Sample size considerations in active-control non-inferiority trials with binary data based on the odds ratio

This paper presents an approximate closed form sample size formula for determining non-inferiority in active-control trials with binary data. We use the odds-ratio as the measure of the relative treatment effect, derive the sample size formula based on the score test and compare it with a second, well-known formula based on the Wald test. Both closed form formulae are compared with simulations based on the likelihood ratio test. Within the range of parameter values investigated, the score test closed form formula is reasonably accurate when non-inferiority margins are based on odds-ratios of about 0.5 or above and when the magnitude of the odds ratio under the alternative hypothesis lies between about 1 and 2.5. The accuracy generally decreases as the odds ratio under the alternative hypothesis moves upwards from 1. As the non-inferiority margin odds ratio decreases from 0.5, the score test closed form formula increasingly overestimates the sample size irrespective of the magnitude of the odds ratio under the alternative hypothesis. The Wald test closed form formula is also reasonably accurate in the cases where the score test closed form formula works well. Outside these scenarios, the Wald test closed form formula can either underestimate or overestimate the sample size, depending on the magnitude of the non-inferiority margin odds ratio and the odds ratio under the alternative hypothesis. Although neither approximation is accurate for all cases, both approaches lead to satisfactory sample size calculation for non-inferiority trials with binary data where the odds ratio is the parameter of interest.

Exploration of relational factors: Sino-foreign joint-venture partnering

Purpose – Despite recent threats of economic contraction, China still offers attractive opportunities for foreign companies seeking to expand their business activities through joint venturing (JV) partnering entry strategies. Recent research has indicated a growing recognition of the importance of relational factors in JV partnering. The purpose of this paper is to build on recent research findings that identify critical relation success factors in JVs and explores these in the context of a Hong Kong-based civil aviation services company seeking to expand business activities in Greater China. Design/methodology/approach – While the extant management literature focuses primarily on factors relevant to the inter-partner relationship between partners in the formation stage of a joint venture, this research takes a dynamic stakeholder perspective in respect of the relevant relational factors over the evolution of a partnership. The research described in this paper is based on a case-based study that identifies and examines the relevance and importance of uniquely Chinese factors such as guanxi, renqing and mianzi in the specific context of a strategic partnering relationship. Findings – This phenomenological study provides empirical evidence of critical linkages of these to intrinsically Chinese notions of guanxi, mianzi and renqing – it links these to key strategic partnering success factors identified to be trust, conflict resolution, commitment and cooperation. This study thereby reinforces the importance of the uniquely Chinese relational context in cross-border JVs. Moreover, the research findings suggest that these factors underpin the dynamic bi-directional stakeholder relationship in a Sino-foreign strategic partnership. Originality/value – This study conceptually links the uniquely Chinese relational factors (guanxi, mianzi and renqing) to key success factors supporting the establishment of a strategic partnership in a Sino-foreign context; moreover, it contributes empirical evidence substantiating the proposed conceptual linkage.

Validation of a priori CME arrival predictions made using real-time heliospheric imager observations

Between December 2010 and March 2013, volunteers for the Solar Stormwatch (SSW) Citizen Science project have identified and analyzed coronal mass ejections (CMEs) in the near real-time Solar Terrestrial Relations Observatory Heliospheric Imager observations, in order to make “Fearless Forecasts” of CME arrival times and speeds at Earth. Of the 60 predictions of Earth-directed CMEs, 20 resulted in an identifiable Interplanetary CME (ICME) at Earth within 1.5–6 days, with an average error in predicted transit time of 22 h, and average transit time of 82.3 h. The average error in predicting arrival speed is 151 km s−1, with an average arrival speed of 425km s−1. In the same time period, there were 44 CMEs for which there are no corresponding SSW predictions, and there were 600 days on which there was neither a CME predicted nor observed. A number of metrics show that the SSW predictions do have useful forecast skill; however, there is still much room for improvement. We investigate potential improvements by using SSW inputs in three models of ICME propagation: two of constant acceleration and one of aerodynamic drag. We find that taking account of interplanetary acceleration can improve the average errors of transit time to 19 h and arrival speed to 77 km s−1.

Is cognitive bias modification training truly beneficial for adolescents?

