Rivastigmine for treatment-refractory posttraumatic stress disorder: a systematic review.

We conducted a systematic review evaluating the efficacy of rivastigmine augmentation for treatment-refractory posttraumatic stress disorder (PTSD). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. The databases Ovid MEDLINE, PubMed, CINAHL, and EMBASE were searched using key words: 'rivastigmine' OR 'Exelon' OR 'rivastigmine augmentation' OR 'Exelon augmentation' AND 'posttraumatic stress disorder*' OR 'post-traumatic stress disorder*' OR 'PTSD' OR 'combat disorder*' OR 'post-traumatic symptoms'. The asterisk specified plural forms of the relevant word. Four papers were identified, comprising one double-blind randomised controlled trial, one non-controlled open trial, one case series (presenting three case studies), and one paper with two case studies. The randomised controlled trial found no statistically significant difference in efficacy, using the PTSD CheckList-Military Version as the relevant outcomes measure, between the active add-on rivastigmine interventions and placebo or treatment as usual. The open trial, although reporting relatively positive outcomes, had a weak study design and lacked reporting of key information, including participant sex and age and pre-rivastigmine PTSD measures. The assessment of efficacy was based on participants' reporting of subjective benefits, and clinician-rating using a Clinical Global Impression, rather than established PTSD assessments scales. Although the five case studies reported improvement in PTSD symptoms, there were confounding factors and limitations in clinical and demographic data, warranting caution regarding attributed benefits. There is a lack of methodologically robust evidence supporting the efficacy of add-on rivastigmine for the treatment of refractory PTSD. Additional research may help in further evaluating its possible clinical efficacy.

Surgeon-administered ilio-inguinal and pudendal nerve blocks for major vulval surgery: An observational study with visual analogue pain scoring.

Surgical excision of the groin and vulva is a painful procedure. Traditionally following general or regional anaesthesia, local anaesthetic was infiltrated around the wound. Thedistribution varied and the somatic pain control was not reliable. Inspired by the success of the application of peripheral nerve blocks for postoperative pain control with open abdominal procedures, we introduced blockade of the ilioinguinal nerve (IIN) and pudendal nerve (PN) into our vulval surgery to assess the requirement for parenteral and oral analgesia in the postoperative period. This is an observational study of all patients undergoing major vulval and/or related groin surgery. Sampling biopsies were excluded. Levobipuvicaine 0.25% (2.5 mg/ml) or 0.5% (5 mg/ml) was used for and dosage was calculated based on the patient's weight with no more than 2 mg/kg. For example, using 0.25% of levobupivacaine (2.5 mg/ml) for a 70 kg patient, 56 ml is administered divided into 4, giving 14mls at each site (2 sites abdominally for IIN block and 2 sites for pudendal block). Eighteen women were included in the analysis. Median age was 67 (range 34-81) years and thirteen (72%) were >60 years. Visual analogue scores (VAS) ranged from 0 to 3 for seventeen patients from day 0 to day 1 and fifteen patients from day 2 to day 5. Two patients had pain scores >4 on one or more postoperative days: one had chronic arthralgia and one had received a lower volume of bupivacaine. This observational study demonstrates that ilioinguinal and pudendal nerve LA blocks may be a valuable addition to the multimodal postoperative analgesic pathway for women undergoing major surgical excision in the vulva and groin.

Microfluidic ratio metering devices fabricated in PMMA by CO2 laser.

We describe microfluidic fabrication results achieved using a 10.6 µm CO2 engraving laser on cast PMMA, in both raster and vector mode, with a 1.5″ lens and a High Power Density Focussing Optics lens. Raster written channels show a flatter base and are more U-shaped, while vector written channels are V shaped. Cross-sectional images, and, where possible, stylus profilometry results are presented. The sides of V-grooves become increasing steep with laser power, but broader shallower channels may be produced in vector mode by laser defocus, as illustrated. Smoothing of raster engraved channels by heated IPA etch, and transparency enhancement by CHCl3 vapour treatment are briefly discussed. An asymmetric Y meter is discussed as one method of diluting acid into seawater for dissolved CO2 analysis. Alternatively, microfluidic snake channel restrictors of different lengths in 2 channels may achieve the same result. Samples are fabricated with bases bonded by CHCl3 vapour treatment, and the devices are flow tested with either dilute food dye or DI water. Microfluidics fabricated in this manner have applications in ocean sensing of dissolved CO2 and other analytes, as well as broader sensing measurements, including biomedical sensors.

