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The association between cannabis and psychosis is established, but the role of underlying genetics is unclear. We used data from the EU-GEI case-control study and UK Biobank to examine the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS) on risk for psychosis.
Methods
Genome-wide association study summary statistics from the Psychiatric Genomics Consortium and the Genomic Psychiatry Cohort were used to calculate schizophrenia and cannabis use disorder (CUD) PRS for 1098 participants from the EU-GEI study and 143600 from the UK Biobank. Both datasets had information on cannabis use.
Results
In both samples, schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use in the EU-GEI cases or controls or UK Biobank cases. It was associated with lifetime and daily cannabis use among UK Biobank participants without psychosis, but the effect was substantially reduced when CUD PRS was included in the model. In the EU-GEI sample, regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS (OR daily use high-potency cannabis adjusted for PRS = 5.09, 95% CI 3.08–8.43, p = 3.21 × 10−10). We found no evidence of interaction between schizophrenia PRS and patterns of cannabis use.
Conclusions
Regular use of high-potency cannabis remains a strong predictor of psychotic disorder independently of schizophrenia PRS, which does not seem to be associated with heavy cannabis use. These are important findings at a time of increasing use and potency of cannabis worldwide.
Product architecture decisions are made early in the product development process and have far-reaching effects. Unless anticipated through experience or intuition, many of these effects may not be apparent until much later in the development process, making changes to the architecture costly in time, effort and resources. Many researchers through the years have studied various elements of product architecture and their effects. By using a repeatable process for aggregating statements on the effects of architecture strategies from a selection of the literature on the topic and storing them in a systematic database, this information can then be recalled and presented in the form of a Product Architecture Strategy and Effect (PASE) matrix. PASE matrices allow for the identification, comparison, evaluation, and then selection of the most desirable product architecture strategies before expending resources along a specific development path. This paper introduces the PASE Database and matrix and describes their construction and use in guiding design decisions. This paper also provides metrics for understanding the robustness of this database.
Cannabis use and familial vulnerability to psychosis have been associated with social cognition deficits. This study examined the potential relationship between cannabis use and cognitive biases underlying social cognition and functioning in patients with first episode psychosis (FEP), their siblings, and controls.
Methods
We analyzed a sample of 543 participants with FEP, 203 siblings, and 1168 controls from the EU-GEI study using a correlational design. We used logistic regression analyses to examine the influence of clinical group, lifetime cannabis use frequency, and potency of cannabis use on cognitive biases, accounting for demographic and cognitive variables.
Results
FEP patients showed increased odds of facial recognition processing (FRP) deficits (OR = 1.642, CI 1.123–2.402) relative to controls but not of speech illusions (SI) or jumping to conclusions (JTC) bias, with no statistically significant differences relative to siblings. Daily and occasional lifetime cannabis use were associated with decreased odds of SI (OR = 0.605, CI 0.368–0.997 and OR = 0.646, CI 0.457–0.913 respectively) and JTC bias (OR = 0.625, CI 0.422–0.925 and OR = 0.602, CI 0.460–0.787 respectively) compared with lifetime abstinence, but not with FRP deficits, in the whole sample. Within the cannabis user group, low-potency cannabis use was associated with increased odds of SI (OR = 1.829, CI 1.297–2.578, FRP deficits (OR = 1.393, CI 1.031–1.882, and JTC (OR = 1.661, CI 1.271–2.171) relative to high-potency cannabis use, with comparable effects in the three clinical groups.
Conclusions
Our findings suggest increased odds of cognitive biases in FEP patients who have never used cannabis and in low-potency users. Future studies should elucidate this association and its potential implications.
Transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique, has shown some promise as a novel treatment approach for a range of mental health disorders, including OCD. This study provides a systematic review of the literature involving randomized controlled trials of tDCS for OCD and evaluates the quality of reporting using the CONSORT (Consolidating Standards of Reporting Trials) statement. This study also examined the outcomes of tDCS as a therapeutic tool for OCD.
Methods:
This systematic review was prospectively registered with PROSPERO (CRD42023426005) and the data collected in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The quality of reporting of included studies was evaluated in accordance with the CONSORT statement.
Results:
Eleven randomized controlled trials were identified. Evaluation of the reviewed studies revealed low levels of overall compliance with the CONSORT statement highlighting the need for improved reporting. Key areas included insufficient information about - the intervention (for replicability), participant flow, recruitment, and treatment effect sizes. Study discussions did not fully consider limitations and generalizability, and the discussion/interpretation of the findings were often incongruent with the results and therefore misleading. Only two studies reported a significant difference between sham and active tDCS for OCD outcomes, with small effect sizes noted.
Conclusions:
The variability in protocols, lack of consistency in procedures, combined with limited significant findings, makes it difficult to draw any meaningful conclusions about the effectiveness of tDCS for OCD. Future studies need to be appropriately powered, empirically driven, randomized sham-controlled clinical trials.