Background Cognitive Bias Modification (CBM) has been shown to change interpretation biases commonly associated with anxiety and depression and may help ameliorate symptoms of these disorders. However, its evidence base for adolescents is scarce. Previous results have been hard to interpret because of methodological issues. In particular, many studies have used negative bias training as the control condition. This would tend to inflate any apparent benefits of CBM compared to a neutral control. Most studies also only examined the effects of a single training session and lacked follow-up assessment or ecologically valid outcome measures. Method Seventy-four adolescents, aged 16–18 years, were randomised to two sessions of CBM training or neutral control. Interpretation bias and mood were assessed three times: at baseline, immediately post-training and 1 week post-training. A controlled experimental stressor was also used, and responses to everyday stressors were recorded for 1 week after training to assess responses to psychological challenges. Feedback for the training programme was collected. Results The CBM group reported a greater reduction in negative affect than control participants. However, other hypothesised advantages of CBM were not demonstrated. Regardless of training group, participants reported increased positive interpretations, decreased negative interpretations, reduced depressive symptoms and no change in trait anxiety. The two groups did not differ in their stress reactivity. After controlling for group differences in training performance, all the mood effects disappeared. Conclusions When tested under stringent experimental conditions the effects of CBM in healthy adolescents appear to be minimal. Future studies should concentrate on participants with elevated cognitive biases and/or mood symptoms who may be more sensitive to CBM.

In situ gelling systems based on Pluronic F127/Pluronic F68 formulations for ocular drug delivery

This study evaluated the use of Pluronic F127 and Pluronic F68 as excipients for formulating in situ gelling systems for ocular drug delivery. Thermal transitions have been studied in aqueous solutions of Pluronic F127, Pluronic F68 as well as their binary mixtures using differential scanning calorimetry, rheological measurements, and dynamic light scattering. It was established that the formation of transparent gels at physiologically relevant temperatures is observed only in the case of 20 wt % of Pluronic F127. The addition of Pluronic F68 to Pluronic F127 solutions increases the gelation temperature of binary formulation to above physiological range of temperatures. The biocompatibility evaluation of these formulations using slug mucosa irritation assay and bovine corneal erosion studies revealed that these polymers and their combinations do not cause significant irritation. In vitro drug retention study on glass surfaces and freshly excised bovine cornea showed superior performance of 20 wt % Pluronic F127 compared to other formulations. In addition, in vivo studies in rabbits demonstrated better retention performance of 20 wt % Pluronic F127 compared to Pluronic F68. These results confirmed that 20 wt % Pluronic F127 offers an attractive ocular formulation that can form a transparent gel in situ under physiological conditions with minimal irritation.

Internal nanoparticle structure of temperature-responsive self-assembled PNIPAM-b-PEG-b-PNIPAM triblock copolymers in aqueous solutions: NMR, SANS and light scattering studies

In this study we report detailed information on the internal structure of PNIPAM-b-PEG-b-PNIPAM nanoparticles formed from self-assembly in aqueous solutions upon increase in temperature. NMR spectroscopy, light scattering and small-angle neutron scattering (SANS) were used to monitor different stages of nanoparticle formation as a function of temperature, providing insight into the fundamental processes involved. The presence of PEG in a copolymer structure significantly affects the formation of nanoparticles, making their transition to occur over a broader temperature range. The crucial parameter that controls the transition is the ratio of PEG/PNIPAM. For pure PNIPAM, the transition is sharp; the higher the PEG/PNIPAM ratio results in a broader transition. This behavior is explained by different mechanisms of PNIPAM block incorporation during nanoparticle formation at different PEG/PNIPAM ratios. Contrast variation experiments using SANS show that the structure of nanoparticles above cloud point temperatures for PNIPAM-b-PEG-b-PNIPAM copolymers is drastically different from the structure of PNIPAM mesoglobules. In contrast with pure PNIPAM mesoglobules, where solid-like particles and chain network with a mesh size of 1-3 nm are present; nanoparticles formed from PNIPAM-b-PEG-b-PNIPAM copolymers have non-uniform structure with “frozen” areas interconnected by single chains in Gaussian conformation. SANS data with deuterated “invisible” PEG blocks imply that PEG is uniformly distributed inside of a nanoparticle. It is kinetically flexible PEG blocks which affect the nanoparticle formation by prevention of PNIPAM microphase separation.

