A Decade of Death and Other Dynamics: Deepening Perspectives on the Diversity and Distribution of Sea Stars and Wasting.

AbstractMass mortality events provide valuable insight into biological extremes and also ecological interactions more generally. The sea star wasting epidemic that began in 2013 catalyzed study of the microbiome, genetics, population dynamics, and community ecology of several high-profile species inhabiting the northeastern Pacific but exposed a dearth of information on the diversity, distributions, and impacts of sea star wasting for many lesser-known sea stars and a need for integration across scales. Here, we combine datasets from single-site to coast-wide studies, across time lines from weeks to decades, for 65 species. We evaluated the impacts of abiotic characteristics hypothetically associated with sea star wasting (sea surface temperature, pelagic primary productivity, upwelling wind forcing, wave exposure, freshwater runoff) and species characteristics (depth distribution, developmental mode, diet, habitat, reproductive period). We find that the 2010s sea star wasting outbreak clearly affected a little over a dozen species, primarily intertidal and shallow subtidal taxa, causing instantaneous wasting prevalence rates of 5%-80%. Despite the collapse of some populations within weeks, environmental and species variation protracted the outbreak, which lasted 2-3 years from onset until declining to chronic background rates of ∼2% sea star wasting prevalence. Recruitment began immediately in many species, and in general, sea star assemblages trended toward recovery; however, recovery was heterogeneous, and a marine heatwave in 2019 raised concerns of a second decline. The abiotic stressors most associated with the 2010s sea star wasting outbreak were elevated sea surface temperature and low wave exposure, as well as freshwater discharge in the north. However, detailed data speaking directly to the biological, ecological, and environmental cause(s) and consequences of the sea star wasting outbreak remain limited in scope, unavoidably retrospective, and perhaps always indeterminate. Redressing this shortfall for the future will require a broad spectrum of monitoring studies not less than the taxonomically broad cross-scale framework we have modeled in this synthesis.

Latitudinal variation in long-term stability of North American rocky intertidal communities.

Although long-term ecological stability is often discussed as a community attribute, it is typically investigated at the species level (e.g. density, biomass), or as a univariate metric (e.g. species diversity). To provide a more comprehensive assessment of long-term community stability, we used a multivariate similarity approach that included all species and their relative abundances. We used data from 74 sites sampled annually from 2006 to 2017 to examine broad temporal and spatial patterns of change within rocky intertidal communities along the west coast of North America. We explored relationships between community change (inverse of stability) and the following potential drivers of change/stability: (a) marine heatwave events; (b) three attributes of biodiversity: richness, diversity and evenness and (c) presence of the mussel, Mytilus californianus, a dominant space holder and foundation species in this system. At a broad scale, we found an inverse relationship between community stability and elevated water temperatures. In addition, we found substantial differences in stability among regions, with lower stability in the south, which may provide a glimpse into the patterns expected with a changing climate. At the site level, community stability was linked to high species richness and, perhaps counterintuitively, to low evenness, which could be a consequence of the dominance of mussels in this system. Synthesis. Assessments of long-term stability at the whole-community level are rarely done but are key to a comprehensive understanding of the impacts of climate change. In communities structured around a spatially dominant species, long-term stability can be linked to the stability of this 'foundation species', as well as to traditional predictors, such as species richness.

Large-scale impacts of sea star wasting disease (SSWD) on intertidal sea stars and implications for recovery.

Disease outbreaks can have substantial impacts on wild populations, but the often patchy or anecdotal evidence of these impacts impedes our ability to understand outbreak dynamics. Recently however, a severe disease outbreak occurred in a group of very well-studied organisms-sea stars along the west coast of North America. We analyzed nearly two decades of data from a coordinated monitoring effort at 88 sites ranging from southern British Columbia to San Diego, California along with 2 sites near Sitka, Alaska to better understand the effects of sea star wasting disease (SSWD) on the keystone intertidal predator, Pisaster ochraceus. Quantitative surveys revealed unprecedented declines of P. ochraceus in 2014 and 2015 across nearly the entire geographic range of the species. The intensity of the impact of SSWD was not uniform across the affected area, with proportionally greater population declines in the southern regions relative to the north. The degree of population decline was unrelated to pre-outbreak P. ochraceus density, although these factors have been linked in other well-documented disease events. While elevated seawater temperatures were not broadly linked to the initial emergence of SSWD, anomalously high seawater temperatures in 2014 and 2015 might have exacerbated the disease's impact. Both before and after the onset of the SSWD outbreak, we documented higher recruitment of P. ochraceus in the north than in the south, and while some juveniles are surviving (as evidenced by transition of recruitment pulses to larger size classes), post-SSWD survivorship is lower than during pre-SSWD periods. In hindsight, our data suggest that the SSWD event defied prediction based on two factors found to be important in other marine disease events, sea water temperature and population density, and illustrate the importance of surveillance of natural populations as one element of an integrated approach to marine disease ecology. Low levels of SSWD-symptomatic sea stars are still present throughout the impacted range, thus the outlook for population recovery is uncertain.

