Baseline Stage Research Articles

Proton Pump Inhibitor Use and Worsening Kidney Function: A Retrospective Cohort Study Including 122,606 Acid-Suppressing Users.

The impact of proton pump inhibitors (PPIs) use on worsening renal function is controversial and lacks a solid pathophysiological explanation. To assess the risk of worsening renal function and acute kidney injury (AKI) in PPI initiators as compared with H2-blockers initiators. Retrospective cohort study using longitudinal records from BIGAN, a population-based health database of Aragón (Spain). PPIs (n = 119,520) and H2-blockers (n = 3,086) initiators between 2015 and 2020 with preserved renal function. They were followed until the occurrence of an adverse kidney event, death, lost to follow-up or June 2021. Primary endpoints were worsening kidney function (measured as sCr ≥ 2 times baseline, eGFR < 60ml/min/1.73m2, a decrease in eGFR 30-50% from baseline or end stage renal disease) and AKI (measured by Aberdeen algorithm or hospitalization due to AKI). Incidence rates (IRs) per 1,000 persons-years were reported and Cox regression was used to calculate Hazard ratios (HRs), adjusted for confounders. Crude IRs for worsening kidney function were consistently lower for ranitidine than for PPIs (eGFR < 60ml/min/1.73m2: IR 18.7 95%CI (12.0-27.8) for ranitidine, IR 31.2 95%CI (29.9-32.5) for omeprazole). However, the risk of incident worsening function did not significantly differ in the Cox regression analysis adjusting for confounders (HR 0.99 95%CI (0.66-1.48) for omeprazole, as compared to ranitidine). PPI initiators consistently showed lower IRs of AKI using Aberdeen algorithm (IR 33.8 95%CI (32.4-35.1) for omeprazole, IR 52.8 95%CI (40.9-67.1) for ranitidine) and lower risk of AKI (HR 0.54 95%CI (0.42-0.70) for omeprazole, as compared to ranitidine). No clinically relevant differences were observed for worsening kidney function between PPIs and H2-blockers initiators. PPIs users presented a reduced risk of AKI compared to ranitidine initiators.

Effects of optimism and stage of change on alcohol use and problems among sexual minority men with HIV participating in a brief motivational interviewing intervention.

Disseminating effective alcohol interventions for sexual minority men (SMM) with HIV remains a crucial public health endeavor. Motivational interviewing (MI) interventions are an established approach to reducing alcohol use, yet more research is needed to determine predictors of MI treatment outcomes and underlying mechanisms related to sustained behavior change among SMM with HIV. This pre-registered secondary analysis tested whether action-related stage of change mediated effects of a MI intervention on future alcohol use and problems among SMM with HIV, and whether individual differences in trait optimism moderated these associations. SMM with HIV who engaged in frequent alcohol use (N = 180) were randomized to MI or assessment-only treatment as usual (TAU). Participants completed a semi-structured Timeline Follow-Back interview to measure past-month alcohol use as well as self-reports assessing stage of change, trait optimism, and alcohol problems at baseline and 3- and 12-months post-baseline. Structural equation models controlling for baseline alcohol use and stage of change indicated that 3-month action significantly mediated effects of MI on 12-month drinks per week. Likewise, the indirect effect of 3-month action was moderated by higher levels of trait optimism. When employment status, education level, and annual family/household income were included as covariates in the model, being employed significantly predicted 12-month alcohol use, and mediation and moderated mediation effects were no longer statistically significant. Stage of change did not mediate effects of MI on 12-month alcohol problems, and this indirect effect was not moderated by trait optimism. The present study provides further evidence supporting action-related stage of change as a mechanism linking MI to alcohol use reductions. Results demonstrated that SMM with HIV who were more optimistic tended to take more action towards reducing their alcohol use and suggest that MI-based interventions may benefit from integrating components aimed at augmenting patients' optimism. Yet, covarying for current economic status substantially impacted findings and underscores the need to critically consider how broader socioecological contexts can impact treatment outcomes.

Wide variation in shape of hypoplastic left ventricles undergoing recruitment and biventricular repair: A statistical shape modeling study.

