Compared to placebo, long-term antibiotics resolve otitis media with effusion (OME) and prevent acute otitis media with perforation (AOMwiP) in a high-risk population: A randomized controlled trial

© 2008 Leach et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background : For children at high risk of chronic suppurative otitis media (CSOM), strategies to prevent acute otitis media with perforation (AOMwiP) may reduce progression to CSOM. Methods : In a double blind study in northern Australia, 103 Aboriginal infants with first detection of OME were randomised to receive either amoxicillin (50 mg/kg/d BD) or placebo for 24 weeks, or until bilateral aerated middle ears were diagnosed at two successive monthly examinations (success). Standardised clinical assessments and international standards for microbiology were used. Results : Five of 52 infants in the amoxicillin group and none of 51 infants in the placebo group achieved success at the end of therapy (Risk Difference = 9.6% [95% confidence interval 1.6,17.6]). Amoxicillin significantly reduced the proportion of children with i) perforation at the end of therapy (27% to 12% RD = -16% [-31,-1]), ii) recurrent perforation during therapy (18% to 4% RD = -14% [-25,-2]), and iii) reduced the proportion of examinations with a diagnosis of perforation during therapy (20% to 8% adjusted risk ratio 0.36 [0.15,0.83] p = 0.017). During therapy, the proportion of examinations with penicillin non-susceptible (MIC > 0.1 microg/ml) pneumococci was not significantly different between the amoxicillin group (34%) and the placebo group (40%). Beta-lactamase positive non-capsular H. influenzae (NCHi) were uncommon during therapy but more frequent in the amoxicillin group (10%) than placebo (5%). Conclusion : Aboriginal infants receiving continuous amoxicillin had more normal ears, fewer perforations, and less pneumococcal carriage. There was no statistically significant increase in resistant pneumococci or NCHi in amoxicillin children compared to placebo children who received regular paediatric care and antibiotic treatment for symptomatic illnesses

Hsp90 orchestrates transcriptional regulation by Hsf1 and cell wall remodelling by MAPK signalling during thermal adaptation in a pathogenic yeast

Acknowledgments We thank Rebecca Shapiro for creating CaLC1819, CaLC1855 and CaLC1875, Gillian Milne for help with EM, Aaron Mitchell for generously providing the transposon insertion mutant library, Jesus Pla for generously providing the hog1 hst7 mutant, and Cathy Collins for technical assistance.Peer reviewedPublisher PD

Foot pressure distribution during walking in young and old adults

BACKGROUND: Measurement of foot pressure distribution (FPD) is clinically useful for evaluation of foot and gait pathologies. The effects of healthy aging on FPD during walking are not well known. This study evaluated FPD during normal walking in healthy young and elderly subjects. METHODS: We studied 9 young (30 ± 5.2 years), and 6 elderly subjects (68.7 ± 4.8 years). FPD was measured during normal walking speed using shoe insoles with 99 capacitive sensors. Measured parameters included gait phase characteristics, mean and maximum pressure and force, and relative load. Time-series measurements of each variable for all sensors were grouped into 9 anatomical masks. RESULTS: Elderly subjects had lower normalized maximum pressure for the medial and lateral calcaneal masks, and for all medial masks combined. In the medial calcaneus mask, the elderly group also had a lower absolute maximum and lower mean and normalized mean pressures and forces, compared to young subjects. Elderly subjects had lower maximum force and normalized maximum force and lower mean force and normalized mean forces in the medial masks as well. CONCLUSION: FPD differences between the young and elderly groups were confined to the calcaneus and hallux regions and to the medial side of the foot. In elderly subjects, weight bearing on the lateral side of the foot during heel touch and toe-off phases may affect stability during walking

Academic Performance and Behavioral Patterns

Identifying the factors that influence academic performance is an essential part of educational research. Previous studies have documented the importance of personality traits, class attendance, and social network structure. Because most of these analyses were based on a single behavioral aspect and/or small sample sizes, there is currently no quantification of the interplay of these factors. Here, we study the academic performance among a cohort of 538 undergraduate students forming a single, densely connected social network. Our work is based on data collected using smartphones, which the students used as their primary phones for two years. The availability of multi-channel data from a single population allows us to directly compare the explanatory power of individual and social characteristics. We find that the most informative indicators of performance are based on social ties and that network indicators result in better model performance than individual characteristics (including both personality and class attendance). We confirm earlier findings that class attendance is the most important predictor among individual characteristics. Finally, our results suggest the presence of strong homophily and/or peer effects among university students

Inhibition of tyrosine kinase receptors by SU6668 promotes abnormal stromal development at the periphery of carcinomas

Dynamic contrast-enhanced (albumin-Gd-DTPA) magnetic resonance imaging, performed during 2 weeks of daily administration of an inhibitor of tyrosine kinase receptors (SU6668) in an HT-29 colon carcinoma model, revealed the onset of a hyper-enhancing rim, not observed in untreated tumours. To account for tissue heterogeneity in the quantitative analysis, we segmented tumours into three subunits automatically identified by cluster analysis of the enhancement curves using a k-means algorithm. Transendothelial permeability (Kps) and fractional plasma volume (fPV) were calculated in each subunit. An avascular and necrotic region, an intermediate zone and a well-vascularised periphery were reliably identified. During untreated tumour growth, the identified sub-regions did not substantially change their enhancement pattern. Treatment with SU6668 induced major changes at tumour periphery where a significant increase of Kps and fPV was observed with respect to control tumours. Histology revealed a sub-capsular layer composed of hyper-dense viable tumour cells in the periphery of untreated tumours. The rim of viable neoplastic cells was reduced in treated tumours, and replaced by loose connective tissue characterised by numerous vessels, which explains the observed hyper-enhancement. The present data show a peripheral abnormal development of cancer-associated stroma, indicative of an adaptive response to anti-angiogenic treatment

