How do we compare with best practice? A completed audit of benzodiazepine and z-hypnotic prescribing.

OBJECTIVES: To compare benzodiazepine and z-hypnotic prescribing practices in an inpatient psychiatric unit to best practice standards. METHODS: Medication charts of all inpatients in the psychiatric unit, over a 1-week period, were reviewed. Details of current benzodiazepine and z-hypnotic prescriptions were collected. Information collected included the substance prescribed, duration and administration instructions. Feedback was communicated to medical practitioners through a presentation and email. A re-audit was completed 4 months later. RESULTS: There were increases in total benzodiazepine and z-hypnotic prescribing despite intervention. A reduction of 2 mg occurred in the mean regular dose of benzodiazepine prescribed. Lorazepam was the most prescribed benzodiazepine throughout. In both data sets, at least 50% of regular z-hypnotics and benzodiazepines were initiated before admission. There was an increase of 14% in regular benzodiazepines initiated in hospital exceeding 4 weeks in duration. In neither data collection did regular z-hypnotics initiated in hospital exceed this cut off. A greater number of individuals were in the process of being withdrawn from regular benzodiazepine or z-hypnotic prescriptions in the re-audit. There were minimal improvements in 'as required' prescribing as regards documentation of an indication, time limit and maximum dose. CONCLUSION: The increase in overall prescribing, despite intervention, maybe because these medications continued to be indicated in the acute presentations needing inpatient treatment. The small improvements in 'as required' prescribing patterns suggest that the intervention was limited in effecting change in this area.

Low temperature solution synthesis of silicon, germanium and Si-Ge axial heterostructures in nanorod and nanowire form.

Herein, we report the formation of silicon, germanium and more complex Si-SixGe1-x and Si-Ge axial 1D heterostructures, at low temperatures in solution. These nanorods/nanowires are grown using phenylated compounds of silicon and germanium as reagents, with precursor decomposition achieved at substantially reduced temperatures (200 °C for single crystal nanostructures and 300 °C for heterostructures), through the addition of a reducing agent. This low energy route for the production of these functional nanostructures as a wet chemical in high yield is attractive to meet the processing needs for next generation photovoltaics, batteries and electronics.

Central venous oxygen saturation during high-risk general surgical procedures-relationship to complications and clinical outcomes.

Major non-cardiac surgery is associated with postoperative morbidity, and perioperative central venous oxygen saturation (ScvO2) may be a predictor of morbidity. This pilot study aimed to define intraoperative ScvO2 and to identify factors associated with postoperative complications. ScvO2 (reflection spectrophotometry) was recorded continuously in a convenience sample of adults undergoing high-risk general surgery. Demographics, intraoperative management, surgery duration, postoperative complications and deaths within 28 days were recorded. Data from 51 patients were analysed. Two (4%) died and 24 (47%) had at least one complication (range 1 to 5). The hospital length-of-stay and duration of surgery were longer in those with complications (22.1±6.1 versus 9.6±3.6 days, P >0.0001, and 328±162 minutes versus 241±94 minutes, P=0.02, respectively). Overall, the ScvO2 was 82±8% and ranged from 40% to 97% with 17 (33%) patients having at least one episode of ScvO2 >70%. Hospital length-of-stay (P >0.0001), time ScvO2 >90% (P=0.003), surgery duration (P=0.005) and blood loss (P=0.02) were correlated with the number of complications. Using multivariate analysis, surgery duration (odds ratio 1.008 [95% confidence interval 1.002 to 1.013]; P=0.006) and change in oxygen extraction ratio (O2ER) at the end of surgery compared to the beginning (odds ratio 1.13 [95% confidence interval 1.001 to 1.28]; P=0.04) were independently associated with complications. The surgery duration and an increased O2ER are factors related to the development of postoperative complications.

Classification of low systemic vascular resistance using photoplethysmogram and routine cardiovascular measurements.

Low systemic vascular resistance (SVR) can be a useful indicator for early diagnosis of critical pathophysiological conditions such as sepsis, and the ability to identify low SVR from simple and noninvasive physiological signals is of immense clinical value. In this study, an SVR classification system is presented to recognize the occurrence of low SVR, among a heterogenous group of patients (N = 48), based on the use of routine cardiovascular measurements and features extracted from the finger photoplethysmogram (PPG) as inputs to a quadratic discriminant classifier. An exhaustive feature search was performed to identify a near optimum feature subset. Cohen's kappa coefficient (κ) was used as a performance measure to compare candidate feature sets. The classifier using the following combination of features performed best (κ = 0.56, sensitivity = 96.30%, positive predictivity = 92.31%): normalized low-frequency power (LFNU) derived from PPG, ratio of low-frequency power to high-frequency power (LF/HF) of the PPG variability signal, and the ratio of mean arterial pressure to heart rate (MAP/HR). Classifiers that used either LF(NU) (κ = 0.43), LF/HF (κ = 0.37) or MAP/HR (κ = 0.43) alone showed inferior performance. Discrimination of patients with and without low SVR can be achieved with reasonable accuracy using multiple features derived from the PPG combined with routine cardiovascular measurements.

