On The Breakdown Properties of some Multivariate M-Functionals

For probability distributions on ℝq, a detailed study of the breakdown properties of some multivariate M-functionals related to Tyler's [Ann. Statist. 15 (1987) 234] ‘distribution-free’ M-functional of scatter is given. These include a symmetrized version of Tyler's M-functional of scatter, and the multivariate t M-functionals of location and scatter. It is shown that for ‘smooth’ distributions, the (contamination) breakdown point of Tyler's M-functional of scatter and of its symmetrized version are 1/q and inline image, respectively. For the multivariate t M-functional which arises from the maximum likelihood estimate for the parameters of an elliptical t distribution on ν ≥ 1 degrees of freedom the breakdown point at smooth distributions is 1/(q + ν). Breakdown points are also obtained for general distributions, including empirical distributions. Finally, the sources of breakdown are investigated. It turns out that breakdown can only be caused by contaminating distributions that are concentrated near low-dimensional subspaces.

Influence of two types of self-retaining retractors on multifidus muscle blood flow during dorsolateral thoracolumbar hemilaminectomy in dogs

OBJECTIVES To assess the influence of the use of Gelpi and Grevel retractors on multifidus muscle blood flow during hemilaminectomy, using a dorsolateral approach, for acute disc extrusion in dogs as measured by laser speckle contrast imaging (LSCI). METHODS Blood flow in the multifidus muscles was measured intra-operatively using LSCI prior to insertion of the retractors, immediately after hemilaminectomy and removal of the retractors, and after 10 minutes of lavage of the surgical site. Plasma creatine kinase levels were measured preoperatively and 12-24 hours postoperatively. RESULTS Muscular blood flow was significantly decreased following retraction and remained lower than initial values 10 minutes after lavage in all dogs. The decrease in blood flow was significantly greater with Gelpi retractors (n = 8) than with Grevel retractors (n = 10). No significant relation was found between the duration of retraction and postoperative changes in creatine kinase levels or blood flow. CLINICAL SIGNIFICANCE Findings in this study demonstrate a drop in blood flow within the multifidus muscles using the dorsolateral approach regardless of retractor type used. Gelpi retractors seem to have greater influence on muscular blood flow than Grevel retractors. Further studies are warranted to confirm this second finding.

Repair of Annulus fibrosus with Genipin-enhanced Fibrin Hydrogel and silk membrane- fleece

Introduction Low back pain is often caused by a trauma causing disc herniation and /or disc degeneration. Although there are some promising approaches for nucleus pulposus repair, the inner tissue of the intervertebral disc (IVD) so far no treatment or repair is available for annulus fibrosus (AF) injuries. Here we aimed to develop a new method to seal and repair AF injuries by using a silk fleece composite and a genipin enhanced hydrogel. Methods Bovine (b) IVDs were harvested under aseptic conditions and kept in free swelling conditions for 24h in high-glucose DMEM containing 5% bovine serum for equilibration (1). A circular 2mm biopsy punch (Polymed Medical Center, Switzerland) was used to form a reproducible defect in the AF. For filling the defect and keeping the silk composite in place a human-derived fibrin gel (Baxter Tisseel, Switzerland) enhanced with 4.2mg/ml of the cross linker genipin (Wako Chemicals GmbH, Germany) was used. The silk composite consists of a mesh- and a membrane side (Spintec Engineering GmbH, Germany); the membrane is facing outwards to form a seal. bIVDs were cultured in vitro for 14 days either under dynamic load in a custom-built bioreactor under physiological conditions (0.2MPa load and ±2° torsion at 0.2Hz for 8h/day) or static diurnal load of 0.2MPa (2). At the end of culture discs were checked for seal failure, disc height, metabolic activity, cell death by necrosis (LDH assay), DNA content and glycosaminoglycan content. Results Silk composite maintained its position throughout the 14 days of culture under loaded conditions. Although repaired discs performed slightly lower in cell activity, DNA and GAG content were in the range of the control. Also LDH resulted in similar values compared to control discs (Fig 1). Height loss in repaired discs was in the same range as for static diurnal loaded control samples. For dynamically loaded samples the decrease was comparable to the injured, unrepaired discs. Fig 1 LDH of repaired discs compared to control disc after 24h in free swelling conditions for equilibration and first three loading cycles. Conclusions Silk-genipin-fibrin reinforced hydrogel is a promising approach to close AF defects as tested by two degree of freedom loading. In further experiments cytocompatibility of genipin has to be investigated. References 1. Chan SC, Gantenbein-Ritter B. Preparation of intact bovine tail intervertebral discs for organ culture. J Vis Exp 2012, Feb 2;60(60):e3490. 2. Walser J, Ferguson SJ, Gantenbein-Ritter B. Design of a mechanical loading device to culture intact bovine caudal motional segments of the spine under twisting motion. In: Davies J, editors. Replacing animal models: a practical guide to creating and using biomimetic alternatives. Chichester, UK: John Wiley & Sons, Ltd.; 2012. p. 89-105. Acknowledgements This project is funded by the Gerbert Rüf Stiftung project # GRS-028/13 and the Swiss National Science Project SNF #310030_153411.