Mass cytometry analysis reveals hyperactive NF Kappa B signaling in myelofibrosis and secondary acute myeloid leukemia.

Myeloproliferative neoplasms (MPNs) feature a malignant clone containing the JAK2 V617F mutation, or another mutation causing dysregulated JAK2 kinase activity. The multiple disease phenotypes of MPNs, and their tendency to transform phenotypically, suggest pathophysiologic heterogeneities beyond a common phenomenon of JAK2 hyperactivation. JAK2 has the potential to activate multiple other signaling molecules, either directly through downstream effectors, or indirectly through induction of target gene expression. We have interrogated myeloproliferative signaling in myelofibrosis (MF) and secondary acute myeloid leukemia (sAML) patient samples using mass cytometry, which allows the quantitative measurement of multiple signaling molecules simultaneously at the single-cell level, in cell populations representing a nearly complete spectrum of hematopoiesis. MF and sAML malignant cells demonstrated a high prevalence of hyperactivation of the JAK-STAT, MAP kinase, PI3 kinase and NFκB signaling pathways. Constitutive NFκB signaling was evident across MF and sAML patients. A supporting gene set enrichment analysis (GSEA) of MF showed many NFκB target genes to be expressed above normal levels in MF patient CD34+ cells. NFκB inhibition suppressed colony formation from MF CD34+ cells. This study indicates that NFκB signaling contributes to human myeloproliferative disease and is abnormally activated in MF and sAML.

Densovirus associated with sea-star wasting disease and mass mortality.

Populations of at least 20 asteroid species on the Northeast Pacific Coast have recently experienced an extensive outbreak of sea-star (asteroid) wasting disease (SSWD). The disease leads to behavioral changes, lesions, loss of turgor, limb autotomy, and death characterized by rapid degradation ("melting"). Here, we present evidence from experimental challenge studies and field observations that link the mass mortalities to a densovirus (Parvoviridae). Virus-sized material (i.e., <0.2 µm) from symptomatic tissues that was inoculated into asymptomatic asteroids consistently resulted in SSWD signs whereas animals receiving heat-killed (i.e., control) virus-sized inoculum remained asymptomatic. Viral metagenomic investigations revealed the sea star-associated densovirus (SSaDV) as the most likely candidate virus associated with tissues from symptomatic asteroids. Quantification of SSaDV during transmission trials indicated that progression of SSWD paralleled increased SSaDV load. In field surveys, SSaDV loads were more abundant in symptomatic than in asymptomatic asteroids. SSaDV could be detected in plankton, sediments and in nonasteroid echinoderms, providing a possible mechanism for viral spread. SSaDV was detected in museum specimens of asteroids from 1942, suggesting that it has been present on the North American Pacific Coast for at least 72 y. SSaDV is therefore the most promising candidate disease agent responsible for asteroid mass mortality.

Incidence of -93 MLH1 promoter polymorphism in familial and sporadic colorectal cancer.

AIM: The MLH1 promoter contains a common single nucleotide polymorphism (-93 guanine > adenine) located in an essential region for maximum transcriptional activity. This has been associated with an increased risk of microsatellite instability (MSI) colorectal cancer. The aim of the study was to compare the distribution of MLH1 -93G>A genotypes between patients with familial colon cancer, sporadic colon cancer and healthy subjects. METHOD: We genotyped 200 familial colon samples, 183 cases of sporadic colon cancer and 236 control subjects. MSI was analysed. RESULTS: The GA genotype was under-represented in patients with familial colon cancer, whereas the AA genotype was over-represented in cases of sporadic colon cancer. A greater frequency of the MLH1 GA genotype was found in the cancer cases with MLH1 focal immunohistochemistry (IHC) for anti-MLH1 antibody. When we compared genotype distribution in the familial colorectal cancer cases with and without MSI, we failed to detect any correlation, although the GA genotype is more frequent in cases with MSI. CONCLUSION: There is a relationship between the MLH1 -93G>A polymorphism in the homozygous state and the risk of sporadic colorectal cancer. The variant MLH1 -93G>A appears to be related to cases with focal IHC activity more than to complete absence of the MLH1 protein in the tumour tissue.