Effects of physiotherapy on hemodynamic variables in newborns with Acute Respiratory Distress Syndrome

Background: Acute respiratory distress syndrome (ARDS) is a frequent respiratory disturbance in preterm newborns. Preceding investigations evaluated chronic physiotherapy effects on newborns with different lung diseases; however, no study analyzed acute physiotherapy treatment on premature newborns with ARDS. In this study we aimed to evaluate the acute effects of chest and motor physiotherapy treatment on hemodynamic variables in preterm newborns with ARDS. Methods: We evaluated heart rate (HR), respiratory rate (RR), systolic (SAP), mean (MAP) and diastolic arterial pressure (DAP), temperature and oxygen saturation (SO(2)%) in 44 newborns with ARDS. We compared all variables between six periods in one day: before first physiotherapy treatment vs. after first physiotherapy treatment vs. before second physiotherapy treatment vs. after second physiotherapy treatment vs. before third physiotherapy treatment vs. after third physiotherapy treatment. Variables were measured 2 minutes before and 5 minutes after each physiotherapy session. We applied Anova one way followed by post hoc Bonferroni test. Results: HR (147.5 +/- 9.5 bpm vs. 137.7 +/- 9.3 bpm; p<0.001), RR (45.5 +/- 8.7cpm vs. 41.5 +/- 6.7 cpm; p=0.001), SAP (70.3 +/- 10.4 mmHg vs. 60.1 +/- 7.1 mmHg; p=0.001) and MAP (55.7 +/- 10 mmHg vs. 46 +/- 6.6 mmHg; p=0.001) were significantly reduced after the third physiotherapy treatment compared to before the first session. There were no significant changes regarding temperature, DAP and SO(2) %. Conclusion: Chest and motor physiotherapy acutely improves HR, RR, SAP, MAP and SO(2) % in newborns with ARDS.

Outcomes of newborns admitted in the intensive care unit at a public hospital

Background: We evaluated the outcome of newborns admitted in the neonatal Intensive Care Unit (ICU) in Diadema, Brazil. Methods: We evaluated 72 newborns, data were extracted from research forms, newborns` hospital records, mothers interviews, domiciliary inquiry made with the responsible for the newborn care, and paediatric accompaniment cards. Results: 48.93% presented low birth weight, 48% were considered to have normal birth weight and 2% had a birth weight higher than 4000g. Concerning gestational age, 57.44% were younger than 37 weeks old. During hospitalisation, newborn had appointments with doctors from other specialties (inter-appointments), around 40% were cardiologists. After hospital discharge 82.98% were referred to local primary health care units, and the main specialities were cardiology and neurology. Among the newborns evaluated 85.11% were accompanied by paediatric health care units. Conclusion: The implementation of a specialised newborn health accompaniment program in Brazil after ICU discharge is important for positive outcomes regarding newborns growth and development.

Peak expiratory flow values are higher in older and taller healthy male children: An observational study

Purpose: Peak expiratory flow (PEF) was measured in healthy children aged five to ten years in order to provide baseline values and to determine correlations between PEF and factors such as gender, age and type of school. Methods: After the Ethical Committee of Research in Human of the School of Medicine of ABC - FMABC approval, PEF and height were measured in 1942 children between five and ten years old from nine public schools and nine private schools throughout Sao Bernardo do Campo City. PEF was measured using the Mini-Wright Peak Flow Meter (Clement Clarke International Ltd.) and. height was measured using a Sanny professional stadiometer. Results: Significant differences were found in values for PEF: higher values were seen in older students in comparison with younger students, in males in comparison with females and in students from private schools in comparison with public schools, with average values ranging from 206 L/min to 248 L/min,. Linear correlations were seen for PEF values with both height and age (Spearman Coefficient). Conclusions: Differences were seen for PEF between genders and between types of school, and a linear correlation was seen for PEF with both age and height in healthy children from five to ten years old.

Lines of heavy elements and Fe II in the UV of CS 31082-001

The abundance of heavy r-elements may provide a better understanding of the r-process, and the determination of several reference r-elements should allow a better determination of a star`s age. The space UV region (lambda < 3000 angstrom) presents a large number of lines of the heavy elements, and in the case of some elements, such as Bi, Pt, Au, detectable lines are not available elsewhere. The extreme ""r-process star"" CS 31082-001 ([Fe/H] = -2.9) was observed in the space UV to determine abundances of the heaviest stable elements, using STIS on board Hubble Space Telescope.

