"Give me some space" : exploring youth to parent aggression and violence

A small scale qualitative project, undertaken by an interdisciplinary domestic violence research group involving academic researchers and research assistants, with colleagues from Independent Domestic Abuse Services (IDAS), investigated youth aggression and violence against parents. Following the literature review, data was generated through several research conversations with young people (n = 2), through semi-structured interviews with mothers (n = 3) and practitioners (n = 5), and through a practitioner focus group (n = 8). Thematic analysis and triangulation of the data from parents, practitioners and young people, elicited interconnected and complex overarching themes. Young people could be both victim and perpetrator. The witnessing or experiencing of domestic aggression and violence raised the concept of ‘bystander children’. The impact of young people experiencing familial violence was underestimated by parents. For practitioners, the effects of working with domestic violence was shown to be significant - both positively and negatively

Drug Discovery Using Chemical Systems Biology: Identification of the Protein-Ligand Binding Network To Explain the Side Effects of CETP Inhibitors

Systematic identification of protein-drug interaction networks is crucial to correlate complex modes of drug action to clinical indications. We introduce a novel computational strategy to identify protein-ligand binding profiles on a genome-wide scale and apply it to elucidating the molecular mechanisms associated with the adverse drug effects of Cholesteryl Ester Transfer Protein (CETP) inhibitors. CETP inhibitors are a new class of preventive therapies for the treatment of cardiovascular disease. However, clinical studies indicated that one CETP inhibitor, Torcetrapib, has deadly off-target effects as a result of hypertension, and hence it has been withdrawn from phase III clinical trials. We have identified a panel of off-targets for Torcetrapib and other CETP inhibitors from the human structural genome and map those targets to biological pathways via the literature. The predicted protein-ligand network is consistent with experimental results from multiple sources and reveals that the side-effect of CETP inhibitors is modulated through the combinatorial control of multiple interconnected pathways. Given that combinatorial control is a common phenomenon observed in many biological processes, our findings suggest that adverse drug effects might be minimized by fine-tuning multiple off-target interactions using single or multiple therapies. This work extends the scope of chemogenomics approaches and exemplifies the role that systems biology has in the future of drug discovery

Multidisciplinary Consideration of Potential Pathophysiologic Mechanisms of Paradoxical Erythema with Topical Brimonidine Therapy

Rosacea is a chronic inflammatory disease with transient and non-transient redness as key characteristics. Brimonidine is a selective α2-adrenergic receptor (AR) agonist approved for persistent facial erythema of rosacea based on significant efficacy and good safety data. The majority of patients treated with brimonidine report a benefit; however, there have been sporadic reports of worsening erythema after the initial response. A group of dermatologists, receptor physiology, and neuroimmunology scientists met to explore potential mechanisms contributing to side effects as well as differences in efficacy. We propose the following could contribute to erythema after application: (1) local inflammation and perivascular inflammatory cells with abnormally functioning ARs may lead to vasodilatation; (2) abnormal saturation and cells expressing different AR subtypes with varying ligand affinity; (3) barrier dysfunction and increased skin concentrations of brimonidine with increased actions at endothelial and presynaptic receptors, resulting in increased vasodilation; and (4) genetic predisposition and receptor polymorphism(s) leading to different smooth muscle responses. Approximately 80% of patients treated with brimonidine experience a significant improvement without erythema worsening as an adverse event. Attention to optimizing skin barrier function, setting patient expectations, and strategies to minimize potential problems may possibly reduce further the number of patients who experience side effects. Funding: Galderma International S.A.S., Paris, France

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article

Correlating preoperative imaging with intraoperative fluoroscopy in iliosacral screw placement.

BackgroundPercutaneous iliosacral screw placement can successfully stabilize unstable posterior pelvic ring injuries. Intraoperative fluoroscopic imaging is a vital component needed in safely placing iliosacral screws. Obtaining and appropriately interpreting fluoroscopic views can be challenging in certain clinical scenarios. We report on a series of patients to demonstrate how preoperative computed tomography (CT) imaging can be used to anticipate the appropriate intraoperative inlet and outlet fluoroscopic views.Materials and methods24 patients were retrospectively identified with unstable pelvic ring injuries requiring operative fixation using percutaneous iliosacral screws. Utilizing the sagittal reconstructions of the preoperative CT scans, anticipated inlet and outlet angle measurements were calculated. The operative reports were reviewed to determine the angles used intraoperatively. Postoperative CT scans were reviewed for repeat measurements and to determine the location and safety of each screw.ResultsPreoperative CT scans showed an average inlet of 20.5° (7°-37°) and an average outlet of 42.8° (30°-59°). Intraoperative views showed an average inlet of 24.9° (12°-38°) and an average outlet of 42.4° (29°-52°). Postoperative CT scans showed an average inlet of 19.4° (8°-31°) and an average outlet of 43.2° (31°-56°). The average difference from preoperative to intraoperative was 4.4° (-21° to 5°) for the inlet and 0.45° (-9° to 7°) for the outlet. The average difference between the preoperative and postoperative CT was 2.04° (0°-6°) for the inlet and 2.54° (0°-7°) for the outlet.ConclusionThere is significant anatomic variation of the posterior pelvic ring. The preoperative CT sagittal reconstruction images allow for appropriate preoperative planning for anticipated intraoperative fluoroscopic inlet and outlet views within 5°. Having knowledge of the desired intraoperative views preoperatively prepares the surgeon, aids in efficiently obtaining correct intraoperative views, and ultimately assists in safe iliosacral screw placement

Catalytic, Sulfur-Free Chain Transfer Agents that Alter the Mechanical Properties of Crosslinked Photopolymers

Thermosetting materials generated by photopolymerization are inherently highly crosslinked and suffer from significant shrinkage stress, are often brittle, and have a limited range of mechanical properties. Various classes of chain transfer agents (CTAs) have been investigated and developed to reduce the crosslinking density of photopolymers by terminating kinetic chains and initiating new chains in situ. Although CTAs are successful in manipulating the mechanical properties of photopolymers, they are traditionally consumed during the polymerization and are therefore required in high loadings (up to 20 wt% of total formulation). Moreover, traditional CTAs frequently contain sulfur which is malodorous and can create unstable formulations. Presented here is a catalytic, sulfur-free CTA that can be added in ppm quantities to exist-ing commercial monomer feedstocks to create photopolymers similar to those prepared using traditional CTAs, but at 10,000x lower loadings. These catalysts, which are based on macrocyclic cobaloximes, were found to tunably reduce the molecular weight of the kinetic chain proportional to catalyst loading. It was shown, using only commercial monomers, that this catalyst could reduce the glass transition temperature (Tg), rubbery modulus (E’rubbery), and stiffness