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Despite the long history and pervasiveness of cognitive offloading as a memory strategy, the memorial fate of offloaded information is not well understood. Recent work has suggested that offloading information may engage similar mechanisms as instructions to forget (e.g., directed forgetting). In the present investigation, we test this prediction by examining the serial position effect for offloaded information. Previous research has demonstrated that "forget" instructions can eliminate the primacy effect while leaving an intact recency effect. Across two experiments, participants completed a number of free recall trials using an external aid and then a final recall trial without the external aid. We compared a group that was expecting to use the aid for the final trial (offloading) with a group that was not (no-offloading). We found a memory impairment for offloaded items that was characterized by a reduced primacy effect but a typical recency effect, similar to what has been reported in research on intentional/directed forgetting.

Background & Aims Patients with cirrhosis are growing older. The overlap between minimal hepatic encephalopathy (MHE) and predementia mild cognitive impairment (MCI) could affect quality of life (QOL). We investigated the performance of elderly patients with cirrhosis on tests for MHE and MCI and their effects on QOL. Methods We recruited outpatients with cirrhosis (n = 109) and without cirrhosis (controls, n = 100), 65 years or older, at 4 centers (derivation cohort). All study participants were assessed for psychometric hepatic encephalopathy score (PHES), EncephalApp score, and QOL. MCI was tested in patients with cirrhosis using the repeatable battery for assessment of neuropsychological status and assigned to the following groups: unimpaired, MCI only, MHE only, and MCI+MHE. We created adjusted norms to detect MHE using PHES and EncephalApp scores from the controls. Findings were validated using data from a separate cohort of 77 patients with cirrhosis (mean age, 69.49 ± 4.36 y; 72% men) at the same study sites. Results Controls were older but were more educated, performed better cognitively, and had better QOL. Among patients with cirrhosis, age, education, model for end-stage liver disease score, EncephalApp score, and QOL were similar, but PHES and repeatable battery for assessment of neuropsychological status differed among sites. In the derivation cohort, the presence of MHE, with or without MCI, was associated with poor QOL, which was lowest in the MCI+MHE group. When we adjusted for age, sex, and education, 49% of patients with cirrhosis had MHE based on the EncephalApp and 8% had MHE based on the PHES. A similar pattern (49% MHE based on EncephalApp and 6% MHE based on PHES) was found in a validation cohort. Conclusions In a multicenter study of patients with cirrhosis (>65 y) and controls, the presence of MHE, regardless of MCI, was associated with poor cognition and QOL. We created adjusted norms that defined the high sensitivity of EncephalApp for the detection of MHE in older individuals and validated it in a separate cohort.

Background & Aims Inpatients with cirrhosis are prone to develop acute-on-chronic liver failure (ACLF). ACLF is associated with dysbiosis of the intestinal microbiota, which might serve as a prognostic factor. We investigated whether features of the intestinal microbiota associate organ failure, transfer to intensive care, and mortality within 30 days in patients admitted to the hospital with cirrhosis. Methods Stool samples were collected from 181 patients with cirrhosis (age 56 years; mean model for end-stage liver disease score, 21; 43% with infections) at time of admission, from multiple hospitals in North America. Patients were followed for 30 days for development of ACLF, extra-hepatic organ failures, and death or hospice care. Microbiota were analyzed by 16s rRNA sequencing for alpha diversity (within groups), beta diversity (between groups), cirrhosis dysbiosis ratio (CDR), and taxa that differed between groups with vs without negative outcomes (individual organ failures, transfer to intensive care, ACLF, death, or hospice). Regression analyses were performed using microbial and clinical variables for each outcome. Results ACLF developed in 8% of study subjects; 16% were transferred to intensive care and 21% died. Beta diversity of the intestinal microbiome was significantly different, whereas alpha diversity was similar, between subjects with vs without outcomes. The CDR was lower in subjects who developed ACLF, especially among those with renal failure. Taxa belonging to phylum Proteobacteria (Enterobacteriaceae, Campylobacteriaceae, and Pasteurellaceae) and Firmicutes (Enterococcaceae and Streptococcaceae) were associated with development of negative outcomes, whereas other Firmicutes members (Lachnospiraceae and Clostridiales) reduced risk of negative outcomes. Changes in the microbiota associated with extra-hepatic organ failure, transfer to intensive care, ACLF, and death, independently on logistic regression analyses. Conclusion In hospitalized patients with cirrhosis, dysbiosis of the intestinal microbiota on admission (particularly changes in Protebacteria constituents) associates with increased risk of extra-hepatic organ failure, ACLF, and death, independent of clinical factors. Strategies to reduce gut dysbiosis might improve outcomes of patients with cirrhosis.