The analysis of dissolved inorganic carbon in liquid using a microfluidic conductivity sensor with membrane separation of CO2.

Autonomous continuous analysis of oceanic dissolved inorganic carbon (DIC) concentration with depth is of great significance with regard to ocean acidification and climate change. However, miniaturisation of in situ analysis systems is hampered by the size, cost and power requirements of traditional optical instrumentation. Here, we report a low-cost microfluidic alternative based on CO2 separation and conductance measurements that could lead to integrated lab-on-chip systems for ocean float deployment, or for moored or autonomous surface vehicle applications. Conductimetric determination of concentration, in the seawater range of 1000-3000 µmol kg-1, has been achieved using a microfluidic thin-film electrode conductivity cell and a membrane-based gas exchange cell. Sample acidification released CO2 through the membrane, reacting in a NaOH carrier, later drawn through a sub-µL conductivity cell, for impedance versus time measurements. Precision values (relative standard deviations) were ~ 0.2% for peak height measurements at 2000 µmol kg-1. Comparable precision values of ~ 0.25% were obtained using a C4D electrophoresis headstage with similar measurement volume. The required total sample and reagent volumes were ~ 500 µL for the low volume planar membrane gas exchange cell. In contrast, previous conductivity-based DIC analysis systems required total volumes between 5000 and 10,000 µL. Long membrane tubes and macroscopic wire electrodes were avoided by incorporating a planar membrane (PDMS) in the gas exchange cell, and by sputter deposition of Ti/Au electrodes directly onto a thermoplastic (PMMA) manifold. Future performance improvements will address membrane chemical and mechanical stability, further volume reduction, and component integration into a single manifold.

Low-dose IL-2 induces CD56bright NK regulation of T cells via NKp44 and NKp46.

Low-dose interleukin (IL)-2 has shown clinical benefits in patients with autoimmune and inflammatory diseases. Both regulatory T cells (Tregs ) and natural killer (NK) cells are increased in response to low-dose IL-2 immunotherapy. The role of regulatory T cells in autoimmune diseases has been extensively studied; however, NK cells have not been as thoroughly explored. It has not been well reported whether the increase in NK cells is purely an epiphenomenon or carries actual benefits for patients with autoimmune diseases. We demonstrate that low-dose IL-2 expands the primary human CD56bright NK cells resulting in a contact-dependent cell cycle arrest of effector T cells (Teffs ) via retention of the cycle inhibitor p21. We further show that NK cells respond via IL-2R-ß, which has been shown to be significant for immunity by regulating T cell expansion. Moreover, we demonstrate that blocking NK receptors NKp44 and NKp46 but not NKp30 could abrogate the regulation of proliferation associated with low-dose IL-2. The increase in NK cells was also accompanied by an increase in Treg cells, which is dependent on the presence of CD56bright NK cells. These results not only heighten the importance of NK cells in low-dose IL-2 therapy but also identify key human NK targets, which may provide further insights into the therapeutic mechanisms of low-dose IL-2 in autoimmunity.

Long-term hydrolytically stable bond formation for future membrane-based deep ocean microfluidic chemical sensors.

