Simulation aided development of pre-chamber ignition system for a lean-burn gasoline direct injection motor-sport engine

Due to recent regulation changes to restricted fuel usage in various motor-sport events, motor-sport engine manufacturers have started to focus on improving the thermal efficiency and often claim thermal efficiency figures well above equivalent road car engines. With limited fuel allowance, motorsport engines are operated with a lean air-fuel mixture to benefit from higher cycle efficiency, requiring an ignition system that is suitable for the lean mixture. Pre-chamber ignition is identified as a promising method to improve lean limit and has the potential to reduce end gas auto-ignition. This paper analyses the full-load performance of a motor-sport lean-burn GDI engine and a passive pre-chamber is developed with the aid of a CFD tool. The finalized pre-chamber design benefited in a significant reduction in burn duration, reduced cyclic variation, knock limit extension and higher performance

Anarchic hand with abnormal agency following right inferior parietal lobe damage: a case report

Anarchic hand syndrome (AHS) is characterized by goal-directed movements performed without volitional control (agency). Different AHS subtypes have been identified; however, few studies have examined the posterior subtype. We report a case of AHS following right-hemisphere parietal damage, with left-sided somatosensory and proprioceptive impairment. Agency was examined for nonanarchic (volitional) movements performed using the anarchic hand. The patient experienced abnormal agency for movements whether motor intention and visual feedback were congruent or incongruent, but not when intention was absent (passive movement). Findings suggest a general disturbance of veridical motor awareness and agency in this case of parietal AHS

Untangling the ATR-CHEK1 network for prognostication, prediction and therapeutic target validation in breast cancer

Background: ATR-Chk1 signalling network is critical for genomic stability. ATR-Chk1 may be deregulated in breast cancer and have prognostic, predictive and therapeutic significance. Patients and methods: We investigated ATR and phosphorylated CHK1Ser345 protein (pChk1) expression in 1712 breast cancers (Nottingham Tenovus series). ATR and Chk1 mRNA were evaluated in 1950 breast cancers (METABRIC cohort). Pre-clinically, biological consequences of ATR gene knockdown or ATR inhibition by small molecule inhibitor (VE-821) were investigated in MCF-7 and MDA-MB-231 breast cancer cell lines and in non-tumorigenic breast epithelial cells (MCF10A). Results: High ATR and high cytoplasmic pChk1 expression was significantly associated with higher tumour stage, higher mitotic index, pleomorphism and lymphovascular invasion. In univariate analysis, high ATR and high cytoplasmic pChk1 protein expression was associated with shorter breast cancer specific survival (BCSS). In multivariate analysis, high ATR remains an independent predictor of adverse outcome. At the mRNA level, high Chk1 remains associated with aggressive phenotypes including lymph node positivity, high grade, Her-2 overexpression, triple-negative phenotype and molecular classes associated with aggressive behaviour and shorter survival.. Pre-clinically, Chk1 phosphorylation at serine 345 following replication stress (induced by gemcitabine or hydroxyurea treatment) was impaired in ATR knockdown and in VE-821 treated breast cancer cells. Doxycycline inducible knockdown of ATR suppressed growth, which was restored when ATR was re-expressed. Similarly, VE-821 treatment resulted in a dose dependent suppression of cancer cell growth and survival (MCF7 and MDA-MB-231) but had no effect on non-tumorigenic breast epithelial cells (MCF10A). Conclusions: We provides evidence that ATR and Chk1 are promising biomarkers and rational drug target for personalized therapy in breast cancer

