Using b-tagging to enhance the SUSY reach of the CERN Large Hadron Collider

Assuming that supersymmetry is realized with parameters in the hyperbolic branch/focus point (HB/FP) region of the minimal supergravity (mSUGRA) model, we show that by searching for multijet + missing E_T events with tagged b jets the reach of experiments at the LHC may be extended by as much as 20% from current projections. The reason for this is that gluino decays to third generation quarks are enhanced because the lightest neutralino has substantial higgsino components. Although we were motivated to perform this analysis because the HB/FP region is compatible with the recent determination of the relic density of cold dark matter, our considerations may well have a wider applicability since decays of gluinos to third generation quarks are favoured in a wide variety of models.Comment: 16 pages, 1 figur

Diphoton Signals for Large Extra Dimensions at the Tevatron and CERN LHC

We analyze the potentiality of hadron colliders to search for large extra dimensions via the production of photon pairs. The virtual exchange of Kaluza--Klein gravitons can significantly enhance this processes provided the quantum gravity scale ($M_S$) is in the TeV range. We studied in detail the subprocesses $q \bar{q} \to \gamma \gamma$ and $g g \to \gamma \gamma$ taking into account the complete Standard Model and graviton contributions as well as the unitarity constraints. We show that the Tevatron Run II will be able to probe $M_S$ up to 1.5--1.9 TeV at 2$\sigma$ level, while the LHC can extend this search to 5.3--6.7 TeV, depending on the number of extra dimensions

Transmucosal fentanyl vs intravenous morphine in doses proportional to basal opioid regimen for episodic-breakthrough pain

The use of supplemental doses of opioids is commonly suggested to manage breakthrough pain. A comparative study of intravenous morphine (IV-MO) and oral transmucosal fentanyl citrate (OTFC) given in doses proportional to the basal opioid regimen was performed in 25 cancer patients receiving stable opioid doses. For each episode, when it occurred and 15 and 30 min after the treatment, pain intensity and opioid-related symptoms were recorded. Fifty-three couples of breakthrough events, each treated with IV-MO and OTFC, were recorded. In episodes treated with IV-MO, pain intensity decreased from a mean of 6.9 to 3.3 and to 1.7 at T1 and T2, respectively. In episodes treated with OTFC, pain intensity decreased from a mean of 6.9 to 4.1 and to 2.4 at T1 and T2, respectively. Statistical differences between the two treatments were found at T1 (P=0.013), but not at T2 (P=0.059). Adverse effects were comparable and were not significantly related with the IV-MO and OTFC doses. Intravenous morphine and OTFC in doses proportional to the scheduled daily dose of opioids were both safe and effective, IV-MO having a shorter onset than OTFC. Future comparative studies with appropriate design should compare titration methods and proportional methods of OTFC dosing

Episodic breathlessness with and without background dyspnea in advanced cancer patients admitted to an acute supportive care unit

Aim: To characterize episodic breathlessness (EB) in patients with advanced cancer, and to determine factors influencing its clinical appearance. Methods: A consecutive sample of advanced cancer patients admitted to an acute palliative care unit was surveyed. Continuous dyspnea and EB were measured by a numerical scale. The use of drugs used for continuous dyspnea and EB was recorded. Patients were asked about the characteristics of EB (frequency, intensity, duration and triggers). The Multidimensional dyspnea profile (MDP), the Brief dyspnea inventory (BDI), the Athens sleep scale (AIS) and the Hospital Anxiety and Depression Scale (HADS) were also administered. Results: From 439 advanced cancer patients surveyed, 34 and 27 patients had EB, without and with background dyspnea, respectively. The mean intensity and the number of episodes were higher in patients with background dyspnea (p < 0.0005 and p = 0.05, respectively). No differences in duration were observed. Most episodes lasted <10 min. A recognizable cause triggering EB was often found. The presence of both background dyspnea and EB was associated with higher values of MDP and BDI. EB was independently associated with frequency and intensity of background dyspnea (OR = 20.9, 95% CI (Confidence interval) 9.1–48.0; p < 0.0005 and OR = 1.97, 95% CI 1.09–3.58; p = 0.025, respectively) and a lower Karnofsky level (OR = 0.96, 95%CI 0.92–0.98, p = 0.05). Discussion: EB may occur in patients with and without continuous dyspnea, and is often induced by physical and psychological factors. EB intensity is higher in patients with continuous dyspnea. The duration was often so short that the use of drugs, as needed, may be too late, unless administered pre-emptively when the trigger was predictable

Tapentadol in cancer pain management: a prospective open-label study.