Future ocean profiling of dissolved inorganic carbon and other analytes will require miniaturised chemical analysis systems based on sealed gas membranes between two fluid channels. However, for long-term deployment in the deep ocean at high pressure, the ability to seal incompatible materials represents an immense challenge. We demonstrate proof of principle high strength bond sealing. We show that polydimethylsiloxane (PDMS) is a preferred membrane material for rapid CO2 transfer, without ion leakage, and report long-term stable bonding of thin PDMS membrane films to inert thermoplastic poly(methyl methacrylate) (PMMA) patterned manifolds. Device channels were filled with 0.01 M NaOH and subjected to repeated tape pull and pressure - flow tests without failure for up to six weeks. Bond formation utilised a thin coating of the aminosilane bis-[3-trimethoxysilylpropyl]amine (BTMSPA) conformally coated onto PMMA channels and surfaces and cured. All surfaces were subsequently plasma treated and devices subject to thermocompressive bond annealing. Successful chemically resistant bonding of membrane materials to thermoplastics opens the possibility of remote environmental chemical analysis and offers a route to float-based depth profiling of dissolved inorganic carbon in the oceans.

Dual endothelin-1 receptor antagonism attenuates platelet-mediated derangements of blood coagulation in Eisenmenger syndrome.

Essentials Eisenmenger syndrome is characterised by thrombotic and hemorrhagic risks of unclear aetiology. Calibrated automated thrombography was used to assess these coagulation derangements. Platelet activity supported abnormalities in procoagulant and anticoagulant pathway function. Endothelin-1 antagonism appeared to ameliorate these derangements. SUMMARY: Aims The mechanisms underlying the competing thrombotic and hemorrhagic risks in Eisenmenger syndrome are poorly understood. We aimed to characterize derangements of blood coagulation and to assess the effect of dual endothelin-1 receptor antagonism in modulating hemostasis in this rare disorder. Methods In a 10-month recruitment period at a tertiary cardiology referral center, during which time there were over 14 000 outpatient consultations, consecutive subjects with Eisenmenger syndrome being considered for macitentan therapy (n = 9) and healthy volunteers (n = 9) were recruited. Plasma thrombin generation in platelet-rich and platelet-poor plasma was assessed by calibrated automated thrombography prior to and following therapy. Results Median peak plasma thrombin generation was higher in platelet-rich plasma obtained from Eisenmenger syndrome subjects relative to controls (median peak thrombin [25th-75th percentile]: 228.3 [206.5-258.6] nm vs. 169.9 [164.3-215.8] nm), suggesting a critical mechanistic role for platelets in supporting abnormal hypercoagulability in Eisenmenger syndrome. Abnormal enhanced sensitivity to the anticoagulant activity of activated protein C was also observed in platelet-rich plasma in Eisenmenger syndrome, suggesting that derangements of platelet activity may influence the activity of anticoagulant pathways in a manner that might promote bleeding in this disease state. Following 6 months of macitentan therapy, attenuations in the derangements in both procoagulant and anticoagulant pathways were observed. Conclusions Abnormal platelet activity contributes to derangements in procoagulant and anticoagulant pathways in Eisenmenger syndrome. Therapies targeting the underlying vascular pathology appear to ameliorate these derangements and may represent a novel strategy for the management of the competing prothrombotic and hemorrhagic tendencies in this disorder.

Tinzaparin thromboprophylaxis prescribing practice after caesarean delivery 2009-2014.

BACKGROUND: National guidelines have been developed to ensure correct dosing of tinzaparin for women delivered by caesarean delivery (CD) to reduce the risk of venous thromboembolism. AIMS: The aim of this study is to examine the impact of implementation of national guidelines on thromboprophylaxis prescribing practice for women undergoing CD in a university maternity hospital. METHODS: Details of tinzaparin usage were obtained from the Hospital pharmacy for the years 2009-2014. Information on CD and pulmonary embolism (PE) were obtained from the Hospital's annual clinical reports. RESULTS: Following guideline recommendations on weight-based tinzaparin for all women undergoing CD, the usage of syringes prefilled with tinzaparin 4500 IU increased from 526 to 8502 (P < 0.001) and usage of syringes prefilled with tinzaparin 10,000 IU increased from 36 to 910 (P < 0.001). Usage of syringes prefilled with tinzaparin 3500 IU decreased from 8216 in 2009 to 39 in 2014 (P < 0.001). During 2008-2010, there were two cases of PE after CD, both of whom received an inadequate dose of prophylactic tinzaparin. During 2011-2014 there were no cases of PE diagnosed after a total of 9427 CDs. CONCLUSIONS: The development of national guidelines on thromboprophylaxis after CD was followed by a significant change in weight-based prescribing of tinzaparin. Following implementation, there have been no cases of PE after CD.

