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Exposure to adversities in early childhood is associated with psychotic experiences and disorders in adulthood. We aimed to examine whether early childhood adversities are associated with middle childhood psychotic experiences in a cohort of children at familial high risk of schizophrenia (FHR-SZ), bipolar disorder (FHR-BP) and population-based controls (controls).
Methods
Four hundred and forty-six children from The Danish High Risk and Resilience Study – VIA7 and VIA11 participated in this study (FHR-SZ = 170; FHR-BP = 103; controls = 173). Exposure to early childhood adversities and psychotic experiences were assessed using face-to-face interviews. Having childhood adversities assessed at baseline (age 7) was used as predictor. Psychotic experiences assessed at follow-up (age 11) were used as outcome.
Results
Across the sample, exposure to early childhood interpersonal adversities was associated with an increased risk for any middle childhood psychotic experiences and subclinical delusions when adjusting for relevant confounders (OR 1.8, 95% CI 1.0–3.1, p = 0.05; OR 3.0, 95% CI 1.6–5.6, p < 0.001). There was no significant dose–response effect of exposure to multiple types of childhood adversities on any psychotic experiences. There were no interaction effects between early childhood adversities and FHR on middle childhood psychotic experiences. Exploratory analyses revealed that experiencing domestic violence in early childhood was associated with any middle childhood psychotic experiences (OR 2.8, 95% CI 1.5–5.1, p = 0.001).
Conclusions
Exposure to interpersonal adversities during early childhood is associated with an increased risk for middle childhood psychotic experiences including specifically subclinical delusions. Future studies should examine associations between exposure to childhood adversities and conversion to psychosis within this cohort.
Preferences for nest box size and position were tested in two groups of common marmoset, Callithrix jacchus jacchus. In a pre-test phase two, new, wooden nest boxes were introduced to each group alongside their old metal one, so that the animals could become familiar with them, and so that any pre-existing preference could be identified. In successive experiments: i) the old metal nest box was closed so that the marmosets had to choose a preferred box from the two new nest boxes; ii) the size of the preferred nest box was systematically reduced; and iii) in one of the groups the reduced nest box was restored to full size, but its position interchanged with the non-preferred box. In a further experiment, the position of the preferred, and then of the non-preferred box was raised to the highest point in the cage. The marmosets showed strong positional preferences which could not have been predicted without performing the tests. One of the groups also showed a strong preference for the high nest box. It was concluded that marmosets may exhibit preferences for their cage furniture, the basis of which may not be clear to us. These preferences should, however, be taken into account when designing cages to maximize the welfare of the animals.
Outcomes Based Agreements (OBAs) are financial arrangements that offer the opportunity to align payment to health outcomes in the real-world, and share the financial risk by providing long-term solutions that grant access to medicines, with reimbursement only when performance is achieved. OBAs are most likely to be useful when there is high uncertainty in the clinical data, but they are difficult to design and implement, and other financial options are usually preferred by payers. As a result, OBAs have been more the exception than the norm, and there is not a clear pattern that indicates if an OBA is likely to succeed in practice.
Methods
Through a retrospective OBA exercise with NHS Wales (Project IDEATE: Innovation in Data to Evolve Agreements That Enhance patient health outcomes), we have explored the circumstances under which an OBA might be most appealing to payers, and assessed implementation challenges and solutions, to propose a framework to evaluate the feasibility of a medicine for an OBA.
Results
Along with mitigating some of the clinical uncertainties associated with a lack of mature data at the time of launch, an OBA must also consider other factors: the commercial viability of the agreement, the associated administrative burden, and its cost of implementation. Also, the Health System commitment to a Value-Based Healthcare agenda and, most importantly, its willingness to offer long-term sustainable solutions to optimise treatment, are key to support this approach.
Practical considerations include: how the relevant outcomes are going to be selected and tracked in the real-world, how the whole model is going to fit within the current procurement and finance infrastructures, and how industry works in collaboration with the Health System.
Conclusions
Insights from Project IDEATE will be used to explore how our OBA feasibility framework might be applied in the future.
Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy and a severe threat to pregnant people and offspring health. The molecular origins of GDM, and in particular the placental responses, are not fully known. The present study aimed to perform a comprehensive characterisation of the lipid species in placentas from pregnancies complicated with GDM using high-resolution MS lipidomics, with a particular focus on sphingolipids and acylcarnitines in a semi-targeted approach. The results indicated that despite no major disruption in lipid metabolism, placentas from GDM pregnancies showed significant alterations in sphingolipids, mostly lower abundance of total ceramides. Additionally, very long-chain ceramides and sphingomyelins with twenty-four carbons were lower, and glucosylceramides with sixteen carbons were higher in placentas from GDM pregnancies. Semi-targeted lipidomics revealed the strong impact of GDM on the placental acylcarnitine profile, particularly lower contents of medium and long-chain fatty-acyl carnitine species. The lower contents of sphingolipids may affect the secretory function of the placenta, and lower contents of long-chain fatty acylcarnitines is suggestive of mitochondrial dysfunction. These alterations in placental lipid metabolism may have consequences for fetal growth and development.
