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The implications of cannabis use in the onset of early psychosis and the severity of psychotic symptoms have resulted in a proliferation of studies on this issue. However, few have examined the effects of cannabis use on the cognitive symptoms of psychosis (i.e., neurocognitive functioning) in patients with first-episode psychosis (FEP). This systematic review and meta-analysis aim to assess the neurocognitive functioning of cannabis users (CU) and nonusers (NU) with FEP.
Of the 110 studies identified through the systematic review of 6 databases, 7 met the inclusion criteria, resulting in 14 independent samples and 78 effect sizes. The total sample included 304 CU with FEP and 369 NU with FEP. The moderator variables were age at first use, duration of use, percentage of males, and age.
Effect sizes were not significantly different from zero in any neurocognitive domain when users and NU were compared. Part of the variability in effect sizes was explained by the inclusion of the following moderator variables: (1) frequency of cannabis use (β = 0.013, F = 7.56, p = 0.017); (2) first-generation antipsychotics (β = 0.019, F = 34.46, p ≤ 0.001); and (3) country where the study was carried out (β = 0.266, t = 2.06, p = 0.043).
This meta-analysis indicates that cannabis use is not generally associated with neurocognitive functioning in patients with FEP. However, it highlights the deleterious effect of low doses of cannabis in some patients. It also stresses the importance of the type of antipsychotic prescription and cannabis dose as moderator variables in the neurocognitive functioning of CU with FEP.
This study explored the effect of the perceived social content of affective pictures on the subjective evaluation of affective valence and arousal. For this purpose, we established three categories of social content (pictures without people, with one person and with two or more people). A sample of 161 subjects rated 200 pictures varying in affective valence (unpleasant, neutral, and pleasant), arousal and social content. Results of two-factor analysis of variance, F(4, 157) = 71.7, p < .001, ηp2 = .31, showed that perceived social content influenced the ratings of affective valence, specially for unpleasant pictures, with the greatest social content (two or more people) leading subjects to rate unpleasant pictures with the lowest ratings (all pairwise comparisons’ p < .001). Regarding arousal, F(4, 157) = 64.0, p < .001, ηp2 = .29), the higher the social content, the higher the arousal ratings, but only for pleasant (all pairwise comparisons’ p < .007) and unpleasant (all pairwise comparisons’ p < .001) pictures. Overall, this study demonstrated an effect of the perceived social content on the subjective evaluation of affective valence and arousal of emotional stimuli.
TwinsMX is a national twin registry in Mexico recently created with institutional support from the Universidad Nacional Autónoma de México. It aims to serve as a platform to advance epidemiological and genetic research in the country and to disentangle the genetic and environmental contributions to health and disease in the admixed Mexican population. Here, we describe our recruitment and data collection strategies and discuss both the progress to date and future directions. More information about the registry is available on our website: https://twinsmxofficial.unam.mx/ (content in Spanish).
Despite the well-known relevance of twin studies in the medical and social sciences and the growing number of twin registries throughout the world, Latin America has not fully incorporated into the twin research community. We describe the first steps taken toward developing a twin registry in Mexico: its aim, organization, recruiting potential and main short-term objectives.
The Murcia Twin Registry (MTR) is the only population-based registry in Spain. Created in 2006, the registry has been growing more than a decade to become one of the references for twin research in the Mediterranean region. The MTR database currently comprises 3545 adult participants born between 1940 and 1977. It also holds a recently launched satellite registry of university students (N = 204). Along five waves of data collection, the registry has gathered questionnaire and anthropometric data, as well as biological samples. The MTR keeps its main research focus on health and health-related behaviors from a public health perspective. This includes lifestyle, health promotion, quality of life or environmental conditions. Future short-term development points to the expansion of the biobank and the continuation of the collection of longitudinal data.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
To determine the prevalence of low scores for two neuropsychological tests with five total scores that evaluate learning and memory functions.
