Agitation is an acute behavioral emergency requiring immediate intervention. Traditional methods of treating agitated patients, ie, routine restraints and involuntary medication, have been replaced with a much greater emphasis on a noncoercive approach. Experienced practitioners have found that if such interventions are undertaken with genuine commitment, successful outcomes can occur far more often than previously thought possible. In the new paradigm, a 3-step approach is used. First, the patient is verbally engaged; then a collaborative relationship is established; and, finally, the patient is verbally de-escalated out of the agitated state. Verbal de-escalation is usually the key to engaging the patient and helping him become an active partner in his evaluation and treatment; although, we also recognize that in some cases nonverbal approaches, such as voluntary medication and environment planning, are also important. When working with an agitated patient, there are 4 main objectives: (1) ensure the safety of the patient, staff, and others in the area; (2) help the patient manage his emotions and distress and maintain or regain control of his behavior; (3) avoid the use of restraint when at all possible; and (4) avoid coercive interventions that escalate agitation. The authors detail the proper foundations for appropriate training for de-escalation and provide intervention guidelines, using the “10 domains of de-escalation.”

Agitation is common in the medical and psychiatric emergency department, and appropriate management of agitation is a core competency for emergency clinicians. In this article, the authors review the use of a variety of first-generation antipsychotic drugs, second-generation antipsychotic drugs, and benzodiazepines for treatment of acute agitation, and propose specific guidelines for treatment of agitation associated with a variety of conditions, including acute intoxication, psychiatric illness, delirium, and multiple or idiopathic causes. Pharmacologic treatment of agitation should be based on an assessment of the most likely cause of the agitation. If agitation results from a delirium or other medical condition, clinicians should first attempt to treat the underlying cause instead of simply medicating with antipsychotics or benzodiazepines.

oBjective: We describe fundamental weaknesses in U.S. chemicals policy, present principles of chemicals policy reform, and articulate interdisciplinary research questions that should be addressed. With global chemical production projected to double over the next 24 years, federal policies that shape the priorities of the U.S. chemical enterprise will be a cornerstone of sustainability. To date, these policies have largely failed to adequately protect public health or the environment or motivate investment in or scientific exploration of cleaner chemical technologies, known collectively as green chemistry. On this trajectory, the United States will face growing health, environmental, and economic problems related to chemical exposures and pollution. conclusions: Existing policies have produced a U.S. chemicals market in which the safety of chemicals for human health and the environment is undervalued relative to chemical function, price, and performance. This market barrier to green chemistry is primarily a consequence of weaknesses in the Toxic Substances Control Act. These weaknesses have produced a chemical data gap, because producers are not required to investigate and disclose sufficient information on chemicals' hazard traits to government, businesses that use chemicals, or the public; a safety gap, because government lacks the legal tools it needs to efficiently identify, prioritize, and take action to mitigate the potential health and environmental effects of hazardous chemicals; and a technology gap, because industry and government have invested only marginally in green chemistry research, development, and education. Policy reforms that close the three gaps-creating transparency and accountability in the market-are crucial for improving public and environmental health and reducing the barriers to green chemistry. The European Union's REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) regulation has opened an opportunity for the United States to take this step; doing so will present the nation with new research questions in science, policy, law, and technology.

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a congenital visceral myopathy characterized by severe dilation of the urinary bladder and defective intestinal motility. The genetic basis of MMIHS has been ascribed to spontaneous and autosomal dominant mutations in actin gamma 2 (ACTG2), a smooth muscle contractile gene. However, evidence suggesting a recessive origin of the disease also exists. Using combined homozygosity mapping and whole exome sequencing, a genetically isolated family was found to carry a premature termination codon in Leiomodin1 (LMOD1), a gene preferentially expressed in vascular and visceral smooth muscle cells. Parents heterozygous for the mutation exhibited no abnormalities, but a child homozygous for the premature termination codon displayed symptoms consistent with MMIHS. We used CRISPR-Cas9 (CRISPR-associated protein) genome editing of Lmod1 to generate a similar premature termination codon. Mice homozygous for the mutation showed loss of LMOD1 protein and pathology consistent with MMIHS, including late gestation expansion of the bladder, hydronephrosis, and rapid demise after parturition. Loss of LMOD1 resulted in a reduction of filamentous actin, elongated cytoskeletal dense bodies, and impaired intestinal smooth muscle contractility. These results define LMOD1 as a disease gene for MMIHS and suggest its role in establishing normal smooth muscle cytoskeletal–contractile coupling.

Syntactic persistence is a tendency for speakers to reproduce sentence structures independently of accompanying meanings, words, or sounds. The memory mechanisms behind syntactic persistence are not fully understood. Though some properties of syntactic persistence suggest a role for procedural memory, current evidence suggests that procedural memory (unlike declarative memory) does not maintain the abstract, relational features that are inherent to syntactic structures. To evaluate the contribution of procedural memory to syntactic persistence, patients with anterograde amnesia and matched control speakers (a) reproduced prime sentences with different syntactic structures; (b) reproduced 0, 1, 6, or 10 neutral sentences; (c) described pictures that elicited the primed structures spontaneously; and (d) made recognition judgments for the prime sentences. Amnesic and control speakers showed significant and equivalent syntactic persistence, despite the amnesic speakers' profoundly impaired recognition memory for primes. Syntax is thus maintained by procedural memory mechanisms, revealing that procedural memory is capable of supporting abstract, relational knowledge.Speakers often produce sentences using syntactic structures that they have recently spoken or heard. For example, speakers who produce or understand a sentence with a prepositional dative structure like "The governess made a pot of tea for the princess" are prone to describe a subsequent unrelated event with another prepositional dative structure, like "The boy is handing the paintbrush to a man." But if speakers initially produce or understand a sentence with a double-object structure like "The governess made the princess a pot of tea," they are more likely to describe the subsequent event with another double-object structure, like "The boy handed the man the paintbrush."This effect is known as syntactic persistence or structural or syntactic priming (for recent reviews, see Ferreira & Bock, 2006; Pickering & Ferreira, in press). Syntactic persistence has been observed in laboratory settings (Bock, 1986), controlled dialogue (Branigan, Pickering, & Cleland, 2000), natural discourse (Szmrecsanyi, 2004(Szmrecsanyi, , 2005, in different languages (Hartsuiker & Kolk, 1998b) and modalities (Cleland & Pickering, 2006), in children (Huttenlocher, Vasilyeva, & Shimpi, 2004; Thothathiri & Snedeker, in press), and even from one of a bilingual speaker's languages to the other (Hartsuiker, Pickering, & Veltkamp, 2004;Loebell & Bock, 2003). In certain paradigms (including the one used here), syntactic persistence is sensitive specifically to syntactic structure, rather than conceptual, lexical, or phonological information (Bock, 1986(Bock, , 1989Bock & Loebell, 1990;Bock, Loebell, & Morey, 1992 Syntactic persistence reflects memory for abstract syntax, because a prime sentence can only influence target production when some trace of the prime's syntactic structure is preserved in memory. However, the nature of the memory processes that underlie syntactic persi...

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Numerous medical and psychiatric conditions can cause agitation; some of these causes are life threatening. It is important to be able to differentiate between medical and nonmedical causes of agitation so that patients can receive appropriate and timely treatment. This article aims to educate all clinicians in nonmedical settings, such as mental health clinics, and medical settings on the differing levels of severity in agitation, basic triage, use of de-escalation, and factors, symptoms, and signs in determining whether a medical etiology is likely. Lastly, this article focuses on the medical workup of agitation when a medical etiology is suspected or when etiology is unclear.