Cis and Trans Effects of Human Genomic Variants on Gene Expression

This work was funded by the Louis-Jeantet Foundation (http://www.jeantet.ch/), the European Research Council (Grant ID: 260927 http://erc.europa.eu/), the Swiss National Foundation (Grant ID: 130342 http://www.snf.ch), NCCR Frontiers In Genetics (http://www.frontiers-in-genetics.org), the UK Medical Research Council (http://www.mrc.ac.uk) and the Wellcome Trust (Grant ID: 092731).

How managers can build trust in strategic alliances: a meta-analysis on the central trust-building mechanisms

Trust is an important driver of superior alliance performance. Alliance managers are influential in this regard because trust requires active involvement, commitment and the dedicated support of the key actors involved in the strategic alliance. Despite the importance of trust for explaining alliance performance, little effort has been made to systematically investigate the mechanisms that managers can use to purposefully create trust in strategic alliances. We use Parkhe’s (1998b) theoretical framework to derive nine hypotheses that distinguish between process-based, characteristic-based and institutional-based trust-building mechanisms. Our meta-analysis of 64 empirical studies shows that trust is strongly related to alliance performance. Process-based mechanisms are more important for building trust than characteristic- and institutional-based mechanisms. The effects of prior ties and asset specificity are not as strong as expected and the impact of safeguards on trust is not well understood. Overall, theoretical trust research has outpaced empirical research by far and promising opportunities for future empirical research exist

Biomechanical evaluation of fixation of comminuted olecranon fractures: one-third tubular versus locking compression plating

New concepts in plate fixation have led to an evolution in plate design for olecranon fractures. The purpose of this study was to compare the stiffness and strength of locking compression plate (LCP) fixation to one-third tubular plate fixation in a cadaveric comminuted olecranon fracture model with a standardised osteotomy. Five matched pairs of cadaveric elbows were randomly assigned for fixation by either a contoured LCP combined with an intramedullary screw and unicortical locking screws or a one-third tubular plate combined with bicortical screws. Construct stiffness was measured by subjecting the specimens to cyclic loading while measuring gapping at the osteotomy site. Construct strength was measured by subjecting specimens to ramp load until failure. There was no significant difference in fixation stiffness and strength between the two fixation methods. All failures consisted of failure of the bone and not of the hardware. Contoured LCP and intramedullary screw fixation can be used as an alternative treatment method for comminuted olecranon fractures as its stiffness and strength were not significantly different from a conventional plating techniqu

The measurement and therapeutic implications of circulating tumour cells in breast cancer

Circulating tumours cells (CTCs) represent an important biologic link in the spread of breast cancer from primary to metastatic disease. CTCs are strong predictors of prognosis in patients with metastatic breast cancer. Research to date has focused on development of methods with adequate sensitivity and specificity to reproducibly identify these rare events. Future research will focus on the biologic phenotypes of these cells with goals to understand mechanisms of metastasis, to identify novel therapeutic targets, and to monitor response to therapy

The prevention of anaphylactoid reactions to iodinated radiological contrast media: a systematic review