N = 5402 healthy adults from 11 countries in Latin America and the commonwealth of Puerto Rico were administered the Rey–Osterrieth Complex Figure (ROCF) and the Hopkins Verbal Learning Test (HVLT-R). Two-thirds of the participants were women, and the average age was 53.5 ± 20.0 years. Z-scores were calculated for ROCF Copy and Memory scores and HVLT-R Total Recall, Delayed Recall, and Recognition scores, adjusting for age, age2, sex, education, and interaction variables if significant for the given country. Each Z-score was converted to a percentile for each of the five subtest scores. Each participant was categorized based on his/her number of low scoring tests in specific percentile cutoff groups (25th, 16th, 10th, 5th, and 2nd).
Between 57.3% (El Salvador) and 64.6% (Bolivia) of the sample scored below the 25th percentile on at least one of the five scores. Between 27.1% (El Salvador) and 33.9% (Puerto Rico) scored below the 10th percentile on at least one of the five subtests. Between 5.9% (Chile, El Salvador, Peru) and 10.3% (Argentina) scored below the 2nd percentile on at least one of the five scores.
Results are consistent with other studies that found that low scores are common when multiple neuropsychological outcomes are evaluated in healthy individuals. Clinicians should consider the higher probability of low scores when evaluating learning and memory using various sets of scores to reduce false-positive diagnoses of cognitive deficits.
The paper shows the connections between some importance indices for the components in an engineering coherent system and the performance of the system obtained when a redundancy mechanism is applied to a specific component. A copula approach is used to model the dependency among the components. This approach includes the popular case of independent components. Under some assumptions, it is proved that if component i is more important than component j, then the system obtained by applying a redundancy procedure to the ith component is better, under different stochastic criteria, than that obtained with the jth component. These results can be applied to several redundancy mechanisms. A new importance index is defined to study active redundancies. Some illustrative examples are provided.
A 6–18 GHz high-power amplifier (HPA) design in GaN on SiC technology is presented. This power amplifier consists of a two-stage corporate amplifier with two and four transistors, respectively. It has been fabricated on UMS using their 0.25 µm gate length process, GH25. A study of the suitable attachment method and measurement on wafer and on jig are detailed. This HPA exhibits an averaged output power of 39.2 dBm with a mean gain of 11 dB in saturation and a 24.5% maximum power added efficiency in pulse mode operation with a duty cycle of 10% with a 25 µs pulse width.
Two preferred textures were observed in the Alhama de Murcia Fault rocks: (a) foliated bands (>100 µm thick) rich in well-crystallized dioctahedral micas, quartz, hematite and dolomite; and (b) ultrafine-grained bands (<100 µm thick) made of patches composed of small mica crystals (<15 µm) and dispersed Fe-oxides. In both textures, kaolinite forms intergrowths or patches of randomly oriented crystals filling gaps or opening layers of presumably inherited detrital mica crystals, which is interpreted as an epitaxial growth from fluids. The Na/K ratio of mica crystals in the thin ultrafine-grained bands shows a wider range than the micas from the foliated bands including muscovitic, intermediate Na/K and paragonitic compositions. The absence of the 0.98 nm intermediate peak in the diffractograms indicates that the small micas are submicroscopically paragonite and phengite intergrowths. The d001 values of the K-dioctahedral micas in the <2 µm and whole fractions are clearly different from each other. The d001 values of micas of the <2 µm fraction are larger, indicating a higher K and lower Na content in the small micas. Their composition corresponds to lower temperatures, suggesting their growth during a genetic episode in the fault. The textural relationships indicate a late growth of kaolinite, probably due to the fluid–rock interaction along fault planes and fractures. The neoformed clay minerals might alter the stability of the fault plane. The absence of expandable clay minerals and the relatively high frictional strength of kaolinite under wet conditions might explain the observed velocity-neutral behaviour of this gouge and earthquake propagation towards the surface.
El gobierno de K'ihnich Bahlam Chapaht corresponde a uno de los más longevos de todos los gobernantes conocidos de Tonina. Con excepción de su nacimiento y entronización, conocidos por referencias retrospectivas muy reiteradas, es poco lo que se conoce de su vida. Sin embargo, gracias al recientemente restaurado Monumento 181 y al altar identificado como Monumento 182, hemos logrado reconstruir pormenores adicionales de su gobierno. En el presente ensayo, presentamos nuevos datos sobre ritualidad y jerarquía político-religiosa en Tonina durante el reinado de K'ihnich Bahlam Chapaht resultado del análisis de estos dos monumentos.
