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Animal behaviours that are superficially similar can express different intents in different contexts, but how this flexibility is achieved at the level of neural circuits is not understood. For example, males of many species can exhibit mounting behaviour towards same- or opposite-sex conspecifics1, but it is unclear whether the intent and neural encoding of these behaviours are similar or different. Here we show that female- and male-directed mounting in male laboratory mice are distinguishable by the presence or absence of ultrasonic vocalizations (USVs)2–4, respectively. These and additional behavioural data suggest that most male-directed mounting is aggressive, although in rare cases it can be sexual. We investigated whether USV+ and USV− mounting use the same or distinct hypothalamic neural substrates. Micro-endoscopic imaging of neurons positive for oestrogen receptor 1 (ESR1) in either the medial preoptic area (MPOA) or the ventromedial hypothalamus, ventrolateral subdivision (VMHvl) revealed distinct patterns of neuronal activity during USV+ and USV− mounting, and the type of mounting could be decoded from population activity in either region. Intersectional optogenetic stimulation of MPOA neurons that express ESR1 and vesicular GABA transporter (VGAT) (MPOAESR1∩VGAT neurons) robustly promoted USV+ mounting, and converted male-directed attack to mounting with USVs. By contrast, stimulation of VMHvl neurons that express ESR1 (VMHvlESR1 neurons) promoted USV− mounting, and inhibited the USVs evoked by female urine. Terminal stimulation experiments suggest that these complementary inhibitory effects are mediated by reciprocal projections between the MPOA and VMHvl. Together, these data identify a hypothalamic subpopulation that is genetically enriched for neurons that causally induce a male reproductive behavioural state, and indicate that reproductive and aggressive states are represented by distinct population codes distributed between MPOAESR1 and VMHvlESR1 neurons, respectively. Thus, similar behaviours that express different internal states are encoded by distinct hypothalamic neuronal populations. Ultrasonic vocalizations of male mice distinguish aggressive, male-directed mounting from reproductive, female-directed mounting behaviours, which are represented by distinct ESR1-expressing populations of neurons in the ventromedial hypothalamus and medial preoptic area, respectively.

Despite advances in multimodal therapy for neuroblastoma, survival from advanced disease remains poor. Children are now offered a wide variety of salvage regimens following relapse. A retrospective review was performed on 31 patients with recurrent neuroblastoma treated at one institution between 1995 and 2001. At initial diagnosis, 27 patients had metastatic disease and 11 had N-myc amplification (NMA). The median time to recurrence from diagnosis was 16.1 months. Seventeen patients received salvage therapy, with a median of three salvage regimens per patient. The median survival time from relapse was 8.4 months. The median survival time was significantly shorter for recurrence less than 6 months after stem cell transplantation (2.9 vs. 13.3 months; P = 0.003) and for patients with NMA (2.7 vs. 15.1 months; P < 0.0001). Overall, salvage therapy led to a significantly longer median survival time (22.4 vs. 3.3 months; P = 0.0003); however, salvage therapy extended the median survival time only from 2.2 to 3.2 months for patients with NMA and from 0.7 to 5.8 months for patients with early relapse after stem cell transplantation. Multiple salvage regimens prolong survival significantly, especially for patients with no NMA and for relapses more than 6 months after stem cell transplantation, but the long-term disease-free survival after recurrent disease remains dismal.

Objective To develop a comorbidity model for children that can be used with hospital discharge administrative databases. Design Retrospective study using administrative data obtained from the Canadian Institute for Health Information Discharge Abstract Database and the Deaths File to develop a logistic regression model. Hosmer-Lemeshow χ2test was used to examine model fit. The C statistic was used to assess model discrimination. Bootstrapping was used to determine the stability of regression coefficients. Setting We used linked administrative databases to compile 339 077 hospital discharge abstracts from April 1, 1991, through March 31, 2002. Participants Children between ages 1 and 14 years in Ontario, Canada. Main Outcome Measure Death within 1 year of hospital discharge. Results The 27-variable pediatric comorbidity model predicted 1-year mortality with a C statistic of 0.83 in the Ontario data set from which it was derived. The presence of brain cancer (odds ratio, 76.38 [95% confidence interval, 53.40-109.27]) at hospital admission was the strongest predictor, followed by diabetes insipidus (odds ratio, 39.23 [95% confidence interval, 20.75-74.17]). Conclusion Using clinical judgment and empirical modeling strategies, we were able to identify 27 diagnoses highly predictive of death for children between 1 and 14 years of age within 1 year of hospital discharge.