Emergency Preparedness Drills for Active and Mass Shootings in Schools.

PURPOSE OF REVIEW: There is widespread use of emergency preparedness drills in public K-12 schools across the US, but considerable variability exists in the types of protocols used and how these practices are conducted. This review examines research into both "lockdown drills" and "active shooter drills" as it relates to their impact on participants across different outcomes and evaluations of their procedural integrity. RECENT FINDINGS: A number of studies on lockdown drills yielded largely consistent findings about their impacts, whereas findings related to the effects of active shooter drills are less uniform. The research also demonstrated that lockdown drills, though not active shooter drills, can help participants build skill mastery to be able to successfully deploy the procedure. Differences in how drills impact participants and whether they cultivate skill mastery are largely attributable to the type of drill being conducted. This review suggests that employing clearly defined drill procedures incorporating best practices, coupled with instructional training, can help schools prepare for emergencies without creating trauma for participants.

Input from the frontlines: parole and probation officers' perceptions of policies directed at those convicted of sexual offenses.

Sex offender laws were designed to decrease sexual violence. The current mixed methods study examined attitudes and opinions of parole and probation officers who have supervised individuals convicted of sexual offenses (n = 361) regarding sex offender legislation and how these policies can be most effective in preventing recidivism. About half of the officers reported that registration and notification, sexually violent predator and Halloween laws were largely effective in preventing sexual victimization. Conversely, they perceived residence restriction laws and the tier system to be largely ineffective. A consistent theme that emerged from the qualitative responses was a movement away from blanket approaches towards a case-specific approach, tailoring the laws to individuals based upon their needs and risk level.

Experiences and Perceptions of Online Sexual Solicitation and Grooming of Minors: A Retrospective Report.

Internet predation of minors has become a focus of child sexual abuse research and legislation. Studies reveal that many American youth report experiencing sexual solicitation and sexual grooming online, but the youth perspective of these experiences has not been examined. This study examined retrospective perspectives of online sexual solicitation and grooming experienced as a minor. Participants were 1,133 undergraduate college students at two public institutions in the United States who completed an online survey retrospectively exploring Internet behaviors, experiences of online sexual solicitation or online grooming, and perceptions of the experience. Results showed that one-quarter of total participants conversed with adult strangers online as minors. Importantly, 65% of participants who chatted with adult strangers as minors experienced sexual solicitation from an adult stranger. Twenty-three percent of 1,133 total participants recalled having a long, intimate conversation as a minor with an adult stranger from an online chatroom that followed a pattern of online sexual grooming. While less than half (38%) of the youth who engaged in an intimate online relationship with an adult stranger met the adult in-person, a large majority of those who did meet in-person (68%) reported physical sexual intercourse. Implications for Internet safety and guidelines are discussed.

Preventing Suicide in Forensic Settings: Assessment and Intervention for Inmates With Serious Mental Illness.

Suicide is one of the leading causes of inmate deaths in correctional settings. Furthermore, there is heightened risk for suicide among individuals diagnosed with serious mental illness (SMI) who present in jails and prisons. In the present article, the authors review suicide risk factors associated with SMI, with emphasis on incarcerated individuals, and discuss the best practices in assessing risk for suicide. The authors review interventions designed to prevent suicide among individuals with SMI in forensic settings. The article also points to the need for continued research to inform the development of assessment tools and intervention strategies for this population.

Both maternal and pup genotype influence ultrasonic vocalizations and early developmental milestones in tsc2 (+/-) mice.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by tumor growth and neuropsychological symptoms such as autistic behavior, developmental delay, and epilepsy. While research has shed light on the biochemical and genetic etiology of TSC, the pathogenesis of the neurologic and behavioral manifestations remains poorly understood. TSC patients have a greatly increased risk of developmental delay and autism spectrum disorder, rendering the relationship between the two sets of symptoms an extremely pertinent issue for clinicians. We have expanded on previous observations of aberrant vocalizations in Tsc2 (+/-) mice by testing vocalization output and developmental milestones systematically during the early postnatal period. In this study, we have demonstrated that Tsc2 haploinsufficiency in either dams or their pups results in a pattern of developmental delay in sensorimotor milestones and ultrasonic vocalizations.

Neuronal Tsc1/2 complex controls autophagy through AMPK-dependent regulation of ULK1.

Tuberous sclerosis complex (TSC) is a disorder arising from mutation in the TSC1 or TSC2 gene, characterized by the development of hamartomas in various organs and neurological manifestations including epilepsy, intellectual disability and autism. TSC1/2 protein complex negatively regulates the mammalian target of rapamycin complex 1 (mTORC1) a master regulator of protein synthesis, cell growth and autophagy. Autophagy is a cellular quality-control process that sequesters cytosolic material in double membrane vesicles called autophagosomes and degrades it in autolysosomes. Previous studies in dividing cells have shown that mTORC1 blocks autophagy through inhibition of Unc-51-like-kinase1/2 (ULK1/2). Despite the fact that autophagy plays critical roles in neuronal homeostasis, little is known on the regulation of autophagy in neurons. Here we show that unlike in non-neuronal cells, Tsc2-deficient neurons have increased autolysosome accumulation and autophagic flux despite mTORC1-dependent inhibition of ULK1. Our data demonstrate that loss of Tsc2 results in autophagic activity via AMPK-dependent activation of ULK1. Thus, in Tsc2-knockdown neurons AMPK activation is the dominant regulator of autophagy. Notably, increased AMPK activity and autophagy activation are also found in the brains of Tsc1-conditional mouse models and in cortical tubers resected from TSC patients. Together, our findings indicate that neuronal Tsc1/2 complex activity is required for the coordinated regulation of autophagy by AMPK. By uncovering the autophagy dysfunction associated with Tsc2 loss in neurons, our work sheds light on a previously uncharacterized cellular mechanism that contributes to altered neuronal homeostasis in TSC disease.

