafts are thus safe for revascularization in aortoiliac occlusive disease.