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

Differentiation-Dependent Secretion of Proangiogenic Factors by Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are a promising cell population for cell-based bone repair due to their proliferative potential, ability to differentiate into bone-forming osteoblasts, and their secretion of potent trophic factors that stimulate angiogenesis and neovascularization. To promote bone healing, autogenous or allogeneic MSCs are transplanted into bone defects after differentiation to varying degrees down the osteogenic lineage. However, the contribution of the stage of osteogenic differentiation upon angiogenic factor secretion is unclear. We hypothesized that the proangiogenic potential of MSCs was dependent upon their stage of osteogenic differentiation. After 7 days of culture, we observed the greatest osteogenic differentiation of MSCs when cells were cultured with dexamethasone (OM+). Conversely, VEGF protein secretion and upregulation of angiogenic genes were greatest in MSCs cultured in growth media (GM). Using conditioned media from MSCs in each culture condition, GM-conditioned media maximized proliferation and enhanced chemotactic migration and tubule formation of endothelial colony forming cells (ECFCs). The addition of a neutralizing VEGF165/121 antibody to conditioned media attenuated ECFC proliferation and chemotactic migration. ECFCs seeded on microcarrier beads and co-cultured with MSCs previously cultured in GM in a fibrin gel exhibited superior sprouting compared to MSCs previously cultured in OM+. These results confirm that MSCs induced farther down the osteogenic lineage possess reduced proangiogenic potential, thereby providing important findings for consideration when using MSCs for bone repair

Spatially Resolved Operando Synchrotron-Based X-Ray Diffraction Measurements of Ni-Rich Cathodes for Li-Ion Batteries

Understanding the performance of commercially relevant cathode materials for lithium-ion (Li-ion) batteries is vital to realize the potential of high-capacity materials for automotive applications. Of particular interest is the spatial variation of crystallographic behavior across (what can be) highly inhomogeneous electrodes. In this work, a high-resolution X-ray diffraction technique was used to obtain operando transmission measurements of Li-ion pouch cells to measure the spatial variances in the cell during electrochemical cycling. Through spatially resolved investigations of the crystallographic structures, the distribution of states of charge has been elucidated. A larger portion of the charging is accounted for by the central parts, with the edges and corners delithiating to a lesser extent for a given average electrode voltage. The cells were cycled to different upper cutoff voltages (4.2 and 4.3 V vs. graphite) and C-rates (0.5, 1, and 3C) to study the effect on the structure of the NMC811 cathode. By combining this rapid data collection method with a detailed Rietveld refinement of degraded NMC811, the spatial dependence of the degradation caused by long-term cycling (900 cycles) has also been shown. The variance shown in the pristine measurements is exaggerated in the aged cells with the edges and corners offering an even lower percentage of the charge. Measurements collected at the very edge of the cell have also highlighted the importance of electrode alignment, with a misalignment of less than 0.5 mm leading to significantly reduced electrochemical activity in that area.</jats:p

Breast cancer screening in women at increased risk according to different family histories: an update of the Modena Study Group experience

BACKGROUND: Breast cancer (BC) detection in women with a genetic susceptibility or strong family history is considered mandatory compared with BC screening in the general population. However, screening modalities depend on the level of risk. Here we present an update of our screening programs based on risk classification. METHODS: We defined different risk categories and surveillance strategies to identify early BC in 1325 healthy women recruited by the Modena Study Group for familial breast and ovarian cancer. Four BC risk categories included BRCA1/2 carriers, increased, intermediate, and slightly increased risk. Women who developed BC from January 1, 1994, through December 31, 2005 (N = 44) were compared with the number of expected cases matched for age and period. BRCA1/2 carriers were identified by mutational analysis. Other risk groups were defined by different levels of family history for breast or ovarian cancer (OC). The standardized incidence ratio (SIR) was used to evaluate the observed and expected ratio among groups. All statistical tests were two-sided. RESULTS: After a median follow-up of 55 months, there was a statistically significant difference between observed and expected incidence [SIR = 4.9; 95% confidence interval (CI) = 1.6 to 7.6; p < 0.001]. The incidence observed among BRCA carriers (SIR = 20.3; 95% CI = 3.1 to 83.9; P < 0.001), women at increased (SIR = 4.5; 95% CI = 1.5 to 8.3; P < 0.001) or intermediate risk (SIR = 7.0, 95% CI = 2.0 to 17.1; P = 0.0018) was higher than expected, while the difference between observed and expected among women at slightly increased risk was not statistically significant (SIR = 2.4, 95% CI = 0.9 to 8.3; P = .74). CONCLUSION: The rate of cancers detected in women at high risk according to BRCA status or strong family history, as defined according to our operational criteria, was significantly higher than expected in an age-matched general population. However, we failed to identify a greater incidence of BC in the slightly increased risk group. These results support the effectiveness of the proposed program to identify and monitor individuals at high risk, whereas prospective trials are needed for women belonging to families with sporadic BC or OC