Patients with hypoplastic left ventricles (LV) who undergo volume-loading procedures (recruitment, biventricular [BIV] repair) are at risk for adverse outcomes, including heart failure and death. We investigated pre-BIV LV shape as a predictor of outcome after BIV repair in patients with hypoplastic LVs. Baseline and post-recruitment cardiac magnetic resonance imaging and computed tomography data were analyzed in patients with hypoplastic LV (<50mL/m2). Statistical shape modeling (SSM) was utilized to generate a model of the shape and variability of LVs. Traditional measures of LV sphericity and eccentricity were also measured. Major adverse cardiovascular events (MACE) included heart failure, transplant, and death. Of 95 patients with baseline mean LV volume 29±13mL/m2, 45/95 (47%) had a right dominant atrioventricular canal defect, 31/95 (33%) had a variant of hypoplastic left heart syndrome, and 18/95 (19%) had endocardial fibroelastosis (EFE). A wide variation in LV shape was found by SSM, and shape modes were associated with right ventricle (RV) and LV size, and diagnosis. BIV repair was achieved in 74/95 (78%) patients; 13/74 (18%) of BIV patients had MACE. Predictors of MACE following BIV repair included EFE, higher RV mass index, and higher RV end-diastolic volume index. No baseline or post-recruitment LV shape parameter was associated with the outcome after BIV repair. The shape model of hypoplastic LVs demonstrated a wide array of LV shapes. LVs gained sphericity and size and lost eccentricity with recruitment. Though the ventricles changed shape with recruitment, no specific LV shape characteristic at the baseline or post-recruitment stage was predictive of decision to proceed with BIV repair or outcome. Higher RV mass and volume may represent new biomarkers that predict outcomes following BIV repair in patients with hypoplastic LV. Further investigation could determine the reproducibility of these findings.

Contribution of physiological dynamics in predicting major depressive disorder severity

AbstractThis study aimed to explore the physiological dynamics of cognitive stress in patients with Major Depressive Disorder (MDD) and design a multiparametric model for objectively measuring severity of depression. Physiological signal recordings from 40 MDD patients and 40 healthy controls were collected in a baseline stage, in a stress‐inducing stage using two cognitive tests, and in the recovery period. Several features were extracted from electrocardiography, photoplethysmography, electrodermal activity, respiration, and temperature. Differences between values of these features under different conditions were used as indexes of autonomic reactivity and recovery. Finally, a linear model was designed to assess MDD severity, using the Beck Depression Inventory scores as the outcome variable. The performance of this model was assessed using the MDD condition as the response variable. General physiological hyporeactivity and poor recovery from stress predict depression severity across all physiological signals except for respiration. The model to predict depression severity included gender, body mass index, cognitive scores, and mean heart rate recovery, and achieved an accuracy of 78%, a sensitivity of 97% and a specificity of 59%. There is an observed correlation between the behavior of the autonomic nervous system, assessed through physiological signals analysis, and depression severity. Our findings demonstrated that decreased autonomic reactivity and recovery are linked with an increased level of depression. Quantifying the stress response together with a cognitive evaluation and personalization variables may facilitate a more precise diagnosis and monitoring of depression, enabling the tailoring of therapeutic interventions to individual patient needs.

Aortic stenosis and the evolution of cardiac damage after transcatheter aortic valve replacement

Abstract Aims Cardiac damage staging has been postulated as a prognostic tool in patients undergoing transcatheter aortic valve replacement (TAVR). The aim of our study is to show the echocardiographic and clinical outcome of patients one-year after TAVR. Methods and results Patients undergoing TAVR from 2017 to 2021 were included in a single-centre prospective registry. Transthoracic echocardiography was performed in all patients before TAVR and at one-year. Patients were classified according to a previously published staging model.1 496 patients (mean age 82.1±5.9 years, 53% female) were included. At baseline, Stage 0 included 24.5% of patients, Stage 1 included 42.8%, Stage 2 included 16.5%, and Stage 3 included 16.2% of patients. One-year overall mortality was 17.7% (n=88). Among patients who survived, after one-year of follow-up, the higher the baseline stage of cardiac damage, patients showed larger LVEDV (p= 0.223), LV mass (p= 0.207) and LAVI (p= &amp;lt;0.001); higher E/e’ ratio (p= 0.284) and PASP (p= &amp;lt;0.001). As for LVEF, at one-year; it was significantly lower the higher the baseline stage of cardiac damage (p= 0.005); the same was observed with GLS (p= &amp;lt;0.001) and right ventricle-arterial coupling (p= &amp;lt;0.001), Table 1. Conclusions The higher the stage of initial cardiac damage, the lower the possibility of morphological and functional improvement, despite undergoing TAVR. The use of staging systems and earlier intervention could help improve the prognosis of these patients.