A late Neoproterozoic paleomagnetic pole for the Congo craton: Tectonic setting, paleomagnetism and geochronology of the Nola dike swarm (Central African Republic)

New structural, geochronological and paleomagnetic data were obtained on dolerite dikes of the Nola region (Central African Republic) at the northern border of the Congo craton. In this region metavolcanic, successions were thrust southward onto the craton during the Panafrican orogenic events. Our structural data reveal at least two structural klippes south of the present-day limits of the Panafrican nappe suggesting that it has once covered the whole Nola region, promoting the pervasive hydrothermal green-schist metamorphism observed in the underlying cratonic basement and also in the intrusive dolerite dikes. Paleomagnetic measurements revealed a stable dual-polarity low-inclination magnetization component in nine dikes (47 samples), carried by pyrrhotite and magnetite. This component corresponds to a paleopole at 304.8 degrees E and 61.8 degrees S (dp = 5.4, dm = 10.7) graded at 2 = 6. Both metamorphism and magnetic resetting were dated by the Ar-40/Ar-39 method on amphibole grains separated from the dikes at 571 +/- 6 Ma. The Nola pole is the first well-dated paleomagnetic pole for the Congo craton between 580 and 550 Ma. It marks a sudden change in direction of the Congo craton apparent polar wander path at the waning stages of the Panafrican orogenic events. (c) 2008 Elsevier B.V. All rights reserved.

Untangling associations between chironomid taxa in Neotropical streams using local and landscape filters

1. Analyses of species association have major implications for selecting indicators for freshwater biomonitoring and conservation, because they allow for the elimination of redundant information and focus on taxa that can be easily handled and identified. These analyses are particularly relevant in the debate about using speciose groups (such as the Chironomidae) as indicators in the tropics, because they require difficult and time-consuming analysis, and their responses to environmental gradients, including anthropogenic stressors, are poorly known. 2. Our objective was to show whether chironomid assemblages in Neotropical streams include clear associations of taxa and, if so, how well these associations could be explained by a set of models containing information from different spatial scales. For this, we formulated a priori models that allowed for the influence of local, landscape and spatial factors on chironomid taxon associations (CTA). These models represented biological hypotheses capable of explaining associations between chironomid taxa. For instance, CTA could be best explained by local variables (e.g. pH, conductivity and water temperature) or by processes acting at wider landscape scales (e.g. percentage of forest cover). 3. Biological data were taken from 61 streams in Southeastern Brazil, 47 of which were in well-preserved regions, and 14 of which drained areas severely affected by anthropogenic activities. We adopted a model selection procedure using Akaike`s information criterion to determine the most parsimonious models for explaining CTA. 4. Applying Kendall`s coefficient of concordance, seven genera (Tanytarsus/Caladomyia, Ablabesmyia, Parametriocnemus, Pentaneura, Nanocladius, Polypedilum and Rheotanytarsus) were identified as associated taxa. The best-supported model explained 42.6% of the total variance in the abundance of associated taxa. This model combined local and landscape environmental filters and spatial variables (which were derived from eigenfunction analysis). However, the model with local filters and spatial variables also had a good chance of being selected as the best model. 5. Standardised partial regression coefficients of local and landscape filters, including spatial variables, derived from model averaging allowed an estimation of which variables were best correlated with the abundance of associated taxa. In general, the abundance of the associated genera tended to be lower in streams characterised by a high percentage of forest cover (landscape scale), lower proportion of muddy substrata and high values of pH and conductivity (local scale). 6. Overall, our main result adds to the increasing number of studies that have indicated the importance of local and landscape variables, as well as the spatial relationships among sampling sites, for explaining aquatic insect community patterns in streams. Furthermore, our findings open new possibilities for the elimination of redundant data in the assessment of anthropogenic impacts on tropical streams.

Chronic resistance training decreases MuRF-1 and Atrogin-1 gene expression but does not modify Akt, GSK-3 beta and p70S6K levels in rats

Long-term adaptation to resistance training is probably due to the cumulative molecular effects of each exercise session. Therefore, we studied in female Wistar rats the molecular effects of a chronic resistance training regimen (3 months) leading to skeletal muscle hypertrophy in the plantaris muscle. Our results demonstrated that muscle proteolytic genes MuRF-1 and Atrogin-1 were significantly decreased in the exercised group measured 24 h after the last resistance exercise session (41.64 and 61.19%, respectively; P < 0.05). Nonetheless, when measured at the same time point, 4EBP-1, GSK-3 beta and eIF2B epsilon mRNA levels and Akt, GSK-3 beta and p70S6K protein levels (regulators of translation initiation) were not modified. Such data suggests that if gene transcription constitutes a control point in the protein synthesis pathway this regulation probably occurs in early adaptation periods or during extreme situations leading to skeletal muscle remodeling. However, proteolytic gene expression is modified even after a prolonged resistance training regimen leading to moderate skeletal muscle hypertrophy.