Observation of graphene bubbles and effective mass transport under graphene films.

Mechanically exfoliated graphene mounted on a SiO2/Si substrate was subjected to HF/H(2)O etching or irradiation by energetic protons. In both cases gas was released from the SiO2 and accumulated at the graphene/SiO2 interface resulting in the formation of "bubbles" in the graphene sheet. Formation of these "bubbles" demonstrates the robust nature of single layer graphene membranes, which are capable of containing mesoscopic volumes of gas. In addition, effective mass transport at the graphene/SiO2 interface has been observed.

Salmonella enterica phage-resistant mutant colonies display an unusual phenotype in the presence of phage Felix 01.

AIMS: To investigate irregular colony morphology formation in Salmonella enterica serovar Typhimurium DPC6046 in the presence of a lytic phage, Felix 01. METHODS AND RESULTS: Phage-resistant derivatives of the parent strain DPC6046 were isolated which exhibited an irregular colony morphology. These were subjected to viability studies by using confocal scanning laser microscopy and live/dead BacLight stain to evaluate the cell viability within the colony. The phenomenon was also observed with other S. enterica serotypes tested which were normally sensitive to phage Felix. In the case of strain DPC6046, dead cells were clearly evident at the irregular edges of the phage-resistant colonies in locations where the cell density was lower. This colony morphology was not apparent with two other Salmonella phages tested. CONCLUSIONS: These findings support the hypothesis that the unusual morphology is due to reversion to phage sensitivity and consequent cell death within the colony as it forms. SIGNIFICANCE AND IMPACT OF THE STUDY: The irregular colony morphology observed is peculiar to phage Felix. The confocal scanning laser microscopy methodology allowed the basis for the irregular morphology to be elucidated.

The newly isolated lytic bacteriophages st104a and st104b are highly virulent against Salmonella enterica.

AIMS: To screen Irish faecal samples from a variety of sources with a view to isolating novel anti-Salmonella phages and to subsequently evaluate their lytic capability. METHODS AND RESULTS: Two novel anti-Salmonella phages st104a and st104b were isolated from a screening programme based on their lytic capability. The phages produced significantly larger plaques (2 mm) on the chosen indicator Salmonella enterica strain, DPC6046, when compared with the well-known control phage, Felix 01 (0.5 mm). Both phages st104a and st104b were found to have a broad host range within the Salm. enterica species. During in vitro trials, both phages (st104a and st104b) reduced Salm. enterica numbers more than 99% within 1 h. In vivo studies, involving the addition of the phage to porcine gastric juice (pH 2.5) demonstrated that phage st104a and phage Felix 01 were capable of surviving (10 and 30% survival respectively) the acidic conditions, unlike st104b, which was undetectable after 2 h exposure. CONCLUSIONS: Two novel lytic anti-Salmonella phages were isolated and characterized. SIGNIFICANCE AND IMPACT OF THE STUDY: With the exception of phage Felix 01, there has been relatively little phage therapy work performed using lytic Salmonella phage. In this study, the lytic phages st104a and st104b were isolated as a result of a faecal screening programme. Subsequently, phage st104a was found to have potential for biocontrol of Salm. enterica numbers if administered orally to pigs given their survival in porcine gastric juice, whereas, phage st104b may have potential in reducing cell numbers if applied by alternative approaches.

Evaluation of a cocktail of three bacteriophages for biocontrol of Escherichia coli O157:H7.

Escherichia coli O157:H7 is an endemic pathogen causing a variety of human diseases including mild diarrhea, hemorrhagic colitis, hemolytic-uremic syndrome, and thrombotic thrombocytopenic purpura. This study concerns the exploitation of bacteriophages as biocontrol agents to eliminate the pathogen E. coli O157:H7. Two distinct lytic phages (e11/2 and e4/1c) isolated against a human strain of E. coli O157:H7, a previously isolated lytic phage (pp01), and a cocktail of all three phages were evaluated for their ability to lyse the bacterium in vivo and in vitro. Phage e11/2, pp01, and the cocktail of all three virulent phages resulted in a 5-log-unit reduction of pathogen numbers in 1 h at 37 degrees C. However, bacteriophage-insensitive mutants (BIMs) emerged following the challenge. All tested BIMs had a growth rate which approximated that of the parental O157 strain, although many of these BIMs had a smaller, more coccoid cellular morphology. The frequency of BIM formation (10(-6) CFU) was similar for e11/2, pp01, and the phage cocktail, while BIMs insensitive to e4/1c occurred at the higher frequency (10(-4) CFU). In addition, BIMs commonly reverted to phage sensitivity within 50 generations. In an initial meat trial experiment, the phage cocktail completely eliminated E. coli O157:H7 from the beef meat surface in seven of nine cases. Given that the frequency of BIM formation is low (10(-6) CFU) for two of the phages, allied to the propensity of these mutants to revert to phage sensitivity, we expect that BIM formation should not hinder the use of these phages as biocontrol agents, particularly since low levels of the pathogen are typically encountered in the environment.

