An investigation of the effects of an impact on some of the mechanical properties of aluminum alloy 2014-T6

Static and impact tests were conducted on an Aluminum alloy 2014-T6 specimen. The purpose of this research was to determine the effects of an impact load on some of the mechanical properties of aluminum. The cross section of the specimen measured 4.438 in. by 3.850 in. and it was 12 in. long. It was equipped with a total of four electric resistance gages connected in two pairs. One pair measured longitudinal strain while the other measured transverse strain. Both gages in each pair were mounted on the opposite sides to cancel the bending effect. In the static tests, load was applied with a 300,000 lb. hydraulic testing machine. The longitudinal and transverse strains were read off a Budd strain indicator and recorded against the load. The specimen was then placed in a load frame with a load cell underneath the specimen and a floating head sitting flush on the top. A 2 in. diameter hardened steel ball was welded on the floating head. The ball served as a striking surface for a 107 lb. hammer dropping from a known height. The hammer was guided by two wires, tensioned vertically. An impact load was produced as the hammer, falling freely, struck the floating head of the load frame which contained the specimen. The load was transmitted to the specimen and then to the load cell --Abstract, page ii

(E)-Ethyl 2-cyano-3-(1H-pyrrol-2-yl)acrylate

All the non-H atoms of the title compound, C10H10N2O2, are nearly in the same plane with a maximum deviation of 0.093 (1) Å. In the crystal, adjacent mol­ecules are linked by pairs of inter­molecular N—H⋯O hydrogen bonds, generating inversion dimers with R 2 2(14) ring motifs

Polymyxin B in Combination with Rifampin and Meropenem against Polymyxin B-Resistant KPC-Producing Klebsiella pneumoniae

Safe and effective therapies are urgently needed to treat polymyxin-resistant KPC-producing K. pneumoniae and suppress the emergence of resistance. We investigated the pharmacodynamics of polymyxin B, rifampin, and meropenem alone and as polymyxin B-based double and triple combinations against KPC-producing K. pneumoniae . The rate and extent of killing with polymyxin B (1-128mg/L), rifampin (2-16mg/L), and meropenem (10-120mg/L) were evaluated against polymyxin B-susceptible (PB S ) and -resistant (PB R ) clinical isolates using 48h static time-kills. Additionally, humanized triple drug regimens of polymyxin B (C ss : 0.5, 1, 2mg/L), rifampin 600mg every 12 or 8h, and meropenem 1 or 2g every 8h dosed as an extended 3h infusion were simulated over 48h using a one-compartment in vitro dynamic infection model. Serial bacterial counts were measured to quantify pharmacodynamic effect. Population analysis profiles (PAPs) were used to assess the emergence of polymyxin B resistance. Monotherapy was ineffective against both isolates. Polymyxin B with rifampin demonstrated early bactericidal activity against the PB S isolate followed by regrowth by 48h. Bactericidal activity was sustained at all polymyxin B concentrations ≥2 mg/L in combination with meropenem. No two-drug combinations were effective against the PB R isolate, but all simulated triple-drug regimens showed early bactericidal activity by 8h that was sustained over 48h against both strains. PAPs did not reveal the emergence of resistant subpopulations. The triple drug combination of polymyxin B, rifampin, and meropenem may be a viable consideration for the treatment of PB R KPC-producing K. pneumoniae . Further investigation is warranted to optimize triple combination therapy

4,4′-Dibromo-2-nitro­biphen­yl

The title compound, C12H7Br2NO2, a biphenyl derivative, displays a twisted conformation with the two benzene rings making a dihedral angle of 55.34 (14)°. The dihedral angle between the nitro group and its parent benzene ring is 26.8 (2)°. The crystal structure is stabilized by inter­molecular C—H⋯Br and C—H⋯O inter­actions, which lead to the formation of chains propagating along the c-axis direction

In Vitro Assessment of Combined Polymyxin B and Minocycline Therapy against Klebsiella pneumoniae Carbapenemase (KPC)-Producing K. pneumoniae

