† People involved in the organization of the challenge. ‡ People contributing data from their institutions.§ Equal senior authors.

I ntracranial hemorrhage is a potentially life-threatening problem that has many direct and indirect causes. Accuracy in diagnosing the presence and type of intracranial hemorrhage is a critical part of effective treatment. Diagnosis is often an urgent procedure requiring review of medical images by highly trained specialists and sometimes necessitating confirmation through clinical history, vital signs, and laboratory examinations. The process is complicated and requires immediate identification for optimal treatment.Intracranial hemorrhage is a relatively common condition that has many causes, including trauma, stroke, aneurysm, vascular malformation, high blood pressure, illicit drugs, and blood clotting disorders (1). Neurologic consequences can vary extensively from headache to death depending upon the size, type, and location of the hemorrhage. The role of the radiologist is to detect the hemorrhage, characterize the type and cause of the hemorrhage, and to determine if the hemorrhage could be jeopardizing critical areas of the brain that might require immediate surgery.While all acute hemorrhages appear attenuated on CT images, the primary imaging features that help radiologists determine the cause of hemorrhage are the location, shape, and proximity to other structures. Intraparenchymal hemorrhage is blood that is located completely within the brain itself. Intraventricular or subarachnoid hemorrhage is blood that has leaked into the spaces of the brain that normally contain cerebrospinal fluid (the ventricles or subarachnoid cisterns, respectively). Extra-axial hemorrhage is blood that collects in the tissue coverings that surround the brain (eg, subdural or epidural subtypes). It is important to note that patients may exhibit more than one type of cerebral hemorrhage, which may appear on the same image or imaging study. Although small hemorrhages are typically less morbid than large hemorrhages, even a small hemorrhage can lead to death if it is in a critical location. Small hemorrhages also may herald future hemorrhages that could be fatal (eg, ruptured cerebral aneurysm). The presence or absence of hemorrhage may guide specific treatments (eg, stroke).Detection of cerebral hemorrhage with brain CT is a popular clinical use case for machine learning (2-5). Many of these early successful investigations were based upon relatively small datasets (hundreds of examinations) from single institutions. Chilamkurthy et al created a diverse brain CT dataset that was selected from 20 geographically distinct centers in India (more than 21 000 unique examinations). This was used to create smaller randomly selected subsets for validation and testing on common acute brain abnormalities (6). The ability for machine learning algorithms to generalize to "real-world" clinical imaging data from disparate institutions is paramount to successful use in the clinical environment.The intent for this challenge was to provide a large multiinstitutional and multinational dataset to help develop machine learning algorithms that ca...

These findings support previous research demonstrating alterations in the prefrontal cortex, corpus callosum, and posterior vermis in children with autism and further suggest that alterations are associated with the severity of the autism phenotype. Continued research involving twins who are concordant and discordant for autism is essential to disentangle the genetic and environmental contributions to autism.

In order to disentangle genetic and environmental contributions to cortical anomalies in children with autism, we investigated cortical folding patterns in a cohort of 14 monozygotic (MZ) twin pairs who displayed a range of phenotypic discordance for autism, and 14 typically developing community controls. Cortical folding was assessed with the gyrification index, which was calculated on high resolution anatomic MR images. We found that the cortical folding patterns across most lobar regions of the cerebral cortex was highly discordant within MZ twin pairs. In addition, children with autism and their co-twins exhibited increased cortical folding in the right parietal lobe, relative to age- and gender-matched typical developing children. Increased folding in the right parietal lobe was associated with more symptoms of autism for co-twins. Finally, the robust association between cortical folding and IQ observed in typical children was not observed in either children with autism or their co-twins. These findings, which contribute to our understanding of the limits of genetic liability in autism, suggest that anomalies in the structural integrity of the cortex in this PDD may disrupt the association between cortical folding and intelligence that has been reported in typical individuals, and may account, in part, for the deficits in visual spatial attention and in social cognition that have been reported in children with autism.

One of the fields where pharmacology is allocating much of its efforts is the neuroprotective approach to Alzheimer's disease (AD) therapy. Current available drug treatment is symptomatic with no disease-modifying effects on the underlying progressive processes. Without a target to modulate, it becomes difficult to offer a drug. Currently, the pharmacotherapeutic field seems to be immersed in a chess match, planning victory while simultaneously being vigilant for attack. However, AD is not played on a chessboard with 64 squares where each player controls sixteen pieces and the movement of each piece is predictable. As a matter of fact, while the pathological pieces are known the movement strategies are proving challenging to develop.The pathological hallmarks of AD include high levels of oxidative stress, intraneuronal amyloid beta peptide (Ab) accumulation, extracellular senile amyloid plaques, intraneuronal and extraneuronal neurofibrillary tangles made of hyper-phosphorylated tau, loss of synapses, loss of neurons and neuritic degeneration and gliosis. This pathology culminates in clinical signs predominantly associated with impaired cognitive processes. However, as indicated above, the underlying cause and molecular inter-relationship Address correspondence and reprint requests to Joaquín Jordan, Grupo de Neurofarmacología, Universidad de Castilla-La Mancha, Centro Regional de Investigaciones Biomédicas, Avda. Almansa, 14, 02006 Albacete, Spain. E-mail: joaquin.jordan@uclm.es or Gemma Casadesus, Department of Neurosciences, Case Western Reserve University, Cleveland, OH 44106, USA. E-mail: gxc40@case.eduAbbreviations used: a-KGDH, a-ketoglutarate dehydrogenase; ABAD, Ab-binding alcohol dehydrogenase; AD, Alzheimer's disease; Ab, Amyloid Beta; APP, amyloid precursor protein; BACE, b-site amyloid precursor protein-cleaving enzyme; cPLA2, cytosolic PLA2; ETC, electron transport chain; Hsp, heat-shock protein; MAO, monoamine oxidase; mitDNA, mitochondrial DNA; MPTP, mitochondrial permeability transition pore; NO, nitric oxide; PLA2, phospholipase A2; RAGE, receptor for advanced glycation end products; RNS, reactive nitrogen species; ROS, reactive oxygen species. AbstractDespite the increasing knowledge of Alzheimer's disease (AD) management with novel pharmacologic agents, most of them are only transiently fixing symptomatic pathology. Currently there is rapid growth in the field of neuroprotective pharmacology and increasing focus on the involvement of mitochondria in this devastating disease. This review is directed at understanding the role of mitochondria-mediated pathways in AD and integrating basic biology of the mitochondria with knowledge of possible pharmacologic targets for AD treatment in an attempt to elucidate novel mitochondria-driven therapeutic interventions useful to both clinical and basic research.