Eleven Years of Change: Disease Progression in Biomarker-Defined Sporadic Parkinson's Disease.

Long-term longitudinal data on outcomes in sporadic Parkinson's Disease are limited, especially from cohorts with extensive biological characterization. Recent advances in biomarkers characterization of Parkinson's Disease necessitate an updated examination of long-term progression within contemporary cohorts like the Parkinson's Progression Markers Initiative, which enrolled individuals within 2 years of clinical diagnosis of Parkinson's Disease. Our study leverages the Neuronal Synuclein Disease framework, which defines the disease based on biomarker assessed presence of neuronal alpha-synuclein and dopamine deficit, rather than based on conventional clinical diagnostic criteria. In this study we aimed to provide a comprehensive long-term description of disease progression using the integrated biological and clinical staging system framework. We analyzed data from 344 participants from the sporadic Parkinson's Disease cohort in the Parkinson's Progression Markers Initiative, who met Neuronal Synuclein Disease criteria. We assessed 11-year progression in a spectrum of clinical measures. We used Cox proportional hazards models to assess the association between baseline stage and time to key outcomes, including survival, postural instability (Hoehn & Yahr ≥ 3), loss of independence (Schwab & England < 80%), cognitive decline, and domain-based milestones such as walking and balance, motor complications, autonomic dysfunction, and activities of daily living. Additional analyses were completed to account for death and participant dropout. Biomarker analysis included dopamine transporter binding measures, as well as serum urate, neurofilament light chain and CSF amyloid-beta, phosphorylated tau and total tau. At baseline, despite the cohort consisting of individuals within 2 years of clinical diagnosis, there was clear separation of participants in Neuronal Synuclein Disease Stages (23% Stage 2b, 67% Stage 3, 10% Stage 4). At 11 years, data were available for 153 participants; 35 participants had died over the follow up period. Of retained participants, 59% presented normal cognition, 24% had evidence of postural instability and mean Schwab & England score was 78.5. Serum neurofilament light chain consistently increased over time. No other biofluids had a consistent change in trajectory. Of importance, baseline Neuronal Synuclein Disease Stage predicted progression to clinically meaningful milestones. This study provides data on longitudinal, 11-year progression in Neuronal Synuclein Disease participants within 2 years of clinical diagnosis. We observed better long-term outcomes in this contemporary observational study cohort. It highlights the heterogeneity in the early Parkinson's Disease population as defined by clinical diagnostic criteria and underscores the importance of shifting from clinical to biologically and functionally based inclusion criteria in the design of new clinical trials.

A randomized controlled trial evaluation of a smoking cessation and physical activity intervention delivered via telemedicine in the Norton Sound region of Alaska

ObjectivesTobacco use disproportionately affects Alaska Native people. Physical activity may aid quitting smoking and provides health benefits. We tested telemedicine-delivered heart health interventions in Alaska’s Norton Sound region. MethodsAlaska Native adults (N = 299, 51.5 % male, 60.5 % Inupiaq) with hypertension and/or hypercholesterolemia who smoked daily were randomized to intervention on smoking and physical activity (group 1) or traditional diet and medication adherence (group 2). Intention to change was not required for participation. Stage-tailored mailed workbooks and personalized reports were supported by telehealth counseling at baseline, 3, 6, and 12 months. Study outcomes were assessed at baseline, 3-, 6-, 12-, and 18-months (i.e., 6-months after the final counseling session). Smoking outcomes were self-reported 7-day point prevalence abstinence (7d-PPA),11Abbreviations:7d-PPA: 7-day point prevalence abstinenceMET: Metabolic equivalent of taskMVPA: Moderate-to-vigorous physical activityNRT: Nicotine replacement therapy. bioconfirmed with urine anabasine; 24-hour quit attempts; and 50 % reduction in smoking. Self-reported physical activity outcomes were metabolic equivalent of task (MET) minutes and meeting moderate-to-vigorous physical activity (MVPA) guidelines. ResultsAt baseline, participants averaged 12.4 (SD = 10.0) cigarettes/day, with 19.4 % prepared to quit smoking, and 81.6 % meeting MVPA guidelines. During the study, most (70.2 % group 1; 63.5 % group 2) reported a 24-hr quit attempt (p = 0.219), and Group 1 (53.6 %) was more likely than Group 2 (28.4 %) to use nicotine replacement therapy (NRT), OR = 2.92, p < 0.001. At 18-months, 40.5 % (group 1) and 32.5 % (group 2) had reduced their smoking by half or more (p = 0.343), and 10.8 % vs. 7.9 % (group 1 vs. 2) reported 7d-PPA with 4 % vs. 6 % (group 1 vs. 2) bioconfirmed. Time and baseline stage of change predicted 7d-PPA (p’s≤.015), with no group effect (p = 0.325). Activity levels did not significantly differ by group or time. ConclusionsTelemedicine counseling supported NRT use but did not significantly affect behavioral outcomes.

