Unleashing the full power of LHCb to probe stealth new physics.

In this paper, we describe the potential of the LHCb experiment to detect stealth physics. This refers to dynamics beyond the standard model that would elude searches that focus on energetic objects or precision measurements of known processes. Stealth signatures include long-lived particles and light resonances that are produced very rarely or together with overwhelming backgrounds. We will discuss why LHCb is equipped to discover this kind of physics at the Large Hadron Collider and provide examples of well-motivated theoretical models that can be probed with great detail at the experiment.

Types and risk factors of ambulance accidents: A scoping review.

BACKGROUND: A scoping review was conducted to map out the common research focusses on ambulance accidents, their key findings and some of the major knowledge gaps in this area. MATERIALS AND METHODS: Relevant, peer-reviewed, Englishlanguage articles on land ambulance accidents were independently searched by the authors using the MEDLINE and CINAHL databases. Anecdotal reports, testimonies and stories in trade or popular magazines and other grey literature were excluded. Articles that do not directly address ambulance accidents were also excluded. Additional articles were identified from the reference lists of the selected articles and from Google search engine. RESULTS: From an initial yield of 879 articles, 19 articles were included. Most of these articles were published from 2001 - 2005 (5 articles, 26.3%) and 2006 - 2010 (5 articles, 26.3%). Eighteen articles (78.3%) are original articles (18 articles, 78.3%) and another one article is a review article. Most of these articles focused on (1) the types of collisions and (2) the risk factors of ambulance accidents. Nine risk factors were identified to have contributed to ambulance accidents: (1) driving in urban areas (2) driving on dry road (3) the use of lights & sirens (4) the failure to use restraints (5) driving for emergency use (6) back seating (7) at road intersection (8) driver's previous records of accidents and (9) interfacility transfer. The two most common risk factors studied were (1) the use of lights & sirens and (2) driving at intersection. CONCLUSIONS: Most of the above risk factors can be mapped into three categories of risk factors: task-related factors, vehicle-related factors and environment-related factors. The category of risk factors least studied is the category of driver-related factors.

Anabolic androgenic steroids, an easily forgotten cause of polycythaemia and cerebral infarction.

Excessive anabolic androgenic steroids (both exogenous and endogenous) are known causes of polycythaemia and ischaemic cardiovascular events. Despite this, they are commonly forgotten in the workup of patients. We report a case of exogenous anabolic androgenic steroid-induced polycythaemia and stroke and explore possible pitfalls for clinicians.

Why not nursing? A systematic review of factors influencing career choice among healthcare students.

BACKGROUND: A global shortage of healthcare professionals calls for effective recruitment and retention strategies. The nursing profession faces greater staffing shortages compared with other healthcare professions. Identifying these factors for choosing a career in health care is an important step in structuring future nursing recruitment strategies. AIM: This systematic review examined the motivations for choosing a career in health care, then compared them to factors that influence the choice to pursue a career in nursing. METHODS: A literature search of the CINAHL, PubMed, Web of Science and Scopus databases for articles published between 2002 and 2013 was conducted. The search included studies that focused on factors influencing career choice among undergraduate medicine, dentistry, pharmacy and nursing students. RESULTS: A total of 29 papers were included in the review. The themes and subthemes that emerged from this review included: (1) intrinsic factors, including a desire to help others and a personal interest in health care, (2) extrinsic factors, such as financial remuneration, job security, professional prestige and job autonomy, (3) socio-demographic factors such as gender and socio-economic status, and (4) interpersonal factors, encompassing the influence of family and other professional individuals. DISCUSSION: Healthcare professionals were generally motivated by intrinsic factors. However, public perceptions of nursing as a low-paying and low-status job have significantly hindered the participants' choice to pursue it as a career. CONCLUSION AND IMPLICATIONS FOR NURSING AND/OR HEALTH POLICY: Nursing institutions could provide more platforms to help school leavers better understand the nursing career. In turn, hospital administrators could invite parents to nursing career fairs, increase financial remuneration for nurses, and provide decision-making avenues aimed at recruiting and retaining more nurses.

