SMASHing the LMC: A Tidally-induced Warp in the Outer LMC and a Large-scale Reddening Map

We present a study of the three-dimensional (3D) structure of the Large Magellanic Cloud (LMC) using ~2.2 million red clump (RC) stars selected from the Survey of the MAgellanic Stellar History. To correct for line-of-sight dust extinction, the intrinsic RC color and magnitude and their radial dependence are carefully measured by using internal nearly dust-free regions. These are then used to construct an accurate 2D reddening map (165 square degrees with ~10 arcmin resolution) of the LMC disk and the 3D spatial distribution of RC stars. An inclined disk model is fit to the 2D distance map yielding a best-fit inclination angle i = 25.86(+0.73,-1.39) degrees with random errors of +\-0.19 degrees and line-of-nodes position angle theta = 149.23(+6.43,-8.35) degrees with random errors of +/-0.49 degrees. These angles vary with galactic radius, indicating that the LMC disk is warped and twisted likely due to the repeated tidal interactions with the Small Magellanic Cloud (SMC). For the first time, our data reveal a significant warp in the southwestern part of the outer disk starting at rho ~ 7 degrees that departs from the defined LMC plane up to ~4 kpc toward the SMC, suggesting that it originated from a strong interaction with the SMC. In addition, the inner disk encompassing the off-centered bar appears to be tilted up to 5-15 degrees relative to the rest of the LMC disk. These findings on the outer warp and the tilted bar are consistent with the predictions from the Besla et al. simulation of a recent direct collision with the SMC.Comment: 25 pages, 15 figures, published in Ap

Lack of Effect of Induction of Hypothermia after Acute Brain Injury

Background Induction of hypothermia in patients with brain injury was shown to improve outcomes in small clinical studies, but the results were not definitive. To study this issue, we conducted a multicenter trial comparing the effects of hypothermia with those of normothermia in patients with acute brain injury. Methods The study subjects were 392 patients 16 to 65 years of age with coma after sustaining closed head injuries who were randomly assigned to be treated with hypothermia (body temperature, 33°C), which was initiated within 6 hours after injury and maintained for 48 hours by means of surface cooling, or normothermia. All patients otherwise received standard treatment. The primary outcome measure was functional status six months after the injury. Results The mean age of the patients and the type and severity of injury in the two treatment groups were similar. The mean (±SD) time from injury to randomization was 4.3±1.1 hours in the hypothermia group and 4.1±1.2 hours in the normothermia group, and the mean time from injury to the achievement of the target temperature of 33°C in the hypothermia group was 8.4±3.0 hours. The outcome was poor (defined as severe disability, a vegetative state, or death) in 57 percent of the patients in both groups. Mortality was 28 percent in the hypothermia group and 27 percent in the normothermia group (P=0.79). The patients in the hypothermia group had more hospital days with complications than the patients in the normothermia group. Fewer patients in the hypothermia group had high intracranial pressure than in the normothermia group. Conclusions Treatment with hypothermia, with the body temperature reaching 33°C within eight hours after injury, is not effective in improving outcomes in patients with severe brain injury. (N Engl J Med 2001; 344:556-63.

Selective Inhibitors of the JMJD2 Histone Demethylases: Combined Nondenaturing Mass Spectrometric Screening and Crystallographic Approaches†

Ferrous ion and 2-oxoglutarate (2OG) oxygenases catalyze the demethylation of N(epsilon)-methylated lysine residues in histones. Here we report studies on the inhibition of the JMJD2 subfamily of histone demethylases, employing binding analyses by nondenaturing mass spectrometry (MS), dynamic combinatorial chemistry coupled to MS, turnover assays, and crystallography. The results of initial binding and inhibition assays directed the production and analysis of a set of N-oxalyl-d-tyrosine derivatives to explore the extent of a subpocket at the JMJD2 active site. Some of the inhibitors were shown to be selective for JMJD2 over the hypoxia-inducible factor prolyl hydroxylase PHD2. A crystal structure of JMJD2A in complex with one of the potent inhibitors was obtained; modeling other inhibitors based on this structure predicts interactions that enable improved inhibition for some compounds

Minimally Invasive Mitral Valve Surgery III: Training and Robotic-Assisted Approaches.

