A NOVEL AND SIMPLE RULE OF THUMB FOR MULTIPLICITY CONTROL IN EQUIVALENCE TESTING USING TWO ONE-SIDED TESTS

Equivalence testing is growing in use in scientific research outside of its traditional role in the drug approval process. Largely due to its ease of use and recommendation from the United States Food and Drug Administration guidance, the most common statistical method for testing (bio)equivalence is the two one-sided tests procedure (TOST). Like classical point-null hypothesis testing, TOST is subject to multiplicity concerns as more comparisons are made. In this manuscript, a condition that bounds the family-wise error rate (FWER) using TOST is given. This condition then leads to a simple solution for controlling the FWER. Specifically, we demonstrate that if all pairwise comparisons of k independent groups are being evaluated for equivalence, then simply scaling the nominal Type I error rate down by (k - 1) is sufficient to maintain the family-wise error rate at the desired value or less. The resulting rule is much less conservative than the equally simple Bonferroni correction. An example of equivalence testing in a non drug-development setting is given

Transport of Fungal Symbionts by Mountain Pine Beetles

The perpetuation of symbiotic associations between bark beetles (Coleoptera: Curculionidae: Scolytinae) and ophiostomatoid fungi requires the consistent transport of fungi by successive beetle generations to new host trees. We used scanning electron microscopy and culture methods to investigate fungal transport by the mountain pine beetle (MPB), Dendroctonus ponderosae Hopkins. MPB transports its two main fungal associates, Grosmannia clavigera (Robinson-Jeffrey and Davidson) Zipfel, de Beer and Wingfield and Ophiostoma montium (Rumbold) von Arx, in sac-like mycangia on the maxillary cardines as well as on the exoskeleton. Although spores of both species of fungi were observed on MPB exoskeletons, often in pits, O. montium spores were generally more abundant than G. clavigera spores. However, a general scarcity of spores of either species on MPB exoskeletons compared with numbers on scolytines that lack sac-like mycangia indicates that fungal transport exteriorly on MPBs is incidental rather than adaptive. Conidia were the dominant spore type transported regardless of location or species; however, our results suggest that once acquired in mycangia, conidia may reproduce in a yeast-like form and even produce hypha-like strands and compact conidiophore-like structures. Fungi that propagate in mycangia may provide beetles with a continual source of inocula during the extended egg-laying period

Bimodal brush-functionalized nanoparticles selective to receptor surface density.

Nanoparticles or drug carriers which can selectively bind to cells expressing receptors above a certain threshold surface density are very promising for targeting cells overexpressing specific receptors under pathological conditions. Simulations and theoretical studies have suggested that such selectivity can be enhanced by functionalizing nanoparticles with a bimodal polymer monolayer (BM) containing shorter ligated chains and longer inert protective chains. However, a systematic study of the effect of these parameters under tightly controlled conditions is still missing. Here, we develop well-defined and highly specific platforms mimicking particle-cell interface using surface chemistry to provide a experimental proof of such selectivity. Using surface plasmon resonance and atomic force microscopy, we report the selective adsorption of BM-functionalized nanoparticles, and especially, a significant enhanced selective behavior by using a BM with longer protective chains. Furthermore, a model is also developed to describe the repulsive contribution of the protective brush to nanoparticle adsorption. This model is combined with super-selectivity theory to support experimental findings and shows that the observed selectivity is due to the steric energy barrier which requires a high number of ligand-receptor bonds to allow nanoparticle adsorption. Finally, the results show how the relative length and molar ratio of two chains can be tuned to target a threshold surface density of receptors and thus lay the foundation for the rational design of BM-functionalized nanoparticles for selective targeting

Ablation of smooth muscle myosin heavy chain SM2 increases smooth muscle contractility and results in postnatal death in mice