BACKGROUND: Anaphylactoid reactions to iodinated contrast media are relatively common and potentially life threatening. Opinion is divided as to the utility of medications for preventing these reactions. We performed a systematic review to assess regimes for the prevention of anaphylactoid reactions to iodinated contrast media. METHODS: Searches for studies were conducted in the Medline, EMBASE, CINAHL and CENTRAL databases. Bibliographies of included studies and review articles were examined and experts were contacted. Randomised clinical trials that examined agents given prior to iodinated contrast material for the prevention of anaphylactoid reactions were included in the review. The validity of the included studies was examined using a component approach. RESULTS: Six studies met the inclusion criteria, but only one of these fulfilled all of the validity criteria. There were four studies that examined the use of H1 antihistamines, each was used to prevent anaphylactoid reactions to ionic contrast. The random effects pooled relative risk demonstrated a significant reduction in the overall rate of anaphylactoid reactions (RR = 0.4, 95% CI 0.18-0.9, p = 0.027). There were insufficient studies to produce a pooled statistic for the use of corticosteroids, however regimes of steroids (methylprednisolone 32 mg) given at least six hours and again two hours prior to the administration of contrast suggested a reduction in the incidence of anaphylactoid reactions. CONCLUSION: In conclusion, there are few high quality randomised clinical trials that have addressed the question of the optimal methods to prevent allergic type reactions to iodinated radiological contrast media. Allowing for these limitations, the results suggest that H1 antihistamines given immediately prior to the administration of ionic contrast may be useful in preventing reactions to ionic contrast and are suggestive of a protective effect of corticosteroids when given in two doses at least six hours prior and again two hours prior to the administration of contrast, both ionic and non-ionic. These agents should be considered for use in patients who are at high risk of an anaphylactoid reaction to contrast media and for who prophylactic therapy is considered necessary. Further research is needed before definitive recommendations can be made

Recent translational research: circulating tumor cells in breast cancer patients

In breast cancer patients, hematogenous tumor cell dissemination can be detected, even at the single cell level, by applying immunocytochemical and molecular assays. Various methods for the detection of circulating tumor cells in the peripheral blood have been described. Results from recently reported studies suggest that circulating tumor cell levels may serve as a prognostic marker and for the early assessment of therapeutic response in patients with metastatic breast cancer. However, in early-stage breast cancer, the impact of circulating tumor cells is less well established than the presence of disseminated tumor cells in bone marrow; several clinical studies have demonstrated that cells of the latter type are an independent prognostic factor at primary diagnosis. In this article we briefly summarize recent studies examining the presence of circulating tumor cells in the blood and discuss further clinical applications

Is tension band wiring technique the "gold standard" for the treatment of olecranon fractures? A long term functional outcome study

<p>Abstract</p> <p>Background</p> <p>Tension band wiring (TBW) remains the most common operative technique for the internal fixation of olecranon fractures despite the potential occurrence of subjective complaints due to subcutaneous position of the hardware. Aim of this long term retrospective study was to evaluate the elbow function and the patient-rated outcome after TBW fixation of olecranon fractures.</p> <p>Methods</p> <p>We reviewed 62 patients (33 men and 29 women) with an average age of 48.6 years (range, 18–85 years) who underwent TBW osteosynthesis for isolated olecranon fractures. All patients were assessed both clinically with measurement of flexion-extension and pronation-supination arcs and radiologically with elbow X-Rays. Functional outcome was estimated using the Mayo Elbow Performance Score (MEPS), Visual Analogue Scale (VAS) subjective pain score and VAS patient satisfaction score. Follow up: 6–13 years (average 8.2 years).</p> <p>Results</p> <p>There was a higher prevalence of fractures among men until the 5th decade of life and among women in elderly (p = 0.032). Slip or simple fall onto the arm was the main mechanism of injury for 38 fractures (61.3%) while high energy trauma, such as fall from a height (> 2 m) or road accident, was reported in 24 fractures (38.7%). Hardware removal performed in 51 patients (82.3%) but 34 of them (66.6% of removals) were still complaining for mild pain during daily activities. The incidence of pin migration and loosening was not statistically decreased when penetration of the anterior ulnar cortex was accomplished (p = 0.304). Supination was more often affected than pronation (p = 0.027). According to MEPS, 53 patients (85.5%) had a good to excellent result, 6 (9.7%) fair and 3 (4.8%) poor result. The average satisfaction rating was 9.3 out of 10 (range, 6–10) with 31 patients (50%) to remain completely satisfied from the final result. Degenerative changes recorded in 30 elbows (48.4%). However, no correlation could be found between radiographic findings and MEPS (p = 0.073).</p> <p>Conclusion</p> <p>Tension band wiring fixation remains the "gold standard" for the treatment of displaced and minimally comminuted olecranon fractures. In long term, low levels of pain may be evident regardless of whether the metalware is removed and degenerative changes have been developed.</p