BRCA1 5272-1G>A and BRCA2 5374delTATG are founder mutations of high relevance for genetic counselling in breast/ovarian cancer families of Spanish origin.

The distribution of BRCA1 and BRCA2 germ line mutations in breast/ovarian cancer families varies among different populations, which typically present a wide spectrum of unique mutations. Splicing mutation 5272-1G>A of BRCA1 and frameshift mutation 5374delTATG of BRCA2 are highly prevalent mutations in Castilla-León (Spain), accounting for 18.4% and 13.6% of BRCA1 and BRCA2 positive families, respectively. To test the presence of founder effects, 9 Spanish 5272-1G>A and 13 5374delTATG families were genotyped with polymorphic markers linked to BRCA1 or BRCA2. All the 5272-1G>A families shared a common haplotype in eight markers (1.1 Mb region) and the mutation age was estimated in 15 generations (approximately 380 years). A conserved haplotype associated to 5374delTATG was observed in four markers (0.82 Mb). The mutation occurred approximately 48 generations ago (approximately 1200 years). Each mutation likely arose from a common ancestor that could be traced to a small area of Castilla-León and expanded to other Spanish regions. They can have a significant impact on the clinical management of asymptomatic carriers as well as on the genetic screening strategy to be followed in populations with Spanish ancestries.

Necrotizing enterocolitis during the first week of life: a multicentered case-control and cohort comparison study.

OBJECTIVE: Necrotizing enterocolitis (NEC) is rare during the first week of life; most cases occur after 2 to 4 weeks. We hypothesized that when NEC develops in the first week, certain predisposing factors and feeding practices are identifiable. To test this, we sought to identify every case of NEC diagnosed during the first week within the Intermountain Healthcare system during the most recent 6-year period. STUDY DESIGN: Data were collected from neonates admitted to any Intermountain Healthcare neonatal intensive care unit (NICU) with a date of birth from 1 January 2001 through 31 December 2006. Electronic and paper records were obtained for all with a diagnosis of NEC (Bell stage >or=II) within the first 168 h. X-rays, physician notes, nursing records, laboratory reports and operative reports were subjected to critical review to reexamine the diagnosis of NEC. Among those with confirmed NEC, we recorded underlying conditions and every feeding given prior to the diagnosis of NEC. Comparisons were made with patients that did not develop NEC, yet were cared for in the same NICUs, during the same period of time, and of the same gestational ages. RESULT: A total of 28 neonates were identified electronically as having NEC during the first week. Critical review confirmed this in 21, but 5 were determined at laparotomy to have had spontaneous intestinal perforation, and 2 others were found on surgical reports to have had a congenital infarction of the colon. Total 20 of the 21 confirmed cases developed NEC while in a NICU being treated for another condition. The exception was a small-for-gestational-age neonate in a well baby nursery. Compared to 6100 controls, the 21 with early NEC were more likely to have had a meconium-positive test for illicit drug exposure (P<0.005), early onset sepsis (P<0.034) and respiratory distress (P<0.039). They were less likely than case-controls to have been fed human milk (P=0.003) and were more likely to have been fed formula exclusively (P=0.019). None who were fed human milk exclusively developed early NEC. Twelve of the twenty-one were fed (by gavage or bottle) amounts exceeding the upper limit of volumes taken by breastfed neonates. CONCLUSION: We speculate that the prevalence of NEC during the first week could be reduced by identifying at-risk patients, feeding them human milk exclusively for the first week and using feeding volumes that do not exceed that taken by healthy breastfed neonates.

Adherence to NICU transfusion guidelines: data from a multihospital healthcare system.