The smooth muscle myosin heavy chains (SMHC) are motor proteins powering smooth muscle contraction. Alternate splicing of SHMC gene at the C-terminus produces SM1, and SM2 myosin isoforms; SM2 (200 kDa) contains a unique 9-amino-acid sequence at the carboxyl terminus, whereas SM1 (204 kDa) has a 43 amino acid non-helical tail region. To date the functional difference between C-terminal isoforms has not been established; therefore, we used an exon-specific gene targeting strategy and generated a mouse model specifically deficient in SM2. Deletion of exon-41 of the SMHC gene resulted in a complete loss of SM2 in homozygous (_SM2^-/-^_) mice, accompanied by a concomitant down-regulation of SM1 in bladders. While heterozygous (_SM2^+/-^_) mice appeared normal and fertile, _SM2^-/-^_ mice died within 30 days after birth. The peri-mortal _SM2^-/-^_ mice showed reduced body weight, distention of the bladder and alimentary tract, and end-stage hydronephrosis. Interestingly, strips from _SM2^-/-^_ bladders showed increased contraction to K^+^ depolarization or M3 receptor activation. These results suggest that SM2 myosin has a distinct functional role in smooth muscle, and the deficiency of SM2 increases smooth muscle contractility, and causes dysfunctions of smooth muscle organs, including the bladder that leads to the end-stage hydronephrosis and postnatal death

Gambling and the Millennial Generation: A Segmentation Study

This presentation will discuss the results of a segmentation study done in Minnesota on the gambllng habits of the Millennial Generation. While much of the work done on this generation (or others)focuses on central tendencies, this study was designed to explore the diversity in the gambling behavior, motivations, and attitudes of Minnesotans between the ages of 18 and 35. The authors will demonstrate the wide range of gambling behavior and beliefs within this generation, and discuss the importance of understanding these differences for the gambling industry, public policy, responsible gambling, and problem gambling awareness, treatment, and prevention

Home and Work Physical Activity Environments: Associations with Cardiorespiratory Fitness and Physical Activity Level in French Women

The influence of the physical activity environment in the home and at work on cardiorespiratory fitness (CRF) and objectively-measured physical activity has not been extensively studied. We recruited 147 women with a (mean ± SD) age of 54 ± 7 years and without evidence of chronic disease. The physical activity environment was assessed by self-report (Assessing Levels of PHysical Activity or ALPHA questionnaire), CRF using a submaximal step test, usual physical activity using combined heart rate and accelerometry, as well as by a validated questionnaire (Recent Physical Activity Questionnaire). Summary scores of the home environment and the work environment derived from the ALPHA questionnaire were positively correlated with CRF after adjustment for age ($r$ = 0.18, $p$ = 0.03 and $r$ = 0.28, $p$ < 0.01, respectively). Women owning a bicycle or having a garden (which may prompt physical activity) had higher CRF; those with a bicycle at home also had a higher physical activity energy expenditure. Similarly, women who had access to fitness equipment at work had higher CRF. In conclusion, these results provide new insights into potential environmental influences on physical capacity and physical activity that could inform the design of physical activity promotion strategies.European Union (Integrated Project LSHM-CT-2006-037197 in the Framework Programme 6 of the European Community), Medical Research Council (Grant ID: MC_UU_12015/3

Predicting Diabetes: Clinical, Biological, and Genetic Approaches: Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR)

OBJECTIVE—To provide a simple clinical diabetes risk score and to identify characteristics that predict later diabetes using variables available in the clinic setting as well as biological variables and polymorphisms

The Brain Reaction to Viewing Faces of Opposite- and Same-Sex Romantic Partners

We pursued our functional magnetic resonance imaging (fMRI) studies of the neural correlates of romantic love in 24 subjects, half of whom were female (6 heterosexual and 6 homosexual) and half male (6 heterosexual and 6 homosexual). We compared the pattern of activity produced in their brains when they viewed the faces of their loved partners with that produced when they viewed the faces of friends of the same sex to whom they were romantically indifferent. The pattern of activation and de-activation was very similar in the brains of males and females, and heterosexuals and homosexuals. We could therefore detect no difference in activation patterns between these groups