Comparative study of image contrast in scanning electron microscope and helium ion microscope.

Images of Ga+ -implanted amorphous silicon layers in a 110 n-type silicon substrate have been collected by a range of detectors in a scanning electron microscope and a helium ion microscope. The effects of the implantation dose and imaging parameters (beam energy, dwell time, etc.) on the image contrast were investigated. We demonstrate a similar relationship for both the helium ion microscope Everhart-Thornley and scanning electron microscope Inlens detectors between the contrast of the images and the Ga+ density and imaging parameters. These results also show that dynamic charging effects have a significant impact on the quantification of the helium ion microscope and scanning electron microscope contrast.

Evaluation of point-of-care maternal glucose measurements for the diagnosis of gestational diabetes mellitus.

OBJECTIVE: Using updated laboratory standards as the reference, we aimed to compare point-of-care (POC) maternal capillary glucose testing with the diagnostic accuracy of reference and customary venous samples. DESIGN, SETTING, POPULATION: Women screened selectively with a one-step 75-g oral glucose tolerance test (OGTT) at 24-28 weeks' gestation were conveniently recruited to this prospective observational study. METHODS: Two venous samples and one capillary sample were taken at each OGTT time point. Venous sample one was a fluoride-EDTA (FE) tube placed on an ice-slurry until cell separation and analysis within 30 minutes (reference standard). Venous sample two was transported in a tube containing FE (without ice) (customary practice). A capillary sample was used for POC testing. Various cut-off points for the POC sample were examined to evaluate diagnostic accuracy. MAIN OUTCOME MEASURES: The sensitivity, specificity, positive and negative predictive values and accuracy of POC capillary glucose for the diagnosis of GDM. RESULTS: Of 108 women, GDM was detected in 47.2% (n = 51), 17.6% (n = 19) and 24.1% (n = 26) using the reference standard, customary practices and POC, respectively (P < 0.001). However, based on adjustment of the POC fasting diagnostic threshold from ≥5.1 to ≥4.8 mol/l (aPOC), sensitivity, specificity, PPV, NPV and accuracy improved to 92.5, 76.5, 69.8, 94.5 and 94.5%, respectively. CONCLUSIONS: POC capillary maternal glucose tests were superior to customary laboratory practices for diagnosing GDM. This has considerable potential, particularly in healthcare settings where facilities for phlebotomy are distant from the laboratory or pre-analytical sample handling is substandard. TWEETABLE ABSTRACT: Adjusted point-of-care glucose measurements have potential in the diagnosis of gestational diabetes mellitus.

Energy band diagram of device-grade silicon nanocrystals.

Device grade silicon nanocrystals (NCs) are synthesized using an atmospheric-pressure plasma technique. The Si NCs have a small and well defined size of about 2.3 nm. The synthesis system allows for the direct creation of thin films, enabling a range of measurements to be performed and easy implementation of this material in different devices. The chemical stability of the Si NCs is evaluated, showing relatively long-term durability thanks to hydrogen surface terminations. Optical and electrical characterization techniques, including Kelvin probe, ultraviolet photoemission spectroscopy and Mott-Schottky analysis, are employed to determine the energy band diagram of the Si NCs.

Femoral imaging artifacts associated with dorsal recumbency craniocaudal radiographic positioning. Description of a modified bisecting angle technique.

