The European Clozapine Task Force is a group of psychiatrists and pharmacologists practicing in 18 countries under European Medicines Agency (EMA) regulation, who are deeply concerned about the underuse of clozapine in European countries. Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia, a large proportion of them do not have access to this treatment. Concerns about clozapine-induced agranulocytosis and stringent blood monitoring rules are major barriers to clozapine prescribing and use. There is a growing body of evidence that the incidence of clozapine-induced agranulocytosis is very low after the first year of treatment. Maintaining lifelong monthly blood monitoring after this period contributes to unjustified discontinuation of clozapine. We leverage recent and replicated evidence on the long-term safety of clozapine to call for the revision and updating of the EMA’s blood monitoring rules, thus aiming to overcome this major barrier to clozapine prescribing and use. We believe the time has come for relaxing the rules without increasing the risks for people using clozapine in Europe.

A wake model is pursued for potential flow past a submerged, finite-length plate that is perpendicular to a uniform, horizontal stream bounded above by a free surface. The effects of gravity are included along the free surface. The approach is to adopt an open-wake model such that the wake boundaries become parallel to the undisturbed stream at some (unknown) point downstream. Boundary integral equations are formed and then discretised along the wake boundaries and free surface in order to obtain a solution numerically. In terms of the dependency of the solution on various parameters, the problem will be formulated in two ways. First, for a given Froude number and ratio of the length of the vertical plate to the draft (the depth of the bottom of the vertical plate relative to the undisturbed free surface), the effect of the wake underpressure coefficient on the size of the wake will be considered. Then, the problem will be discussed where we instead (more naturally) fix the Froude number, draft and length of the vertical, submerged plate. The dependencies of the solution on these parameters will be analysed regarding the effects on several factors, including the size of the wake, the relative lengths of the upper and lower wake boundaries, and the resulting wake underpressure coefficient.

This study estimated the treatment cost of pediatric abdominal tuberculosis that potentially needs surgical treatment in India. Data were collected from 38 in-patient children at Christian Medical Hospital, Ludhiana as part of a clinical study conducted to establish the patterns of presentation and outcomes of abdominal tuberculosis in an Indian setting. A bottom-up approach was used to estimate the costs from a healthcare provider perspective, and a generalized linear model (GLM) was run to find variables that had an impact on the costs. Costs were reported in international dollars ($) and India Rupees (INR). The results show that the average direct cost was $3095.00 (standard deviation [SD]: 3480.82) or 68,065.13 INR (SD: 76,539.69). The GLM results established that duration of treatment and surgical treatment were significantly associated with higher costs. Efforts of eliminating the condition should be strengthened.

As the IAU heads towards its second century, many changes have simultaneously transformed Astronomy and the human condition world-wide. Amid the amazing recent discoveries of exoplanets, primeval galaxies, and gravitational radiation, the human condition on Earth has become blazingly interconnected, yet beset with ever-increasing problems of over-population, pollution, and never-ending wars. Fossil-fueled global climate change has begun to yield perilous consequences. And the displacement of people from war-torn nations has reached levels not seen since World War II.

A comparison is made of the Holocene records obtained from water isotope measurements along 11 ice cores from coastal and central sites in east Antarctica (Vostok, Dome B, Plateau Remote, Komsomolskaia, Dome C, Taylor Dome, Dominion Range, D47, KM105, and Law Dome) and west Antarctica (Byrd), with temporal resolution from 20 to 50 yr. The long-term trends possibly reflect local ice sheet elevation fluctuations superimposed on common climatic fluctuations. All the records confirm the widespread Antarctic early Holocene optimum between 11,500 and 9000 yr; in the Ross Sea sector, a secondary optimum is identified between 7000 and 5000 yr, whereas all eastern Antarctic sites show a late optimum between 6000 and 3000 yr. Superimposed on the long time trend, all the records exhibit 9 aperiodic millennial-scale oscillations. Climatic optima show a reduced pacing between warm events (typically 800 yr), whereas cooler periods are associated with less-frequent warm events (pacing >1200 yr).

The past few years have seen the introduction of a number of 3D and 4D printingtechniques used to process tough hydrogel materials. The use of‘color’ 3D printing technology where multiple inks areused in the one print allows for the production of composite materials andstructures that can further enhance the mechanical performance of the printedhydrogel. This article reviews a number of 3D and 4D printing techniques forfabricating functional hydrogel based devices.

