The Shaken Baby Syndrome: A Clinical, Pathological, and Biomechanical Study

Because a history of shaking is often lacking in the so-called “shaken baby syndrome,” diagnosis is usually based on a constellation of clinical and radiographic findings. Forty-eight cases of infants and young children with this diagnosis seen between 1978 and 1985 at the Children\u27s Hospital of Philadelphia were reviewed. All patients had a presenting history thought to be suspicious for child abuse, and either retinal hemorrhages with subdural or subarachnoid hemorrhages or a computerized tomography scan showing subdural or subarachnoid hemorrhages with interhemispheric blood. The physical examination and presence of associated trauma were analyzed; autopsy findings for the 13 fatalities were reviewed. All fatal cases had signs of blunt impact to the head, although in more than half of them these findings were noted only at autopsy. All deaths were associated with uncontrollably increased intracranial pressure. Models of 1-month-old infants with various neck and skull parameters were instrumented with accelerometers and shaken and impacted against padded or unpadded surfaces. Angular accelerations for shakes were smaller than those for impacts by a factor of 50. All shakes fell below injury thresholds established for subhuman primates scaled for the same brain mass, while impacts spanned concussion, subdural hematoma, and diffuse axonal injury ranges. It was concluded that severe head injuries commonly diagnosed as shaking injuries require impact to occur and that shaking alone in an otherwise normal baby is unlikely to cause the shaken baby syndrome

Future research directions in injury biomechanics and passive safety research

There has been an increasing trend within the safety environment for funding to be directed towards applied research or towards research developing commercially-exploitable systems. Funding mechanisms such as the EU’s 6th Framework Programme and many national programmes focus on research of likely immediate social benefit, reflecting the use of public finances. These programmes will continue to play an important role in funding safety research, but they typically do not have guidelines specifically directed towards fundamental research questions. Additionally, impartial advice is not always available to help programme managers identify research priorities. This review of biomechanics and passive safety research is intended for use by researchers who may be contemplating research in certain areas and wish independent guidance on specific research questions. It is also intended for use by research funding groups and programme managers who would like impartial guidance on basic research to be supported. It covers engineering research directed at improving vehicles and safety systems for all types of road user. It includes the main research and development tools such as dummy development and humanoid modelling and the important area of crash injury data

New Copy Number Variations in Schizophrenia

Genome-wide screenings for copy number variations (CNVs) in patients with schizophrenia have demonstrated the presence of several CNVs that increase the risk of developing the disease and a growing number of large rare CNVs; the contribution of these rare CNVs to schizophrenia remains unknown. Using Affymetrix 6.0 arrays, we undertook a systematic search for CNVs in 172 patients with schizophrenia and 160 healthy controls, all of Italian origin, with the aim of confirming previously identified loci and identifying novel schizophrenia susceptibility genes. We found five patients with a CNV occurring in one of the regions most convincingly implicated as risk factors for schizophrenia: NRXN1 and the 16p13.1 regions were found to be deleted in single patients and 15q11.2 in 2 patients, whereas the 15q13.3 region was duplicated in one patient. Furthermore, we found three distinct patients with CNVs in 2q12.2, 3q29 and 17p12 loci, respectively. These loci were previously reported to be deleted or duplicated in patients with schizophrenia but were never formally associated with the disease. We found 5 large CNVs (>900 kb) in 4q32, 5q14.3, 8q23.3, 11q25 and 17q12 in five different patients that could include some new candidate schizophrenia susceptibility genes. In conclusion, the identification of previously reported CNVs and of new, rare, large CNVs further supports a model of schizophrenia that includes the effect of multiple, rare, highly penetrant variants

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Animal, physical and analytical models for use in the development of improved head injury criteria. Volume I. Final report.

National Highway Traffic Safety Administration, Washington, D.C.Mode of access: Internet.Author corporate affiliation: Pennsylvania University, PhiladelphiaReport covers the period 1982-1989Subject code: JLTSubject code: OAISubject code: OANBBSubject code: OEB*NLSISubject code: WNBKSubject code: XMCSubject code: XM

A membrane model to serve as the basis for cellular injury and tissue failure criteria. Volume III. Final report.

National Highway Traffic Safety Administration, Washington, D.C.Mode of access: Internet.Author corporate affiliation: Pennsylvania University, PhiladelphiaReport covers the period 1982-1989. Part 4 of 5Subject code: OAISubject code: OAPSubject code: WSMSubject code: YD