Dynamic Failure Properties of the Porcine Medial Collateral Ligament-Bone Complex for Predicting Injury in Automotive Collisions

The goal of this study was to model the dynamic failure properties of ligaments and their attachment sites to facilitate the development of more realistic dynamic finite element models of the human lower extremities for use in automotive collision simulations. Porcine medial collateral ligaments were chosen as a test model due to their similarities in size and geometry with human ligaments. Each porcine medial collateral ligament-bone complex (n = 12) was held in a custom test fixture placed in a drop tower to apply an axial impulsive impact load, applying strain rates ranging from 0.005 s-1 to 145 s-1. The data from the impact tests were analyzed using nonlinear regression to construct model equations for predicting the failure load of ligament-bone complexes subjected to specific strain rates as calculated from finite element knee, thigh, and hip impact simulations. The majority of the ligaments tested failed by tibial avulsion (75%) while the remaining ligaments failed via mid-substance tearing. The failure load ranged from 384 N to 1184 N and was found to increase with the applied strain rate and the product of ligament length and cross-sectional area. The findings of this study indicate the force required to rupture the porcine MCL increases with the applied bone-to-bone strain rate in the range expected from high speed frontal automotive collisions

Metabolic Syndrome features and risk of neural tube defects

Research articl

On Composite Two Higgs Doublet Models

We investigate composite two Higgs doublet models realized as pseudo Goldstone modes, generated through the spontaneous breaking of a global symmetry due to strong dynamic at the TeV scale. A detailed comparative survey of two possible symmetry breaking patterns, SU(5) -> SU(4) x U(1) and SU(5) x SU(4), is made. We point out choices for the Standard Model fermion representations that can alleviate some phenomenological constraints, with emphasis towards a simultaneous solution of anomalous Zb\bar{b} coupling and Higgs mediated Flavor Changing Neutral Currents. We also write down the kinetic lagrangian for several models leading to Two Higgs Doublets and identify the anomalous contributions to the T parameter. Moreover, we describe a model based on the breaking $SO(9)/SO(8)$ in which there is no tree-level breaking of custodial symmetry, discussing also the possible embeddings for the fermion fields.Comment: 17 pages. Mistake corrected, added one section on a T- and flavor safe model based on SO(9)/SO(8). Matches published versio

A case study evaluating the use of clozapine in depression with psychotic features

The purpose of this case study was to use an evidence based medicine approach to work through an unusual way of treating a common problem. We looked at an example of an in-patient with severe refractory psychotic depression who had been resistant to treatment with a combination of antidepressant, antipsychotics, mood stabiliser, and concomitant ECT therapy. We then undertook a literature search for the use of clozapine in a patient with severe refractory depression. Although the resulting evidence was low level and thin, we felt on balance that a trial of clozapine was justified. We used a BPRS inventory to monitor her mood prior to commencing clozapine. Her mood and functional abilities were monitored as her clozapine was titrated upwards. Our patient showed a significant improvement in mood and functional abilities and a reduction in her BPRS score during this period. Her symptoms improved to the point where she was successfully discharged home on a combination of clozapine and an antidepressant. The improvement was sustained for a further two years. We thought this was an important case to highlight the limited evidence in using this successful form of treatment for a common clinical problem and that further research in this area was needed

Symptoms and quality of life in late stage Parkinson syndromes: a longitudinal community study of predictive factors

BACKGROUND Palliative care is increasingly offered earlier in the cancer trajectory but rarely in Idiopathic Parkinson's Disease(IPD), Progressive Supranuclear Palsy(PSP) or Multiple System Atrophy(MSA). There is little longitudinal data of people with late stage disease to understand levels of need. We aimed to determine how symptoms and quality of life of these patients change over time; and what demographic and clinical factors predicted changes. METHODS We recruited 82 patients into a longitudinal study, consenting patients with a diagnosis of IPD, MSA or PSP, stages 3-5 Hoehn and Yahr(H&Y). At baseline and then on up to 3 occasions over one year, we collected self-reported demographic, clinical, symptom, palliative and quality of life data, using Parkinson's specific and generic validated scales, including the Palliative care Outcome Scale (POS). We tested for predictors using multivariable analysis, adjusting for confounders. FINDINGS Over two thirds of patients had severe disability, over one third being wheelchair-bound/bedridden. Symptoms were highly prevalent in all conditions - mean (SD) of 10.6(4.0) symptoms. More than 50% of the MSA and PSP patients died over the year. Over the year, half of the patients showed either an upward (worsening, 24/60) or fluctuant (8/60) trajectory for POS and symptoms. The strongest predictors of higher levels of symptoms at the end of follow-up were initial scores on POS (AOR 1.30; 95%CI:1.05-1.60) and being male (AOR 5.18; 95% CI 1.17 to 22.92), both were more predictive than initial H&Y scores. INTERPRETATION The findings point to profound and complex mix of non-motor and motor symptoms in patients with late stage IPD, MSA and PSP. Symptoms are not resolved and half of the patients deteriorate. Palliative problems are predictive of future symptoms, suggesting that an early palliative assessment might help screen for those in need of earlier intervention

Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection.