OBJECTIVE: We critically reviewed every NICU blood component transfusion (packed erythrocytes, platelets, frozen plasma (FP) and cryoprecipitate) administered during a one-year period. This was done to determine the proportion of transfusions given out of compliance with the Intermountain Healthcare transfusion guidelines, and to look for patterns of non-compliance that could be addressed by quality improvement measures. STUDY DESIGN: A detailed review was made of every transfusion administered to patients with a date of birth of 1 January 2006 through 31 December 2006, in any of three level III, perinatal-center-associated NICUs within Intermountain Healthcare. RESULT: During 2006 the three NICUs cared for 1759 neonates. Seventeen percent of these received one or more (median 3) erythrocyte transfusions, 4% received one or more (median 3) platelet transfusions, 6% received one or more (median 1) FP infusions and 2% received cryoprecipitate (median 1 dose). Seventy percent of the erythrocyte transfusions were given in compliance with the guidelines, as were 69% of the platelet transfusions, 65% of the FP transfusions and 94% of the cryoprecipitate administrations. Patients who received large numbers of transfusions were more likely to receive transfusion that violated the guidelines. Forty-five percent of patients who received 1 to 3 transfusions received all transfusions within guidelines. However, only 18% of patients who received 4 to 10 transfusions received all within guidelines. No patient who received >10 transfusions received all within the guidelines. Erythrocyte transfusions given early in the hospital course were likely to be within guidelines; 72% (588/818) in the first 29 days were compliant with guidelines, but compliance fell to 61% (144/237) for transfusions administered after 29 days (P=0.002). About half of the platelet transfusions given early in the hospital course were in violation of guidelines, but after day 9, 83% of platelet transfusions were compliant with guidelines (P=0.000). CONCLUSION: Opportunities exist in our healthcare system to improve compliance with our transfusion guidelines. Such opportunities are greatest among neonates receiving multiple transfusions, among those receiving erythrocyte transfusions late in their NICU course and among those receiving platelet transfusions early in their NICU course.

Necrotizing enterocolitis in term neonates: data from a multihospital health-care system.

OBJECTIVE: In the past 5(1/2) years, 30 term or near-term neonates in the Intermountain Healthcare system developed necrotizing enterocolitis (NEC) Bell's stage > or =II. We sought to identify possible explanations for why these patients developed NEC, by comparing them with 5847 others that did not develop NEC, from the same hospitals and of the same gestational ages, cared for during the same 5 1/2-year period. STUDY DESIGN: Data were collected from neonates admitted to any of the Intermountain Healthcare NICUs with a birth date from 1 January 2001 to 30 June 2006, and a gestational age >36 weeks. A variety of patient features and feeding practices were compared between those that did vs did not develop NEC. RESULT: Forty-one neonates >36 weeks gestation were listed in the discharge records as having NEC of Bell's stage II or higher. However, on review of these 41 medical records, 11 were seen to have had NEC of Bell's stage I, whereas the remaining 30 had radiographs and clinical courses indicative of Bell's stage > or =II. Those 30 formed the basis of this study. Twenty-eight of the 30 developed NEC after having been admitted to an NICU for some other reason; the other two developed NEC at home, within 2 days of being discharged from an NICU. The 30 that developed NEC were more likely than the 5847 that did not develop NEC, to have congenital heart disease (P=0.000), polycythemia (P=0.002), early-onset bacterial sepsis (P=0.004) or hypotension (P=0.017). All 30 received enteral feedings before NEC developed; 29 were fed either artificial formula or a mixture of formula and breast milk. The one that was exclusively fed human milk was fed human milk with added fortifier (24 cal/oz). The 30 that developed NEC were more likely to be fed formula exclusively (P=0.000). Seven of the 30 had a laparotomy for NEC; two of the seven had total bowel necrosis and support was withdrawn. The other five had perforations and bowel resections. The mortality rate was 13% (4/30). CONCLUSION: In our series, NEC among term or near-term neonates was exclusively a complication developing among patients already admitted to a NICU for some other reason. We speculate that the combination of reduced mesenteric perfusion and feeding with artificial formula were factors predisposing them to develop NEC.

A multiple species approach to sequential learning: are you a man or a mouse?

We have developed a method for studying list learning in animals and humans, and we use variants of the task to examine list learning in rats, mice, and humans. This method holds several advantages over other methods. It has been found to be easily learned without lengthy pretraining. The data gathered with this procedure provide a measure of correct response rates, of incorrect responses and the locations of these responses, and of response latency on a trial-by-trial basis. We have examined mouse, rat, and human list acquisition of patterns ranging from 12 to 48 items in length. This procedure has also been used to examine many aspects of list learning, such as the effects of the placement of phrasing cues that are either consistent or inconsistent with the structure of the list in rats and mice, the effects of phrasing cues of differing modalities in mice, the sensitivity of subjects to violations of list structure in rats, subjects' abilities to "chunk" from nonadjacent serial positions in structured lists in rats, and subjects' sensitivity to serial patterns with multiple levels of hierarchical organization. The procedure has also been used to examine the effects of drugs on sequential learning.

