Recommendations for accelerating open preprint peer review to improve the culture of science

Peer review is an important part of the scientific process, but traditional peer review at journals is coming under increased scrutiny for its inefficiency and lack of transparency. As preprints become more widely used and accepted, they raise the possibility of rethinking the peer-review process. Preprints are enabling new forms of peer review that have the potential to be more thorough, inclusive, and collegial than traditional journal peer review, and to thus fundamentally shift the culture of peer review toward constructive collaboration. In this Consensus View, we make a call to action to stakeholders in the community to accelerate the growing momentum of preprint sharing and provide recommendations to empower researchers to provide open and constructive peer review for preprints

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Estimating the probability of abusive head trauma: a pooled analysis

Context and Objective: To determine which combinations of clinical features assist in distinguishing abusive head trauma (AHT) from nonabusive head trauma. Methods: Individual patient data from 6 comparative studies of children younger than 3 years with intracranial injury were analyzed to determine the association between AHT and combinations of apnea; retinal hemorrhage; rib, skull, and long-bone fractures; seizures; and head and/or neck bruising. An aggregate analysis of data from these studies used multiple imputation of combined clinical features using a bespoke hotdeck imputation strategy, which accounted for uncertainty arising from missing information. Results: Analyzing 1053 children (348 had AHT), excluding nonsignificant variables (gender, age, skull fractures), for a child with an intracranial injury and 1 or 2 of the 6 features, the positive predictive value (PPV) of AHT varies from 4% to 97% according to the different combinations. Although rarely recorded, apnea is significantly associated with AHT (odds ratio [OR]: 6.89 [confidence interval: 2.08–22.86]). When rib fracture or retinal hemorrhage was present with any 1 of the other features, the OR for AHT is >100 (PPV > 85%). Any combination of 3 or more of the 6 significant features yielded an OR of >100 (PPV for AHT > 85%). Conclusions: Probabilities of AHT can be estimated on the basis of different combinations of clinical features. The model could be further developed in a prospective large-scale study, with an expanded clinical data set, to contribute to a more refined tool to inform clinical decisions about the likelihood of AHT

Contact, cigarette and flame burns in physical abuse: A systematic review

This systematic review identifies features of intentional non‐scald burns in physical abuse. Fifteen bibliographic databases of international literature (1950–2011) were searched to identify potential studies that were critically appraised using standardised methods. Primary studies with confirmed intentional non‐scald burns in children aged < 18 years were included to provide a descriptive analysis of the causation, appearance and distribution of burns

Emotional, behavioral, and developmental features indicative of neglect or emotional abuse in preschool children: a systematic review

IMPORTANCE Early intervention for neglect or emotional abuse in preschoolers may mitigate lifelong consequences, yet practitioners lack confidence in recognizing these children. OBJECTIVE To define the emotional, behavioral, and developmental features of neglect or emotional abuse in preschoolers. EVIDENCE REVIEW A literature search of 18 databases, 6 websites, and supplementary searching performed from January 1, 1960, to February 1, 2011, identified 22 669 abstracts. Standardized critical appraisal of 164 articles was conducted by 2 independent, trained reviewers. Inclusion criteria were children aged 0 to 6 years with confirmed neglect or emotional abuse who had emotional, behavioral, and developmental features recorded or for whom the carer-child interaction was documented. FINDINGS Twenty-eight case-control (matched for socioeconomic, educational level, and ethnicity), 1 cross-sectional, and 13 cohort studies were included. Key features in the child included the following: aggression (11 studies) exhibited as angry, disruptive behavior, conduct problems, oppositional behavior, and low ego control; withdrawal or passivity (12 studies), including negative self-esteem, anxious or avoidant behavior, poor emotional knowledge, and difficulties in interpreting emotional expressions in others; developmental delay (17 studies), particularly delayed language, cognitive function, and overall development quotient; poor peer interaction (5 studies), showing poor social interactions, unlikely to act to relieve distress in others; and transition (6 studies) from ambivalent to avoidant insecure attachment pattern and from passive to increasingly aggressive behavior and negative self-representation. Emotional knowledge, cognitive function, and language deteriorate without intervention. Poor sensitivity, hostility, criticism, or disinterest characterize maternal-child interactions. CONCLUSIONS AND RELEVANCE Preschool children who have been neglected or emotionally abused exhibit a range of serious emotional and behavioral difficulties and adverse mother-child interactions that indicate that these children require prompt evaluation and interventions

A systematic review of abusive visceral injuries in childhood - their range and recognition

Objectives. To define what abusive visceral injuries occur, including their clinical features and the value of screening tests for abdominal injury among abused children. Methods. We searched 12 databases, with snowballing techniques, for the period 1950–2011, with all identified studies undergoing two independent reviews by trained reviewers, drawn from pediatrics, radiology, pediatric surgery and pathology. Of 5802 studies identified, 188 were reviewed. We included studies of children aged 0–18, with confirmed abusive etiology, whose injury was defined by computed tomography, contrast studies or at surgery/post mortem. We excluded injuries due to sexual abuse, or those exclusively addressing management or outcome. Results. Of 88 included studies (64 addressing abdominal injuries), only five were comparative. Every organ in the body has been injured, intra-thoracic injuries were commoner in those aged less than five years. Children with abusive abdominal injuries were younger (2.5–3.7 years vs. 7.6–10.3 years) than accidentally injured children. Duodenal injuries were commonly recorded in abused children, particularly involving the third or fourth part, and were not reported in accidentally injured children less than four years old. Liver and pancreatic injuries were frequently recorded, with potential pancreatic pseudocyst formation. Abdominal bruising was absent in up to 80% of those with abdominal injuries, and co-existent injuries included fractures, burns and head injury. Post mortem studies revealed that a number of the children had sustained previous, unrecognized, abdominal injuries. The mortality from abusive abdominal injuries was significantly higher than accidental injuries (53% vs. 21%). Only three studies addressed screening for abdominal injury among abused children, and were unsuitable for meta-analysis due to lack of standardized investigations, in particular those with ‘negative’ screening tests were not consistently investigated. Conclusions. Visceral injuries may affect any organ of the body, predominantly abdominal viscera. A non-motor vehicle related duodenal trauma in a child aged < five years warrants consideration of abuse as an etiology. In the absence of clear evidence for a screening strategy, clinical vigilance is warranted in any young child with suspected abuse for the presence of abdominal injury, where the absence of abdominal bruising or specific symptoms does not preclude significant injury