While window-shopping for his wife’s birthday, a businessman was struck by a speeding taxi that jumped the curb at 55th and Madison. In the few minutes it took the ambulance to reach the University emergency room, he had lapsed into a coma. Brain imaging revealed a large blood clot compressing the brain. The only hope for his survival was immediate drainage of the clot.
In this series of short essays, stories, poems, and personal observations, Robert A. Burton, neurologist and writer, uses both fiction and nonfiction to explore many paradoxes and contradictions inherent in scientific inquiry. A novelist as well as author of On Being Certain and A Skeptic’s Guide to the Mind, Burton brings story to science and science to story.
Accurate anti-aquaporin-4 (AQP4) and anti-myelin oligodendrocyte glycoprotein (MOG) autoantibody assays are needed to effectively diagnose neuromyelitis optica spectrum disorder and MOG antibody-associated disease. A proportion of patients at our centre have been tested for anti-AQP4 and anti-MOG autoantibodies locally, followed by an outsourced test as part of real-world practice. Outsourced testing is costly and of unproven utility. We conducted a quality improvement project to determine the value of outsourced testing for anti-AQP4 and anti-MOG autoantibodies.
Methods:
All patients seen by Calgary neurological services who underwent cell-based testing for anti-AQP4 and/or anti-MOG autoantibodies at both MitogenDx (Calgary, AB) and Mayo Clinic Laboratories (Rochester, MN, USA) between 2016 and 2020 were identified from a provincial database. The interlaboratory concordance was calculated by pairing within-subject results collected no more than 365 days apart. Retrospective chart review was done for subjects with discordant results to determine features associated with discordance and use of outsourced testing.
Results:
Fifty-seven anti-AQP4 and 46 anti-MOG test pairs from January 2016 to July 2020 were analyzed. Concordant tests pairs comprised 54/57 (94.7%, 95%CI 88.9–100.0%) anti-AQP4 and 41/46 (89.1%, 95%CI 80.1–98.1%) anti-MOG results. Discordant anti-AQP4 pairs included two local weak positives (negative when outsourced) and one local negative (positive when outsourced). Discordant anti-MOG pairs were all due to local weak positives (negative when outsourced).
Conclusion:
Interlaboratory discordant results for cell-based testing of anti-AQP4 autoantibodies were rare. Local anti-MOG weak positive results were associated with discordance, highlighting the need for cautious interpretation based on the clinical context. Our findings may reduce redundant outsourced testing.
The 4-hydroxyphenylpyruvate dioxygenase (HPPD)-inhibiting herbicides are primarily used for weed control in corn, barley, oat, rice, sorghum, sugarcane, and wheat production fields in the United States. The objectives of this review were to summarize (1) the history of HPPD-inhibitor and their use in the United States, (2) HPPD-inhibitor resistant weeds, their mechanism of resistance, and management, (3) interaction of HPPD-inhibitor with other herbicides, and (4) the future of HPPD-inhibitor-resistant crops. As of 2022, three broadleaf weeds (Palmer amaranth, waterhemp, and wild radish) have evolved resistance to the HPPD-inhibitor. The predominance of metabolic resistance to HPPD-inhibitor was found in aforementioned three weed species. Management of HPPD-inhibitor-resistant weeds can be accomplished using alternate herbicides such as glyphosate, glufosinate, 2,4-D, or dicamba; however, metabolic resistance poses a serious challenge, as the weeds may be cross-resistant to other herbicide sites of action, leading to limited herbicide options. The HPPD-inhibitor is commonly applied with photosystem II (PS II)-inhibitor to increase efficacy and weed control spectrum. The synergism with HPPD-inhibitor arises from depletion of plastoquinones, which allows increased binding of PS II-inhibitor to the D1 protein. New HPPD-inhibitor from azole carboxamides class is in development and expected to be available in the near future. The HPPD-inhibitor-resistant crops have been developed through overexpression of a resistant bacterial HPPD enzyme in plants and the overexpression of transgenes for HPPD and a microbial gene that enhances the production of HPPD substrate. Isoxaflutole-resistant soybean is commercially available, and it is expected that soybean resistant to other HPPD-inhibitor such as mesotrione, stacked with resistance to other herbicides, will be available in the near future.