Integrating services for schizophrenia and substance abuse.

Over the past decade, several studies have attempted to determine whether integrating psychiatric and substance abuse treatment leads to better outcome for patients with comorbid schizophrenia and substance use disorders. A recent (1999) Cochrane Review (1) analyzed the effectiveness of prospective randomized studies of integrated treatment approaches, and concluded that there was no clear evidence for superiority of integrated treatment. This paper describes one such integrated treatment approach, in Beth Israel Medical Center's COPAD (Combined Psychiatric and Addictive Disorders) program. We summarize findings from an initial outcome study and a recent replication study; and describe clinical and research issues relevant to this population. Our data suggests the benefits of integrated treatment for patients with addictive disorders and schizophrenia, at least with regard to treatment retention. Clinical issues for such patients include identification of patients at risk, proper assessment and treatment planning, decision-making about mainstreaming vs. referral to specialized programs, and the importance of initial engagement and ongoing reengagement in successful treatment.

Simulated and community-based instruction involving persons with mild and moderate mental retardation.

In this study of simulated instruction and/or community training of four functional living tasks was compared across groups of adolescents and young adults with mild and moderate retardation. Forty individuals participated in the assessment and training activities of this study, including 20 participants with mild retardation and 20 individuals with moderate retardation. A mixed factorial design was used to evaluate differences associated with level of mental retardation, simulated versus community-based instruction, and assessments in school and community settings. Participants with mild retardation performed better than their counterparts with moderate retardation on the simulated tasks and in the community settings. Participants with mild retardation were more successful in generalizing from the simulated instructional experiences to the community settings than were their counterparts with moderate retardation. However, in many of the situations, community training was sufficiently powerful to eliminate any advantage associated with some of the participants having experienced prior simulated instruction. Results are discussed in relation to the need to more closely examine the design and delivery of functional living skills instruction involving individuals with different levels of mental retardation. Specifically, the effectiveness of instructional simulations for teaching functional living skills does not appear to be uniform across level of retardation and targeted tasks. The highest priority question no longer appears to be whether or not simulated versus community-based instruction is more efficacious. Future research might more productively focus on the quality of different instructional simulations in combination with community assessment and/or training opportunities for teaching functional living skills to persons who experience different levels of mental retardation.

Cerebral metabolism in opiate-dependent subjects: effects of methadone maintenance.

BACKGROUND: The long-term effects of opiate use on human brain are not known. The goal of this preliminary study was to determine whether human subjects with histories of opiate dependence have persistent differences in brain function as compared with individuals without substance use disorders, and whether methadone maintenance reverses or ameliorates the potential abnormality. METHOD: Positron emission tomographic (PET) [18F]fluorodeoxyglucose (FDG) method was used to compare the regional cerebral metabolic rate for glucose(rCMRglc) in three groups: four opiate-dependent subjects currently receiving methadone maintenance therapy (MM), four opiate-dependent subjects not receiving methadone maintenance therapy (MW), and a comparison group of five subjects without substance use disorders. RESULTS: A significant difference in rCMRglc in the anterior cingulate gyrus was found between the MW and Control groups (Mann-Whitney U=2.0, p=0.05). Generally speaking, rCMRglc's in MM subjects were intermediate between those of MW and Control groups, although the difference did not reach statistical significance. CONCLUSIONS: The results of this study suggest that neurobiological abnormalities can persist in the brain of a chronic opiate user several years after detoxification from methadone. Future research is needed to replicate these results and to determine whether the observed rCMRglc differences are related to opiate use or to neurochemical abnormalities that play a role in developing addictive behavior.

Psychiatric symptom severity and length of stay on an intensive rehabilitation unit.