Efficient evidence generation to assess the clinical and economic impact of medical therapies is critical amid rising healthcare costs and aging populations. However, drug development and clinical trials remain far too expensive and inefficient for all stakeholders. On October 25–26, 2023, the Duke Clinical Research Institute brought together leaders from academia, industry, government agencies, patient advocacy, and nonprofit organizations to explore how different entities and influencers in drug development and healthcare can realign incentive structures to efficiently accelerate evidence generation that addresses the highest public health needs. Prominent themes surfaced, including competing research priorities and incentives, inadequate representation of patient population in clinical trials, opportunities to better leverage existing technology and infrastructure in trial design, and a need for heightened transparency and accountability in research practices. The group determined that together these elements contribute to an inefficient and costly clinical research enterprise, amplifying disparities in population health and sustaining gaps in evidence that impede advancements in equitable healthcare delivery and outcomes. The goal of addressing the identified challenges is to ultimately make clinical trials faster, more inclusive, and more efficient across diverse communities and settings.
From early on, infants show a preference for infant-directed speech (IDS) over adult-directed speech (ADS), and exposure to IDS has been correlated with language outcome measures such as vocabulary. The present multi-laboratory study explores this issue by investigating whether there is a link between early preference for IDS and later vocabulary size. Infants’ preference for IDS was tested as part of the ManyBabies 1 project, and follow-up CDI data were collected from a subsample of this dataset at 18 and 24 months. A total of 341 (18 months) and 327 (24 months) infants were tested across 21 laboratories. In neither preregistered analyses with North American and UK English, nor exploratory analyses with a larger sample did we find evidence for a relation between IDS preference and later vocabulary. We discuss implications of this finding in light of recent work suggesting that IDS preference measured in the laboratory has low test-retest reliability.
Schizotypal traits include abnormalities in cognition, behavior, and interpersonal relationships that are similar, yet less severe than psychotic symptomology. It is estimated that approximately 5% of the general population displays psychotic symptoms and experiences that can be considered schizotypal in nature, but there is little research examining the neurological correlates of these traits. The mismatch negativity (MMN) event-related potential is an objective measure of auditory change detection derived from electroencephalography. The current study contributes to the limited body of evidence examining the neurobiological underpinnings of schizotypy in a non-clinical sample using the MMN. Participants were recruited from the general population and divided into high and low-schizotypy groups for comparison. Individuals with high schizotypal traits displayed reduced MMN amplitudes in response to frequency and location deviants, and longer MMN latencies in response to location deviants. Specific sub-traits of schizotypy were uniquely related to frequency and location amplitudes, suggesting the previously reported inconsistencies in the literature may be due to diverse samples and differing deviant tone types. Finally, impulsivity and sensation-seeking likely contributed to the slower processing seen in location deviance detection. Ultimately, the current results provide evidence that the neurobiological abnormalities seen in clinical populations of schizotypal personality disorder and psychosis also extend to non-clinical populations.
We explore predictions of two models of one-dimensional capillary rise in rigid and partially saturated porous media. One is an existing one from the literature and the second is a free-boundary model based on Richards’ equation with two moving boundaries of the evolving partially saturated region. Both models involve the specification of saturation-dependent functions for local capillary pressure and permeability and connect to classical models for saturated porous media. Existing capillary-rise experiments show two notable regimes: (i) an early-time regime typically well-described by classical capillary-rise theory in a fully saturated porous media, and (ii) a long-time regime that has anomalous dynamics in which the capillary-rise height may scale with a non-classical power law in time or have more complicated dynamics. We demonstrate that the predictions of both models compare well with experimental capillary-rise data over early- and long-time regimes gathered from three independent studies in the literature. The model predictions also shed light on recent scaling laws that relate the capillary pressure and permeability of the partially saturated media to the capillary-rise height. We use these models to probe computationally observed permeability relationships to capillary-rise height. We demonstrate that a recently proposed permeability scaling for the anomalous capillary-rise regime is indeed realized and is particularly apparent in the lower portion of the partially saturated media. For our free-boundary model we also compute capillary pressure measures and show that these reveal the linear relation between the capillary pressure and capillary-rise height expected for a capillarity–gravity balance in the upper portion of the partially saturated porous media.
Background: Degenerative Cervical Myelopathy (DCM) is the functional derangement of the spinal cord because of compression from degenerate tissues. Typical neurological symptoms of DCM include gait imbalance and upper extremity paresthesia. While it is thought that greater spinal cord compression leads to increased neurological deterioration, our clinical experience suggests a more complex mechanism involving spinal canal diameter (SCD). Methods: 124 MRI scans from 59 non-operative DCM patients underwent manual scoring of cord compression and SCD measurements. Unsupervised machine learning dimensionality reduction techniques and k-means clustering were used to establish patient groups. These patient groups underwent manual inspection of common compression patterns and SCD similarities to define their unique risk criteria. Results: We found that compression pattern is unimportant at SCD extremes (≤14.5 mm or >15.75 mm). Otherwise, stenosis with clear signs of cord compression at two disc levels and stenosis without clear signs of cord compression at two disc levels result in a relatively higher and lower likelihood of deterioration, respectively. We elucidated five patient groups with unique associated risks for neurological deterioration, according to both SCD range and their cord compression pattern. Conclusions: The specific combination of narrow SCD with focal cord compression increases the likelihood of neurological deterioration in non-operative patients with DCM.