Polaronic metal state at the LaAlO₃/SrTiO₃ interface

Interplay of spin, charge, orbital and lattice degrees of freedom in oxide heterostructures results in a plethora of fascinating properties, which can be exploited in new generations of electronic devices with enhanced functionalities. The paradigm example is the interface between the two band insulators LaAlO3 and SrTiO3 that hosts a two-dimensional electron system. Apart from the mobile charge carriers, this system exhibits a range of intriguing properties such as field effect, superconductivity and ferromagnetism, whose fundamental origins are still debated. Here we use soft-X-ray angle-resolved photoelectron spectroscopy to penetrate through the LaAlO3 overlayer and access charge carriers at the buried interface. The experimental spectral function directly identifies the interface charge carriers as large polarons, emerging from coupling of charge and lattice degrees of freedom, and involving two phonons of different energy and thermal activity. This phenomenon fundamentally limits the carrier mobility and explains its puzzling drop at high temperatures.

Comparison of two protocols of periosteal distraction osteogenesis in a rabbit calvaria model

The regenerative pathways during periosteal distraction osteogenesis may be influenced by the local environment composed by cells, growth factors, nutrition and mechanical load. The aim of the present study was to evaluate the influence of two protocols of periosteal distraction on bone formation. Custom made distraction devices were surgically fixed onto the calvariae of 60 rabbits. After an initial healing period of 7 days, two groups of animals were submitted to distraction rates of 0.25 and 0.5 mm/24 h for 10 days, respectively. Six animals per group were sacrificed 10 (mid-distraction), 17 (end-distraction), 24 (1-week consolidation), 31 (2-week consolidation) and 77 days (2-month consolidation) after surgery. Newly formed bone was assessed by means of micro-CT and histologically. Expression of transcripts encoding tissue-specific genes (BMP-2, RUNX2, ACP5, SPARC, collagen I α1, collagen II α1 and SOX9) was analyzed by quantitative PCR. Two patterns of bone formation were observed, originating from the old bone surface in Group I and from the periosteum in Group II. Bone volume (BV) and bone mineral density (BMD) significantly increased up to the 2-month consolidation period within the groups (p < 0.05). Significantly more bone was observed in Group II compared to Group I at the 2-month consolidation period (p < 0.001). Expression of transcripts encoding osteogenic genes in bone depended on the time-point of observation (p < 0.05). Low level of transcripts reveals an indirect role of periosteum in the osteogenic process. Two protocols of periosteal distraction in the present model resulted in moderate differences in terms of bone formation.

Life style habits such as alcohol consumption and physical activity in relation to serum apoB / apoA-I ratio amongst 64-year-old women with varying degrees of glucose tolerance.

OBJECTIVES To investigate how life style factors such as alcohol consumption and physical activity relate to the serum apoB / apoA-I ratio in a cohort of middle-aged women with varying degrees of glucose tolerance. DESIGN Observational, cross-sectional cohort study. SETTING Research laboratory at a University Hospital. SUBJECTS A screened cohort of 64-year-old postmenopausal women with varying degrees of glucose tolerance, ranging from diabetes (n = 232), impaired (n = 212) and normal (n = 191) glucose tolerance. MAIN OUTCOME MEASURE ApoB / apoA-I ratio in relation to alcohol consumption and physical activity as assessed by questionnaires. RESULTS Alcohol consumption and regular physical activity at high levels were inversely associated with the serum apoB / apoA-I ratio independently of confounding factors such as obesity, lipid-lowering treatment, degree of glucose tolerance and hormone replacement therapy. Alcohol seemed related to the apoB / apoA-I ratio mainly through increasing apoA-I, whereas physical activity seemed mainly related to lowering of apoB. Alcohol consumption above a daily intake of 8.9 g, i.e. less than a glass of wine was accompanied by a decrease in apoB / apoA-I ratio. CONCLUSIONS Amongst these 64-year-old women with varying degrees of glucose tolerance, a moderate alcohol intake and regular physical exercise leading to sweating were associated with lower apoB / apoA-I ratio and these effects seem to be additive.