Polyphenols are a wide family of phytochemicals present in diverse foods. They might play a role in cancer development and progression. In vivo and in vitro studies have suggested beneficial properties and potential mechanisms. We aimed to evaluate the association between total and main classes of polyphenol intake and breast cancer (BC) risk in the Seguimiento Universidad de Navarra project – a prospective Mediterranean cohort study. We included 10 713 middle-aged, Spanish female university graduates. Polyphenol intake was derived from a semi-quantitative FFQ and matching food consumption data from the Phenol-Explorer database. Women with self-reported BC were asked to return a copy of their medical report for confirmation purposes; death certificates were used for fatal cases. Cox models were fitted to estimate multivariable-adjusted hazard ratios (HR) and 95 % CI for the association between tertiles (T) of polyphenol intake and BC. After 10·3 years of median follow-up, 168 probable incident BC cases were identified, out of which 100 were confirmed. We found no association between polyphenol intake and the overall BC risk. Nevertheless, we observed a significant inverse association between total polyphenol intake and BC risk for postmenopausal women, either for probable or only for confirmed cases (HRT3 v. T1 0·31 (95 % CI 0·13, 0·77; Ptrend=0·010)). Also, phenolic acid intake was inversely associated with postmenopausal BC. In summary, we observed no significant association between total polyphenol intake and BC risk. Despite a low number of incident BC cases in our cohort, higher total polyphenol intake was associated with a lower risk of postmenopausal BC.
Lumateperone is a first-in-class agent in development for schizophrenia that acts synergistically through serotonergic, dopaminergic and glutamatergic systems. Lumateperone is a potent 5-HT2A antagonist, a mesolimbic/mesocortical dopamine phosphoprotein modulator (DPPM) with pre-synaptic partial agonist and post-synaptic antagonist activity at D2, a glutamate GluN2B receptor phosphoprotein modulator with D1-dependent enhancement of both NMDA and AMPA currents via the mTOR protein pathway and an inhibitor of serotonin reuptake.
Lumateperone was evaluated in 3 controlled clinical trials to evaluate efficacy in patients with acute schizophrenia. The primary endpoint was change from baseline on the PANSS total score compared to placebo. In Study ‘005, 335 patients were randomized to receive ITI-007 60mg or 120mg , risperidone 4mg (active control) or placebo QAM for 4weeks. In Study ‘301, 450 patients were randomized to receive ITI-007 60mg or 40mg , or placebo QAM for 4weeks. In Study ‘302, 696 patients were randomized to receive ITI-007 60mg or 20mg , risperidone 4mg (active control) or placebo QAM for 6weeks. Also, an open-label safety switching study was conducted in which 302 patients with stable schizophrenia were switched from standard-of-care (SOC) antipsychotics and treated for 6weeks with lumateperone QPM and then switched back to SOC.
In Studies ‘005 and ‘301, lumateperone (60mg ITI-007) met the primary endpoint with statistically significant superior efficacy over placebo at Day 28. In Study ‘302, neither dose of lumateperone separated from placebo on the primary endpoint; a high placebo response was observed in this study. Across all 3 efficacy trials, lumateperone improved symptoms of schizophrenia with the same trajectory and same magnitude of improvement from baseline to endpoint on the PANSS total score.
Lumateperone was well-tolerated with a favorable safety profile in all studies. In the two studies with risperidone included as an active control, lumateperone was statistically significantly better than risperidone on key safety and tolerability measures. In the open-label safety switching study statistically significant improvements from SOC were observed in body weight, cardiometabolic and endocrine parameters worsened again when switched back to SOC medication. In this study, symptoms of schizophrenia generally remained stable or improved. Greater improvements were observed in subgroups of patients with elevated symptomatology (comorbid symptoms of depression and those with prominent negative symptoms).
Lumateperone represents a novel approach to the treatment of schizophrenia with a favorable safety profile in clinical trials. The lack of cardiometabolic and motor safety issues presents a safety profile differentiated from standard-of-care antipsychotic therapy.