Vegetarians have less hypertension, diabetes mellitus and obesity, hence possibly lower risk of congestive heart failure (HF). We studied associations between vegetarian diets and echocardiographic markers of stage B HF. In a cross-sectional study, dietary pattern was ascertained by a validated FFQ. Echocardiograms were interpreted using standardised criteria. Participants were free-living subjects in Southern California who were older Adventist Health Study-2 cohort members. After exclusions, 133 subjects aged >60 years were enrolled. Their mean age was 72·7 (sd 8·7) years, 48·1 % were female, 32 % were African American and 71 % were vegetarian. Non-vegetarians had higher body weight (80·3 (sd 15·17) kg v. 71·3 (sd 16·2), P < 0·005), body surface area (1·92 (sd 0·24) m2v. 1·81 (sd 0·22) m2, P = 0·01) and prevalence of hypertension (63 % v. 47 %, P = 0·10). Adjusting for age, sex, race and physical activity, it is found that vegetarians had greater echocardiographic mitral annular e’ velocity (a measure of left ventricular (LV) relaxation) 7·44 v. 6·48 (non-vegetarian) cm/s (P = 0·011) and a yet greater contrast when vegans (7·66 cm/s, P = 0·011) were the group of interest. The ratio mid-to-late-diastolic mitral flow velocity (E/A) was also higher in vegans compared with non-vegetarians (1·02 and 0·84, respectively, P = 0·008). Mediation analyses suggested these associations may be partly related to higher blood pressures and BMI in the non-vegetarians. We conclude that vegetarians, especially vegans, appear to have better LV relaxation and fewer diastolic abnormalities than others. As dietary exposure is modifiable, one may speculate pending further investigation about the potential for reduction of stage B HF and later mortality.
Why does human cooperation often unravel in economic experiments despite a promising start? Previous studies have interpreted the decline as the reaction of disappointed altruists retaliating in response to non-altruists (Conditional Cooperators hypothesis). This interpretation has been considered evidence of a uniquely human form of cooperation, motivated by an altruistic concern for equality (‘fairness’) and requiring special evolutionary explanations. However, experiments have typically shown individuals not only information about the decisions of their groupmates (social information) but also information about their own payoffs. Showing both confounds explanations based on conditional cooperation with explanations based on confused individuals learning how to better play the game (Confused Learners hypothesis). Here we experimentally decouple these two forms of information, and thus these two hypotheses, in a repeated public-goods game. Analysing 616 Swiss university participants, we find that payoff information leads to a greater decline, supporting the Confused Learners hypothesis. In contrast, social information has a small or negligible effect, contradicting the Conditional Cooperators hypothesis. We also find widespread evidence of both confusion and selfish motives, suggesting that human cooperation is maybe not so unique after all.
Psychiatric disorders are highly polygenic and show patterns of partner resemblance. Partner resemblance has direct population-level genetic implications if it is caused by assortative mating, but not if it is caused by convergence or social homogamy. Using genetics may help distinguish these different mechanisms. Here, we investigated whether partner resemblance for schizophrenia and bipolar disorder is influenced by assortative mating using polygenic risk scores (PRSs).
Methods
PRSs from The Danish High-Risk and Resilience Study—VIA 7 were compared between parents in three subsamples: population-based control parent pairs (N=198), parent pairs where at least one parent had schizophrenia (N=193), and parent pairs where at least one parent had bipolar disorder (N=115).
Results
The PRS for schizophrenia was predictive of schizophrenia in the full sample and showed a significant correlation between parent pairs (r=0.121, p=0.0440), indicative of assortative mating. The PRS for bipolar disorder was also correlated between parent pairs (r=0.162, p=0.0067), but it was not predictive of bipolar disorder in the full sample, limiting the interpretation.
Conclusions
Our study provides genetic evidence for assortative mating for schizophrenia, with important implications for our understanding of the genetics of schizophrenia.
Optimizing research on the developmental origins of health and disease (DOHaD) involves implementing initiatives maximizing the use of the available cohort study data; achieving sufficient statistical power to support subgroup analysis; and using participant data presenting adequate follow-up and exposure heterogeneity. It also involves being able to undertake comparison, cross-validation, or replication across data sets. To answer these requirements, cohort study data need to be findable, accessible, interoperable, and reusable (FAIR), and more particularly, it often needs to be harmonized. Harmonization is required to achieve or improve comparability of the putatively equivalent measures collected by different studies on different individuals. Although the characteristics of the research initiatives generating and using harmonized data vary extensively, all are confronted by similar issues. Having to collate, understand, process, host, and co-analyze data from individual cohort studies is particularly challenging. The scientific success and timely management of projects can be facilitated by an ensemble of factors. The current document provides an overview of the ‘life course’ of research projects requiring harmonization of existing data and highlights key elements to be considered from the inception to the end of the project.