OBJECTIVES: The aim of this prospective, open-label study was to evaluate the efficacy and tolerability of tapentadol (TP) in the management of cancer pain. METHODS: A 4 weeks' prospective study was carried out in 50 opioid-naive cancer patients with moderate-severe pain. Each patient initially received twice-daily doses of slow-release TP 50 mg. Doses were then managed to maintain adequate relief or dose-limiting toxicity, on the basis of the clinical response. The following parameters were recorded at weekly intervals for 4 weeks: pain and opioid-related adverse effects, quality of life measured with the Spitzer score, TP escalation index percent (TPEI%) and TP escalation index in mg (TPEImg), calculated at the end of the study, pain mechanisms, and PainDETECT at baseline. RESULTS: Of 50 patients, 39 completed the entire study and 11 discontinued the treatment for different reasons. Pain intensity significantly decreased from baseline to all the week intervals (p < 0.0005), and adverse effects did not changed significantly, while quality of life improved. TP escalation indexes were low and no relationship was found with age, gender, and pain mechanisms. CONCLUSION: Tapentalol started in doses of 100 mg/day was well-tolerated and effective in opioid-naive patients with cancer pain, regardless of the pain mechanism. It can be considered as a flexible drug to be used in patients with moderate-severe pain. LIMITATIONS: This was an open-label study for exploratory purposes. Data should be confirmed in controlled studies with a larger number of patient

Quartic Anomalous Couplings in γγ\gamma\gamma Colliders

We study the constraints on the vertices $W^+W^- Z\gamma$, $W^+W^-\gamma\gamma$, and $ZZ\gamma\gamma$ that can be obtained from triple-gauge-boson production at the next generation of linear $e^+e^-$ colliders operating in the $\gamma\gamma$ mode. We analyze the processes $\gamma\gamma \to W^+W^-V$ ($V=Z$, or $\gamma$) and show that these reactions increase the potential of $e^+e^-$ machines to search for anomalous four-gauge-boson interactions.Comment: 15 pages, Latex file using ReVteX, 4 uufiled figures include

Development, validation and application of an HPLC-MS/MS method to quantify urinary mercapturic acids

