Simultaneous Inference Using Multiple Marginal Models.

This tutorial describes single-step low-dimensional simultaneous inference with a focus on the availability of adjusted p values and compatible confidence intervals for more than just the usual mean value comparisons. The basic idea is, first, to use the influence of correlation on the quantile of the multivariate t-distribution: the higher the less conservative. In addition, second, the estimability of the correlation matrix using the multiple marginal models approach (mmm) using multiple models in the class of linear up to generalized linear mixed models. The underlying maxT-test using mmm is discussed by means of several real data scenarios using selected R packages. Surprisingly, different features are highlighted, among them: (i) analyzing different-scaled, correlated, multiple endpoints, (ii) analyzing multiple correlated binary endpoints, (iii) modeling dose as qualitative factor and/or quantitative covariate, (iv) joint consideration of several tuning parameters within the poly-k trend test, (v) joint testing of dose and time, (vi) considering several effect sizes, (vii) joint testing of subgroups and overall population in multiarm randomized clinical trials with correlated primary endpoints, (viii) multiple linear mixed effect models, (ix) generalized estimating equations, and (x) nonlinear regression models.

Designing highly efficient interlocking interactions in anisotropic active particles.

Cluster formation of microscopic swimmers is key to the formation of biofilms and colonies, efficient motion and nutrient uptake, but, in the absence of other interactions, requires high swimmer concentrations to occur. Here we experimentally and numerically show that cluster formation can be dramatically enhanced by an anisotropic swimmer shape. We analyze a class of model microswimmers with a shape that can be continuously tuned from spherical to bent and straight rods. In all cases, clustering can be described by Michaelis-Menten kinetics governed by a single scaling parameter that depends on particle density and shape only. We rationalize these shape-dependent dynamics from the interplay between interlocking probability and cluster stability. The bent rod shape promotes assembly in an interlocking fashion even at vanishingly low particle densities and we identify the most efficient shape to be a semicircle. Our work provides key insights into how shape can be used to rationally design out-of-equilibrium self-organization, key to creating active functional materials and processes that require two-component assembly with high fidelity.

Distance between parapatellar portal and intra-articular space for needle positioning in knee osteoarthritis.

Background: Intra-articular injection is a common therapeutic procedure in osteoarthritis (OA) that need high accuracy. This study was aimed to measure the distance between parapatellar skin and intra-articular space as a guidance to choose the length of needle needed to perform intra-articular injection. Methods: Twenty one knees MRI were taken from 16 females with knee osteoarthritis. The length of the needle needed to reach intra-articular space was reconstructed by drawing straight line from skin to intra-articular fluid. Paired t-test was using to analyze the mean difference of measurement of left side compare with right side with significant indicator if p-value < 0.05. Results: The entry point on both medial and lateral parapatellar were more cranial than transverse mid-patellar line. On medial portal, the closest distance from skin to intra-articular space is 27.81 ± 7.58 mm. Mean point of entry is 4.46 ± 2.16 mm cranial to mid-patellar line, and 14.20 ± 4.45 mm posterior to the prominence of medial border of patella. On lateral portal, the closest distance from skin to intra-articular space is 16.84 ± 6.79 mm. Mean point of entry is 11.10 ± 5.94 mm cranial to mid-patellar line, and 8.91 ± 3.83 mm posterior to the prominence of lateral border of patella. Conclusion: MRI knee osteoarthritis study showed that the mean distance between skin and intra-articular joint space of medial portal is 27.81 ± 7.58 mm, and lateral portal is 16.84 ± 6.79 mm. The portals on both sides is cranial to midpoint of patella, lateral appears more proximal than medial. This should be put into consideration in choosing needle length and portal projection to increase intra-articular injection accuracy.

Decreased basal and acute insulin-stimulated effect on the uptake of glucose and amino acid in vitro by thyroid glands from streptozotocin-diabetic rats

Since experimental diabetes in rats and mice is associated with impairment of several aspects of thyroid function, we determined glucose and amino acid uptake in vitro by isolated thyroid glands from normal and streptozotocin-diabetic rats. Adult male Wistar rats weighing 150-200 g were used. Diabetes was induced by intraperitoneal injection streptozotocin (STZ, 65 mg/kg body weight) and after five days only rats with blood glucose levels higher than 250 mg/dl were used. The thyroid glands were preincubated in Krebs-Ringer bicarbonate buffer in the presence or absence of insulin (0.7 nM to 7 muM) for 90 min and then incubated with the same concentration of the hormone or its vehicle plus 0.2 muCi of [l-l4C]-2-deoxy-D-glucose ([l4C]DG) or [l4C] methylaminoisobutyric acid ([l4C]MeAIB) for 15 to 180 min. The uptake of [l4C]DG or [l4C]MeAIB by the thyroid glands of normal rats increased as a function of incubation time, and the presence of insulin (7 muM) induced a significant increase of labelled DG from 3.30 ñ 0.11 to 4.16 ñ O.12 and of labelled MeAIB from 1.79 ñ 0.06 to 3.10 ñ 0.17 tissue/medium ratio (TIM) after 45 min of incubation. The lowest concentration of insulin that increased both [l4C]DG and [l4C]MeAIB transport was 7 nM. Thyroid glands from STZ rats exhibited lower basal values of [l4C]DG (4.03 ñ 0.11 T/M) or [l4C]MeAIB uptake (1.05 ñ 0.05 T/M) than glands from normal rats (4.62 ñ 0.13 and 1.70 ñ 0.O8 T/M, respectively). Insulin produced a stimulatory effect on the transport of both substrates in STZ rats. However, the maximals stimulating concentration of the hormone did not restore[l4C]DG and [l4C)MeAIB uptake to control values (4.89 + O.17 in STZ rats versus 5.44 ñ 0.17 T/M in controls for [l4C]DG, and 1.51 ñ 0.11 in STZ rats versus 2.19 ñ 0.10 T/M in controls for [l4C]MeAIB). These results indicate that insulin exerts a direct action on the thyroid gland, and its absence or reduction affects thyroid metabolism, contributing, at least in part, to the abnormality in thyroid function associated with diabetes mellitus.