Statistical power and sample size requirements to detect an intervention by time interaction in four-level longitudinal cluster randomized trials.

Cluster/group randomized controlled trials (CRTs) have a long history in the study of health sciences. CRT is a special type of intervention trial in which a complete group is randomly assigned to a study condition (or intervention). It is typically performed when individual randomization is difficult/impossible without substantial risk of contamination across study arms or prohibitive from the cost or group dynamics point of view. In this article, the aim is to design and analyze four-level longitudinal cluster randomized trials. The main interest here is to study the difference between treatment groups over time for such a four-level hierarchical data structure. This work is motivated by a real-life study for education based HIV prevention. Such trials are not only popular for administrative convenience, ethical considerations, subject compliance, but also help to reduce contamination bias. A random intercept mixed effects linear regression including a time by intervention interaction is used for modeling. Closed form expression of the power function to detect the interaction effect is determined. Sample size equations depend on correlation among schools but not on correlations among classes or students while, the power function depends on the product of number of units at different levels. Optimal allocation of units under a fixed cost by minimizing the expected standardized variance is also determined and are shown to be independent of correlations among units in any level. Results of detailed simulation studies find the theoretical power estimates based on the derived formulae close to the empirical estimates.

A history of juvenile mild malaria exacerbates chronic stress-evoked anxiety-like behavior, neuroinflammation, and decline of adult hippocampal neurogenesis in mice.

Children residing in high malaria transmission regions are particularly susceptible to malaria. This early-life window is also a critical period for development and maturation of the nervous system, and inflammatory insults during this period may evoke a persistent increase in vulnerability for psychopathology. We employed a two-hit model of juvenile mild malaria and a two-week chronic unpredictable mild stress (CUMS) regime, commencing 60 days post-parasite clearance, to assess whether a history of juvenile infection predisposed the mice towards mood-related behavioral alterations and neurocognitive deficits. We showed that adult mice with a history of juvenile malaria (A-H/JMAL) exhibited heightened CUMS-associated anxiety-like behavior, with no observable change in cognitive behavior. In contrast, mice with a history of adult malaria did not exhibit such enhanced stress vulnerability. At baseline, A-H/JMAL mice showed increased activated microglia within the hippocampal dentate gyrus subfield. This was accompanied by a decrease in proliferating neuronal progenitors, with total number of immature hippocampal neurons unaltered. This neuroinflammatory and neurogenic decline was further exacerbated by CUMS. At day-14 post-CUMS, hippocampi of A-H/JMAL mice showed significantly higher microglial activation, and a concomitant decrease in progenitor proliferation and number of immature neurons. Taken together, these results suggest that a history of juvenile mild malaria leaves a neuroinflammatory mark within the hippocampal niche, and this may contribute to a heightened stress response in adulthood. Our findings lend credence to the idea that the burden of malaria in early-life results in sustained CNS changes that could contribute to increased vulnerability to adult-onset neuronal insults.

Anomalies in the motion dynamics of long-flagella mutants of Chlamydomonas reinhardtii.

Chlamydomonas reinhardtii has long been used as a model organism in studies of cell motility and flagellar dynamics. The motility of the well-conserved '9+2' axoneme in its flagella remains a subject of immense curiosity. Using high-speed videography and morphological analyses, we have characterized long-flagella mutants (lf1, lf2-1, lf2-5, lf3-2, and lf4) of C. reinhardtii for biophysical parameters such as swimming velocities, waveforms, beat frequencies, and swimming trajectories. These mutants are aberrant in proteins involved in the regulation of flagellar length and bring about a phenotypic increase in this length. Our results reveal that the flagellar beat frequency and swimming velocity are negatively correlated with the length of the flagella. When compared to the wild-type, any increase in the flagellar length reduces both the swimming velocities (by 26-57%) and beat frequencies (by 8-16%). We demonstrate that with no apparent aberrations/ultrastructural deformities in the mutant axonemes, it is this increased length that has a critical role to play in the motion dynamics of C. reinhardtii cells, and, provided there are no significant changes in their flagellar proteome, any increase in this length compromises the swimming velocity either by reduction of the beat frequency or by an alteration in the waveform of the flagella.

Variable selection method for quantitative trait analysis based on parallel genetic algorithm.