Adolescent growth: genes, hormones and the peer group. Proceedings of the 20th Aschauer Soiree, held at Glücksburg castle, Germany, 15th to 17th November 2013.

The association between poverty, malnutrition, illness and poor socioeconomic conditions on the one side, and poor growth and short adult stature on the other side, is well recognized. Yet, the simple assumption by implication that poor growth and short stature result from poor living conditions, should be questioned. Recent evidence on the impact of the social network on adolescent growth and adult height further challenges the traditional concept of growth being a mirror of health. Twenty-nine scientists met at Glücksburg castle, Northern Germany, November 15th - 17th 2013, to discuss genetic, endocrine, mathematical and psychological aspects and related issues, of child and adolescent growth and final height.

Trends in outpatient antibiotic use in Israel during the years 2000-2010: setting targets for an intervention.

PURPOSE: The abundant use of antibiotics (Abs) in the community plays a major role in inducing Ab resistance, but the literature concerning patterns in outpatient Ab use is limited. This study aims to lay the foundations for future policy and interventional programs to address the rise in Ab resistance by looking at long-term trends in Ab usage in Israel. METHODS: Defined daily doses per 1,000 inhabitants per day (DID) of total Ab use, consumption in different age groups, and of different Ab preparations were calculated for the years 2000, 2005, and 2010 in the eight districts of Israel. Data were collected from the pharmacy registries of "Clalit Health Services", the largest Health Maintenance Organization (HMO) in Israel, covering 4 million patients, representing 53 % of the population. Trends in use over time were analyzed. RESULTS: The overall Ab usage in Israel has remained constant in the last decade. Three significant trends were identified in this study: an increase in the consumption of expensive, broad-spectrum Abs, paralleled by a reduction in narrow-spectrum Abs; an increase in Ab consumption among the elderly, counteracted by reduced usage among children; large regional variations in the overall and specific use of Ab agents. CONCLUSIONS: Our main findings of increased broad-spectrum Ab consumption, primarily among the adult population in Israel, and a wide variability in Ab use between the regions in Israel, can focus our future studies on searching for the factors behind these trends to aid in constructing interventional methods for decreasing outpatient Ab overuse.

High-dose cytarabine (24 g/m2) in combination with idarubicin (HiDAC-3) results in high first-cycle response with limited gastrointestinal toxicity in adult acute myeloid leukaemia.

BACKGROUND/AIM: Although induction chemotherapy comprising high-dose cytarabine (HiDAC) in combination with idarubicin and etoposide or 'ICE' for adult acute myeloid leukaemia (AML) produces a complete remission rate of nearly 80%, gastrointestinal toxicity is significant. Omission of etoposide may produce similar clinical outcomes with potentially less gastrointestinal toxicity. METHODS: Fifty-three consecutive patients aged 15-60 with newly diagnosed AML, receiving high-dose cytarabine induction at the Alfred Hospital, Melbourne, were retrospectively analysed. Regimens included HiDAC-3 (idarubicin 12 mg/m(2) day 1-3, cytarabine 3 gm/m(2) bd day 1,3,5,7) or ICE (idarubicin 9 mg/m(2) day 1-3, cytarabine 3 g/m(2) bd day 1,3,5,7, etoposide 75 mg/m(2) day 1-7). Toxicity was assessed using Common Terminology Criteria for Adverse Events version 4.03. RESULTS: Thirty-one patients received HIDAC-3 and 22 patients received ICE induction. HiDAC-3 was better tolerated than ICE in terms of lower frequency of grade 3-4 nausea (0% vs 41%; P < 0.01), grade 3-4 diarrhoea (26% vs 55%; P = 0.05), lower rates of radiologically evident enterocolitis (6% vs 32%; P = 0.03) and less cumulative days of total parenteral nutrition use (1.2 vs 7.3 days; P < 0.01). Times to haematological recovery were similar between the two regimens. Thirty-day mortality was 0% for HiDAC-3 and 9% for ICE. Eighty-four per cent of HiDAC-3-treated patients achieved complete remission after the first cycle of therapy, compared with 77% with ICE. No differences in survival were evident between the two regimens. CONCLUSIONS: HiDAC-3 is a clinically effective induction regimen for adult AML, producing a high rate of first-cycle complete remission with less treatment-related gastrointestinal toxicity than ICE.