Mass extinctions and supernova explosions

A nearby supernova (SN) explosion could have negatively influenced life on Earth, maybe even been responsible for mass extinctions. Mass extinction poses a significant extinction of numerous species on Earth, as recorded in the paleontologic, paleoclimatic, and geological record of our planet. Depending on the distance between the Sun and the SN, different types of threats have to be considered, such as ozone depletion on Earth, causing increased exposure to the Sun's ultraviolet radiation, or the direct exposure of lethal x-rays. Another indirect effect is cloud formation, induced by cosmic rays in the atmosphere which result in a drop in the Earth's temperature, causing major glaciations of the Earth. The discovery of highly intensive gamma ray bursts (GRBs), which could be connected to SNe, initiated further discussions on possible life-threatening events in Earth's history. The probability that GRBs hit the Earth is very low. Nevertheless, a past interaction of Earth with GRBs and/or SNe cannot be excluded and might even have been responsible for past extinction events.Comment: Chapter for forthcoming book: Handbook of Supernovae, P. Murdin and A. Alsabeti (eds.), Springer International Publishing (in press

The DmsABC Sulfoxide Reductase Supports Virulence in Non-typeable Haemophilus influenzae.

Although molybdenum-containing enzymes are well-established as having a key role in bacterial respiration, it is increasingly recognized that some may also support bacterial virulence. Here, we show that DmsABC, a putative dimethylsulfoxide (DMSO) reductase, is required for fitness of the respiratory pathogen Haemophilus influenzae (Hi) in different models of infection. Expression of the dmsABC operon increased with decreasing oxygen availability, but despite this, a Hi2019Δd msA strain did not show any defects in anaerobic growth on chemically defined medium (CDM), and viability was also unaffected. Although Hi2019Δd msA exhibited increased biofilm formation in vitro and greater resistance to hypochlorite killing compared to the isogenic wild-type strain, its survival in contact with primary human neutrophils, in infections of cultured tissue cells, or in a mouse model of lung infection was reduced compared to Hi2019WT. The tissue cell infection model revealed a two-fold decrease in intracellular survival, while in the mouse model of lung infection Hi2019Δd msA was strongly attenuated and below detection levels at 48 h post-inoculation. While Hi2019WT was recovered in approximately equal numbers from bronchoalveolar lavage fluid (BALF) and lung tissue, survival of Hi2019Δd msA was reduced in lung tissue compared to BALF samples, indicating that Hi2019Δd msA had reduced access to or survival in the intracellular niche. Our data clearly indicate for the first time a role for DmsABC in H. influenzae infection and that the conditions under which DmsABC is required in this bacterium are closely linked to interactions with the host

GPs' use of problem solving therapy for depression: a qualitative study of barriers to and enablers of evidence based care

BACKGROUND: Depression is a major health concern, predominantly treated by general practitioners (GPs). Problem solving therapy (PST) is recognised as an effective treatment for depression that is not widely used by GPs. This research aims to explore barriers and enablers that may influence GPs use of this treatment. METHOD: Qualitative methodology was used including individual and focus group interviews of GPs, PST experts and consumers. Analysis was undertaken using the Theory of Planned Behaviour (TPB) as a framework. RESULTS: A spectrum of potential influences, on GPs' use of PST emerged. Both barriers and enablers were identified. PST was perceived as being close to current practice approaches and potentially beneficial to both doctor and patient. In addition to a broadly positive attitude to PST, expressed by those with previous experience of its use, potential solutions to perceived barriers emerged. By contrast some GPs expressed fear that the use of PST would result in loss of doctor control of consultations and associated potential adverse patient outcomes. Patient expectations, which emerged as not always coinciding with GPs' perception of those expectations, were identified as a potential influence on GPs' decision concerning adoption of PST. In addition specific factors, including GP skill and confidence, consultation time constraints and technical issues related to PST were noted as potential concerns. CONCLUSION: This research contributes to our knowledge of the factors that may influence GPs' decisions regarding use of PST as a treatment for depression. It recognises both barriers and enablers. It suggests that for many GPs, PST is viewed in a positive light, providing encouragement to those seeking to increase the provision of PST by GPs. In identifying a number of potential barriers, along with associated options to address many of these barriers, it provides insights which may assist in the planning of GP training in PST

