Antipsychotic use and unexpected death: a hospital-based case-control study.

OBJECTIVE: To examine the risk of unexpected death in patients prescribed an antipsychotic. Unexpected death was defined as death occurring within 7 days of the onset of acute symptoms. METHOD: A case-control study conducted on events occurring between July 2009 and January 2011 in a UK mental health trust providing in-patient and out-patient services. RESULTS: The study included 100 cases (deaths) and 436 unmatched controls. Current users of antipsychotics had a lower risk of unexpected death than non-users--adjusted odds ratio (OR) 0.48 (95% CI 0.24-0.94, P = 0.033). A significant reduction in risk was seen for second-generation [adjusted OR 0.42 (95% CI 0.21-0.86, P = 0.018)], but not first-generation agents [adjusted OR 0.83 (95% CI 0.31-2.20, P = 0.706)]. Treatment with antipsychotics for any duration was associated with reduced risk. Dose and route of administration did not affect risk. In a planned secondary analysis not adjusting for cardiovascular disease, prescription of an antipsychotic was not associated with increased risk of unexpected death [adjusted OR 0.56 (95% CI 0.28-1.08, P = 0.084)]. CONCLUSION: Our findings do not support an association between current antipsychotic use and increased risk of unexpected death.

Aurore: A platform for ultrafast sciences.

We present the Aurore platform for ultrafast sciences. This platform is based on a unique 20 W, 1 kHz, 26 fs Ti:sapphire laser system designed for reliable operation and high intensity temporal contrast. The specific design ensures the high stability in terms of pulse duration, energy, and beam pointing necessary for extended experimental campaigns. The laser supplies 5 different beamlines, all dedicated to a specific field: attosecond science (Aurore 1), ultrafast phase transitions in solids (Aurore 2 and 3), ultrafast luminescence in solids (Aurore 4), and femtochemistry (Aurore 5). The technical specifications of these five beamlines are described in detail, and examples of the recent results are given.

Ammonia influence in anaerobic digestion of OFMSW.

The anaerobic digestion of the organic fraction of municipal solid wastes is taking increasing importance in the recent years. The main problem of some anaerobic digestion process is the large quantity of ammonia that is released, especially when high solid digestion is implemented. A fraction of the supernatant is treated and the remaining is recirculated to maintain the reactor in the optimum solids concentration. The question arising is if this recirculation stream should also be treated to improve biogas production. However, when doing the latter the quantity of ammonia inside the reactor increases too which could lead to inhibit the reactor operation. In this paper it appears that not only free ammonia affects the methanogenic fermentation but also ammonium ion concentration. Biogas production profiles are estimated using the Gompertz model. On the other hand, inhibition constants are fitted using a non-competitive inhibition model equation Thus, 50% inhibition of biomethane production was observed at level of 215 and 468 mg NH3_N/L under mesophilic and thermophilic conditions. However, the methane generation under mesophilic and thermophilic conditions was reduced by 50% when ammonium ion reach concentrations of 3,860 and 5,600 mg NH4+_N/L respectively. Under mesophilic conditions, pH higher than 7 impacted the methanogens bacteria negatively. This threshold pH limit, is variable under thermophilic conditions, depending on the total ammonia concentration.

Integration of a Coagulation/Flocculation step in a biological sequencing batch reactor for COD and nitrogen removal of supernatant of anaerobically digested piggery wastewater.

The supernatant from mesophilic anaerobic digestion of piggery wastewater is characterised by a high amount of COD (4.1 g COD L(-1)), ammonium (2.3g NH(4)(+)-NL(-1)) and suspended solids (2.5 g SS L(-1)). This effluent can be efficiently treated by means of a Sequencing Batch Reactor (SBR) strategy for biological COD, SS and nitrogen removal including a Coagulation/Flocculation step. Total COD and SS reduction yields higher than 66% and 74%, respectively, and a total nitrogen removal (via nitrite) of more than 98% were reached when working with HRT 2.7 days, SRT 12 days, temperature 32 degrees C, three aerobic/anoxic periods, without external control of pH and under limited aeration flow. The inhibition of nitrite oxidizing biomass was achieved by the working free ammonia concentration and the restricted air supply (dissolved oxygen concentration below 1 mg O(2)L(-1)). Since a part of the total COD was colloidal and/or refractory, a Coagulation/Flocculation step was implemented inside the SBR operating strategy to meet a suitable effluent quality to be discharged. Several Jar-Tests demonstrated that the optimal concentration of FeCl(3) was 800 mg L(-1). A respirometric assay showed that this coagulant dosage did not affect the biological activity of nitrifying/denitrifying biomass.

