Carisbamate as adjunctive treatment of partial onset seizures in adults in two randomized,placebo‐controlled trials

Purpose: To assess the efficacy, safety, and tolerability of the investigational drug carisbamate as adjunctive treatment for partial‐onset seizures (POS). Methods: Two identical, randomized, placebo‐controlled, double‐blind studies were conducted in adults with POS uncontrolled for ≥1 year. Therapy‐refractory epilepsy patients (≥16 years) remained on stable doses of prescribed antiepileptic drugs (≤2) for an 8‐week prospective baseline phase and were then randomized (1:1:1) to carisbamate 200 mg/day, carisbamate 400 mg/day, or placebo, for a 12‐week double‐blind phase. Primary efficacy end points were percent reduction in seizure frequency and responder rate (patients with ≥50% reduction in POS frequency) during the double‐blind phase compared with the prospective baseline phase. Results: Of the 565 patients randomized in study 1, 93% completed the study; of the 562 randomized in study 2, 94% completed the study. Patient characteristics were similar across both studies and treatment arms: mean age, 35 years (study 1, range 16–75 years) and 36 years (study 2, range 16–74 years); approximately 50% were men. Treatment with carisbamate 400 mg/day resulted in significant improvement (p < 0.01) in both efficacy measures compared with placebo in study 1 but not in study 2. Carisbamate 200 mg/day did not differ statistically from placebo in either study. Among the most common treatment‐emergent adverse events (≥5% in any group), those with an incidence exceeding placebo (≥3%) were dizziness (400 mg/day group) and somnolence. Conclusions: Carisbamate 400 mg/day was effective in patients with refractory partial‐onset seizures in one of these global studies. More than 200 mg/day of carisbamate is required for efficacy. Carisbamate was well‐tolerated in both studies.     

The Anonymous Spectator

In this article, I attempt to illuminate points of similarity between the process of “working through” in psychological treatment, and the ordinary day-to-day developmental potential of college life, suggesting that when students can be helped to make optimal use of the college interpersonal milieu, brief, analytically informed psychotherapy can work in concert with the average, expectable experimentation of late adolescence to facilitate growth and maturation.     

Psychoanalytic Mommies and Psychoanalytic Babies: A Long View

I offer a retrospective view of the evolving baby metaphor in relational thinking. Early relational critiques of developmental tilt models and the concept of holding in clinical work, amplified by feminist writers, sharply skewed relationalists toward a vision of the patient-as-adult and a view of the analytic dialogue as inherently intersubjective. Bringing my own Winnicottian/relational perspective to this critique, I expanded the notion of holding and proposed a way to bridge Winnicottian holding with a relational perspective by exploring the analyst's participation in establishing and maintaining a holding experience. Here, I review and update this controversy, offering new ideas about holding's clinical function in buffering shame states.     

Modulation of sensitivity to alcohol by cortical and thalamic brain regions

The nucleus accumbens core (AcbC) is a key brain region known to regulate the discriminative stimulus/interoceptive effects of alcohol. As such, the goal of the present work was to identify AcbC projection regions that may also modulate sensitivity to alcohol. Accordingly, AcbC afferent projections were identified in behaviorally naïve rats using a retrograde tracer which led to the focus on the medial prefrontal cortex (mPFC), insular cortex (IC) and rhomboid thalamic nucleus (Rh). Next, to examine the possible role of these brain regions in modulating sensitivity to alcohol, neuronal response to alcohol in rats trained to discriminate alcohol (1 g/kg, intragastric [IG]) vs. water was examined using a two‐lever drug discrimination task. As such, rats were administered water or alcohol (1 g/kg, IG) and brain tissue was processed for c‐Fos immunoreactivity (IR), a marker of neuronal activity. Alcohol decreased c‐Fos IR in the mPFC, IC, Rh and AcbC. Lastly, site‐specific pharmacological inactivation with muscimol + baclofen (GABA_A agonist + GABA_B agonist) was used to determine the functional role of the mPFC, IC and Rh in modulating the interoceptive effects of alcohol in rats trained to discriminate alcohol (1 g/kg, IG) vs. water. mPFC inactivation resulted in full substitution for the alcohol training dose, and IC and Rh inactivation produced partial alcohol‐like effects, demonstrating the importance of these regions, with known projections to the AcbC, in modulating sensitivity to alcohol. Together, these data demonstrate a site of action of alcohol and the recruitment of cortical/thalamic regions in modulating sensitivity to the interoceptive effects of alcohol.     

The association of elaborative or maintenance rehearsal with age,reading comprehension,and verbal working memory performance

Elaborative or maintenance rehearsal strategy-use during a verbal working memory task was the grouping variable for a study that tested whether group membership distinguished 53 healthy adults by age, education, or performance on reading comprehension and verbal working memory tasks. No significant differences in age or reading comprehension emerged as a function of strategy-use. However, the elaborative strategy group had significantly better performance on one measure of verbal working memory. Several within age-group differences as a function of strategy-use were also significant. Younger adults who used elaborative rehearsal had superior working memory measures, and older adults who used elaborative rehearsal had superior reading comprehension measures, suggesting elaborative rehearsal's memory-enhancing function in verbal working memory and reading comprehension tasks.     