Prenatal rapamycin results in early and late behavioral abnormalities in wildtype C57BL/6 mice.

Mammalian target of rapamycin (mTOR) signaling has been shown to be deregulated in a number of genetic, neurodevelopmental disorders including Tuberous Sclerosis Complex, Neurofibromatosis, Fragile X, and Rett syndromes. As a result, mTOR inhibitors, such as rapamycin and its analogs, offer potential therapeutic avenues for these disorders. Some of these disorders-such as Tuberous Sclerosis Complex-can be diagnosed prenatally. Thus, prenatal administration of these inhibitors could potentially prevent the development of the devastating symptoms associated with these disorders. To assess the possible detrimental effects of prenatal rapamycin treatment, we evaluated both early and late behavioral effects of a single rapamycin treatment at embryonic day 16.5 in wildtype C57Bl/6 mice. This treatment adversely impacted early developmental milestones as well as motor function in adult animals. Rapamycin also resulted in anxiety-like behaviors during both early development and adulthood but did not affect adult social behaviors. Together, these results indicate that a single, prenatal rapamycin treatment not only adversely affects early postnatal development but also results in long lasting negative effects, persisting into adulthood. These findings are of importance in considering prenatal administration of rapamycin and related drugs in the treatment of patients with neurogenetic, neurodevelopmental disorders.

Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice.

Autism spectrum disorders (ASDs) are highly prevalent neurodevelopmental disorders, but the underlying pathogenesis remains poorly understood. Recent studies have implicated the cerebellum in these disorders, with post-mortem studies in ASD patients showing cerebellar Purkinje cell (PC) loss, and isolated cerebellar injury has been associated with a higher incidence of ASDs. However, the extent of cerebellar contribution to the pathogenesis of ASDs remains unclear. Tuberous sclerosis complex (TSC) is a genetic disorder with high rates of comorbid ASDs that result from mutation of either TSC1 or TSC2, whose protein products dimerize and negatively regulate mammalian target of rapamycin (mTOR) signalling. TSC is an intriguing model to investigate the cerebellar contribution to the underlying pathogenesis of ASDs, as recent studies in TSC patients demonstrate cerebellar pathology and correlate cerebellar pathology with increased ASD symptomatology. Functional imaging also shows that TSC patients with ASDs display hypermetabolism in deep cerebellar structures, compared to TSC patients without ASDs. However, the roles of Tsc1 and the sequelae of Tsc1 dysfunction in the cerebellum have not been investigated so far. Here we show that both heterozygous and homozygous loss of Tsc1 in mouse cerebellar PCs results in autistic-like behaviours, including abnormal social interaction, repetitive behaviour and vocalizations, in addition to decreased PC excitability. Treatment of mutant mice with the mTOR inhibitor, rapamycin, prevented the pathological and behavioural deficits. These findings demonstrate new roles for Tsc1 in PC function and define a molecular basis for a cerebellar contribution to cognitive disorders such as autism.

Graded loss of tuberin in an allelic series of brain models of TSC correlates with survival, and biochemical, histological and behavioral features.

Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder with prominent brain manifestations due to mutations in either TSC1 or TSC2. Here, we describe novel mouse brain models of TSC generated using conditional hypomorphic and null alleles of Tsc2 combined with the neuron-specific synapsin I cre (SynIcre) allele. This allelic series of homozygous conditional hypomorphic alleles (Tsc2(c-del3/c-del3)SynICre(+)) and heterozygote null/conditional hypomorphic alleles (Tsc2(k/c-del3)SynICre(+)) achieves a graded reduction in expression of Tsc2 in neurons in vivo. The mice demonstrate a progressive neurologic phenotype including hunchback, hind limb clasp, reduced survival and brain and cortical neuron enlargement that correlates with a graded reduction in expression of Tsc2 in the two sets of mice. Both models also showed behavioral abnormalities in anxiety, social interaction and learning assays, which correlated with Tsc2 protein levels as well. The observations demonstrate that there are graded biochemical, cellular and clinical/behavioral effects that are proportional to the extent of reduction in Tsc2 expression in neurons. Further, they suggest that some patients with milder manifestations of TSC may be due to persistent low-level expression of functional protein from their mutant allele. In addition, they point to the potential clinical benefit of strategies to raise TSC2 protein expression from the wild-type allele by even modest amounts.

A novel, multiple symptom model of obsessive-compulsive-like behaviors in animals.

BACKGROUND: Current animal models of obsessive-compulsive disorder (OCD) typically involve acute, drug-induced symptom provocation or a genetic association with stereotypies or anxiety. None of these current models demonstrate multiple OCD-like behaviors. METHODS: Neonatal rats were treated with the tricyclic antidepressant clomipramine or vehicle between days 9 and 16 twice daily and behaviorally tested in adulthood. RESULTS: Clomipramine exposure in immature rats produced significant behavioral and biochemical changes that include enhanced anxiety (elevated plus maze and marble burying), behavioral inflexibility (perseveration in the spontaneous alternation task and impaired reversal learning), working memory impairment (e.g., win-shift paradigm), hoarding, and corticostriatal dysfunction. Dopamine D2 receptors were elevated in the striatum, whereas serotonin 2C, but not serotonin 1A, receptors were elevated in the orbital frontal cortex. CONCLUSIONS: This is the first demonstration of multiple symptoms consistent with an OCD-like profile in animals. Moreover, these behaviors are accompanied by biochemical changes in brain regions previously identified as relevant to OCD. This novel model of OCD demonstrates that drug exposure during a sensitive period can program disease-like systems permanently, which could have implications for current and future therapeutic strategies for this and other psychiatric disorders.