Operation and model description of a sequencing batch reactor treating reject water for biological nitrogen removal via nitrite.

The aim of this study was the operation and model description of a sequencing batch reactor (SBR) for biological nitrogen removal (BNR) from a reject water (800-900 mg NH(4)(+)-NL(-1)) from a municipal wastewater treatment plant (WWTP). The SBR was operated with three cycles per day, temperature 30 degrees C, SRT 11 days and HRT 1 day. During the operational cycle, three alternating oxic/anoxic periods were performed to avoid alkalinity restrictions. Oxygen supply and working pH range were controlled to achieve the BNR via nitrite, which makes the process more economical. Under steady state conditions, a total nitrogen removal of 0.87 kg N (m(3)day)(-1) was reached. A four-step nitrogen removal model was developed to describe the process. This model enlarges the IWA activated sludge models for a more detailed description of the nitrogen elimination processes and their inhibitions. A closed intermittent-flow respirometer was set up for the estimation of the most relevant model parameters. Once calibrated, model predictions reproduced experimental data accurately.

Comparison of reject water treatment with nitrification/denitrification via nitrite in SBR and SHARON chemostat process.

A comparison between three feasible ways of developing Biological Nitrogen Removal (BNR) via nitrite to treat real reject water of 800-900 mg NH4(+)-N l(-1) is proposed. A Sequencing Batch Reactor (SBR) and a chemostat SHARON (Single reactor High activity Ammonium Removal Over Nitrite) continuous reactor were operated. In the SBR operation 0.8 kg N (d m3)(-1) was achieved, whereas in SHARON/denitrification the removal reached was 0.4 kg N (d m3)(-1). SHARON was also developed with partial nitrification of ammonium in order to obtain a stream ready for Anammox (Anaerobic Ammonia Oxidation) process obtaining an effluent with an average composition of 400 mg NO2(-)-N l(-1) and 350 mg NH4(-)-N l(-1).

Low energy Ne ion beam induced-modifications of magnetic properties in MnAs thin films.

Investigations of the complex behavior of the magnetization of manganese arsenide thin films due to defects induced by irradiation of slow heavy ions are presented. In addition to the thermal hysteresis suppression already highlighted in Trassinelli et al (2014 Appl. Phys. Lett. 104 081906), we report here on new local magnetic features recorded by a magnetic force microscope at different temperatures close to the characteristic sample phase transition. Complementary measurements of the global magnetization in different conditions (applied magnetic field and temperatures) enable the film characterization to be completed. The obtained results suggest that the ion bombardment produces regions where the local mechanical constraints are significantly different from the average, promoting the local presence of magneto-structural phases far from the equilibrium. These regions could be responsible for the thermal hysteresis suppression previously reported, irradiation-induced defects acting as seeds in the phase transition.

Dry anaerobic digestion of differently sorted organic municipal solid waste: a full-scale experience.

This paper presents a comparison of dry anaerobic digestion reactors fed with differently sorted municipal organic solid wastes. One reactor was fed with source sorted organic wastes and a second reactor was fed with mixed organic wastes consisting of grey wastes, mechanically selected municipal solid wastes and sludge. The two reactors utilised the same process (Valorga) and operational conditions at full scale. The results of the study emphasise the influence of the kind of treated material on the process performances, especially in terms of biogas and methane production, thus, energy reclamation. The reactor treating the source sorted organic waste and the reactor treating the mixed organic wastes generated some 200 m3 and 60 m3 of biogas per ton of waste treated, respectively, while the specific methane production was some 0.40 and 0.13 m3CH4/kgTVS, respectively. The mass balance and the final fate of the digested material from the two reactors were also clearly different. As for the costs, these were some 29 Euro per ton of treated waste (50% for personnel) and 53 Euro/ton for disposing of the rejected materials. Incomes were some 100 Euro/ton (on average) and an other 15 Euro/ton came from green certificates. The initial investment was 16 million Euros.

Start-up of a biological sequencing batch reactor to treat supernatant from anaerobic sludge digester.