Abnormal adaptations to stress and impaired cardiovascular function in mice lacking corticotropin-releasing hormone receptor-2.

The actions of corticotropin-releasing hormone (Crh), a mediator of endocrine and behavioural responses to stress, and the related hormone urocortin (Ucn) are coordinated by two receptors, Crhr1 (encoded by Crhr) and Crhr2. These receptors may exhibit distinct functions due to unique tissue distribution and pharmacology. Crhr-null mice have defined central functions for Crhr1 in anxiety and neuroendocrine stress responses. Here we generate Crhr2-/- mice and show that Crhr2 supplies regulatory features to the hypothalamic-pituitary-adrenal axis (HPA) stress response. Although initiation of the stress response appears to be normal, Crhr2-/- mice show early termination of adrenocorticotropic hormone (Acth) release, suggesting that Crhr2 is involved in maintaining HPA drive. Crhr2 also appears to modify the recovery phase of the HPA response, as corticosterone levels remain elevated 90 minutes after stress in Crhr2-/- mice. In addition, stress-coping behaviours associated with dearousal are reduced in Crhr2-/- mice. We also demonstrate that Crhr2 is essential for sustained feeding suppression (hypophagia) induced by Ucn. Feeding is initially suppressed in Crhr2-/- mice following Ucn, but Crhr2-/- mice recover more rapidly and completely than do wild-type mice. In addition to central nervous system effects, we found that, in contrast to wild-type mice, Crhr2-/- mice fail to show the enhanced cardiac performance or reduced blood pressure associated with systemic Ucn, suggesting that Crhr2 mediates these peripheral haemodynamic effects. Moreover, Crhr2-/- mice have elevated basal blood pressure, demonstrating that Crhr2 participates in cardiovascular homeostasis. Our results identify specific responses in the brain and periphery that involve Crhr2.

Shorter TB treatment regimens should be safer as well.

Most ongoing and planned TB therapeutic trials are focused on shortening the duration of treatment while giving less consideration to other aspects of TB care that are important to people with TB. Here we argue that other variables besides duration of TB treatment should also be considered when developing new TB treatment regimens, including drug toxicity, time spent in monitoring and overall quality of life while on therapy. We examine the specific use of linezolid in treatment-shortening trials for drug-susceptible TB and propose additional endpoints that should be prioritised in TB treatment studies.

La majorité des essais thérapeutiques en cours et prévus sur la TB se concentrent sur la réduction de la durée du traitement tout en accordant moins d'attention à d'autres aspects des soins de la TB qui sont importants pour les personnes atteintes de la TB. Nous soutenons ici que d'autres variables que la durée du traitement de la TB devrait également être prises en compte lors de l'élaboration de nouveaux schémas thérapeutiques, notamment la toxicité des médicaments, le temps passé à la surveillance et la qualité de vie globale pendant le traitement. Nous examinons l'utilisation spécifique du linézolide dans les essais de raccourcissement du traitement de la TB sensible aux médicaments et proposons des critères d'évaluation supplémentaires qui devraient être prioritaires dans les études sur le traitement de la TB.

Limited gene flow may enhance adaptation to local optima in isolated populations of the Roesel's bush cricket (Metrioptera roeselii).

Variation in morphological traits along latitudinal gradients often manifests as size clines. In insects, both positive and negative correlations are seen, and the mechanism behind the response is unclear. We studied variation in seven morphological traits of Roesel's bush cricket, Metrioptera roeselii, sampled from seven latitude-matched-pair populations that were either geographically isolated from or connected to the species continuous distribution range. The aim was to examine whether morphological traits differed between isolated and continuous populations, and whether latitudinal variation was apparent. The data were used to indicate whether variation in trait means originates from plastic responses to the environment or genetic adaptation to local conditions. To evaluate the influence of gene flow on trait means, we analysed the genetic variation in seven microsatellites. Data showed that individuals from isolated populations display a positive relationship between latitude and body size, whereas individuals from continuous populations show little or no such relationship. The combined morphological and genetic data suggest that the isolated populations have adapted to local optima, while gene flow between continuous populations appears to counteract this process.