Ricci Flow Gravity

A theory of gravitation is proposed, modeled after the notion of a Ricci flow. In addition to the metric an independent volume enters as a fundamental geometric structure. Einstein gravity is included as a limiting case. Despite being a scalar-tensor theory the coupling to matter is different from Jordan-Brans-Dicke gravity. In particular there is no adjustable coupling constant. For the solar system the effects of Ricci flow gravity cannot be distinguished from Einstein gravity and therefore it passes all classical tests. However for cosmology significant deviations from standard Einstein cosmology will appear.Comment: 15 pages. V2: improved presentation, in particular Jordan vs. Brans-Dicke and on viability. Added section on physical interpretation. V3: more references. Reworked to agree with published versio

Pharmacokinetic and pharmacodynamic modelling after subcutaneous, intravenous and buccal administration of a high-concentration formulation of buprenorphine in conscious cats

The aim of this study was to describe the joint pharmacokinetic-pharmacodynamic model and evaluate thermal antinociception of a high-concentration formulation of buprenorphine (Simbadol™) in cats

Who wants to join preventive trials? – Experience from the Estonian Postmenopausal Hormone Therapy Trial [ISRCTN35338757]

BACKGROUND: The interest of patients in participating in randomized clinical trials involving treatments has been widely studied, but there has been much less research on interest in preventive trials. The objective of this study was to find out how many women would be interested in a trial involving postmenopausal hormone therapy (PHT) and how the women's background characteristics and opinions correlated to their interest. METHODS: The data come from recruitment questionnaires (n = 2000) sent to women in Estonia in 1998. A random sample of women aged 45 to 64 was drawn from the Population Registry. The trial is a two-group randomized trial comparing estrogen-progestogen therapy with placebo or no drugs. A brief description of the study was attached to the questionnaires. Women were not told at this stage of the recruitment which group they would be assigned to, however, they were told of the chance to receive either hormone, placebo or no treatment. RESULTS: After two reminders, 1312 women (66%) responded. Eleven percent of the women approached (17% of the respondents) were interested in joining the trial, and 8% wanted more information before deciding. When the 225 women who stated clearly that they were interested in joining and the 553 women who said they were not interested were compared, it was found that interested women were younger and, adjusting for age, that more had given birth; in other respects, the sociodemographic characteristics and health habits of the interested women were similar to those of the non-interested women. The interested women had made more use of more health services, calcium preparations and PHT, they were more often overweight, and more had chronic diseases and reported symptoms. Interested women's opinions on the menopause were more negative, and they favoured PHT more than the non-interested women. CONCLUSION: Unlike the situation described in previous reports on preventive trials, in this case Estonian women interested in participating in a PHT trial were not healthier than other women. This suggests that trials involving PHT are more similar to treatment trials than to preventive trials. In a randomized controlled trial, more information should be obtained from those women who decline to participate

How do patients want to learn of results of clinical trials? A survey of 1431 breast cancer patients

Questionnaires were circulated to UK patients and health care professionals (HCPs) participating in the Taxotere as Adjuvant ChemoTherapy (TACT) trial in autumn 2004 asking if and how trial results, when available, should be conveyed to patients. A total of 1431 (37% of surviving UK TACT patients) returned questionnaires. In all, 30 (2%) patients did not want results. In all, 554 (40%) patients preferred to receive them via their hospital; 664 (47%) preferred results posted directly to their home, 177 (13%) preferred a letter providing a telephone number to request results. Six hundred and twelve patients thought results should come directly from the trials office. One hundred and seventy-six HCPs from 89 UK centres (86%) returned questionnaires. In all, 169 out of 176 patients (96%) thought results should be written in lay terms for patients. Seventy (41%) preferred patients to receive results via their hospital; 64 (38%) preferred a letter providing a telephone number to request results, and 32 (19%) preferred results posted directly to patients. Thirty-one HCPs (18%) thought results to patients should come directly from the trials office. A total of 868 (61%) patients thought next of kin of deceased patients should receive results, 543 (38%) did not; 47 (27%) HCPs thought they should; 118 (68%) did not