Selection of important genetic and environmental factors is of strong interest in quantitative trait analyses. In this study, we use parallel genetic algorithm (PGA) to identify genetic and environmental factors in genetic association studies of complex human diseases. Our method can take account of both multiple markers across the genome and environmental factors, and also can be used to do fine mapping based on the results of haplotype analysis to select the markers that are associated with the quantitative traits. Using both simulated and real examples, we show that PGA is able to choose the variables correctly and is also an easy-to-use variable selection tool.

Tensile bond strength of an adhesive resin cement to different alloys having various surface treatments.

STATEMENT OF PROBLEM: The ability of a resin cement to bond to a restorative alloy is critical for maximal crown retention to nonideal preparations. Surface treatment and metal type may have an important role in optimizing resin-to-metal strength. PURPOSE: The purpose of this study was to examine the effect of surface pretreatment on the tensile strength of base and noble metals bonded using a conventional resin cement. MATERIAL AND METHODS: Cylindrical plastic rods (9.5 mm in diameter), cast in base (Rexillium NBF) or noble metal (IPS d.SIGN 53), were divided into rods 10 mm in length (n=10-12). Specimens were heated in a porcelain furnace to create an oxide layer. Test specimens were further subjected to airborne-particle abrasion (50-microm Al(2)O(3) particles) alone or with the application of a metal primer (Alloy Primer). Similarly treated rod ends were joined using resin cement (RelyX ARC), thermocycled (x500, 5 degrees -55 degrees C) and stored (24 hours, 37 degrees C) before debonding using a universal testing machine. Debond strength and failure site were recorded. Rank-based ANOVA for unbalanced designs was used to test for significant interaction (alpha=.050). Each pair of treatments was compared separately for each metal (Bonferroni-adjusted significance level of .0083, overall error rate for comparisons, .05). The 2 metals were compared separately for each of the 3 treatments using an adjusted significance level of .017, maintaining an overall error rate of .05. A multinomial logit model was used to describe the effect of metal type and surface pretreatment on failure site location (alpha=.05). RESULTS: Interaction between metal type and surface pretreatment was significant for stress values (P=.019). Metal type did not significantly affect tensile bond strength for any of the compared surface pretreatments. Metal primer significantly improved tensile bond strength for each metal type. Most failures tended to occur as either adhesive or mixed in nature. CONCLUSIONS: Metal primer application significantly enhanced tensile bond strength to base and noble metal. No significant differences in tensile strength were found between alloys. Differences in failure site incidence were found to be related to metal type and surface pretreatment.

Effect of metal type and surface treatment on in vitro tensile strength of copings cemented to minimally retentive preparations.

STATEMENT OF PROBLEM: Due to the potential lack of ideal preparation form, the type of alloy and its surface pretreatment may have clinically relevant correlations with the retentive strength of castings to minimally retentive preparations. PURPOSE: The purpose of this study was to evaluate the effect of alloy type and surface pretreatments of base and noble metal copings on their tensile strength to minimally retentive preparations. MATERIAL AND METHODS: Minimally retentive, standardized crown preparations were made on recently extracted human third molars (n=68). Noble (IPS d.SIGN 53) and base metal (Rexillium NBF) copings were fabricated. All copings received heat treatment for oxide formation. Three experimental groups were then developed for each metal type (groups ranging from 10 to 12 specimens each): oxide only, airborne-particle abraded, or metal-primed. Copings were cemented using a self-adhesive universal resin cement (RelyX Unicem) and were thermal cycled (500 cycles between 5 and 55 degrees C) and stored (24 hours, 37 degrees C) before debonding using a universal testing machine. Frequency of debond location was compared among specimen groups. A 2-way ANOVA was used to test for interaction between the metal type and surface treatment, and, if no significant interaction was found, to test the main effects for metal type and surface treatment (alpha=.05). A multinomial logit model using the likelihood ratio test was used to describe the effect of metal type and surface treatment on failure site location (alpha=.05). RESULTS: The 2-way ANOVA indicated no significant influence of any factor on debond load: metal type (P=.885), surface treatment (P=.555), or their interaction (P=.644). The multinomial logit statistical model showed that noble metals and metal primers significantly (P<.05) shifted debond failures to occur more frequently at the resin/tooth interface or within the tooth itself. CONCLUSIONS: Neither metal type nor surface pretreatment affected bond strength. However, alloy type and surface treatment affected site of debond location. (J Prosthet Dent 2007;98:199-207).