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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.
Researchers generally do an excellent job tracking the scientific impacts of their scholarship in ways that are relevant for academia (e.g., publications, grants) but too often neglect to focus on broader impacts on population health and equity. The National Cancer Institute’s Implementation Science Centers in Cancer Control (ISC3) includes 7 P50 Centers that are interested in broad measures of impact. We provide an overview of the approach underway within the ISC3 consortium to identify health and social impacts.
Methods:
ISC3 adapted and applied the Translational Science Benefits Model (TSBM) to identify the impact on the discipline of D&I science and to consider dissemination and implementation (D&I) impacts in the four original TSBM domains: (1) clinical; (2) community; (3) economic; and (4) policy. To collect data from all Centers, we: (1) co-developed a set of detailed impact indicators with examples; (2) created a data collection template; and (3) summarized the impact data from each center.
Results:
Based on data from 48 ISC3 pilot studies, cores, or consortium activities, we identified 84 distinct benefits. The most common impacts were shown for implementation science (43%), community (28%), and clinical (18%). Frequent audiences included primary care providers, public health practitioners, and community partners. ISC3 members highlighted the need for product feedback, and storytelling assistance to advance impact.
Conclusions:
The ISC3 consortium is using a participatory approach to successfully apply the TSBM, thus seeking to maximize the real-world impacts of D&I science. The D&I field needs to prioritize ways to more fully document and communicate societal impacts.
Diagnostic stability is a controversial issue in first episode psychosis (FEP) due to heterogenous symptoms and unclear affective symptoms. Differencing affective and non-affective psychoses is important as treatment strategies are different. Initial affective symptomatology has low specificity for predicting the subsequent diagnosis of affective psychosis. Sex has proven to be relevant for clinical and functional outcomes but it remains unclear how sex may contribute to diagnosis switch of FEP.
Objectives
To determine the role of sex in diagnostic stability in a sample of FEP after 1-year follow-up.
Methods
Diagnoses of FEP patients from Hospital del Mar of Barcelona were assessed at baseline and 1 year after. Univariate analyses was perfomed for all diagnoses and dichotomic variable (affective/non-affective). Logistic regression model was perfomed to know which variables predict diagnosis switch.
Results
256 patients were enrolled. No differences were found at baseline between completers and non-completers (Table 1). No significant differences between men and women at baseline diagnosis were found, neither all diagnoses (p=0.274) nor the dichotomic variable affective/non-affective (p=0.829) (Table 2AB). Significant differences were found at 1-year follow-up between men and women, for all diagnoses (p=0.043) and the dichotomic variable (p=0.039). Sex was the only variable that predicted diagnosis switch (Figure 1), PANSS, CDSS, YMRS, GAF and cannabis did not.Table 1.
Baseline characteristics of participants
Completers (n=188)
Non-completers (n=68)
p
Women (n, %)
71 (37.8)
30 (44.1)
0.111
Age (M, IQR)
24 (20-28)
22 (20-28)
0.899
Cannabis use (M, IQR)
5.5 (0-18)
7 (0-21)
0.231
DUP (M, IQR)
45 (12.5-130)
36 (11.25-115.75)
0.213
PANSS (m, sd)
44.55 (10.17)
40.93 (10.42)
0.761
CDSS (M, IQR)
2 (0-7)
3 (0-5.5)
0.199
YMRS (m, sd)
19 (9.64)
17.6 (9.15)
0.845
GAF (M, IQR)
30 (25-50)
30 (25-35)
0.114
TABLE 2A and 2B.
Diagnosis comparison (n, %)
Baseline
1-year follow-up
Men
Women
Total
Men
Women
Total
Psychosis NOS
69 (59)
39 (54.9)
108 (57.4)
28 (23.9)
10 (14.1)
38 (20.2)
Schizophreniform disorder
22 (18.8)
16 (22.5)
38 (20.2)
14 (12
9 (12.7)
23 (12.2)
Induced psychosis
4 (3.4)
0 (0)
4 (2.1)
15 (12.8)
4 (5.6)
19 (10.1)
Affective psychosis
17 (14.5)
9 (12.7)
26 (13.8)
24 (20.5)
25 (35.2)
49 (26.1)
Schizophrenia
0 (0)
0 (0)
1 (0.4)
30 (25.6)
14 (19.7)
44 (23.4)
Brief psychotic disorder
5 (4.3)
7 (9.9)
12 (6.4)
6 (5.1)
8 (11.3)
14 (7.4)
Baseline
1-year follow-up
Men
Women
Total
Men
Women
Total
Affective psychosis
17 (14.5)
9 (12.7)
26 (13.8)
24 (20.5)
25 (35.2)
49 (26.1)
Non-affective psychosis
100 (85.5)
62 (87.3)
162 (86.2)
93 (79.5)
46 (64.8)
139 (73.9)
Image:
Conclusions
Sex has proven to be the main predictor of switching initial diagnosis of FEP.