ABSTRACT The multidrug resistance profiles of Klebsiella pneumoniae carbapenemase (KPC) producers have led to increased clinical polymyxin use. Combination therapy with polymyxins may improve treatment outcomes, but it is uncertain which combinations are most effective. Clinical successes with intravenous minocycline-based combination treatments have been reported for infections caused by carbapenemase-producing bacteria. The objective of this study was to evaluate the in vitro activity of polymyxin B and minocycline combination therapy against six KPC-2-producing K. pneumoniae isolates (minocycline MIC range, 2 to 32 mg/liter). Polymyxin B monotherapy (0.5, 1, 2, 4, and 16 mg/liter) resulted in a rapid reduction of up to 6 log in bactericidal activity followed by regrowth by 24 h. Minocycline monotherapy (1, 2, 4, 8, and 16 mg/liter) showed no reduction of activity of >1.34 log against all isolates, although concentrations of 8 and 16 mg/liter prolonged the time to regrowth. When the therapies were used in combination, rapid bactericidal activity was followed by slower regrowth, with synergy (60 of 120 combinations at 24 h, 19 of 120 combinations at 48 h) and additivity (43 of 120 combinations at 24 h, 44 of 120 combinations at 48 h) against all isolates. The extent of killing was greatest against the more susceptible polymyxin B isolates (MICs of ≤0.5 mg/liter) regardless of the minocycline MIC. The pharmacodynamic activity of combined polymyxin B-minocycline therapy against KPC-producing K. pneumoniae is dependent on polymyxin B susceptibility. Further in vitro and animal studies must be performed to fully evaluate the efficacy of this drug combination

Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults

BACKGROUND: There is no evidence-based guidance to facilitate design decisions for confirmatory trials or systematic reviews investigating treatment efficacy for adults with tinnitus. This systematic review therefore seeks to ascertain the current status of trial designs by identifying and evaluating the reporting of outcome domains and instruments in the treatment of adults with tinnitus. METHODS: Records were identified by searching PubMed, EMBASE CINAHL, EBSCO, and CENTRAL clinical trial registries (ClinicalTrials.gov, ISRCTN, ICTRP) and the Cochrane Database of Systematic Reviews. Eligible records were those published from 1 July 2006 to 12 March 2015. Included studies were those reporting adults aged 18 years or older who reported tinnitus as a primary complaint, and who were enrolled into a randomised controlled trial, a before and after study, a non-randomised controlled trial, a case-controlled study or a cohort study, and written in English. Studies with fewer than 20 participants were excluded. RESULTS: Two hundred and twenty-eight studies were included. Thirty-five different primary outcome domains were identified spanning seven categories (tinnitus percept, impact of tinnitus, co-occurring complaints, quality of life, body structures and function, treatment-related outcomes and unclear or not specified). Over half the studies (55 %) did not clearly define the complaint of interest. Tinnitus loudness was the domain most often reported (14 %), followed by tinnitus distress (7 %). Seventy-eight different primary outcome instruments were identified. Instruments assessing multiple attributes of the impact of tinnitus were most common (34 %). Overall, 24 different patient-reported tools were used, predominantly the Tinnitus Handicap Inventory (15 %). Loudness was measured in diverse ways including a numerical rating scale (8 %), loudness matching (4 %), minimum masking level (1 %) and loudness discomfort level (1 %). Ten percent of studies did not clearly report the instrument used. CONCLUSIONS: Our findings indicate poor appreciation of the basic principles of good trial design, particularly the importance of specifying what aspect of therapeutic benefit is the main outcome. No single outcome was reported in all studies and there was a broad diversity of outcome instruments. PROSPERO REGISTRATION: The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525. Registered on 12 March 2015 revised on 15 March 2016. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1399-9) contains supplementary material, which is available to authorized users

Cost effectiveness of support for people starting a new medication for a long term condition through community pharmacies: an economic evaluation of the New Medicine Service (NMS) compared with normal practice

Background: The English community pharmacy New Medicine Service (NMS) significantly increases patient adherence to medicines, compared with normal practice. We examined the cost-effectiveness of NMS compared with normal practice by combining adherence improvement and intervention costs with the effect of increased adherence on patient outcomes and healthcare costs. Methods: We developed Markov models for diseases targeted by the NMS (hypertension, type 2 diabetes, chronic obstructive pulmonary disease, asthma and antiplatelet regimens) to assess the impact of patients’ non-adherence. Clinical event probability, treatment pathway, resource-use and costs were extracted from literature and costing tariffs. Incremental costs and outcomes associated with each disease were incorporated additively into a composite probabilistic model and combined with adherence rates and intervention costs from the trial. Costs per extra quality-adjusted-life-year(QALY) were calculated from the perspective of NHS England, using a lifetime horizon. Results: NMS generated a mean of 0.05 (95%CI: 0.00, 0.13) more QALYs per patient, at a mean reduced cost of -£144 (95%CI: -769, 73). The NMS dominates normal practice with probability of 0.78 (ICER: - £3166 per QALY). NMS has a 96.7% probability of cost-effectiveness compared with normal practice at a willingness-to-pay of £20000 per QALY. Sensitivity analysis demonstrated that targeting each disease with NMS has a probability over 0.90 of cost-effectiveness compared with normal practice at a willingness-to-pay of £20000 per QALY. Conclusions: Our study suggests that the New Medicine Service increased patient medicine adherence compared with normal practice, which translated into increased health gain at reduced overall cost