Release of the rat T cell alloantigen RT-6.2 from cell membranes by phosphatidylinositol-specific phospholipase C.

The mechanism by which the rat T cell alloantigen, RT-6.2, is attached to the membrane was investigated. Treatment of rat lymph node and T-hybridoma cells with phosphatidylinositol-specific phospholipase C (PI-PLC) caused a substantial reduction in the amount of RT-6.2 on the cell surface. No significant release of a rat T helper marker (visualized by the mAb W3/25) was observed in response to PI-PLC treatment. This is in sharp contrast to the effects of trypsin, which removes most of the T helper marker but had little effect on RT-6.2. SDS-PAGE analysis of the RT-6.2 released by PI-PLC indicated that the Mr was not significantly changed by this treatment. Phase separation of the released RT-6.2 in Triton X-114 showed that the PI-PLC had converted it from an amphiphilic membrane form to a water-soluble form, apparently by removing its hydrophobic membrane anchoring domain. These results strongly suggest that RT-6.2, in common with Thy-1 and several other cell surface proteins, is anchored in the membrane by the 1,2-diacylglycerol moiety of a covalently attached phosphatidylinositol molecule.

Release of decay-accelerating factor (DAF) from the cell membrane by phosphatidylinositol-specific phospholipase C (PIPLC). Selective modification of a complement regulatory protein.

Decay-accelerating factor (DAF) is a 70,000 Mr membrane protein that inhibits amplification of the complement cascade on the cell surface, and protects cells from damage. Purified DAF can be reincorporated into the membrane of red cells and is functional. DAF is deficient in paroxysmal nocturnal hemoglobinuria (PNH), a disease characterized by increased sensitivity of erythrocytes to complement lysis. We show here that DAF is part of a newly described family of membrane proteins anchored to the lipid bilayer by means of phosphatidylinositol (PI). Treatment with PI-specific phospholipase C (PIPLC) releases 70-80, 60, and 10% of cell surface DAF from mononuclear cells, neutrophils, and erythrocytes, respectively. The PIPLC-released DAF (DAF-S) is slightly smaller (67,000 Mr) than the membrane form. DAF and DAF-S cannot be distinguished antigenically. Furthermore, DAF-S has lost its ability to significantly inhibit the C3-convertase, as well as its ability to incorporate into cell membranes. Since DAF can only inhibit C3-convertase endogenously, i.e., within the membrane of the same cell, it is likely that the loss of activity of DAF-S is causally related to its inability to reincorporate in the lipid bilayer. As shown by others, the complement-sensitive red cells from PNH patients lack acetylcholinesterase, which is also anchored to the membrane by PI (9). Thus it is possible that the molecular defect in PNH lies in the biosynthetic pathways leading to the attachment of PI to the polypeptide chains, in the transport of these proteins to the surface, or in their release by the action of endogenous phospholipases. From a practical standpoint the specific release of DAF by PIPLC could facilitate killing of tumor cells by amplifying the effects of the complement cascade on the surface of antibody-sensitized cells.

Deficiency of lymphocyte function-associated antigen 3 (LFA-3) in paroxysmal nocturnal hemoglobinuria. Functional correlates and evidence for a phosphatidylinositol membrane anchor.