Funding Acknowledgements: Intra-Cellular Therapies, Inc.
Autism is a neurodevelopmental disorder characterized by alterations in the intellectual, social, communication, and behavioral capabilities of an individual, and is rarely detected in children before 24 months of age. Early diagnosis and intervention may be more effective at a younger age. Functional connectivity magnetic resonance imaging (fcMRI) of 6-month old infants may be able to identify brain connection patterns related to at least one of the characteristics of autism, which normally appear at 24 months of age, by using a mathematical model to analyze the neuroimaging data.
Clinical studies published up to December 2018 that used fcMRI to detect autism in infants were reviewed. The literature databases searched included PubMed, Web of Science, the Trip Database, DynaMed, the Cochrane Library, the International Clinical Trials Registry Platform, and ClinicalTrials.gov. Early assessments of fcMRI analysis were identified through the Early Awareness and Alert System of the Agencia de Evaluación de Tecnologías Sanitarias.
Only one prospective study of 59 infants at 6-months of age was retrieved. A fcMRI analysis was performed to identify 2,635 pairs of functional connections from 230 brain regions. The infants were subsequently assessed for autism at 24 months of age using gold standard tests. The functional connections correlated with at least one of the behaviors related to autism evaluated at 24 months of age. Eleven infants (19%) were diagnosed with autism at 24 months. Compared with the gold standard test results, the predictive model achieved the following: sensitivity 0.82 (95% confidence interval [CI]: 0.52 - 0.95); specificity 1.00 (95% CI: 0.93–1.00); positive predictive value 1.00 (95% CI: 0.70–1.00); negative predictive value 0.96 (95% CI: 0.87–0.99); and negative likelihood ratio 0.18 (95% CI: 0.05–0.64). Adverse effects were not reported in the study.
The fcMRI analysis could help in early detection of autism and the development of preventive interventions. However, the evidence is sparse and more well-designed studies are needed.
In this work, the synthesis of starch-clay nanocomposites was carried out. For this purpose, natural starch was extracted from rice grains and it was characterized by structural and spectrophotometric techniques. Afterwards, it was used as the polymer matrix for the synthesis of nanocomposites crosslinked with different agents: glycerol, citric acid (CA) and sodium trimetaphosphate (STMP). As a reinforcement phase, a natural Mexican clay from the Montmorillonite-type (Mt), was employed, which was modified with a cationic surfactant, hexadecyltrimethylammonium bromide (HDTMA-Br), in order to exchange cations, present in the interlaminar spaces of the raw clay mineral with those of the cationic surfactant; thus, changing its nature from hydrophilic to hydrophobic. Characterization, of both natural and organo-modified clays, was carried out by means of scanning electron microscopy (SEM), to determine the change in morphology between these two minerals; X-ray diffraction analysis (XRD), to obtain the crystalline structure of the organo-modified clay and that of the raw clay mineral (Mt). Also, the Fourier transform infrared spectroscopy (FTIR) was employed to determine materials spectra, and their thermal stability was evaluated by means of the thermogravimetric analysis (TGA). On the other hand, the synthesis of these nanocomposites was performed using different crosslinking agents, glycerol, CA or STMP, in order to identify the effect of them into the final properties of these materials.
In the present investigation, biocomposites were synthesized from a polymeric alginate matrix in which the carrot residue and a natural bentonite (ANat / Bio) or an iron-modified clinoptilolite-type zeolite (ZFe / Bio) were supported. Their properties were evaluated adsorbents in contact with aqueous solutions of methylene blue (MB). In the first hour of contact, 46% removal was obtained for the ZFe / Bio biocomposite and 60% for the ANat / Bio biocomposite; reaching 100% removal for the ZFe / Bio biocomposite and 98% for the ANat / Bio biocomposite after 24 hours. The biocomposites were characterized by Scanning Electron Microscopy (SEM) and Fourier Transformed Infrared Spectroscopy (FTIR).