This paper demonstrates experimentally that imposed periodic forcing can significantly alter the global flow characteristics of the flow over a double backward-facing step. The geometry consists of two equal height steps spaced up to eight step heights apart. A periodic zero-mass flux jet located at the first step's top corner was issued at frequencies ranging from below the step-mode instability frequency up to approximately five times the shear-layer instability frequency. Reattachment of the flow onto the first step was achieved for step separations as low as three single-step heights with imposed forcing; significantly shorter than the five single-step heights that occurred without forcing. A significant reduction in mean base pressure on the first step, and increase on the second step, occurred for low forcing frequencies. Even for large step separations, the effect of forcing on the flow persisted sufficiently far downstream to appreciably influence the development of the second recirculation zone. Importantly, previous forced single and unforced double backward-facing step flows provide reference cases to examine and discuss similarities and differences. This study offers insight into possibilities and potential outcomes of flow control for applications ranging from the drag reduction of ground vehicles such as pickup trucks, to enhanced mixing in industrial processes.
To measure rates of racism experienced and witnessed by Junior Doctors working at Derbyshire Healthcare NHS Foundation Trust.
Methods
Surveys were sent out via e-mail and WhatsApp to all Junior Doctors from 22 November 2021 to 1 December 2021.
Questions asked about personal experiences of racism, witnessing racism to/from patients and/or staff whilst working in Derbyshire, knowledge of how to report incidents and if routinely reported. Doctor race and gender recorded.
Results
88 Junior Doctors contacted. Response rate 55% (48 out of 88). 63% female, 35% male and 2% gender undisclosed. 37.5% White, 12.5% Black, 37.5% Asian, 6.3% Mixed-race, 4.2% Arab or other ethnic group and 2% Race undisclosed. 13% of doctors experienced racism from staff: 75% of the Black female population, 50% of the Black male population, 8% of the Asian female population and 17% of the Asian male population. 27% of doctors experienced racism from patients: 50% Black female population, 50% Black male population, 58% Asian female population, 16% Asian male population, 100% Mixed-race female population and 1 Race unspecified male. 13% of doctors witnessed racism from staff to other staff: 75% Black female population, 50% Black male population, 11% Asian female population and 16% Asian male population. 63% of doctors witnessed racism from patients towards staff: 75% Black female population, 50% Black male population, 67% Asian female population, 33% Asian male population, 100% of the Mixed-race population, 58% White female population, 83% of the White male population and by 1 male Race unspecified. Two reports of racism witnessed from staff towards patients. 50% of doctors do not know how to report racism. 54% of doctors would report racism if they knew how.
Conclusion
Black, Asian, and Minority Ethnic (BAME) Junior Doctors are disproportionately affected by racism with female gender as an additional vulnerability. Mixed-race females, Asian females, and Black doctors gave highest reported experience of racism from patients. Black doctors gave a higher reported experience of racism from staff and reported witnessing the most racism from staff towards other staff. Mixed-race and White male doctors represent a high number of those that witness patients be racist towards staff. Additional support is required in encouraging allyship, confidence and ability to report racism.
This study investigates indicators of disorganized caregiving among caregivers of children who have a familial predisposition of schizophrenia spectrum psychosis (SZ) or bipolar disorder (BP), and whether indicators of disorganized caregiving are associated with the caregivers’ and children’s level of functioning as well as the children’s internalizing and externalizing behavior problems. Indicators of disorganized caregiving were assessed with the Caregiving Helplessness Questionnaire (CHQ). Level of functioning was evaluated using the Children’s Global Assessment Scale and the Personal and Social Performance Scale, while dimensional psychopathology were measured with the Child Behavior Checklist. 185 caregivers belonging to a SZ combined group (i.e., SZ-I + SZ co-caregiver), 110 caregivers to a BP combined group (i.e., BP-I + BP co-caregiver), and 184 caregivers to a population-based control group provided data on CHQ. Having a history of SZ or BP or being a co-caregiver to a parent with SZ or BP was associated with higher levels of experiences of helplessness and fear. Higher scores on helplessness were associated with lower level of functioning among caregivers and children and with children having externalizing/internalizing behavior problems. These results emphasize the need for interventions addressing indicators of disorganized caregiving in families with SZ or BP.
In recent years, the company called CB Resourcing has established itself in the recruitment business and regularly advertises for positions in the knowledge management, business research, legal tech and law librarianship worlds. In this short article one of the Directors of CB Resourcing, Simon Burton, offers some thoughts about the recruitment business, the current state of the market and describes the services that are provided by the company. The article has been written in the form of an interview with questions posed by the editor of this journal and answers given by Simon Burton.