Lymphocyte function-associated antigen 3 (LFA-3) is a widely distributed cell surface glycoprotein that binds to the T lymphocyte CD2 surface glycoprotein. This interaction mediates CTL-target cell conjugate formation and adhesion of thymocytes to thymic epithelial cells. CD2 is also the E rosette receptor of T lymphocytes and mediates rosetting with autologous E by binding to LFA-3. We describe deficient expression of LFA-3 on E from paroxysmal nocturnal hemoglobinuria (PNH) patients. PNH is an acquired defect affecting phosphatidylinositol-anchored membrane proteins, of which decay-accelerating factor (DAF) is most important in the clinical symptoms of PNH. LFA-3-negative, weakly positive, and positive populations were found among PNH E. There was a good correlation with DAF deficiency. PNH E exhibited decreased binding of 125I-CD2 and rosetting with a human T lymphoma cell line. PNH E readily incorporated purified LFA-3, restoring LFA-3 expression and the CD2 binding and rosetting activity to normal levels. The expression of DAF was not restored after the incorporation of purified LFA-3 into PNH E, showing that LFA-3 and DAF are different molecules. Phosphatidylinositol-specific phospholipase C (PIPLC) treatment of a B lymphoma cell line released 35% of the cell surface LFA-3 and 62% of DAF. LFA-3 on E was resistant to PIPLC. However, when LFA-3 purified from human E was reconstituted in sheep E or human E and subjected to PIPLC treatment, 40-50% of LFA-3 was released from the cell membrane. The results show that LFA-3 is attached to the cell membrane by a phosphatidylinositol glycolipid moiety, and confirm previous findings (37-41) that LFA-3 is a cell adhesion molecule that mediates adhesion by interacting with CD2 antigen.

Variability in outpatient antimicrobial consumption in Israel.

BACKGROUND: Antibiotic consumption has an important effect on microbial resistance. Nationwide data on the comparative use of antibiotics in outpatient settings in Israel have only been partially collected and published. The aim of our study was to analyze the use of antibiotics in the outpatient setting in Israel and assess a number of influencing factors. MATERIALS AND METHODS: Defined daily doses per 1,000 inhabitants per day (DID) of total antibiotic use, consumption in different age groups, and consumption of different antibiotic groups were calculated for the years 2003-2005 in the districts of Israel. The data was collected from prescription data compiled by the pharmaceutical services of "Clalit Health Services", the largest health maintenance organization (HMO) in Israel, covering 55% of the population.Trends in use and variables associated with antibiotic consumption were analyzed. RESULTS: There was a significant decrease in antibiotic use from 2003 to 2005, ranging from 1.8 to 8.2% in the different districts. The highest consumption was noted in the youngest age groups, with more than half of all antibiotics prescribed to children < or = 18 years of age. Antibiotic consumption was significantly different between the different regions in Israel. A multivariate analysis revealed that a higher prevalence of diabetes mellitus was the only significant variable associated with antibiotic use. Variability in the use of different antibiotics was also found; for example, amoxicillin comprised 19.5-33.4% of total antibiotic consumption in the different districts, while fluoroquinolone consumption ranged from 3.2 to 7.3%. CONCLUSIONS: Outpatient antibiotic use in the population insured by "Clalit Health Services" declined between 2003 and 2005. Children had the highest consumption rates. There were large differences in antibiotic use between geographic regions, and diabetes mellitus was the only variable significantly associated with antibiotic use. We therefore conclude that most of the differences in antibiotic use are likely due to doctor preferences, local routines, and patients' attitudes and expectations.

Endothelium-Independent Vasodilatory Effect of Sailuotong (SLT) on Rat Isolated Tail Artery.