Local host specialization,host-switching,and dispersal shape the regional distributions of avian haemosporidian parasites

The drivers of regional parasite distributions are poorly understood, especially in comparison with those of free-living species. For vector-transmitted parasites, in particular, distributions might be influenced by host-switching and by parasite dispersal with primary hosts and vectors. We surveyed haemosporidian blood parasites (Plasmodium and Haemoproteus) of small land birds in eastern North America to characterize a regional parasite community. Distributions of parasite populations generally reflected distributions of their hosts across the region. However, when the interdependence between hosts and parasites was controlled statistically, local host assemblages were related to regional climatic gradients, but parasite assemblages were not. Moreover, because parasite assemblage similarity does not decrease with distance when controlling for host assemblages and climate, parasites evidently disperse readily within the distributions of their hosts. The degree of specialization on hosts varied in some parasite lineages over short periods and small geographic distances independently of the diversity of available hosts and potentially competing parasite lineages. Nonrandom spatial turnover was apparent in parasite lineages infecting one host species that was well-sampled within a single year across its range, plausibly reflecting localized adaptations of hosts and parasites. Overall, populations of avian hosts generally determine the geographic distributions of haemosporidian parasites. However, parasites are not dispersal-limited within their host distributions, and they may switch hosts readily.A regional community can be thought of as a set of species whose distributions partially overlap within a large geographic area (1, 2). The structure of the regional community (i.e., the relative abundances of species across space and the degree to which populations cooccur) is governed by local (e.g., interspecific competition) and regional (e.g., species diversification and dispersal) processes (3). Although regional communities include all species, parasites and pathogens are rarely considered integral community members (4). Indeed, impacts of parasites on community structure are frequently associated with epidemics—often following introductions to nonnative regions—that have driven naïve hosts to extinction or near extinction (5–7). However, parasites likely play a critical role in shaping regional community structure. Parasites can comprise a large proportion of the community biomass (8), form the majority of links in a community food web (9), and influence regional diversity by variously accelerating (10) or slowing (11) host diversification.Nevertheless, few studies have investigated the processes influencing the regional community structure of both parasites and their hosts. Parasite populations are integrated into community studies with difficulty, partly because these populations are distributed across multiple dimensions—space, host species, and host individuals (12)—and also because parasites are difficult to sample. Moreover, although parasites tend to specialize on one or a few host species, host-breadth may vary across a parasite’s range (13).Regional studies of birds and their dipteran-vectored haemosporidian (“malaria”) blood parasites (14–19) have shown that many parasites are heterogeneously distributed across space despite the availability of suitable hosts. Specialized associations between specific parasites and vectors (20–22) may drive such heterogeneity, although a recent analysis suggests that parasite–host compatibility is also important (23), and local coevolutionary relationships between parasites and their hosts likely influence geographic distributions of both host and parasite populations (11, 14, 15). However, most regional studies of these parasites have focused on individual host species (24–30).Here, we investigate the regional community structure of avian hosts and their haemosporidian parasites with respect to abiotic and biotic drivers of both host and parasite distributions. We surveyed local assemblages of avian haemosporidian parasites across eastern North America and related the distributions of individual parasite lineages to regional climate variation and to the distributions and abundances of their avian hosts. Community dissimilarities between sampling locations based on host assemblage structure (i.e., the relative abundances of potential host species) were positively correlated with those based on parasite assemblage structure, suggesting interdependence of host and parasite population distributions. However, when controlling statistically for that interdependence, local host assemblages responded strongly to environmental gradients and differed more with increasing geographic separation, whereas parasite assemblages did not. This finding suggests that haemosporidian parasites disperse readily across the distributions of their host populations in eastern North America, independently of difference in climate and geographic distance. The degree to which some parasite lineages specialized on particular hosts varied across years and locations, and the nonrandom parasite lineage turnover across the distribution of one well-sampled host species suggested that adaptations of hosts and parasites may also shape regional community structure. Despite evidence of pathogenicity of haemosporidian parasites in birds (31), correlations between host abundances and parasite relative abundances across the region were statistically indistinguishable from random. Taken together, these results suggest that the distributions of parasite populations largely follow the distributions of their hosts but that parasites readily switch hosts and may replace each other across the ranges of individual hosts, resulting in a complex and dynamic regional community.     

Evaluation of a "nondieting" stress reduction program for overweight women: a randomized trial

PURPOSE: Determine if a "nondieting" intervention focused on intensive training in eliciting the relaxation response enhances health outcomes compared with nondieting interventions without such training. DESIGN: Randomized trial with follow-up at 10 weeks, 4 months, and 12 months. SETTING: General community. SUBJECTS: Total of 225 overweight and obese women with at least one other cardiovascular risk factor. INTERVENTIONS: Three 10-week nondieting interventions: a group program (P1) focused on intensive training in techniques for eliciting the relaxation response (n = 60), a group program (P2) focused on healthy eating and physical activity (n = 61), and a self-guided, mail-delivered version of P2 (P3; n = 101). MEASURES: The Revised Symptom Checklist measured psychological distress, the Medical Symptoms Checklist measured the experience of medical symptoms, and the Health-Promoting Lifestyle Profile measured a range of lifestyle behaviors. Self-efficacy for low-fat eating intuitive eating, and body mass index were also assessed. ANALYSIS: An intention-to-treat analysis was used. RESULTS: At 12 months, P1 produced statistically greater improvements in stress management behaviors and medical symptom discomfort and was the only program to significantly improve self-efficacy for low-fat eating. In P1, the effect sizes for reductions in depression (0.75) and interpersonal sensitivity (0.85) were large. At 12 months, mean weight was unchanged. CONCLUSION: Inclusion of intensive relaxation response training in a nondieting program for overweight women enhanced stress management and medical symptoms outcomes but not weight outcomes.