The purpose of this study was to evaluate the role of psychiatric symptoms in the medical and surgical rehabilitation of patients on an intensive rehabilitation unit and to examine whether psychiatric symptom severity contributes to length of hospital stay (LOS). Forty-four patients (21 men and 23 women) were assessed at admission and before discharge with the Functional Independence Measure (FIM). Subjects were evaluated with the Mini-Mental State Exam (MMSE), the Hamilton Rating Scale for Depression (Ham-D), Positive and Negative Symptom Scale, (PANSS), and Scale for the Assessment of Negative Symptoms (SANS). Thirty-six percent of subjects were cognitively impaired (MMSE < 25), 14% had significant depressive symptoms (Ham-D > 12), and 52% had significant negative symptomatology (PANSS-N > 15). A regression analysis yielded a model of three predictive factors. Gender, the PANSS General subscale, and the SANS Attention subscale accounted for 42.4% of LOS variance. These results indicate that psychiatric symptoms are common in medical rehabilitation inpatients and, together with demographic factors, are associated with increased LOS.

The value of rapid functional assays of germline p53 status in LFS and LFL families.

We have tested two rapid assays of p53 function, namely the apoptotic assay and the FASAY as means of detecting germline p53 mutations in members of Li-Fraumeni and Li-Fraumeni-like families. Results of the functional assays have been compared with direct sequencing of all 11 exons of the p53 gene. The results show good agreement between the two functional assays and between them and sequencing. No false-positives or negatives were seen with either functional assay although the apoptotic assay gave one borderline result for an individual without a mutation. As an initial screen the apoptotic assay is not only rapid but inexpensive and very simple to perform. It would be expected to detect any germline defect that leads to loss of p53 function. The apoptotic assay could be ideal as a means of prescreening large numbers of samples and identifying those that require further investigation. The FASAY detects mutations in exons 4-10, is rapid and distinguishes between functionally important and silent mutations.

Treatment of dementia-associated agitation with gabapentin.

The authors describe the use of gabapentin in the treatment of 4 outpatients with dementia-associated agitation. On the basis of clinical case reports and the Overt Agitation Severity Scale, all 4 patients had reduced agitation with gabapentin. Three of 4 patients were successfully titrated to a full dose of 2,400mg/day. These findings suggest a possible role for gabapentin in the behavioral management of patients with dementia.

Discontinuation of clonazepam in the treatment of social phobia.

Patients with social phobia who responded well to 6 months of open-label treatment with clonazepam were assigned to receive either continuation treatment (CT) with clonazepam for another 5 months, or to undergo discontinuation treatment (DT) using a clonazepam taper at the rate of 0.25 mg every 2 weeks, with double-blind placebo substitution. Clinical efficacy was compared between the CT and DT groups using three different social phobia scales. Benzodiazepine withdrawal symptoms were also measured. Relapse rates were 0 and 21.1% in the CT and DT groups, respectively. Subjects in the CT group generally showed a more favorable clinical response at midpoint and/or endpoint, although even in the DT group clinical response remained good. With respect to withdrawal symptoms, the rates were low in both groups (12.5% for CT and 27.7% for DT) with no real evidence suggesting significant withdrawal difficulties. At the end of 11 months of treatment with clonazepam, however, a more rapid withdrawal rate was associated with greater distress. This study offers preliminary evidence to suggest that continuation therapy with clonazepam in the treatment of social phobia is safe and effective, producing a somewhat greater clinical benefit than a slow-taper discontinuation regime. However, even in the DT group, withdrawal symptoms were not found to be a major problem. The study can be taken as supportive of benefit for longterm clonazepam treatment in social phobia, as well as being compatible with a reasonably good outcome after short-term treatment and slow taper.

A pilot open randomized trial of valproate and phenobarbital in the treatment of acute alcohol withdrawal.

The authors conducted a randomized, open comparison of the GABAergic anticonvulsant sodium valproate (divalproex sodium; Depakote) and phenobarbital as an active control in the management of acute withdrawal from alcohol. Repeated measures ANOVA was used to assess treatment effects in the first 37 inpatients, evaluating mood, hostility, and subjective and objective measures of withdrawal at index, 3, and 5 days of detoxification. Subjective and objective ratings of abstinence symptoms and subjective mood disturbance decreased significantly in intensity in both groups over 5 days, but there were no significant treatment differences nor treatment by time interactions. Hostility scores did not differ overall, but a group by time effect was observed (F = 5.42, df = [1,13], P < 0.05), with phenobarbital subjects reporting less hostility/aggression than those in the valproate group. There were no withdrawal-related seizures or other acute sequelae. This study offers pilot confirmation that sodium valproate is as effective as phenobarbital in the management of acute alcohol withdrawal, but it is unclear whether valproate offers a clinical advantage with respect to stabilizing changes in mood and interpersonal hostility during detoxification.