Treating the supernatant (reject water) from an anaerobic sludge digestion (800-1200 mg NH4(+)-N l(-1)) may be a good solution for meeting local requirements. As reject water represents 0.6% of the total wastewater influent flow and contains 10-30% of the total N it is recirculated to the head plant. In this study, a lab-scale start-up of biological nitrification/denitrification process to treat reject water was developed in a sequencing batch reactor. Sludge acclimation to the denitrification process was quite fast (6-7 days) for both NO2(-)-N and NO3(-)-N, whereas in nitrification it was slower (20 days). The use of a sequencing batch reactor to treat reject water produced a complete biological reduction of the NH4(+)-N via nitrite, working with sludge age of 15 days, hydraulic retention time of 1.3 days, temperature of 28 degrees C, pH between 7-8.5 and biomass concentration around 3500 mg VSS l(-1). Specific efficiencies were 14 mg NH4(+)-N (g VSS h(-1)) and 30 mg NO2(-)-N (g VSS h)(-1).

Biological nutrient removal by a sequencing batch reactor (SBR) using an internal organic carbon source in digested piggery wastewater.

Experiments in a lab-scale SBR were conducted to demonstrate the feasibility of using an internal carbon source (non-digested pig manure) for biological nitrogen and phosphorus removal in digested piggery wastewater. The internal C-source used for denitrification had similar effects to acetate. 99.8% of nitrogen and 97.8% of phosphate were removed in the SBR, from an initial content in the feed of 900 mg/l ammonia and 90 mg/l phosphate.

Autonomic nervous control of heart rate: sympathetic-parasympathetic interactions and age related differences.

A factorial experimental design was used to quantify the changes in heart rate produced by stimulation of the cardiac sympathetic and vagal nerves in eleven adult dogs and four puppies, and to quantify the extent of the peripheral sympathetic-vagal interactions. The chronotropic responses to autonomic stimulation were significantly less in the puppies than in the adult dogs, which suggests that autonomic regulation is functionally incomplete in the puppies. In both adult dogs and puppies, the chronotropic responses to autonomic nerve stimulation were bilaterally asymmetrical. The heart rate responses to a given level of right-sided stimulation of either the sympathetic or vagal nerves were greater than those to comparable left-sided stimulation. In both adult dogs and puppies, there were significant sympathetic-vagal interactions, such that the sympathetic enhancement of heart rate was less effective the higher the background level of vagal activity. The sympathetic-vagal interactions were prominent in the puppies as well as in the adult animals, regardless of whether the stimulated sympathetic and vagal nerves were located ipsilaterally or contralaterally to one another. Thus, the mechanisms responsible for the sympathetic-vagal interactions appear to be fully developed in puppies. Also, the cardiac sympathetic nerve endings that originate from one side of the body must lie in close apposition to the cardiac vagal nerve endings that originate from either the same side or from the opposite side of the body.

A proposed architecture for lecithin cholesterol acyl transferase (LCAT): identification of the catalytic triad and molecular modeling.

The enzyme cholesterol lecithin acyl transferase (LCAT) shares the Ser/Asp-Glu/His triad with lipases, esterases and proteases, but the low level of sequence homology between LCAT and these enzymes did not allow for the LCAT fold to be identified yet. We, therefore, relied upon structural homology calculations using threading methods based on alignment of the sequence against a library of solved three-dimensional protein structures, for prediction of the LCAT fold. We propose that LCAT, like lipases, belongs to the alpha/beta hydrolase fold family, and that the central domain of LCAT consists of seven conserved parallel beta-strands connected by four alpha-helices and separated by loops. We used the conserved features of this protein fold for the prediction of functional domains in LCAT, and carried out site-directed mutagenesis for the localization of the active site residues. The wild-type enzyme and mutants were expressed in Cos-1 cells. LCAT mass was measured by ELISA, and enzymatic activity was measured on recombinant HDL, on LDL and on a monomeric substrate. We identified D345 and H377 as the catalytic residues of LCAT, together with F103 and L182 as the oxyanion hole residues. In analogy with lipases, we further propose that a potential "lid" domain at residues 50-74 of LCAT might be involved in the enzyme-substrate interaction. Molecular modeling of human LCAT was carried out using human pancreatic and Candida antarctica lipases as templates. The three-dimensional model proposed here is compatible with the position of natural mutants for either LCAT deficiency or Fish-eye disease. It enables moreover prediction of the LCAT domains involved in the interaction with the phospholipid and cholesterol substrates.

Vagal control of heart period in alloxan diabetic rats.