N budget and NH3 exchange of a grass/clover crop at two levels of N application

Atmospheric ammonia (NH3) exchange during a single growing season was measured over two grass/clover fields managed by cutting and treated with different rates of mineral nitrogen (N) fertilizer. The aim was to quantify the total NH3 exchange of the two systems in relation to their N budget, the latter was split into N derived from symbiotic fixation, from fertilization, and from the soil. The experimental site was located in an intensively managed agricultural area on the Swiss plateau. Two adjacent fields with mixtures of perennial ryegrass (Lolium perenne L.), cocks foot (Dactylis glomerata L.), white clover (Trifolium repens L.) and red clover (Trifolium pratense L.) were used. These were treated with either 80 or 160 kg N ha−1 applied as NH4NO3 fertilizer in equal portions after each of four cuts. Continuous NH3 flux measurements were carried out by micrometeorological techniques. To determine the contribution of each species to the overall NH3 canopy compensation point, stomatal NH3 compensation points of the individual plant species were determined on the basis of NH4+ + NH3 (NHx) concentrations and pH in the apoplast. Symbiotic N2 fixation was measured by the 15N dilution method.

Gene expression profile in newborn rat lungs after two days of recovery of mechanical ventilation.

BACKGROUND Preterm infants having immature lungs often require respiratory support, potentially leading to bronchopulmonary dysplasia (BPD). Conventional BPD rodent models based on mechanical ventilation (MV) present outcome measured at the end of the ventilation period. A reversible intubation and ventilation model in newborn rats recently allowed discovering that different sets of genes modified their expression related to time after MV. In a newborn rat model, the expression profile 48 h after MV was analyzed with gene arrays to detect potentially interesting candidates with an impact on BPD development. METHODS Rat pups were injected P4-5 with 2 mg/kg lipopolysaccharide (LPS). One day later, MV with 21 or 60% oxygen was applied during 6 h. Animals were sacrified 48 h after end of ventilation. Affymetrix gene arrays assessed the total gene expression profile in lung tissue. RESULTS In fully treated animals (LPS + MV + 60% O(2)) vs. controls, 271 genes changed expression significantly. All modified genes could be classified in six pathways: tissue remodeling/wound repair, immune system and inflammatory response, hematopoiesis, vasodilatation, and oxidative stress. Major alterations were found in the MMP and complement system. CONCLUSION MMPs and complement factors play a central role in several of the pathways identified and may represent interesting targets for BPD treatment/prevention.Bronchopulmonary dysplasia (BPD) is a chronic lung disease occurring in ~30% of preterm infants born less than 30 wk of gestation (1). Its main risk factors include lung immaturity due to preterm delivery, mechanical ventilation (MV), oxygen toxicity, chorioamnionitis, and sepsis. The main feature is an arrest of alveolar and capillary formation (2). Models trying to decipher genes involved in the pathophysiology of BPD are mainly based on MV and oxygen application to young mammals with immature lungs of different species (3). In newborn rodent models, analyses of lung structure and gene and protein expression are performed for practical reasons directly at the end of MV (4,5,6). However, later appearing changes of gene expression might also have an impact on lung development and the evolution towards BPD and cannot be discovered by such models. Recently, we developed a newborn rat model of MV using an atraumatic (orotracheal) intubation technique that allows the weaning of the newborn animal off anesthesia and MV, the extubation to spontaneous breathing, and therefore allows the evaluation of effects of MV after a ventilation-free period of recovery (7). Indeed, applying this concept of atraumatic intubation by direct laryngoscopy, we recently were able to show significant differences between gene expression changes appearing directly after MV compared to those measured after a ventilation-free interval of 48 h. Immediately after MV, inflammation-related genes showed a transitory modified expression, while another set of more structurally related genes changed their expression only after a delay of 2 d (7). Lung structure, analyzed by conventional 2D histology and also by 3D reconstruction using synchrotron x-ray tomographic microscopy revealed, 48 h after end of MV, a reduced complexity of lung architecture compared to the nonventilated rat lungs, similar to the typical findings in BPD. To extend these observations about late gene expression modifications, we performed with a similar model a full gene expression profile of lung tissue 48 h after the end of MV with either room air or 60% oxygen. Essentially, we measured changes in the expression of genes related to the MMPs and complement system which played a role in many of the six identified mostly affected pathways.