Interakcije nekih plijesni i aflatoksinogenog soja Asspergillus flavus NRRL 3251

The objective of this study was to evaluate biotic interaction between some mould species and active producer of aflatoxin B1 Aspergillus flavus NRRL 3251, co-cultured in yeast-extract sucrose (YES) broth. Twenty-five mould strains of Alternaria spp., Cladosporium spp., Mucor spp., A. flavus and A. niger, used as biocompetitive agents, were isolated from outdoor and indoor airborne fungi, scrapings of mouldy household walls, and from stored and post-harvest maize. Aflatoxin B1 was extracted from mould biomasses with chloroform and detected using the multitoxin TLC method. The results confirm antagonistic interaction between all strains tested. With Alternaria spp. and Cladosporium spp., aflatoxin B1 production decreased 100 %, compared to detection in a single culture of A. flavus NRRL 3251 (Cmean=18.7 µg mL-1). In mixed cultures with Mucor spp., aflatoxin B1 levels dropped to (5.6-9.3) µg mL-1, and the inhibition was from 50 % to 70 %. Four of five aflatoxin non-producing strains of A. flavus interfered with aflatoxin production in mixed culture, and reduced AFB1 productivity by 100 %. One strain showed a lower efficacy in inhibiting AFB1 production (80 %) with a detectable amount of AFB1 3.7 µg mL-1 when compared to control. A decrease in toxin production was also observed in dual cultivation with A. niger strains. It resulted in 100 % reduction in three strains), 90 % reduction in one strain (Cmean=1.9 µg mL-1) and 80 % reduction in one strain (Cmean=3.7 µg mL-1) inhibition.Cilj rada bio je procijeniti biotske interakcije između sojeva različitih vrsta plijesni i kontrolnog soja Aspergillus flavus NRRL 3251, producenta aflatoksina B1 (AFB1). Inhibitorno djelovanje u miješanim kulturama na tvorbu AFB1 ispitano je na dvadeset pet sojeva Alternaria, Cladosporium, Mucor i Aspergillus vrsta izoliranih iz zraka, strugotina pljesnivih zidova te uskladištenog i prezimljenog kukuruza. Biosinteze su provedene u tekućoj hranjivoj podlozi s kvaščevim ekstraktom (YESbujon). Ekstrakcije AFB1 iz biomase izvršene su multitoksinskom metodom tankoslojne kromatografije. Rezultati biotskih interakcija pokazali su antagonistički odnos svih testiranih sojeva. Alternaria i Cladosporium vrste simultano inokulirane sporama A. flavus NRRL 3251 inhibirale su tvorbu AFB1 100 % u odnosu na dokazani toksin u kontrolnoj biosintezi (konc. 18,7 µg mL-1). U miješanim kulturama vrstama roda Mucor dokazane su padajuće koncentracije AFB1 (9,3 µg mL-1, 7,5 µg mL-1 i 5,6 µg mL-1), odnosno inhibicija tvorbe toksina 50 % do 70 %. Atoksinogeni sojevi A. flavus inhibirali su tvorbu AFB1 80 % (1 soj, konc. 3,7 µg mL-1) i 100 % (4 soja). Antagonističko djelovanje prema toksinogenom soju, smanjujući tvorbu AFB1 u rasponu 80 % do 100 % (konc. 1,9 µg mL-1 i 3,7 µg mL-1), dokazano je u uzgojnim biosintezama s A. niger

Diet, physical activity, and adiposity in children in poor and rich neighbourhoods: a cross-sectional comparison

BACKGROUND: Obesity in Canadian children increased three-fold in twenty years. Children living in low-income neighborhoods exercise less and are more overweight than those living in more affluent neighborhoods after accounting for family socio-economic status. Strategies to prevent obesity in children have focused on personal habits, ignoring neighborhood characteristics. It is essential to evaluate diet and physical activity patterns in relation to socio-economic conditions to understand the determinants of obesity. The objective of this pilot study was to compare diet, physical activity, and the built environment in two Hamilton area elementary schools serving socio-economically different communities. METHODS: We conducted a cross-sectional study (November 2005-March 2006) in two public elementary schools in Hamilton, Ontario, School A and School B, located in low and high socioeconomic areas respectively. We assessed dietary intake, physical activity, dietary restraint, and anthropometric measures in consenting children in grades 1 and higher. From their parents we assessed family characteristics and walkability of the built environment. RESULTS: 160 children (n = 48, School A and n = 112, School B), and 156 parents (n = 43, School A and n = 113, School B) participated in this study. The parents with children at School A were less educated and had lower incomes than those at School B. The School A neighborhood was perceived to be less walkable than the School B neighborhood. Children at School A consumed more baked foods, chips, sodas, gelatin desserts, and candies and less low fat dairy, and dark bread than those at School B. Children at School A watched more television and spent more time in front of the computer than children studying at School B, but reported spending less time sitting on weekdays and weekends. Children at both schools were overweight but there was no difference in their mean BMI z-scores (School A = 0.65 versus School B = 0.81, p-value = 0.38). CONCLUSION: The determinants of overweight in children may be more complex than imagined. In future intervention programs researchers may consider addressing environmental factors, and customizing lifestyle interventions so that they are closer to community needs