Psychotic disorders are strongly linked to a higher risk of mandatory hospitalization, often affecting men more, though some studies report the opposite. Recent investigations also show a higher rate of involuntary admissions in younger individuals. Knowledge in this area is still limited despite extensive research.
Objectives
Analyze whether there is an association between sex and age with involuntary admissions of individuals with psychotic disorders.
Methods
Retrospectively, 254 people with psychotic disorders admitted between 2018-2023 to the adult psychiatric inpatient unit at Hospital Universitari Germans Trias i Pujol were selected, collecting their nature of admission, sex, age, and discharge diagnosis. Comparisons between voluntary and involuntary admissions, with respect to sex and age variables, were conducted using independent sample t-tests, Mann-Whitney U tests, Fisher’s exact test, and chi-square tests. A logistic regression model was used to identify variables significantly associated with mandatory admission.
Results
In both the male and female groups, there were no statistically significant differences in terms of the mean age at admission (p = 0.162) or the nature of admission (p = 0.586) (Table 1). When analyzing the voluntary nature of admission based on age and sex, statistically significant differences were only found in the female group (p = 0.01), resulting in a 9.18 year age difference among those admitted voluntarily (Table 2). The model that best predicted the probability of involuntary admission in individuals with psychotic disorders included the sex variable (OR = 4.88) and the interaction between sex and age (OR = 0.97) (Table 3).Table 1:
Differences between sex regarding voluntariness of patients with psychotic disorders.
Male
Female
p value
N (%)
122 (48%)
132 (52%)
Age, m (SD)
38.39 (16.64)
44.15 (18.44)
0.162
Admissions, N (%)
Voluntary
38 (31.1%)
37 (28.0%)
0.586
Involuntary
84 (68.9%)
95 (72.0%)
Table 2:
Analysis of voluntariness by sex and age.
Age, m (SD)
Voluntary
Involuntary
p value
Male
37.45 (16.38)
38.81 (16.84)
0.677
Female
50.76 (18.19)
41.58 (17.98)
0.01*
Total
44.01 (18.44)
40.28 (17.46)
0.127
Table 3:
Predictors of involuntariness in psychotic patients: Logistic regression model (ENTER METHOD).
Predictor
-2log likelihood
Nagelkerke R2
x2 (df*)
OR* (95% CI*)
p value
301.22
0.039
0.03 (1)
Age
1.01 (0.98; 1.03)
0.674
Sex
4.88 (1.15; 20.72)
0.032*
Age x Sex Interaction
0.97 (0.94; 0.99)
0.046*
Conclusions
Young women with psychotic disorders face a higher risk of involuntary admissions, emphasizing the need for gender-specific strategies to improve care of these patients.
Obsessive-compulsive disorder (OCD) is a chronic disorder with a wide range of manifestations but primarily intrusive thoughts (obsessions) and/or ritualized actions (compulsions) that can cause a huge distress in patients’ life. First-line treatment for OCD are selective serotonin reuptake inhibitors (SSRIs). Tricyclic antidepressants are used as second-line treatment due to secondary effects. Also antipsychotics such as aripiprazole are approved for treating OCD. Vortioxetine is has 5-HT3, 5-HT7 and 5-HT1D antagonists, 5-HT1B partial agonist and a 5-HT1A agonist and serotonin transporter inhibitor property. It is used in major depressive and anxiety disorders. A male 48 years old patient with an OCD diagnosis since he was 21, was reffered to psychiatry department. Previously, he had no response with SSRIs at full dosage and clomipramine 75mg was effective. At 46 years old, he had an acute myocardial infarction. He also admited not taking the medication regularly due to sexual disfunction and having affective symptoms related to the distress caused by OCD.
Objectives
To evaluate efficacy of vortioxetine in treating OCD in a patient with contraindications for tricyclic antidepressants and no response to SSRIs.
Methods
Clomipramine dose was reduced until discontinuation. After one week without treatment, basal scores for Hamilton Scale and Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS) were collected. Same data was collected again after 10 weeks treatment.
