A Prospective Cohort Study on the Intergenerational Transmission of Childhood Adversity and Subsequent Risk of Psychotic Experiences in Adolescence

BACKGROUND AND HYPOTHESIS: Previous studies have shown a robust relationship between childhood adversity and subsequent psychotic symptoms. However, the role of familial risk factors underlying this relationship remains largely unclear. Here, we tested whether offspring childhood adversity and postnatal maternal psychopathology mediated the relationship between maternal childhood adversity and offspring psychotic experiences. STUDY DESIGN: N = 3068 mother-offspring dyads were included. Maternal history of childhood adversity was retrospectively assessed using the Childhood Trauma Questionnaire during pregnancy. Maternal psychopathology was assessed during and after pregnancy. Twenty-four offspring childhood adversities were assessed by maternal interview when the child was 10 years old. Offspring psychotic experiences were examined using self-report at 14 years. Structural equation mediation models were conducted to explore whether maternal postnatal psychopathology and offspring childhood adversities sequentially mediated the relationship between maternal childhood adversity and offspring psychotic experiences. Analyses were adjusted for sociodemographic confounders. STUDY RESULTS: Maternal history of childhood adversity was associated with offspring childhood adversities (β = 0.12, 95% CI: 0.09 to 0.16). Offspring childhood adversity mediated the association of maternal childhood adversity with offspring hallucinations (βindirect effect = 0.008, 95% CI: 0.002 to 0.014, proportion mediated = 16.3%) and delusions (βindirect effect = 0.006, 95% CI: 0.000 to 0.012, proportion mediated = 13.1%). CONCLUSIONS: Intergenerational transmission of childhood adversity can be considered of relevance in the etiology of psychosis vulnerability and can potentially serve as a modifiable risk factor

Money for medication

Background: Non-adherence with antipsychotic medication is a frequently occurring problem, particularly among patients with psychotic disorders. Prior research has generally shown encouraging results for interventions based on ‘Contingency Management’ (CM), in which desirable behaviour is encouraged by providing rewards contingent upon the behaviour. However, little is known about the application of CM on medication adherence in patients with psychotic disorders. An earlier pilot-study by our study group showed promising results in reducing admission days and increasing adherence. The current study is a randomized controlled trial concerning the effectiveness of a CM procedure called ‘Money for Medication’ (M4M), aimed at improving adherence with antipsychotic depot medication in psychotic disorder patients. Methods/Design: Outpatients (n =168) with a psychotic disorder will be randomly assigned to either the experimental group (n =84), receiving a financial reward for each accepted antipsychotic medication depot, or the control group (n =84), receiving treatment as usual without financial rewards. Patients are included regardless of their previous adherence. The intervention has a duration of twelve months. During the subsequent six months follow-up, the effects of discontinuing the intervention on depot acceptance will be assessed. The primary goal of this study is to assess the effectiveness of providing financial incentives for improving adherence with antipsychotic depot medication (during and after the intervention). The primary outcome measure is the percentage of accepted depots in comparison to prescription. Secondary, we will consider alternative measures of medication acceptance, i.e. the longest period of uninterrupted depot acceptance and the time expired before depot is taken. Additionally, the effectivene

Minimally invasive complete response assessment of the breast after neoadjuvant systemic therapy for early breast cancer (micra trial) : interim analysis of a multicenter observational cohort study

Background The added value of surgery in breast cancer patients with pathological complete response (pCR) after neoadjuvant systemic therapy (NST) is uncertain. The accuracy of imaging identifying pCR for omission of surgery, however, is insufficient. We investigated the accuracy of ultrasound-guided biopsies identifying breast pCR (ypT0) after NST in patients with radiological partial (rPR) or complete response (rCR) on MRI. Methods We performed a multicenter, prospective single-arm study in three Dutch hospitals. Patients with T1-4(N0 or N +) breast cancer with MRI rPR and enhancement <= 2.0 cm or MRI rCR after NST were enrolled. Eight ultrasound-guided 14-G core biopsies were obtained in the operating room before surgery close to the marker placed centrally in the tumor area at diagnosis (no attempt was made to remove the marker), and compared with the surgical specimen of the breast. Primary outcome was the false-negative rate (FNR). Results Between April 2016 and June 2019, 202 patients fulfilled eligibility criteria. Pre-surgical biopsies were obtained in 167 patients, of whom 136 had rCR and 31 had rPR on MRI. Forty-three (26%) tumors were hormone receptor (HR)-positive/HER2-negative, 64 (38%) were HER2-positive, and 60 (36%) were triple-negative. Eighty-nine patients had pCR (53%; 95% CI 45-61) and 78 had residual disease. Biopsies were false-negative in 29 (37%; 95% CI 27-49) of 78 patients. The multivariable associated with false-negative biopsies was rCR (FNR 47%; OR 9.81, 95% CI 1.72-55.89; p = 0.01); a trend was observed for HR-negative tumors (FNR 71% in HER2-positive and 55% in triple-negative tumors; OR 4.55, 95% CI 0.95-21.73; p = 0.058) and smaller pathological lesions (6 mm vs 15 mm; OR 0.93, 95% CI 0.87-1.00; p = 0.051). Conclusion The MICRA trial showed that ultrasound-guided core biopsies are not accurate enough to identify breast pCR in patients with good response on MRI after NST. Therefore, breast surgery cannot safely be omitted relying on the results of core biopsies in these patients

Genetic variants for head size share genes and pathways with cancer

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.</p

NeuroBench:Advancing Neuromorphic Computing through Collaborative, Fair and Representative Benchmarking

