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Objectives: To illustrate the use of machine learning methods to search for heterogeneous effects of a target modifiable risk factor on suicide in observational studies. The illustration focuses on secondary analysis of a matched case‐control study of vitamin D deficiency predicting subsequent suicide. Methods: We describe a variety of machine learning methods to search for prescriptive predictors; that is, predictors of significant variation in the association between a target risk factor and subsequent suicide. In each case, the purpose is to evaluate the potential value of selective intervention on the target risk factor to prevent the outcome based on the provisional assumption that the target risk factor is causal. The approaches illustrated include risk modeling based on the super learner ensemble machine learning method, Least Absolute Shrinkage and Selection Operator (Lasso) penalized regression, and the causal forest algorithm. Results: The logic of estimating heterogeneous intervention effects is exposited along with the illustration of some widely used methods for implementing this logic. Conclusions: In addition to describing best practices in using the machine learning methods considered here, we close with a discussion of broader design and analysis issues in planning an observational study to investigate heterogeneous effects of a modifiable risk factor. [ABSTRACT FROM AUTHOR]

Abstract Background Episodes of explosive rage and violence comprise a symptom complex which can have a devastating effect on a person's life. In the community this behavior is seen as workplace violence, domestic abuse and road rage, while in the clinical setting, this behavior is rarely mentioned by patients, despite evidence that it can signify an important biological disorder that may afflict more than three percent of the population. Discussion Patients are often reluctant to seek help for episodic attacks of rage, especially attacks which are accompanied by physical violence. Although, in the past, clinicians have had few treatment options to offer, recent neuroscience advances have created new possibilities to understand and help patients with this neglected problem. No formal medical guidelines for treating violence exist; however, many patients can be helped by diagnosis, referral and treatment. Treatment can include pharmaceuticals and nutrients, as well as referral for anger management or behavioral therapy. Summary The astute clinician has an opportunity to positively impact an important problem through the diagnosis and treatment of patients with symptoms of intermittent explosive disorder.

Largely underutilized in North America, the use of medications to treat alcohol dependence is frequently a successful method of reducing alcohol craving and promoting abstinence. Recovery from alcohol addiction can be a complicated process, requiring nutritional, social, psychological, spiritual, and physical aspects of healing and self-directed behavioral change. Nurses can intervene in alcohol use disorder via screening, referrals, support of medical and behavioral treatments, and spiritual care that emphasizes hope, forgiveness, and relief from shame and guilt. [ABSTRACT FROM AUTHOR]

Background: The apolipoprotein E ϵ4 (APOE4) allele is the strongest genetic risk factor identified for developing Alzheimer's disease (AD). Among brain lipids, alteration in the ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) homeostasis is implicated in AD pathogenesis. APOE4 may influence both brain DHA metabolism and cognitive outcomes. Methods: Using positron emission tomography, regional incorporation coefficients (k*), rates of DHA incorporation from plasma into the brain using [1-11C]-DHA (Jin), and regional cerebral blood flow using [15O]-water were measured in 22 middle-aged healthy adults (mean age 35 years, range 19-65 years). Data were partially volume error-corrected for brain atrophy. APOE4 phenotype was determined by protein expression, and unesterified DHA concentrations were quantified in plasma. An exploratory post hoc analysis of the effect of APOE4 on DHA brain kinetics was performed. Results: The mean global gray matter DHA incorporation coefficient, k*, was significantly higher (16%) among APOE4 carriers (n = 9) than among noncarriers (n = 13, p = 0.046). Higher DHA incorporation coefficients were observed in several brain regions, particularly in the entorhinal subregion, an area affected early in AD pathogenesis. Cerebral blood flow, unesterified plasma DHA, and whole brain DHA incorporation rate (Jin) did not differ significantly between the APOE groups. Conclusions: Our findings suggest an increase in the DHA incorporation coefficient in several brain regions in APOE4 carriers. These findings may contribute to understanding how APOE4 genotypes affect AD risk. [ABSTRACT FROM AUTHOR]

We developed a novel method to study dopaminergic neurotransmission using positron emission tomography (PET) with [1-11C]arachidonic acid ([1-11C]AA). Previous preclinical studies have shown the utility of [1-11C]AA as a marker of signal transduction coupled to cytosolic phospholipase A2 (cPLA2). Using [1-11C]AA and [15O]water PET, we measured regional incorporation coefficients K* for AA and regional cerebral blood flow (rCBF), respectively, in healthy male volunteers given the D1/D2 agonist (10 or 20 μg/kg subcutaneous) apomorphine. We confirmed a robust central dopaminergic response to apomorphine by observing significant increases in the serum concentration of growth hormone. We observed significant increases, as well as decreases in K* and increases in rCBF in response to apomorphine. These changes remained significant after covarying for handedness and apomorphine dosage. The magnitude of increases in K* was lower than those in our previous animal experiments, likely reflecting the smaller dose of apomorphine used in the current human study. Changes in K* may reflect neuronal signaling downstream of activated D2-like receptors coupled to cPLA2. Changes in rCBF are consistent with previous studies showing net functional effects of D1/D2 activation. [1-11C]AA PET may be useful for studying disturbances of dopaminergic neurotransmission in conditions such as Parkinson's disease and schizophrenia. [ABSTRACT FROM AUTHOR]