Chronic low frequency/low volume resistance training reduces pro-inflammatory cytokine protein levels and TLR4 mRNA in rat skeletal muscle

Skeletal muscle is the source of pro- and anti-inflammatory cytokines, and recently, it has been recognized as an important source of interleukin 6 (IL-6), a cytokine that exerts inhibitory effects on several pro-inflammatory cytokines. Although dynamic chronic resistance training has been shown to produce the known ""repeated bout effect"", which abolishes the acute muscle damage, performing of high-intensity resistance training has been regarded highly advisable, at least from the hypertrophy perspective. On the other hand, a more therapeutic, ""non-damaging"" resistance training program, mainly composed of concentric forces, low frequency/low volume of training, and the same exercise, could theoretically benefit the muscle when the main issue is to avoid muscle inflammation (as in the treatment of several ""low-grade"" inflammatory diseases) because the acute effect of each resistance exercise session could be diminished/avoided, at the same time that the muscle is still being overloaded in a concentric manner. However, the benefits of such ""less demanding"" resistance training schedule on the muscle inflammatory profile have never been investigated. Therefore, we assessed the protein expression of IL-6, TNF-alpha, IL-10, IL-10/TNF-alpha ratio, and HSP70 levels and mRNA expression of SCF(beta-TrCP), IL-15, and TLR-4 in the skeletal muscle of rats submitted to resistance training. Briefly, animals were randomly assigned to either a control group (S, n = 8) or a resistance-trained group (T, n = 7). Trained rats were exercised over a duration of 12 weeks (two times per day, two times per week). Detection of IL-6, TNF-alpha, IL-10, and HSP70 protein expression was carried out by western blotting and SCF(beta-TrCP) (SKP Cullin F-Box Protein Ligases), a class of enzymes involved in the ubiquitination of protein substrates to proteasomal degradation, IL-15, and TLR-4 by RT-PCR. Our results show a decreased expression of TNF-alpha and TLR4 mRNA (40 and 60%, respectively; p < 0.05) in the plantar muscle from trained, when compared with control rats. In conclusion, exercise training induced decreased TNF-alpha and TLR-4 expressions, resulting in a modified IL-10/TNF-alpha ratio in the skeletal muscle. These data show that, in healthy rats, 12-week resistance training, predominantly composed of concentric stimuli and low frequency/low volume schedule, down regulates skeletal muscle production of cytokines involved in the onset, maintenance, and regulation of inXammation.

Matrix metalloproteinases, TIMPs and growth factors regulating ameloblastoma behaviour

Aims: Ameloblastoma is an odontogenic neoplasm with local invasiveness and recurrence. We have previously suggested that growth factors and matrix metalloproteinases (MMPs) influence ameloblastoma invasiveness(1). The aim was to study expression of MMPs, tissue inhibitor of metalloproteinases (TIMPs) and growth factors in ameloblastoma. Methods and results: Thirteen cases of solid/multicystic ameloblastoma were examined. As a control, calcifying cystic odontogenic tumour (CCOT), a non-invasive odontogenic neoplasm with ameloblastomatous epithelium was also studied. Immunohistochemistry detected MMPs, TIMPs and growth factors in ameloblastoma and CCOT. The labelling index (LI) of MMP-9 and TIMP-2 was significantly higher in ameloblastoma compared with CCOT. The LI of epidermal growth factor (EGF), transforming growth factor (TGF)-alpha and epidermal growth factor receptor (EGFR) was also increased in ameloblastoma. This neoplasm showed greater expression of MMPs, TIMPs and growth factors compared with CCOT. We then analysed these molecules in ameloblastoma cells and stroma. Ameloblastoma cells exhibited increased LI of MMP-1, -2 and EGFR. We found a positive correlation between EGF and TIMP-1, and between TGF-alpha and TIMP-2. It is known that signals generated by growth factors are transduced by the ERK pathway. Ameloblastoma stroma exhibited the phosphorylated (activated) form of ERK. Conclusions: These results suggest an interplay involving growth factors MMPs and TIMPs that may contribute to ameloblastoma behaviour. Signals generated by this molecular network would be transduced by ERK 1/2 pathway.