Appropriate involvement of stakeholders is one of the founding principles of the European Cooperation on Health Technology Assessment. The European Network for Health Technology Assessment (EUnetHTA) produces Rapid Relative Effectiveness Assessments (REAs) to assess pharmaceutical (PT) or other technologies (OT). Stakeholders essentially participate in the scoping, the draft assessment phase, or both.
All REAs published since 2013 were reviewed. Stakeholder participation in scoping (project plan) and draft assessment was evaluated. We aggregated categories of stakeholders in four groups (Health Care Providers and Academia, Patients and Consumers, Manufacturers, and Regulators and Payers). Means of collaboration (meetings, comments to project plan and draft assessment, questionnaires, focus groups) are also analyzed. Data is continuously updated with new REAs.
More than 20 REAs have been published at the moment, with a higher number of OT. Health Care Providers and Academia acted as experts in both phases, participating in all REA of OT, and less of PT. Manufacturers participated in all REA in the scoping phase. Regulators and Payers, less involved, participated mainly in the scoping phase. The main methods are providing comments in a standardized form and meetings. Patients' contribution, similar in OT and PT, has increased over the years. Questionnaires or interviews were the main method of involvement, followed by participation in meetings and focus groups. Visibility and transparency have also improved, with a clearer reporting of the stakeholder contribution in the last assessments.
The stakeholder involvement in EUnetHTA REAs is steadily growing, with the different nature of stakeholders’ categories reflected in their contribution to the assessments. EUnetHTA is standardizing stakeholder involvement procedures taking into account the particularities of each group when generating guidance for stakeholder involvement.
There is no information about the characteristics of early cleavage in the Patagonian blennie (Eleginops maclovinus), which can be used as a diagnostic tool for embryo quality. The purpose of this investigation, therefore, was to characterize the first blastomeres of E. maclovinus morphologically. Of a ‘pool’ of incubated eggs at 10.7 ± 0.5°C, 100 microphotographs of blastodiscs were extracted at different incubation periods from 0.25 to 5 h after fertilization and analyzed. Blastodiscs taken at 3.5, 4.0 and 5.0 h were characterized and classified into symmetric or asymmetric groups according to their morphology. The proportions of length (L) and width (W) of each blastomere were determined to establish its symmetry. Additionally, 20 microphotographs of blastodiscs of normal appearance were analyzed morphologically (control blastodisc: CB) and compared other blastodiscs (4.0 and 5.0 h). The results showed that before fertilization oocytes presented a somehow turgid aspect (maximum average diameter of 987 ± 41 µm) and after fertilization and hydration, their diameter increased to 1001.5 ± 11 µm (but not statistically significant) and presented a spherical shape. First cleavage ends after 3.5 h of development, forming two blastomeres 467 ± 45 μm length (L) and 328 ± 21 μm width (W) with a L/W ratio of 1.43 ± 0.19. The second cleavage ends after development at 4.5 h forming four blastomeres 238 ± 65 μm length and 227 ± 65 μm width with a ratio L/W of 1.06 ± 0.09. Five categories were identified during the blastomere characterization: 70% normal or symmetric; 8% with odd numbers of blastomeres; 6% unequal; 6% ‘pie shaped’ and 10% amorphous.
Between the years of 30 b.c. to a.d. 80, during the Late Formative period, the site of Izapa was flooded by lahars associated with an explosive eruption of the San Antonio volcano (part of the Tacaná Volcanic Complex). Computer simulations suggest that hot pyroclastic flows did not impact Izapa directly, but did impact the region considerably, filling and clogging the Cahuacan and Mixcun rivers with hot debris. The material was quickly saturated by heavy rains and, as the water from the rivers overtopped the obstruction, remobilized in the form of a hot mixture of mud and water known as a lahar (or flood of volcanic origin), which flowed down through the piedmont zone along the Cahuacan, Mixcun-Suchiate, and Izapa rivers. At Izapa, the flood took the form of a 6-m catastrophic wave of mud and water that likely destroyed crops and caused many causalities, surrounding the architectural mounds at Izapa with a muddy landscape. The floods also dramatically affected the rivers downstream, undoubtedly wreaking serious damage to the transport and trade of goods along the coast.