49 research outputs found

    What Drives Animal Fluency Performance in Cantonese-Speaking Chinese Patients with Adult-Onset Psychosis?

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    Among the numerous studies investigating semantic factors associated with functioning in psychotic patients, most have been conducted on western populations. By contrast, the current cross-sectional study involved native Cantonese-speaking Chinese participants. Using the category fluency task, we compared performance between patients and healthy participants and examined clinical and sociodemographic correlates. First-episode psychosis patients (n = 356) and gender- and age-matched healthy participants (n = 35) were asked to generate as many ‘animals’ as they could in a minute. As expected, patients generated fewer correct responses (an average of 15.5 vs. 22.9 words), generated fewer clusters (an average of 3.7 vs. 5.4 thematically grouped nouns), switched less between clusters (on average 8.0 vs. 11.9 switches) and, interestingly, produced a larger percentage of Chinese zodiac animals than healthy participants (an average of 37.7 vs. 24.2). However, these significant group differences in the clusters and switches disappeared when the overall word production was controlled for. Within patients, education was the strongest predictor of category fluency performance (namely the number of correct responses, clusters, and switches). The findings suggest that an overall slowness in patients may account for the group differences in category fluency performance rather than any specific abnormality per se

    State of the art conference on weight management in VA: Policy and research recommendations for advancing behavioral interventions

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    This article summarizes outcomes of the behavioral interventions work group for the Veterans Health Administration (VHA) State of the Art Conference (SOTA) for Weight Management. Sixteen VHA and non-VHA subject matter experts, representing clinical care delivery, research, and policy arenas, participated. The work group reviewed current evidence of efficacy, effectiveness, and implementation of behavioral interventions for weight management, participated in phone- and online-based consensus processes, generated key questions to address gaps, and attended an in-person conference in March 2016. The work group agreed that there is strong evidence for efficacy and effectiveness of core behavioral intervention components and processes, but insufficient evidence to determine the comparative effectiveness of multiple clinician delivered weight management modalities, as well as technologies that may or may not supplement clinician delivered treatments. Effective strategies for implementation of weight management services in VHA were identified. The SOTA work group’s foremost policy recommendations are to establish a system-wide culture for weight management and to identify a population-level health metric to measure the impact of weight management interventions that can be tracked and clearly communicated throughout VHA. The work group’s top research recommendation is to determine how to deploy and scale the most effective behavioral weight management interventions for Veterans

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

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    IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

    COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

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    Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≀ 18 years: 69, 48, 23; 85%), older adults (≄ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

    Chilling of Atlantic salmon (Salmo salar) in Refrigerated Seawater. Its effect on water holding properties and general quality through the whole value chain

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    Water holding properties, including drip loss and water holding capacity, are important fish quality parameters. Superchilling is a preservation method prolonging the shelf life of food, where products are stored at subzero temperatures. An alternative fish slaughter method has been introduced in recent years, where fish are directly slaughtered onboard a vessel and superchilled in refrigerated seawater (RSW) at subzero temperatures during transportation. This vessel is currently the first-of-its-kind. Therefore, how this method affects the water holding properties and general quality through the whole value chain of Atlantic salmon is not fully studied. The main objective of this thesis was to examine the water holding properties of Atlantic salmon with RSW storage at subzero temperatures through two value chains: 1. from whole fish to cold-smoked and vacuum packaged fillets; 2. from whole fish to portioned and packaged fresh fillets. This method was compared to the conventional method of ice storage. In addition, the effect of the two whole fish storage methods combined with different packaging techniques (vacuum skin, traditional vacuum) was studied on raw fillet portions. Finally, a physics-based mathematical model on heat and mass transfer was developed to predict the water and salt uptake after dry salting and cold-smoking. This model was validated with experiments and compared with a previous empirical model. Results from the mathematical model were also used as input parameters for further simulation of water activity, validated with experimental values. Overall, this thesis presents the notion that RSW storage increases water and salt uptake and provides good water holding properties. Therefore, it is a feasible method for fish transportation, giving good quality salmon as those on ice. Furthermore, slaughtering fish onboard a vessel and RSW-superchilling condenses the traditional three handling steps, where fish are usually pumped into well-boats and transported to land before processing, into only one. This potentially introduces advantages like quicker cooling and the ability to store large volumes of fish that could be widely implemented with a possibility in a logistical shift of slaughter from land to sea. In addition, introducing numerical modelling into this study provides opportunities to strengthen and expand this tool for other industrial applications and process optimization

    The Effect of Osmotic Pressure on Rigor Mortis in Salmonids

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    Rigor mortis is a natural phenomenon caused by a series of complicated chemical changes in the muscles after the death of an animal. This concept is important especially in meat technology since it affects texture, yield and meat palatability. However, the understanding of rigor mortis in animals is currently not fully discovered, and research is still ongoing. The rigor process is frequently explained by the sliding filament theory, where actomyosin bridges form and cause stiffness during rigor. Yet adenosine triphosphate (ATP) concentration gradually depletes as the muscle enters rigor, so little or no ATP is available for rigor resolution and muscles remain stiff. Hence, this theory does not explain the rigor resolution process, where muscles eventually become soft and limp. An alternative hypothesis of rigor mortis is postulated describing the rigor process via changes in osmotic pressure in muscle cells. Since catabolic reactions (glucose to lactate) predominate after death, the number of molecules inside muscle cells increase. This induces an increase in osmotic pressure and water flows into the cells to achieve osmotic equilibrium between compartments, thus creating stiffness. Therefore, this thesis investigates the hypothesis by analysing the movement of water in muscles immersed in solutes of varying salinities, together with texture and morphological analysis. It was found that mass changes in salmonid muscles were significantly affected by the movement of water in different salinities and were independent with the contraction rates. Rigor index measurements showed that the individual fish reached 63.2% of their maximum rigor within 4 to 6 hours post mortem. Shear force was expected to be highest at this time point but texture analysis did not follow the same trend and gave a general decrease in breaking force. Even so, there were high variations observed with the individual texture measurements explained by multiple reasons. The effect of formalin fixation also revealed that prolonged fixation of muscle tissues can lead to cell shrinkage. Morphological analysis of muscle cells by image processing in Matlab further showed that there were distinct differences in the amount of intra and extracellular spaces and inter-fibre distances from the tissue surface and center in the various solutions
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