Chemokines, chemokine receptors and adhesion molecules on different human endothelia: discriminating the tissue-specific functions that affect leucocyte migration.

The selective accumulation of different leucocyte populations during inflammation is regulated by adhesion molecules and chemokines expressed by vascular endothelium. This study examined how chemokine production and the expression of adhesion molecules and chemokine receptors vary between endothelia from different vascular beds. Human saphenous vein endothelium was compared with lung and dermal microvascular endothelia and with umbilical vein endothelium and a bone-marrow endothelial cell line. All endothelia produced CCL2 and CXCL8 constitutively, whereas CXCL10 and CCL5 were only secreted after tumour necrosis factor (TNF)-alpha or interferon (IFN)-gamma stimulation. In combination with TNF-alpha, IFN-gamma suppressed CXCL8 but enhanced CCL5 and CXCL10, whereas transforming growth factor (TGF)-beta reduced secretion of all chemokines. Basal chemokine secretion was higher from umbilical vein than other endothelial cells. Chemokine receptors, CXCR1, CXCR3 and CCR3, were present on all endothelia but highest on saphenous vein. CCR4, CCR5, CCR6, CXCR2, CXCR4 and CXCR5 were also detected at variable levels on different endothelia. The variation between endothelia in chemokine secretion was much greater than the variations in adhesion molecules, both on resting cells and following cytokine stimulation. These results indicate that it is the tissue-specific variations in endothelial chemokine secretion rather than variations in adhesion molecules that can explain the different patterns of inflammation and leucocyte traffic seen in non-lymphoid tissues.

Relationship of hairless mouse skin surface temperature to wound severity and maturation time.

Skin surface temperature (SST) changes measured on live hairless mice are presented as a simple means of following wound healing. SST is generally determined by 3 factors which are the ambient temperature, the rate of water loss from the surface of the skin and the diffusion of thermal energy from the body's core. The SST increase immediately after a burn injury reflects the amount of thermal energy absorbed by the skin surface. For burns and other injuries, the drop in SST following injury, but after thermal equilibrium has been established, provides an early indication of the degree of impairment of the skin's barrier. Three kinds of mouse skin wounds, mechanical (tape stripping), thermal and chemical (phenol application), were investigated. SST nadirs ranged from 2.1 to 4.4 degrees C with mild to full-thickness burns, respectively. Except for the earliest moments after wounding, striking parallels were noted between SST and transepidermal water loss profiles for these injuries. The SST profile over the full course of wound healing clearly indicates the severity of the injury, the stages of wound maturation and the time to complete skin healing.

Predicting the dermal absorption of thalidomide and its derivatives.

Concern has been expressed about the ability of simple algorithms to predict skin permeability and hence skin flux. For a series of thalidomide analogues, a number of software packages have been used to predict octanol water partition coefficients. These, in conjunction with molecular weight, have then been used to calculate skin permeability coefficients. These compare favourably with experimental values. Some of the software packages also predict aqueous solubilities, which can be subsequently used to calculate maximum skin flux. The predicted and measured solubilities have been compared together with the maximum fluxes. The results show that software can be used to predict octanol water partition coefficients and aqueous solubilities (more accurately if the melting point of the compound is known) and hence to obtain very reasonable estimates of skin permeation parameters. These are useful in predicting which analogue has the most appropriate properties for dermal delivery; in the case of the thalidomide analogues, it is the methyl-substituted compound that is best.

Identification of iron sulphide grains in protoplanetary disks.

Sulphur is depleted in cold dense molecular clouds with embedded young stellar objects, indicating that most of it probably resides in solid grains. Iron sulphide grains are the main sulphur species in cometary dust particles, but there has been no direct evidence for FeS in astronomical sources, which poses a considerable problem, because sulphur is a cosmically abundant element. Here we report laboratory infrared spectra of FeS grains from primitive meteorites, as well as from pyrrhotite ([Fe, Ni](1-x)S) grains in interplanetary dust, which show a broad FeS feature centred at approximately 23.5 micrometres. A similar broad feature is seen in the infrared spectra of young stellar objects, implying that FeS grains are an important but previously unrecognized component of circumstellar dust. The feature had previously been attributed to FeO. The observed astronomical line strengths are generally consistent with the depletion of sulphur from the gas phase, and with the average Galactic sulphur/silicon abundance ratio. We conclude that the missing sulphur has been found.

The synthesis and tubulin binding activity of thiophene-based analogues of combretastatin A-4.

A number of analogues of combretastatin A-4 (1), containing a thiophene ring interposed between the two phenyl groups, have been prepared. The synthesis of these compounds employed a combination of palladium-mediated coupling and iodocyclization techniques. The thiophene compounds 11, 14, 18, and 19 also represent non-benzofused analogues of some recently described tubulin binding benzo[b]thiophenes 3-5. The most active thiophene compounds identified in this study were 11, 14, and 18. Overall they are less active than 1 but exhibit comparable activity to the most active of the benzo[b]thiophenes 3-5. A structure-activity relationship of these compounds is considered.