The field of neuromorphic computing holds great promise in terms of advancing computing efficiency and capabilities by following brain-inspired principles. However, the rich diversity of techniques employed in neuromorphic research has resulted in a lack of clear standards for benchmarking, hindering effective evaluation of the advantages and strengths of neuromorphic methods compared to traditional deep-learning-based methods. This paper presents a collaborative effort, bringing together members from academia and the industry, to define benchmarks for neuromorphic computing: NeuroBench. The goals of NeuroBench are to be a collaborative, fair, and representative benchmark suite developed by the community, for the community. In this paper, we discuss the challenges associated with benchmarking neuromorphic solutions, and outline the key features of NeuroBench. We believe that NeuroBench will be a significant step towards defining standards that can unify the goals of neuromorphic computing and drive its technological progress. Please visit neurobench.ai for the latest updates on the benchmark tasks and metrics

NeuroBench: Advancing Neuromorphic Computing through Collaborative, Fair and Representative Benchmarking

The field of neuromorphic computing holds great promise in terms of advancing computing efficiency and capabilities by following brain-inspired principles. However, the rich diversity of techniques employed in neuromorphic research has resulted in a lack of clear standards for benchmarking, hindering effective evaluation of the advantages and strengths of neuromorphic methods compared to traditional deep-learning-based methods. This paper presents a collaborative effort, bringing together members from academia and the industry, to define benchmarks for neuromorphic computing: NeuroBench. The goals of NeuroBench are to be a collaborative, fair, and representative benchmark suite developed by the community, for the community. In this paper, we discuss the challenges associated with benchmarking neuromorphic solutions, and outline the key features of NeuroBench. We believe that NeuroBench will be a significant step towards defining standards that can unify the goals of neuromorphic computing and drive its technological progress. Please visit neurobench.ai for the latest updates on the benchmark tasks and metrics

The ladies trial: laparoscopic peritoneal lavage or resection for purulent peritonitisA and Hartmann's procedure or resection with primary anastomosis for purulent or faecal peritonitisB in perforated diverticulitis (NTR2037)

Background: Recently, excellent results are reported on laparoscopic lavage in patients with purulent perforated diverticulitis as an alternative for sigmoidectomy and ostomy. The objective of this study is to determine whether LaparOscopic LAvage and drainage is a safe and effective treatment for patients with purulent peritonitis (LOLA-arm) and to determine the optimal resectional strategy in patients with a purulent or faecal peritonitis (DIVA-arm: perforated DIVerticulitis: sigmoidresection with or without Anastomosis). Methods/Design: In this multicentre randomised trial all patients with perforated diverticulitis are included. Upon laparoscopy, patients with purulent peritonitis are treated with laparoscopic lavage and drainage, Hartmann's procedure or sigmoidectomy with primary anastomosis in a ratio of 2:1:1 (LOLA-arm). Patients with faecal peritonitis will be randomised 1:1 between Hartmann's procedure and resection with primary anastomosis (DIVA-arm). The primary combined endpoint of the LOLA-arm is major morbidity and mortality. A sample size of 132:66:66 patients will be able to detect a difference in the primary endpoint from 25% in resectional groups compared to 10% in the laparoscopic lavage group (two sided alpha = 5%, power = 90%). Endpoint of the DIVA-arm is stoma free survival one year after initial surgery. In this arm 212 patients are needed to significantly demonstrate a difference of 30% (log rank test two sided alpha = 5% and powe

NeuroBench:A Framework for Benchmarking Neuromorphic Computing Algorithms and Systems

Neuromorphic computing shows promise for advancing computing efficiency and capabilities of AI applications using brain-inspired principles. However, the neuromorphic research field currently lacks standardized benchmarks, making it difficult to accurately measure technological advancements, compare performance with conventional methods, and identify promising future research directions. Prior neuromorphic computing benchmark efforts have not seen widespread adoption due to a lack of inclusive, actionable, and iterative benchmark design and guidelines. To address these shortcomings, we present NeuroBench: a benchmark framework for neuromorphic computing algorithms and systems. NeuroBench is a collaboratively-designed effort from an open community of nearly 100 co-authors across over 50 institutions in industry and academia, aiming to provide a representative structure for standardizing the evaluation of neuromorphic approaches. The NeuroBench framework introduces a common set of tools and systematic methodology for inclusive benchmark measurement, delivering an objective reference framework for quantifying neuromorphic approaches in both hardware-independent (algorithm track) and hardware-dependent (system track) settings. In this article, we present initial performance baselines across various model architectures on the algorithm track and outline the system track benchmark tasks and guidelines. NeuroBench is intended to continually expand its benchmarks and features to foster and track the progress made by the research community

A multidisciplinary perspective on COVID-19 exit strategies

Lockdowns and associated measures imposed in response to the COVID-19 crisis inflict severe damage to society. Across the globe, scientists and policymakers study ways to lift measures while maintaining control of virus spread in circumstances that continuously change due to the evolution of new variants and increasing vaccination coverage. In this process, it has become clear that finding and analysing exit strategies, which are a key aspect of pandemic mitigation in all consecutive waves of infection, is not solely a matter of epidemiological modeling but has many different dimensions that need to be balanced and therefore requires input from many different disciplines. Here, we document an attempt to investigate exit strategies from a multidisciplinary perspective through the Science versus Corona project in the Netherlands. In this project, scientists and laypeople were challenged to submit (components of) exit strategies. A selection of these were implemented in a formal model, and we have evaluated the scenarios from a multidisciplinary perspective, utilizing expertise in epidemiology, economics, psychology, law, mathematics, and history. We argue for the integration of multidisciplinary perspectives on COVID-19 and more generally in pandemic mitigation, highlight open challenges, and present an agenda for further research into exit strategies and their assessmen