Introduction Mercapturic acids are metabolic end products of some occupational and environmental toxicants such as volatile organic compounds. They are metabolites formed by the conjugation of an electrophilic compound with glutathione. These electrophilic metabolic intermediates are believed to be the active species able to react with DNA and responsible for the genotoxicity associated with parent compounds [1]. Mercapturates can be found in urine and, therefore, they can be considered useful non-invasive biomarkers of exposure. Although several analytical methods were reported for the analysis of single or small groups of mercapturates [2], only two papers describes the analysis of several mercapturates [3,4]. The aim of this work was to set up a LC-MS/MS method able to determine mercapturic acids derived from different toxicants. Experimental For the preparation of standard solution, the majority of standard compounds were purchased from Toronto Research Chemicals (Ontario, Canada), along with relative isotopically labelled standards. The complete list of analytes is reported in Table 1. The simple sample preparation developed includes dilution with formic acids (0.2 M), addition of an internal standard mixture of 16 deuterated analogs and filtration with 0.45 \u3bcm regenerated cellulose membrane filter (Agilent Technologies, Santa Clara, California). Analysis were carried out using a hybrid triple quadrupole/linear ion trap mass spectrometer (QTRAP 5500, AB Sciex, Monza, Italy) interfaced with an ultrahigh pressure liquid chromatograph (UHPLC, Agilent 1220, Cernusco sul Naviglio, Italy) equipped with a Betasil C18 column (150 x2.1 mm, 5 \u3bcm; Thermo Fisher Scientific, Rodano, Italy) and a pre-column BETASIL C18 (10 x 2,1 mm, 5\u3bc; Thermo Fisher Scientific, Rodano, Italy). Chromatographic separation was performed using a linear gradient with an aqueous mobile phase composed by an aqueous solution of ammonium formiate 5 mM and 0.1% formic acid and an organic mobile phase composed by acetonitrile. A complete validation was carried out: linearity, sensitivity, accuracy, precision, selectivity, matrix effect, recovery and process efficiency were evaluated according to both FDA guidelines and the considerations reported in the review written by Gonz\ue1lez and co-workers [5,6]. The method was then applied to the analysis of urine samples from adult subjects with different smoking habits: non-smokers, electronic cigarette smokers, and traditional tobacco smokers. Results Results from linearity assays showed that correlation coefficients (R2) were close to 1 for most of compounds, demonstrating optimal linear responses for the considered concentrations ranges, although a polynomial regression was necessary for AAMA since it showed a saturation at high concentrations. Limits of quantitation (LOQ) values were between 0.15 and 1 \u3bcg/L, except for HEMA and AAMA (1.93 and 1.30 \u3bcg/L respectively). Precision, evaluated as relative standard deviations (RDS), was below 15% for most analytes in both intra-day and inter-day tests. Accuracy was between 85 and 110 % of expected values, with few exceptions exceeding 120% at the lowest concentrations. Selectivity was verified by injection of a blank sample (synthetic urine) showing no chromatographic peak having an area at 20% of LOQ at the relative retention time and mass transition of compounds of interest. The same condition was verified analysing a blank sample immediately after the injection of the standard mixture at the highest concentration of the calibration curve, indicating the absence of carry-over. Results from the matrix effect, recovery and process efficiency tests were suitable in most of the cases, with some exceptions that were partially corrected using the internal standards. Results from urine samples of individuals with different smoking habit showed significant differences between smokers and non-smokers: 11 different mercapturic acids were significantly higher (P-value 640.005) in traditional tobacco smokers than in non-smokers (an example is illustrated in Figure 1). Conclusion In this work, we developed a method useful to quantify mercapturic acids in urine samples. The method was subjected to a complete validation and showed to be suitable for most of the considered analytes. Despite some critical issues with some analytes (in particular HEMA), it demonstrated to be an useful tool for fast determination of mercapturates. The first application carried out using human urine samples suggests that mercapturic acids are suitable biomarkers for toxicants in tobacco smoke. References 1. B.M. De Rooij, J.N.M. Commandeur, N.P.E; Biomarkers, 3 (1998), pp 239-303. 2. P.I. Mathias, C. B'hymer; Biomarkers, 21 (2016), pp 293-315. 3. K.U. Alwis, B.C. Blount, A.S. Britt, D. Patel, D.L. Ashley; Analytica Chimica Acta, 750 (2012), pp 152-160. 4. N. Pluym, G. Gilch, G. Scherer, M. Scherer; Analytical and Bioanalytical Chemistry, 407 (2015), pp 5463-5476. 5. FDA. Guidance for Industry - Bioanalytical Method Validation. (2013) Available at: https://www.fda.gov/downloads/Drugs/Guidances/ucm368107.pdf 6. O. Gonz\ue1lez, M.E. Blanco, G. Iriarte, L. Bartolom\ue9, M.I. Maguregui, R.M. Alonso; Journal of Chromatography A, 1353 (2014), pp10-27

A longitudinal study of breakthrough cancer pain: An extension of iops-ms study

The aim of this study was to longitudinally assess the characteristics of background pain and breakthrough pain (BTcP), analgesic treatment, and satisfaction with treatment four weeks after the first assessment. Methods: Adult cancer patients with a diagnosis of BTcP were included. At T0, age, gender, visit setting, cancer diagnosis, the extent of the disease, ongoing anticancer treatments, and Karnofsky level were recorded. The background pain intensity in the last 24 h (on a numerical scale 0–10), opioids used for background pain, and their doses, expressed as oral morphine equivalents (OME), as well as other analgesic drugs, were recorded. The number of BTcP episodes, their intensity, predictability and precipitating factors, onset duration of untreated episodes, and interference with daily activities were collected. Analgesics and doses used for BTcP, and the mean time to meaningful pain relief after taking medication, were assessed. The level of satisfaction with BTcP medication was also assessed. Adverse effects to be attributed to these medications were also recorded. At T4, the same data were evaluated. Results: After one-month follow-up, patients had a lower number of BTcP episodes and peak intensity, possibly due to the optimization of background analgesia. The principal characteristics of BTcP did not change significantly. Conclusion: A careful and continuous assessment should be guaranteed to all patients to limit the burden induced by BTcP, other than treating BTcP episodes with short-onset opioids