BACKGROUND: Sailuotong (SLT) is a standardized three-herb formulation consisting of extracts of Panax ginseng, Ginkgo biloba, and Crocus sativus for the treatment of vascular dementia (VaD). Although SLT has been shown to increase cerebral blood flow, the direct effects of SLT on vascular reactivity have not been explored. This study aims to examine the vasodilatory effects of SLT and the underlying mechanisms in rat isolated tail artery. METHODS: Male (250-300 g) Wistar Kyoto (WKY) rat tail artery was isolated for isometric tension measurement. The effects of SLT on the influx of calcium through the cell membrane calcium channels were determined in Ca2+-free solution experiments. RESULTS: SLT (0.1-5,000 µg/ml) caused a concentration-dependent relaxation in rat isolated tail artery precontracted by phenylephrine. In the contraction experiments, SLT (500, 1,000, and 5,000 µg/mL) significantly inhibited phenylephrine (0.001 to 10 µM)- and KCl (10-80 mM)-induced contraction, in a concentration-dependent manner. In Ca2+-free solution, SLT (500, 1,000, and 5,000 µg/mL) markedly suppressed Ca2+-induced (0.001-3 mM) vasoconstriction in a concentration-dependent manner in both phenylephrine (10 µM) or KCl (80 mM) stimulated tail arteries. L-type calcium channel blocker nifedipine (10 µM) inhibited PE-induced contraction. Furthermore, SLT significantly reduced phenylephrine-induced transient vasoconstriction in the rat isolated tail artery. CONCLUSION: SLT induces relaxation of rat isolated tail artery through endothelium-independent mechanisms. The SLT-induced vasodilatation appeared to be jointly meditated by blockages of extracellular Ca2+ influx via receptor-gated and voltage-gated Ca2+ channels and inhibition of the release of Ca2+ from the sarcoplasmic reticulum.

Structural and functional roles of glycosyl-phosphatidylinositol in membranes.

Glycosylated forms of phosphatidylinositol, which have only recently been described in eukaryotic organisms, are now known to play important roles in biological membrane function. These molecules can serve as the sole means by which particular cell-surface proteins are anchored to the membrane. Lipids with similar structures may also be involved in signal transduction mechanisms for the hormone insulin. The utilization of this novel class of lipid molecules for these two distinct functions suggests new mechanisms for the regulation of proteins in biological membranes.

Restricted lateral diffusion of PH-20, a PI-anchored sperm membrane protein.

The rate of lateral diffusion of integral membrane proteins is constrained in cells, but the constraining factors for most membrane proteins have not been defined. PH-20, a sperm surface protein involved in sperm-egg adhesion, was shown to be anchored in the plasma membrane by attachment to the lipid phosphatidylinositol and to have a diffusion rate that is highly restricted on testicular sperm, being more than a thousand times slower than lipid diffusion. These results support the hypothesis that lateral mobility of a membrane protein can be regulated exclusively by interactions of its ectodomain.

Automatic classification of electroencephalograms: Kullback-Leibler nearest neighbor rules.

A prototypic problem in screening of electroencephalograms in the automatic classification of stationary electroencephalogram time series is treated here by the Kullback-Leibler nearest neighbor rule approach. In that problem, the category or state of an individual is classified by comparison of his or her electroencephalogram with those taken from other individuals in the alternative categories. The Kullback-Leibler nearest neighbor classification rules yield a statistically reliable estimate of the smallest possible probability of electroencephalogram misclassification with a relatively small number of labeled sample electroencephalograms. The automatic classification of anesthesia levels L1 and L3, respectively the anesthesia levels insufficient and sufficient for deep surgery, is treated by machine computation on the electroencephalogram alone.

Gonadotroph-specific expression of metallothionein fusion genes in pituitaries of transgenic mice.

Transgenic mice expressing a metallothionein-somatostatin fusion gene contain high concentrations of somatostatin in the anterior pituitary gland, a tissue that does not normally produce somatostatin. Immunoreactive somatostatin within the anterior pituitaries was found exclusively within gonadotrophs. Similarly, a metallothionein-human growth-hormone fusion gene was also expressed selectively in gonadotrophs. It is proposed that sequences common to the two fusion genes are responsible for the gonadotroph-specific expression.

[Intrahospital transport of critically ill patients]. / Innerklinischer Transport des kritisch kranken Patienten.

Transport of critically ill patients from the ICU for diagnostic and therapeutic purposes (e.g. CT, endoscopy, radiological catheter-assisted interventions) is a challenge and has steadily increased over the years. After risk-benefit analysis careful planning is the first step in minimizing the risk of complications. Knowledge and skillful handling of the transport equipment is mandatory to avoid life-threatening incidents as monitoring and therapy have to be continued during the transport. Proper education and experience in critical care medicine are additional characteristics of the transport team. When these prerequisites are fulfilled a "non-transportable" patient is just as unlikely as a "non-anesthetizable" patient.