OBJECTIVES: To describe the radiographic length distortion associated with femoral tilt during cranio-caudal positioning. To describe a modified bisecting angle technique to alleviate image foreshortening. METHODS: Five pairs of femurs were imaged. The femurs were tilted from 0 to 50 degrees and the X-ray anode was tilted from 0 to 40 degrees. Femoral length was measured on the resulting images. A geometric model depicting sagittal femoral positioning was described with two trigonometric formulas. Trigonometric formula 1 (TF¹) was designed to predict apparent femoral length. Data generated by TF¹ were compared to the cadaveric study results. Trigonometric formula 2 (TF²), based on the same model, was used to predict the ideal anode angle (iAA) to alleviate foreshortening. Unrelated to the model, a simplified linear formula (SF) was created to approximate the TF². Data generated with the SF and the TF² were compared. RESULTS: When the femoral specimens were tilted to 20 degrees or greater, significant foreshortening was appreciated (p <0.001). Increasing the anode angle increased apparent length, eliminating foreshortening. Data generated by the TF¹ agreed closely with the results of the cadaveric study (R² = 0.999). The SF and the TF² demonstrated close agreement and were able to predict an iAA consistent with the results of the cadaveric study. CLINICAL SIGNIFICANCE: A femoral tilt of 20 degrees or greater results in significant image foreshortening and may warrant alternate radiographic techniques. If the femur is tilted, adjusting the anode angle can alleviate femoral foreshortening.

Synthesis of surfactant-free electrostatically stabilized gold nanoparticles by plasma-induced liquid chemistry.

Plasma-induced non-equilibrium liquid chemistry is used to synthesize gold nanoparticles (AuNPs) without using any reducing or capping agents. The morphology and optical properties of the synthesized AuNPs are characterized by transmission electron microscopy (TEM) and ultraviolet-visible spectroscopy. Plasma processing parameters affect the particle shape and size and the rate of the AuNP synthesis process. Particles of different shapes (e.g. spherical, triangular, hexagonal, pentagonal, etc) are synthesized in aqueous solutions. In particular, the size of the AuNPs can be tuned from 5 nm to several hundred nanometres by varying the initial gold precursor (HAuCl4) concentration from 2.5 µM to 1 mM. In order to reveal details of the basic plasma-liquid interactions that lead to AuNP synthesis, we have measured the solution pH, conductivity and hydrogen peroxide (H2O2) concentration of the liquid after plasma processing, and conclude that H2O2 plays the role of the reducing agent which converts Au(+3) ions to Au(0) atoms, leading to nucleation growth of the AuNPs.

Disinfection of meticillin-resistant Staphylococcus aureus and Staphylococcus epidermidis biofilms using a remote non-thermal gas plasma.

The effective disinfection of hospital surfaces is recognised as an important factor in preventing hospital-acquired infections. The purpose of this study was to quantify the disinfection rate of a novel gas plasma system on clinically relevant biofilms. Clinical isolates of Staphylococcus epidermidis and meticillin-resistant Staphylococcus aureus (MRSA) were grown as biofilms on glass surfaces and tested in a disinfection container remote from the plasma source. The strains used in this study were known to produce substantial quantities of biofilm and average log10 counts were 9.0 and 9.1 cfu/cm(2) for S. epidermidis and MRSA respectively. Counts were reduced by between 4 and 4.5 log10 after 1h of exposure for MRSA and S. epidermidis respectively. More prolonged treatment in the case of MRSA biofilms resulted in a 5.5 log10 reduction after 90 min. Biofilm samples were also placed in medical device packaging bags and similar rates of disinfection were observed.

Electrical and Raman spectroscopic studies of vertically aligned multi-walled carbon nanotubes.