Minimally invasive mitral valve operations are increasingly common in the United States, but robotic-assisted approaches have not been widely adopted for a variety of reasons. This expert opinion reviews the state of the art and defines best practices, training, and techniques for developing a successful robotics program

Minimally Invasive Mitral Valve Surgery I: Patient Selection, Evaluation, and Planning.

Widespread adoption of minimally invasive mitral valve repair and replacement may be fostered by practice consensus and standardization. This expert opinion, first of a 3-part series, outlines current best practices in patient evaluation and selection for minimally invasive mitral valve procedures, and discusses preoperative planning for cannulation and myocardial protection

Minimally Invasive Mitral Valve Surgery II: Surgical Technique and Postoperative Management.

Techniques for minimally invasive mitral valve repair and replacement continue to evolve. This expert opinion, the second of a 3-part series, outlines current best practices for nonrobotic, minimally invasive mitral valve procedures, and for postoperative care after minimally invasive mitral valve surgery

Belonging, social connection and non-clinical care: Experiences of HIV peer support among recently diagnosed people living with HIV in Australia

Effective HIV treatments have transformed the medical needs of people living with HIV (PLHIV) to a chronic condition. However, stigma, poorer mental health outcomes and social isolation remain significant challenges for many PLHIV. HIV peer support programs have assisted PLHIV in navigating the clinical, emotional and social aspects of living with HIV. We draw on semi-structured interviews with 26 recently diagnosed PLHIV in Australia to explore experiences of HIV peer support services. Our thematic analysis identified three overarching themes. First, participants commonly reported that peer support programs offered a sense of belonging and connection to a broader HIV community. This established a network, sometimes separate to their existing social networks, of other PLHIV with whom to share experiences of HIV. Second, peer-based programs provided an opportunity for participants to hear firsthand, non-clinical perspectives on living with HIV. While participants valued the clinical care they received, the perspectives of peers gave participants insights into how others had managed aspects of living with HIV such as disclosure, sex and relationships. Finally, participants highlighted important considerations around ensuring referrals were made to socially and culturally appropriate support programs. Peer support programs fill an important gap in HIV care, working alongside and extending the work of the clinical management of HIV. Incorporating formal referrals to peer support services as part of the HIV diagnosis process could assist recently diagnosed PLHIV in adjusting to a positive diagnosis

Clinical Trials in Head Injury

Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate signficant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63185/1/089771502753754037.pd

Serum IL-6: a candidate biomarker for intracranial pressure elevation following isolated traumatic brain injury

<p>Abstract</p> <p>Background</p> <p>Increased intracranial pressure (ICP) is a serious, life-threatening, secondary event following traumatic brain injury (TBI). In many cases, ICP rises in a delayed fashion, reaching a maximal level 48-96 hours after the initial insult. While pressure catheters can be implanted to monitor ICP, there is no clinically proven method for determining a patient's risk for developing this pathology.</p> <p>Methods</p> <p>In the present study, we employed antibody array and Luminex-based screening methods to interrogate the levels of inflammatory cytokines in the serum of healthy volunteers and in severe TBI patients (GCS≤8) with or without incidence of elevated intracranial pressure (ICP). De-identified samples and ELISAs were used to confirm the sensitivity and specificity of IL-6 as a prognostic marker of elevated ICP in both isolated TBI patients, and polytrauma patients with TBI.</p> <p>Results</p> <p>Consistent with previous reports, we observed sustained increases in IL-6 levels in TBI patients irrespective of their ICP status. However, the group of patients who subsequently experienced ICP ≥ 25 mm Hg had significantly higher IL-6 levels within the first 17 hours of injury as compared to the patients whose ICP remained ≤20 mm Hg. When blinded samples (n = 22) were assessed, a serum IL-6 cut-off of <5 pg/ml correctly identified 100% of all the healthy volunteers, a cut-off of >128 pg/ml correctly identified 85% of isolated TBI patients who subsequently developed elevated ICP, and values between these cut-off values correctly identified 75% of all patients whose ICP remained ≤20 mm Hg throughout the study period. In contrast, the marker had no prognostic value in predicting elevated ICP in polytrauma patients with TBI. When the levels of serum IL-6 were assessed in patients with orthopedic injury (n = 7) in the absence of TBI, a significant increase was found in these patients compared to healthy volunteers, albeit lower than that observed in TBI patients.</p> <p>Conclusions</p> <p>Our results suggest that serum IL-6 can be used for the differential diagnosis of elevated ICP in isolated TBI.</p