Background:Centers for Disease Control (CDC) data suggest that Latinos are less likely to be physically active and more likely to be overweight and suffer from resulting complications than are Whites and that within the Latino population, Latina women are especially at risk. Therefore, promoting physical activity among Latinos, and understanding gender participation patterns within that population, is particularly important. One strategy for encouraging physical activity is to promote active uses of public parks.Methods:A national, multiyear, multisite study funded by the USDA Forest Service sought to understand use of public parks by Latinos and Latinas in Los Angeles, Minneapolis, and Chicago.Results:More than 50% of our sample visited parks to engage in physical activity, and in part, activity choice was related to gender. Furthermore, nearly half of all respondents walked to city park sites, whereas few or none walked to state or regional park sites.Conclusions:Our data suggest that Latinos are using some parks repeatedly and, in the case of city parks, are using them for physical as well as social activity. Therefore, we suggest specific ways that parks could be managed to encourage more physical activity while taking into account gender variations.

OBJECTIVE To describe an association between renal cell carcinoma (RCC) and multiple myeloma (MM) in patients with both disorders, and suggest possible explanations for the association. PATIENTS AND METHODS We retrospectively reviewed the records of patients with MM and RCC at the Cleveland Clinic between 1990 and 2005, and identified 1100 with MM, 2704 with RCC and eight with concomitant MM and RCC. The medical records of these eight patients were reviewed. RESULTS In four of the eight patients, RCC was diagnosed after the MM at 3, 8, 23 and 46 months, respectively; in the remaining four, the RCC was diagnosed before MM by 108, 35, 13 and 1 months, respectively. The number of cases of RCC expected in the present 1100 patients with MM over 15 years was lower than the four recorded (P

Clonotypic B lymphocytes may underlie relapse of patients with multiple myeloma. Rituximab, a CD20 monoclonal antibody, may result in eradication of the monoclonal B cells. We conducted a phase II study of rituximab in combination with melphalan and prednisone therapy (MP) followed by rituximab maintenance in newly diagnosed multiple myeloma patients. Sixteen patients (35%) had CD20 positive bone marrow plasma cells, while 9 patients (20%) had unknown CD20 status. No patient had a complete remission, 26 patients (58%) had a partial response, 6 patients (13%) had a minimal response, and 8 patients (18%) had stable disease. The median event-free survival was 14 months, and the 7-year overall survival was 30%. The toxicity of the combination was overall manageable and consistent with what is generally noted with MP chemotherapy. The combination of rituximab to MP therapy did not result in improved response rate or event-free survival.

BackgroundThe common mental disorders (CMDs) of anxiety and depression are the most common form of poor mental health in the general population. Evidence from the small number of previous cohort studies on the role of neighbourhood factors in mental health is inconclusive. We tested the hypothesis that high levels of neighbourhood social cohesion modify an adverse association between change in individual mental health and neighbourhood deprivation.MethodWe carried out a longitudinal multilevel analysis using data from the Caerphilly Health and Social Needs Cohort Study with a 7-year follow-up (n = 4426; age range 18–74 years at baseline). Neighbourhood deprivation and neighbourhood social cohesion were assessed at baseline and change in mental health between follow-up and baseline was assessed using the five-item Mental Health Inventory (MHI-5).ResultsResidence in the most deprived neighbourhoods was negatively associated with change in mental health, after adjusting for baseline individual socio-economic risk factors and transitions in life events. This negative effect was significantly reduced in high social cohesion neighbourhoods. The predicted change in mental health score was calculated for the 10th and 90th centiles of the household low-income distribution. The difference between them was −2.8 in the low social cohesion group and 1.1 in the high cohesion group. The difference between the groups was 3.9 [95% confidence interval (CI) 0.2–7.6].ConclusionsThe public health burden of poor mental health and mental health inequality could potentially be reduced by strengthening social cohesion in deprived neighbourhoods. This offers a mechanism to address the adverse effect of neighbourhood deprivation on population mental health.