Results
The dosage of vortioxetine was progressively titrated until 20mg daily in 3 weeks lapse. Diazepam 5mg was added in case of insomnia or anxiety. Aripiprazole 5mg was added in the third week of treatment as adjunctive treatment due to the recurrence of some intrusive thoughts (discontinued by himself because of akathisia). Finally, the patient reported an improvement in affective and OCD symptoms in the sixth week of treatment that was sustained until the tenth week, when data was recollected. The patient did not refer sexual disfunction.
The pre and post results are summarized in tables 1 and 2.Table 1.
Hamilton Depresion Rating Scale (0-52)
Basal
Post 10-week treatment
21
4
Dimensional Y-BOCS (0-15)
Basal
Post 10-week treatment
Aggressive-related obsessions and compulsions
10
2
Religious-related obsessions and compulsions
5
1
Symmetry and order
7
1
Pollution and cleaning
0
0
Collecting and accumulation
2
0
Miscellaneous
10
3
Conclusions
Vortioxetine might be a promising molecule for treating OCD in patients with contraindications for first and second-line treatments.
A common design of a high-level radioactive waste (HLW) disposal system consists of the waste canisters emplaced in tunnels or shafts, with the space between the heat-emitting canisters and the surrounding rock filled with a bentonite-based material. Understanding the behavior of this barrier, in particular the effect of prolonged heating on its properties, is important to assess the barrier’s long-term performance. The objective of the present study was to add to this understanding and to supply experimental data about the state of bentonite hydrated and heated for a long period of time. To that end, a 50 cm long column of Wyoming-type bentonite pellets was heated at its base at 140 °C (simulating the waste canister) while a synthetic sodium-chloride-rich groundwater including sulfate, calcium, and magnesium was supplied through its upper surface for almost 10 y. At the end of the experiment the upper half of the column was saturated, but in the lower half the water content decreased sharply toward the heater, where it was close to 0%. No relevant mineralogical changes occurred, and the main component of the bentonite continued to be a predominantly sodium montmorillonite with no structural changes with respect to the initial one. In the area where the temperatures were >60°C and the material very dry, however, the smectite was not able to completely develop the 1-layer hydrate after 48 h of stabilization at RH 55%, although its expandability was fully recovered when the smectite was hydrated with liquid water. The ions solubilized as a result of the water-content increase were transported toward the heater and concentrated in two distinct areas: sodium and calcium chlorides closer to the heater than calcium and sodium sulfates. At the heater contact, the bentonite microstructure was of dense packets with carbon and Na-S-coated cavities. Precipitation of calcite and calcium sulfates and possibly dissolution of silica minerals also took place close to the heater.
The hoverfly Eristalinus aeneus is an important pollinator of crops and wild plants. However, there is a lack of detailed information about its foraging behaviour and its potential as a managed pollinator of mango. Given the growing economic importance of protected cultivation of mango, our aim is to study the flight activity and foraging behaviour of E. aeneus on this crop. Eristalinus aeneus displayed a bimodal daily activity, with peaks during mid-morning and mid-afternoon. The activity was maintained over a wide range of temperature (from 17.8 up to 37.4°C), light intensity (from 8.2 up to 57.4 klux) and relative humidity (from 19.0 up to 88.8%). The syrphids were active most of the time in this crop, and we observed five different types of activity: foraging (67%), resting (17%), flying (10%), grooming (4%) and walking (2%). This hoverfly visited hermaphrodite flowers more often than male flowers. On average, it visited 36.46 ± 13.92 flowers per 5 min, with a higher number of floral visits for nectar feeding. The duration of the visits to hermaphrodite and male flowers was similar but pollen-feeding visits lasted longer (6.44 s per flower) than nectar-feeding ones (5.51 s per flower). The highest number of visits to mango inflorescences was observed during the morning, but the longest visits occurred at midday. The implication of these results for the potential use of E. aeneus as a managed pollinator in protected cultivation of mango is discussed.
Sleep disorders are a substantial public health issue with serious consequences on patients’ quality of life. Cannabis has been recently suggested as a potential treatment for patients with sleep disorders; however, research on the relationship between cannabis and sleep is still in its infancy.
Objectives
The aim of this investigation was to assess whether cannabis use was associated with improved sleep quality.
Methods
Our study comprised 173 participants, 42 cannabis users and 131 non-cannabis users, who completed the Pittsburgh Sleep Quality Index (PSQI), the most common self-reported measure of sleep quality. The scale provides a global PSQI score and seven component domain scores, including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime functions.
Results
Cannabis users self-reported statistically significantly healthier scores than non-cannabis users in the global PSQI as well as the specific domains of subjective sleep quality, sleep latency, as well as sleep disturbances.