We present radio observations of the galaxy cluster Abell S1136 at 888 MHz, using the Australian Square Kilometre Array Pathfinder radio telescope, as part of the Evolutionary Map of the Universe Early Science program. We compare these findings with data from the Murchison Widefield Array, XMM-Newton, the Wide-field Infrared Survey Explorer, the Digitised Sky Survey, and the Australia Telescope Compact Array. Our analysis shows the X-ray and radio emission in Abell S1136 are closely aligned and centered on the Brightest Cluster Galaxy, while the X-ray temperature profile shows a relaxed cluster with no evidence of a cool core. We find that the diffuse radio emission in the centre of the cluster shows more structure than seen in previous low-resolution observations of this source, which appeared formerly as an amorphous radio blob, similar in appearance to a radio halo; our observations show the diffuse emission in the Abell S1136 galaxy cluster contains three narrow filamentary structures visible at 888 MHz, between $\sim$80 and 140 kpc in length; however, the properties of the diffuse emission do not fully match that of a radio (mini-)halo or (fossil) tailed radio source.
We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe.
Methods
We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use.
Results
The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39–2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38–2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25–4.79) to 1.61 (95% CI 0.74–3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07–6.15) to 1.67 (95% CI 0.62–4.53).
Conclusions
The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.
Over the years, so-called univentricular hearts represented one of the greatest challenges for surgical correction. All this changed with the advent of the Fontan procedure,1 along with the realization that it could become the final stage of the sequence of procedures used to correct lesions such as those included in the hypoplastic left heart syndrome,2 which previously had been beyond surgical repair. The overall group of lesions also posed significant problems in adequate description and categorization. Even these days, many continue to describe patients with a double inlet left ventricle as having a single ventricle, despite the fact that, with the availability of clinical diagnostic techniques producing three-dimensional datasets, patients with this lesion can be seen to have two chambers within their ventricular mass, one being large and the other small (Figure 9.1.1). The semantic problems with description can now be resolved by the simple expedient of describing the patients as having functionally univentricular hearts.3
Understanding the anatomy of septal defects is greatly facilitated if the heart is thought of as having three distinct septal structures: the atrial septum, the atrioventricular septum, and the ventricular septum (Figure 8.1.1). The normal atrial septum is relatively small. It is made up, for the most part, by the floor of the oval fossa. When viewed from the right atrial aspect, the fossa has a floor, surrounded by rims. As we have shown in Chapter 2, the floor is derived from the primary atrial septum, or septum primum. Although often considered to represent a secondary septum, or septum secundum, the larger parts of the rims, specifically the superior, antero-superior, and posterior components, are formed by infoldings of the adjacent right and left atrial walls.1 Infero-anteriorly, in contrast, the rim of the fossa is a true muscular septum (Figure 8.1.2).
It is axiomatic that a thorough knowledge of valvar anatomy is a prerequisite for successful surgery, be it valvar replacement or reconstruction. The surgeon will also require a firm understanding of the arrangement of other aspects of cardiac anatomy to ensure safe access to a diseased valve or valves. These features were described in the previous chapter. Knowledge of the surgical anatomy of the valves themselves, however, must be founded on appreciation of their component parts, the relationships of the individual valves to each other, and their relationships to the chambers and arterial trunks within which they reside. This requires understanding of, first, the basic orientation of the cardiac valves, emphasizing the intrinsic features that make each valve distinct from the others. Such information must then be supplemented by attention to their relationships with other structures that the surgeon must avoid, notably the conduction tissues and the major channels of the coronary circulation.
The surgical problems posed by cardiac malformations may be considerably increased when the heart itself is in an abnormal position. This is, in part, due to the unusual anatomical perspective presented to the surgeon because of the malposition, and also to the abnormal locations of the cardiac chambers, which may necessitate approaches other than those already discussed. Cardiac malposition in itself, nonetheless, does not constitute a diagnosis. Any normal or abnormal segmental combination can be found in a heart which itself is abnormally located. The heart may be normal, despite its abnormal location, but extremely complex anomalies are frequently present. Consequently, the very presence of an abnormal cardiac position emphasizes the need for a full and detailed segmental analysis of the heart. All the rules enunciated in Chapter 7 apply should the heart not be in its anticipated position.
Systems for describing congenital cardiac malformations have frequently been based on embryological concepts and theories. As useful as these systems have been, they have often had the effect of confusing the clinician, rather than clarifying the basic anatomy of a given lesion. As far as the surgeon is concerned, the essence of a particular malformation lies not in its presumed morphogenesis, but in the underlying anatomy. An effective system for describing this anatomy must be based on the morphology as it is observed. At the same time, it must be capable of accounting for all congenital cardiac conditions, even those that, as yet, might not have been encountered. To be useful clinically, the system must be not only broad and accurate, but also clear and consistent. The terminology used, therefore, should be unambiguous. It should be as simple as possible. The sequential segmental approach provides such a system.1