Background: The International Myeloma Working Group (IMWG) proposed response and progression criteria using serum free light chain (sFLC) testing for patients with nonsecretory multiple myeloma (MM). We attempt to validate these criteria by comparing paraprotein responses with sFLC responses in patients with secretory myeloma. Patients and Methods: Prospectively entered data for 89 patients with MM enrolled on various clinical trials at the Cleveland Clinic between April 2004 and December 2006 were reviewed. Results: By standard paraprotein criteria, 4 patients had complete remission (CR), 22 had partial remission (PR), 34 had stable disease (SD), 26 had progressive disease (PD), and 3 were inevaluable. Only 43 patients (48%) had an involved sFLC ≥ 10 mg/dL (which is considered evaluable by the IMWG), of which 14 had PR, 8 had SD, 18 had PD, and 3 were inevaluable. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for sFLC in predicting response were 81%, 83%, 64%, and 92% respectively. The sensitivity, specificity, PPV, and NPV for sFLC in predicting progression were 93%, 80%, 72%, and 95% respectively. Conclusion: sFLC reliably predicts response and progression in MM. However, half of the patients had inevaluable disease by sFLC, thus limiting the utility of sFLC testing in patients with nonmeasurable disease by electrophoretic methods.

OBJECTIVE To evaluate the efficacy and safety of adding thalidomide to the pegylated liposomal doxorubicin, vincristine, and decreased-frequency dexamethasone (DVd) regimen for multiple myeloma. PATIENTS AND METHODS Patients newly diagnosed as having active multiple myeloma and those with relapsed-refractory disease were studied between August 2001 and October 2003. Patients received DVd as previously described. Thalidomide was given at 50 mg/d orally and the dose increased slowly to a maximum of 400 mg/d. At the time of best response, patients received maintenance prednisone, 50 mg orally every other day, and daily thalidomide at the maximum tolerated dose for each patient. The primary end point was the rate of complete responses plus very good partial responses as defined by the European Group for Blood and Marrow Transplantation criteria and the Intergroupe Francais du Myelome, respectively. RESULTS Of 102 eligible patients, 53 were newly diagnosed as having multiple myeloma, and 49 had been previously treated for multiple myeloma. The complete response plus very good partial response rate was 49% and 45%, with an overall response rate of 87% and 90% for patients with newly diagnosed and previously treated multiple myeloma, respectively. Furthermore, better responses were associated with improved progression-free and overall survival. The most common grade 3 and 4 adverse events were thromboembolic events (25%), peripheral neuropathy (22%), and neutropenia (14%). CONCLUSIONS The addition of thalidomide to the DVd regimen significantly improves the response rate and quality of responses compared with the DVd regimen alone. This improvement is associated with longer progression-free and overall survival. The rate of observed quality responses is comparable to responses seen with high-dose therapy.

Single-agent arsenic trioxide has shown promising results in patients with relapsed or refractory multiple myeloma (MM). Because preclinical data suggested greater activity with dexamethasone and ascorbic acid, a phase 2 trial of the combination of arsenic trioxide, dexamethasone, and ascorbic acid in patients with relapsed or refractory MM was conducted. Twenty patients in whom no more than two previous therapies had failed were enrolled. The mean age was 62 yr, and 55% of the patients had refractory disease. The regimen consisted of 14- or 15-wk cycles, with the first cycle considered induction, followed by one or two consolidation cycles with a reduced steroid schedule and then a maintenance cycle in responding patients. The overall response rate was 30%, with at least stable disease in 80% of patients. Median progression-free survival was 316 d in all patients and 584 d in those with a response. The regimen was well tolerated, with most adverse events being mild or moderate. This study showed the clinical efficacy and tolerability of the combination of arsenic trioxide, dexamethasone, and ascorbic acid. Further study is warranted.