Autonomic neuropathies are a frequent complication to diabetes in humans. Similar neuropathies have not been well-documented in animal models. To determine if diabetic rats would develop parasympathetic neuropathies, rats were made diabetic by the injection of alloxan into the tail vein and then maintained on daily injections of insulin. At various times subsequent to the induction of diabetes (3-5 weeks, 7-9 weeks, and 14 weeks), the effect of constant frequencies of vagal stimulation on the efferent cardiac chronotropic response was evaluated using analysis of variance techniques. It was found that the vagal parasympathetic effect was accentuated in diabetic rats. That is, at a given frequency of supramaximal vagal stimulation, the heart rate slowed more in diabetic rats than in nondiabetic rats. Whether a similar phenomenon exists in humans is not known.

Differences in plasma lidocaine levels with endotracheal drug therapy secondary to total volume of diluent administered.

Endotracheal drug therapy provides an effective alternative method for the administration of drugs in the numerous clinical settings in which intravenous access is difficult or impossible to obtain. However, the specific factors affecting endotracheal drug absorption and thus, the drug's plasma levels and effectiveness, has not yet been fully determined. Lidocaine alone or lidocaine mixed with normal saline was given endotracheally in four volumes (Volume I = undiluted with less than or equal to 5.5 cc total volume; Volume II = diluted to 6 cc total volume; Volume III = diluted to 12 cc total volume; Volume IV = diluted to 25 cc total volume) by the same technique of administration and in the same dosage of 4 mg/kg. Each dog served as its own control and received all four volumes of endotracheal lidocaine on different occasions. Plasma lidocaine levels at all four volumes and at all four time periods (5, 15, 30 and 60 min after giving endotracheal lidocaine) were obtained in each of the six dogs for a total of 96 plasma lidocaine levels measured in the study. Mean plasma lidocaine levels (micrograms/ml) at 5 min were: Volume I = 1.9, Volume II = 10.0, Volume III = 3.2 and Volume IV, = 4.3. These results were highly significant (P less than 0.001). The highest plasma lidocaine levels were obtained in the diluted volume, Volume II and the lowest plasma lidocaine levels in the undiluted volume, Volume I, with Volumes III and IV being intermediate.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of hypoxemia on pharmacokinetics of endotracheal lidocaine in dogs.

Endotracheal administration is an effective alternative method for giving drugs in the many clinical situations in which it is difficult or impossible to quickly obtain an intravenous line. Yet whether various clinical conditions such as hypoxemia have any effect on endotracheal drug therapy is not known. Sixteen sets of plasma lidocaine levels were measured at 5, 15, 30, and 60 min after endotracheal lidocaine administration in eight dogs. Each dog was given the same dose of endotracheal lidocaine by the same technique of administration while in both a normal control state (Group I = 'Non-hypoxemia', mean Po2 = 98) and during hypoxemia (Group II = "Hypoxemia", mean Po2 = 36). Significantly higher plasma lidocaine levels occurred in the hypoxemic state (Group II) at time = 5 min while there was no significant difference in plasma lidocaine levels at time = 15, 30, and 60 min. Mean plasma lidocaine levels (micrograms/ml) at 5 min were: Group I = 1.38, Group II = 2.36 (significant at P less than 0.05). Plasma lidocaine levels were: Group I = 1.61 vs. Group II = 1.63 at time = 15 min, Group I = 1.11 vs. Group II = 1.10 at time = 30 min, and Group I = 0.54 vs. Group II = 0.51 at time = 60 min. Thus, there was a higher peak plasma lidocaine level and a shorter time to peak plasma lidocaine levels in the hypoxemic dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma lidocaine levels occurring with endotracheal administration during hemorrhagic shock.

During the many emergency situations in which venous access is difficult or impossible, endotracheal drug administration is an effective alternative means of delivering life-saving medications. Shock is a commonly encountered emergency situation in which endotracheal drug therapy can and is often used. Yet whether a drug given endotracheally during shock can be absorbed from the lungs and pass into the bloodstream is not known. Forty-five sets of plasma lidocaine levels drawn at 5, 15, 30 and 60 min after the administration of endotracheal lidocaine at a dose of 2 or 4 mg/kg were obtained in dogs either in shock or in a normal control group: Group I = "Non-shock" or normal control, N = 27; Group II = "Shock", N = 18. Significantly higher plasma lidocaine levels occurred in the shock group in all time periods and with either dose of lidocaine (P less than 0.001). Mean plasma lidocaine levels (micrograms/ml) at 5 min were: (at 2 mg/kg dose) Group I = 1.1, Group II = 2.0; and (at 4 mg/kg dose) Group I = 2.3, and Group II = 5.1. The dose of lidocaine, the technique of administration, and the time at which the plasma lidocaine level was drawn as well as whether shock vs. non-shock was present were all highly significant factors (P less than 0.001) in determining plasma lidocaine levels. In summary: (1) endotracheal lidocaine is absorbed during shock and (2) higher plasma lidocaine levels occur during shock than during the non-shock control state. This suggests that the dosage of endotracheal medication may need to be adjusted for various clinical conditions such as shock.