Innate immune cells quickly infiltrate the site of pathogen entry and not only stave off infection but also initiate antigen presentation and promote adaptive immunity. The recruitment of innate leukocytes has been well studied in the context of extracellular bacterial and fungal infection but less during viral infections. We have recently shown that the understudied cytokine Interleukin (IL)-17D can mediate neutrophil, natural killer (NK) cell and monocyte infiltration in sterile inflammation and cancer. Herein, we show that early immune cell accumulation at the peritoneal site of infection by mouse cytomegalovirus (MCMV) is mediated by IL-17D. Mice deficient in IL-17D or the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an inducer of IL-17D, featured an early decreased number of innate immune cells at the point of viral entry and were more susceptible to MCMV infection. Interestingly, we were able to artificially induce innate leukocyte infiltration by applying the Nrf2 activator tert-butylhydroquinone (tBHQ), which rendered mice less susceptible to MCMV infection. Our results implicate the Nrf2/IL-17D axis as a sensor of viral infection and suggest therapeutic benefit in boosting this pathway to promote innate antiviral responses

Accretion Disks Around Black Holes: Twenty Five Years Later

We study the progress of the theory of accretion disks around black holes in last twenty five years and explain why advective disks are the best bet in explaining varied stationary and non-stationary observations from black hole candidates. We show also that the recently proposed advection dominated flows are incorrect.Comment: 30 Latex pages including figures. Kluwer Style files included. Appearing in `Observational Evidence for Black Holes in the Universe', ed. Sandip K. Chakrabarti, Kluwer Academic Publishers (DORDRECHT: Holland

The Bipolar X-Ray Jet of the Classical T Tauri Star DG Tau

This is the author accepted manuscript. The final version is available from the Astronomical Society of the Pacific via the link in this record16th Cambridge Workshop on Cool Stars, Stellar Systems and the Sun, 28 August-3 September 2010, Seattle, USAWe report on new X-ray observations of the classical T Tauri star DG Tau. DG Tau drives a collimated bi-polar jet known to be a source of X-ray emission perhaps driven by internal shocks. The rather modest extinction permits study of the jet system to distances very close to the star itself. Our initial results presented here show that the spatially resolved X-ray jet has been moving and fading during the past six years. In contrast, a stationary, very soft source much closer (≈ 0.15 − 0.2 ′′) to the star but apparently also related to the jet has brightened during the same period. We report accurate temperatures and absorption column densities toward this source, which is probably associated with the jet base or the jet collimation region.Swiss National Science Foundatio

Revising the WHO verbal autopsy instrument to facilitate routine cause-of-death monitoring.

OBJECTIVE: Verbal autopsy (VA) is a systematic approach for determining causes of death (CoD) in populations without routine medical certification. It has mainly been used in research contexts and involved relatively lengthy interviews. Our objective here is to describe the process used to shorten, simplify, and standardise the VA process to make it feasible for application on a larger scale such as in routine civil registration and vital statistics (CRVS) systems. METHODS: A literature review of existing VA instruments was undertaken. The World Health Organization (WHO) then facilitated an international consultation process to review experiences with existing VA instruments, including those from WHO, the Demographic Evaluation of Populations and their Health in Developing Countries (INDEPTH) Network, InterVA, and the Population Health Metrics Research Consortium (PHMRC). In an expert meeting, consideration was given to formulating a workable VA CoD list [with mapping to the International Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) CoD] and to the viability and utility of existing VA interview questions, with a view to undertaking systematic simplification. FINDINGS: A revised VA CoD list was compiled enabling mapping of all ICD-10 CoD onto 62 VA cause categories, chosen on the grounds of public health significance as well as potential for ascertainment from VA. A set of 221 indicators for inclusion in the revised VA instrument was developed on the basis of accumulated experience, with appropriate skip patterns for various population sub-groups. The duration of a VA interview was reduced by about 40% with this new approach. CONCLUSIONS: The revised VA instrument resulting from this consultation process is presented here as a means of making it available for widespread use and evaluation. It is envisaged that this will be used in conjunction with automated models for assigning CoD from VA data, rather than involving physicians

Stop! In the name of transforming growth factor-β: keeping estrogen receptor-α-positive mammary epithelial cells from proliferating

Recent genetic and cell biological studies illustrate the importance of active transforming growth factor-β signaling in preventing the proliferation of estrogen receptor-positive cells in the normal mammary gland, and suggest how the loss of this inhibition may be important in early breast cancer progression