Microwave plasma enhanced chemical vapour deposition (MPECVD) was used for the production of carbon nanotubes. Vertically aligned multi-walled carbon nanotubes (MWCNTs) were grown on silicon substrates coated with cobalt thin films of thickness ranging from 0.5 nm to 3 nm. Prior to the nanotube growth the catalyst were treated with N2 plasma for 5-10 minutes that break the films into small nanoparticles which favour the growth of nanotubes. The CNTs were grown at a substrate temperature of 700 degrees C for 5, 10 and 15 minutes. The height of the CNT films ranging from 10 microm-30 microm indicating that the initial growth rate of the CNTs are very high at a rate of approximately 100 nm/sec. Electrical resistivity of the above samples was evaluated from I-V measurements. The activation energy (E(a)) was also calculated from the temperature dependent studies and it was found that the E(a) lies in the range of 15-35 meV. Raman spectroscopy was used to identify the quality of the nanotubes.

Differential stimulation of monocytic cells results in distinct populations of microparticles.

BACKGROUND: Microparticles (MPs), small vesicles shed from stimulated cells, permit cross-talk between cells within a particular environment. Their composition is thought to reflect their cell of origin, and differs according to whether they are produced by stimulation or by apoptosis. Whether MP properties vary according to stimulus is not yet known. METHODS: We studied the characteristics of MPs produced from monocytic THP-1 cells upon stimulation with lipopolysaccharide or a soluble P-selectin chimera, using proteomics, flow cytometry, western blotting, and electron microscopy. RESULTS: Utilizing a novel criterion of calcein-AM staining to define MPs, we found that MP populations were similar with respect to size, presence and organization of cytoskeleton, and expression of certain antigens. The MPs shared the same level of procoagulant activity. We found that MPs also have distinct characteristics, depending on stimuli. These include differences in phosphatidylserine expression and expression of proteins from specific subcellular locations such as the mitochondria, and of unique antigens such as leukocyte-associated immunoglobin-like-receptor (LAIR)-1, which was found only upon stimulation with the soluble P-selectin chimera. CONCLUSION: We found that the properties of MPs depend on the stimulus that produced them. This supports the concept that monocytic MPs differentially modulate thrombosis, inflammation and immune regulation according to stimulus.

Can a brief psychological intervention prevent anxiety or depressive disorders in cancer patients? A randomised controlled trial.

BACKGROUND: We tested whether a brief psychological intervention could prevent anxiety or depressive disorders among newly diagnosed cancer patients. PATIENTS AND METHODS: Patients free of anxiety or depressive disorder were randomised to receive immediate intervention (start of cancer treatment), delayed intervention (8 weeks after starting treatment) or usual care. They were stratified according to risk of developing anxiety or depressive disorders. Primary outcome was measured using a standardised psychiatric interview to detect any anxiety or depressive disorder at 6 and 12 months following the cancer diagnosis. Analyses used conditional odds logistic regression models adjusting for age, gender, concerns and past history to compare outcome of all intervention patients with usual care. RESULTS: A total of 465 patients were recruited. In all, 313 (79%) of the 397 well enough to be interviewed completed the study. At 12 months, there was no difference between the groups receiving the intervention and usual care [odds ratio (OR) = 0.69, 95% confidence interval (CI) 0.41-1.17, P = 0.17]. In high-risk patients, those who received the intervention were less likely to develop an anxiety or depressive disorder compared with those who received usual care (OR = 0.54, 95% CI 0.29-1.00, P = 0.050). In low-risk patients, there was no difference (OR = 1.50, 95% CI 0.51-4.43, P = 0.47). CONCLUSION: A brief intervention, delivered by nonspecialists, promoted adjustment among newly diagnosed cancer patients at high risk of developing anxiety or depressive disorders.

Characterisation of an optical clock recovery method based on a mode-locked laser diode using spectrographic pulse measurement.

As channels rates in optical networks are expected to exceed 100 Gb/s in the near future, new optical techniques for clock recovery will have to be developed for optical regeneration. This paper describes an optical clock recovery method based on a mode-locked laser diode. Experimental results show that a 42 GHz high quality optical clock can be retrieved from a 170 Gb/s OTDM data signal. Chirp transfer between the incident signal and the recovered clock signal is investigated using the SHG-FROG method. Results demonstrate that this clock recovery technique is invariant to input dispersion varying between +/-75 ps/nm, making it ideal for use in 3R regenerators.