Stroke is a leading cause of morbidity and mortality in the US, with secondary damage following the initial insult contributing significantly to overall poor outcome. Prior investigations have shown that the metabolism of certain polyamines such as spermine, spermidine, and putrescine are elevated in ischemic parenchyma, resulting in an increase in their metabolite concentration. Polyamine metabolites tend to be cytotoxic, leading to neuronal injury in the penumbra following stroke and expansion of the area of infarcted tissue. Although the precise mechanism is unclear, the presence of reactive aldehydes produced through polyamine metabolism, such as 3-aminopropanal and acrolein, have been shown to correlate with the incidence of cerebral vasospasm, disruption of oxidative metabolism and mitochondrial functioning, and disturbance of cellular calcium ion channels. Regulation of the polyamine metabolic pathway, therefore, may have the potential to limit injury following cerebral ischemia. To this end, we review this pathway in detail with an emphasis on clinical applicability.

The mechanical characteristics of ionic-covalent entanglement hydrogels consisting of combinations of the biopolymers gellan gum and kappa-carrageenan, and the synthetic polymers polyacrylamide and an epoxy amine were investigated. Compression testing showed that these gels exhibited “double network” behavior, i.e. strong tough gels.

Dietary interventions with flavan-3-ols have shown beneficial effects on vascular function. The translation of these findings into the context of the health of the general public requires detailed information on habitual dietary intake. However, only limited data are currently available for European populations. Therefore, in the present study, we assessed the habitual intake of flavan-3-ol monomers, proanthocyanidins (PA) and theaflavins in the European Union (EU) and determined their main food sources using the EFSA (European Food Safety Authority) Comprehensive European Food Consumption Database. Data for adults aged 18–64 years were available from fourteen European countries, and intake was determined using the FLAVIOLA Flavanol Food Composition Database, developed for the present study and based on the latest US Department of Agriculture and Phenol-Explorer databases. The mean habitual intake of flavan-3-ol monomers, theaflavins and PA ranged from 181 mg/d (Czech Republic) to 793 mg/d (Ireland). The highest intakes of flavan-3-ol monomers and theaflavins were observed in Ireland (191/505 mg/d) and the lowest intakes in Spain (24/9 mg/d). In contrast, the daily intake of PA was highest in Spain (175 mg/d) and lowest in The Netherlands (96 mg/d). Main sources were tea (62 %), pome fruits (11 %), berries (3 %) and cocoa products (3 %). Tea was the major single contributor to monomer intake (75 %), followed by pome fruits (6 %). Pome fruits were also the main source of PA (28 %). The present study provides important data on the population-based intake of flavanols in the EU and demonstrates that dietary intake amounts for flavan-3-ol monomers, PA and theaflavins vary significantly across European countries. The average habitual intake of flavan-3-ols is considerably below the amounts used in most dietary intervention studies.

Background: We describe the hospital system response to the Interstate 35W bridge collapse in Minneapolis into the Mississippi River on August 1, 2007, which resulted in 13 deaths and 127 injuries. Comparative analysis of response activities at the 3 hospitals that received critical or serious casualties is provided.

Methods: First-hand experiences of hospital physicians, issues identified in after-action reports, injury severity scores, and other relevant patient data were collected from the 3 hospitals that received seriously injured patients, including the closest hospitals to the collapse on each side of the river.

Results/Discussion: Injuries were consistent with major acceleration/deceleration force injuries. The most critical patients arrived first at each hospital, suggesting appropriate prehospital triage. Capacity of the health care system was not overwhelmed and the involved hospitals generally reported an overresponse by staff. Communication and patient tracking problems occurred at all of the hospitals. Situational awareness was limited due to the scope of structural collapse and incomplete information from the scene.

Conclusions: Hospitals were generally satisfied with their surge capacity and incident management plan activation. Issues such as communications, patient tracking, and staff overreporting that have been identified in past incidents also were problematic in this event. Hospitals will need to address deficiencies and build on successful actions to cope with future, potentially larger incidents. (Disaster Med Public Health Preparedness. 2008;2(Suppl 1):S11–S16)

Mass casualty triage is a critical skill. Although many systems exist to guide providers in making triage decisions, there is little scientific evidence available to demonstrate that any of the available systems have been validated. Furthermore, in the United States there is little consistency from one jurisdiction to the next in the application of mass casualty triage methodology. There are no nationally agreed upon categories or color designations. This review reports on a consensus committee process used to evaluate and compare commonly used triage systems, and to develop a proposed national mass casualty triage guideline. The proposed guideline, entitled SALT (sort, assess, life-saving interventions, treatment and/or transport) triage, was developed based on the best available science and consensus opinion. It incorporates aspects from all of the existing triage systems to create a single overarching guide for unifying the mass casualty triage process across the United States. (Disaster Med Public Health Preparedness. 2008;2(Suppl 1):S25–S34)