Conclusions
This preliminary evidence points to the possibility that cannabis could provide effective treatment for patients with sleep disorders. Research into the constituents of cannabis that may have a differential impact on sleep and sleep disorders is warranted.
A detailed geochronological study was conducted on zircons from a diorite sample of the Posets pluton (Axial Zone, Pyrenees). The extracted igneous zircons constrain the emplacement of the pluton to 302 ± 2 Ma and 301 ± 3 Ma, by means of U–Pb sensitive high-resolution ion microprobe (SHRIMP) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) analyses, respectively. Considering the syn- to late-tectonic emplacement of the Posets pluton during the main Variscan deformation event (D2), the obtained ages constrain the long-lasting D2, associated with the dextral transpression registered through the Axial Zone of the Pyrenees.
Mexico has a wealth of plant genetic resources, including Capsicum species. In southern Mexico, specifically in the western part of the Yucatan Peninsula, Maya farmers have preserved a great diversity of chilli pepper landraces of C. annuum, C. frutescens and C. chinense. However, the morphological diversity, capsaicinoid content, conservation status and potential use of these species have not been studied. To fill this gap and generate information to support the conservation and use of these species, we characterized the phenotypic diversity and capsaicinoid content for nine chilli pepper landraces from the western Yucatan Peninsula by assessing 15 quantitative and 39 qualitative traits for 10 plants of each landrace. For quantitative variables, two groups of chilli pepper landraces were obtained by principal component analysis and cluster analysis. Group I was formed by Rosita, Bobo, Dulce, Xcat'ik1, Xcat'ik2 and Verde landraces; Group II included the Maax, Bolita and Pico Paloma landraces. For qualitative variables, three groups of chilli pepper landraces were obtained; Group I included Dulce, Bobo, Xcat'ik1, Xcat'ik2 and Verde landraces, Group II only included the Rosita landrace, and Group III included Maax, Bolita and Pico Paloma landraces. Ultra-performance liquid chromatography–photodiode array (UPLC-PDA) quantification of capsaicinoids indicated higher values in landraces Rosita (14,062.3 μg/g D.W), Bolita (5928.1 μg/g D.W), Maax (3438.4 μg/g D.W) and Pico Paloma (3138.9 μg/g D.W). The Yucatan chilli pepper landraces provide valuable diverse germplasm for morphological characteristics and capsaicinoid content that can be used in breeding and conservation programmes.
There is a long history of exploitation of the South American river turtle Podocnemis expansa. Conservation efforts for this species started in the 1960s but best practices were not established, and population trends and the number of nesting females protected remained unknown. In 2014 we formed a working group to discuss conservation strategies and to compile population data across the species’ range. We analysed the spatial pattern of its abundance in relation to human and natural factors using multiple regression analyses. We found that > 85 conservation programmes are protecting 147,000 nesting females, primarily in Brazil. The top six sites harbour > 100,000 females and should be prioritized for conservation action. Abundance declines with latitude and we found no evidence of human pressure on current turtle abundance patterns. It is presently not possible to estimate the global population trend because the species is not monitored continuously across the Amazon basin. The number of females is increasing at some localities and decreasing at others. However, the current size of the protected population is well below the historical population size estimated from past levels of human consumption, which demonstrates the need for concerted global conservation action. The data and management recommendations compiled here provide the basis for a regional monitoring programme among South American countries.
Based on wettability and reaction interfaces previously reported, as well as on thermodynamic considerations, a likely mechanism has been proposed for the chemical interaction taking place at the metal/ceramic interface during wettability experiments carried out by the so-called “sessile drop” method. The experiments involved three Ag-Cu-based brazing alloys [Cusil (Ag-28wt.%Cu), Cusil-ABA (Ag-34.6wt.%Cu-1.58wt.%Ti) and Incusil-ABA (Ag-26.6wt.%Cu-12.4wt.%In-0.89wt.%Ti)] and as polished and pre-oxidized pressure-less sintered silicon carbide (PLS-SiC), with a total holding time of 90 minutes at 850 °C, under a Zr sponge-gettered vacuum of 10-4/10-5 Torr.
An alternative method for the standardless quantitative x-ray diffraction analysis of mixtures of inorganic crystalline phases proposed in the literature several years ago is presented. Our method requires only previously calculated μ*i values from tabulated data for all phases present in the mixtures. It does not require either the determination of calibration constants or the use of external standards, but it does require that the number of analyzed mixtures is larger than or equal to the number of phases present in them, and that the chemical composition of the mixtures are significantly different from each other. The integrated intensities of the chemically pure phases are estimated by a least-squares procedure from XRD data obtained from the mixtures. The method was tested against data published in the literature, with good results. Finally, a general expression for the “Normalized Height Law” proposed on an empirical basis by other researchers, has been theoretically derived.