Assessment of the effect on statistical power of regression model misspecification by using techniques of mathematical statistics and simulation study

Objectives. This paper seeks to assess the effect on statistical power of regression model misspecification in a variety of situations. ^ Methods and results. The effect of misspecification in regression can be approximated by evaluating the correlation between the correct specification and the misspecification of the outcome variable (Harris 2010).In this paper, three misspecified models (linear, categorical and fractional polynomial) were considered. In the first section, the mathematical method of calculating the correlation between correct and misspecified models with simple mathematical forms was derived and demonstrated. In the second section, data from the National Health and Nutrition Examination Survey (NHANES 2007-2008) were used to examine such correlations. Our study shows that comparing to linear or categorical models, the fractional polynomial models, with the higher correlations, provided a better approximation of the true relationship, which was illustrated by LOESS regression. In the third section, we present the results of simulation studies that demonstrate overall misspecification in regression can produce marked decreases in power with small sample sizes. However, the categorical model had greatest power, ranging from 0.877 to 0.936 depending on sample size and outcome variable used. The power of fractional polynomial model was close to that of linear model, which ranged from 0.69 to 0.83, and appeared to be affected by the increased degrees of freedom of this model.^ Conclusion. Correlations between alternative model specifications can be used to provide a good approximation of the effect on statistical power of misspecification when the sample size is large. When model specifications have known simple mathematical forms, such correlations can be calculated mathematically. Actual public health data from NHANES 2007-2008 were used as examples to demonstrate the situations with unknown or complex correct model specification. Simulation of power for misspecified models confirmed the results based on correlation methods but also illustrated the effect of model degrees of freedom on power.^

BEST SUBSET SELECTION FOR CATEGORICAL DATA

When choosing among models to describe categorical data, the necessity to consider interactions makes selection more difficult. With just four variables, considering all interactions, there are 166 different hierarchical models and many more non-hierarchical models. Two procedures have been developed for categorical data which will produce the "best" subset or subsets of each model size where size refers to the number of effects in the model. Both procedures are patterned after the Leaps and Bounds approach used by Furnival and Wilson for continuous data and do not generally require fitting all models. For hierarchical models, likelihood ratio statistics (G('2)) are computed using iterative proportional fitting and "best" is determined by comparing, among models with the same number of effects, the Pr((chi)(,k)('2) (GREATERTHEQ) G(,ij)('2)) where k is the degrees of freedom for ith model of size j. To fit non-hierarchical as well as hierarchical models, a weighted least squares procedure has been developed.^ The procedures are applied to published occupational data relating to the occurrence of byssinosis. These results are compared to previously published analyses of the same data. Also, the procedures are applied to published data on symptoms in psychiatric patients and again compared to previously published analyses.^ These procedures will make categorical data analysis more accessible to researchers who are not statisticians. The procedures should also encourage more complex exploratory analyses of epidemiologic data and contribute to the development of new hypotheses for study. ^

Family Reunification among Two Groups of Runaway Adolescents Utilizing Emergency Shelters

Limited research has addressed reunification of runaway youths with their families following an emergency shelter stay; however, recent studies have shown that those who reunify with their families following a shelter stay have more positive outcomes than those relocated to other residences. This study evaluated differences between two samples of runaway youth utilizing youth emergency shelters in New York (n = 155) and Texas (n = 195) and identified factors associated with reunification among these two groups of adolescents. Less than half (43.7%) of the youths were reunited with their families. Among New York runaway youths, those who had lived primarily with someone other than a parent before shelter admission, were physically abused, or neglected were less likely to return home. Among youths admitted to emergency shelter services in Texas, those with longer shelter stays, living primarily with someone other than a parent before shelter admission, or being pregnant or a parent were less likely to reunify. This study provides valuable information concerning family reunification following shelter service use; however, additional research is needed to delineate youth, family, and shelter system factors that distinguish successful from unsuccessful reunification over an extended period of time.