Selective serotonin reuptake inhibitors: a review of efficacy and tolerability in depression.

Selective serotonin reuptake inhibitors (SSRIs) are now generally regarded as effective and better tolerated alternatives to tricyclic antidepressants (TCAs) for the treatment of depression. SSRIs also seem to be as well tolerated as moclobemide, mirtazapine, venlafaxine, reboxetine and nefazodone and show comparable efficacy. Minor differences have been observed between some SSRIs and some of the newer antidepressants but these findings are far from conclusive. Widespread use of the SSRIs has highlighted some unforseen adverse effects associated with SSRIs, namely hyponatraemia, EPSE and sexual dysfunction. Overall, differences in efficacy and tolerability between individual SSRIs are small and clinically insignificant.

Nitrification, denitrification and biological phosphorus removal in piggery wastewater using a sequencing batch reactor.

Nutrients in piggery wastewater with high organic matter, nitrogen (N) and phosphorus (P) content were biologically removed in a sequencing batch reactor (SBR) with anaerobic, aerobic and anoxic stages. The SBR was operated with 3 cycles/day, temperature 30 degrees C, sludge retention time (SRT) 1 day and hydraulic retention time (HRT) 11 days. With a wastewater containing 1500 mg/l ammonium and 144 mg/l phosphate, a removal efficiency of 99.7% for nitrogen and 97.3% for phosphate was obtained. Experiments set up to evaluate the effect of temperature on the process showed that it should be run at temperatures higher than 16 degrees C to obtain good removals (> 95%). Batch tests (ammonia utilization rate, nitrogen utilization rate and oxygen utilization rate) proved to be good tools to evaluate heterotrophic and autotrophic biomass activity. The SBR proved to be a very flexible tool, and was particularly suitable for the treatment of piggery wastewater, characterized by high nutrient content and by frequent changes in composition and therefore affecting process conditions.

Asthma therapy in the observation unit.

The management of asthma is a commonly encountered clinical problem. There have been major advances in the treatment of asthma, including an increase in the drugs available for treatment, as well as in knowledge of the pathophysiology of the disease. Despite these advances, however, the prevalence, morbidity, and mortality for asthma have shown a disturbing upward trend over the past few decades. Experience with the OU management of asthma has shown many advantages: decreased inpatient hospitalization, better quality of life for patients, higher patient satisfaction, cost-effectiveness, and effective patient care. It is estimated that 60% to 70% of asthmatic patients could be treated in an ED observation unit instead of in an inpatient hospital ward. There is a tremendous opportunity for the OU management of asthma to improve patient care, as well as decrease costs, thereby reducing asthma morbidity and mortality.

Pediatric observation medicine.

Observing pediatric patients in an OU (whether a pediatric or combined or hybrid unit) has many advantages: better patient care, a decrease in missed diagnoses and acuity, better risk management, decreased malpractice liability, cost effectiveness, increased patient and family satisfaction, and psychosocial benefits. Key principles of observation medicine (purpose, time frame, general patient inclusion and exclusion criteria, administration, CQI, and so forth) are equivalent for pediatric and adult observation patients, but there are important differences. Unique characteristics of pediatric observation patients include specific diagnosis, decreased length of stay, less need for cardiac monitoring, a highly variable admission rate, and a decreased percentage or admission rate to the OU from the ED. Whereas the adult OU is primarily a cardiac-monitoring unit, the pediatric OU is a respiratory and infectious disease unit with a frequent need for an i.v. therapy and hydration. Types of pediatric patients commonly treated in an OU include respiratory illnesses (asthma, croup, bronchiolitis, pneumonia), gastrointestinal disorders (gastroenteritis, abdominal pain), dehydration, infections (fever, cellulitis, lymphangitis, pyelonephritis or UTI), overdoses or poisonings, and seizures.