An initial mixture of raw materials (batch) typically used for the manufacture of conventional soda-lime float glass was subjected to a mechanical activation process for 30 or 60 minutes in a planetary ball mill. An intensification of the chemical reactivity of the batch, which was directly related with the increase in the milling time, was observed. This accelerated the chemical reactions that took place during the batch melting process between sodium, calcium and magnesium carbonates and other components of the mixture, which happened at significantly lower temperatures with respect to the batch without mechanical activation. The heat of fusion of the batch, estimated using a methodology previously reported in the literature, indicated that the mechanical activation given to the initial mixture of raw materials decreased the energy consumed during the batch melting. This was also evidenced by a decrease in the temperature at which the release of CO2 ended, which was considerably larger than that previously reported in the literature based solely on the decrease in the particle size of a batch of similar composition achieved by dry sieving.
An old procedure used to carry out a graphical derivation of curves, which is based on the optical properties of plane mirrors, has been adapted for the measurement of the contact angle (θ) formed between a liquid drop and a flat solid substrate in wettability experiments carried out by the so-called “sessile drop” method. The method was tested for mercury on soda-lime glass at room temperature in air as well as for Cusil (Ag-28wt.%Cu) and Incusil-ABA (Ag-27wt.%Cu-12wt.%In-2wt.%Ti) brazing alloys on pressureless-sintered silicon carbide (PLS-SiC) at 850 °C, under a vacuum of 10-4/10-5 Torr. The proposed method is fast, simple and accurate enough from high (∼140°) to relatively low (∼10°) contact angles. Although the proposed method has been tested for metal-ceramic systems, it is of general application, so that it would be useful for any liquid-solid system. The method is applicable for any temperature, pressure and atmospheric experimental conditions employed, as well as for any chemical composition of liquid and solid. It is also useful for both low and high contact angles, as well as for reactive and non-reactive systems, as long as a photograph of a liquid drop resting on a flat solid surface is available for the studied system.
Saponitic bentonite mined in the Magan deposit (Toledo, Spain), has been classified as a suitable clay barrier in the storage of high-level radioactive waste. Several hydrothermal alteration assays have been carried out in Teflon reactors at 45, 60, 90, 120, 175 and 200°C for periods of up to 1 y. The mineral components of bentonite are stable below 175°C. At and above this temperature, the accessory sepiolite transforms into a monomineral phase of saponitic composition. The texture of the clay also changes. A rise in temperature above 120°C causes a decrease in the proportion of the <2 μm size-fraction, a reduction of BET and total surface areas and an increase in the relative volume of micropores (<20 Å). This process has been interpreted as the formation of granular aggregates that preserve a micropore network. This new arrangement of the aggregates produces a significant reduction in the free swelling volume.
A mineralogical and microtextural study of Somosaguas Miocene deposits, located in the Madrid Basin (western Madrid, Spain), was carried out using X-ray diffraction, scanning electron microscopy, transmission electron microscopy and optical microscopy, whereas crystal chemistry data were obtained by analytical electron microscopy-transmission electron microscopy and electron icroprobe analysis. Four stratigraphic sections were studied, compising detrital rocks representing intermediate and distal facies from alluvial fan deposits. The predominant source area of these sediments was the granitic rocks of the Spanish Central System with a lesser contribution of metamorphic rocks. Clayey arkoses are the most abundant rocks of these sections, typical of granite alteration under warm, semi-arid climates. The mineralogy is characterized by phyllosilicates, followed by feldspars and quartz. The data obtained reveal mineral mixtures of detrital (quartz, feldspars, kaolinite, micas and chlorite), transformed (illite and beidellite) and neoformed (montmorillonite) origin. Clay minerals resulted from interactions between detrital minerals and meteoric waters. Two trends of degradation of micas are detected. The first shows a transition from muscovites and dioctahedral illites, to beidellites. The other trend is defined by the biotite degradation to beidellites with different layer charge and octahedral Fe content. Montmorillonites were neoformed from the hydrolysis and weathering of primary minerals (feldspars and muscovite). Magnesian clay minerals such as sepiolite, palygorskite and trioctahedral smectites, extremely abundant in the centre of the basin, were not detected in Somosaguas sediments.