Neuronal alpha-Synuclein Disease integrated staging system performance in PPMI, PASADENA, and SPARK baseline cohorts

The Neuronal alpha-Synuclein Disease (NSD) biological definition and Integrated Staging System (NSD-ISS) provide a research framework to identify individuals with Lewy body pathology and stage them based on underlying biology and increasing degree of functional impairment. Utilizing data from the PPMI, PASADENA, and SPARK studies, we developed and applied biologic and clinical data-informed definitions for the NSD-ISS across the disease continuum. Individuals enrolled as Parkinson’s disease, Prodromal, or Healthy Controls were defined and staged based on biological, clinical, and functional anchors at baseline. Across the three studies 1741 participants had SAA data and of these 1030 (59%) were S+ consistent with NSD. Among sporadic PD, 683/736 (93%) were NSD, and the distribution for Stages 2B, 3, and 4 was 25%, 63%, and 9%, respectively. Median (95% CI) time to developing a clinically meaningful outcome was 8.3 (6.2, 10.1), 5.9 (4.1, 6.0), and 2.4 (1.0, 4.0) years for baseline stage 2B, 3, and 4, respectively. We propose pilot biologic and clinical anchors for NSD-ISS. Our results highlight the baseline heterogeneity of individuals currently defined as early PD. Baseline stage predicts time to progression to clinically meaningful milestones. Further research on validation of the anchors in longitudinal cohorts is necessary.

Neuronal alpha-Synuclein Disease Integrated Staging System performance in PPMI, PASADENA, and SPARK baseline cohorts.

The Neuronal alpha-Synuclein Disease (NSD) biological definition and Integrated Staging System (NSD-ISS) provide a research framework to identify individuals with Lewy body pathology and stage them based on underlying biology and increasing degree of functional impairment. Utilizing data from the PPMI, PASADENA and SPARK studies, we developed and applied biologic and clinical data-informed definitions for the NSD-ISS across the disease continuum. Individuals enrolled as Parkinson's disease, Prodromal, or Healthy Controls were defined and staged based on biological, clinical, and functional anchors at baseline. Across the three studies 1,741 participants had SAA data and of these 1,030 (59%) were S+ consistent with NSD. Among sporadic PD, 683/736 (93%) were NSD, and the distribution for Stages 2B, 3, and 4 was 25%, 63%, and 9%, respectively. Median (95% CI) time to developing a clinically meaningful outcome was 8.3 (6.2, 10.1), 5.9 (4.1, 6.0), and 2.4 (1.0, 4.0) years for baseline stage 2B, 3, and 4, respectively. We propose pilot biologic and clinical anchors for NSD-ISS. Our results highlight the baseline heterogeneity of individuals currently defined as early PD. Baseline stage predicts time to progression to clinically meaningful milestones. Further research on validation of the anchors in longitudinal cohorts is necessary.

Influence of the yoga breathing exercise “uddiyana” on blood flow in the marginal sinus

Purpose: Studying the effect of the Uddiyana Bandha (UB) yoga breathing exercise on blood flow in the marginal sinus (MS).Materials and methods: The study involved 16 people in whom blood flow in the MS was assessed against the background of free breathing, during voluntary expiratory apnea (VEA) — 5 seconds, and during UB — 5 seconds. The maximum blood flow velocity (Vmax), the time-averaged maximum velocity Vmean, and the index phase character (IP) were recorded.Results: When recording Vmax during VEA (stage 2) for 5 seconds, it did not show significant differences compared to free breathing (stage 1); within 5 seconds of execution, the UB (stage 3) was significantly higher than the baseline (stage 1), p &lt; 0.001, and also higher than the VEA (stage 2), p &lt; 0.001. Vmean PEA (stage 2) for 5 seconds was without significant differences compared to free breathing (stage 1). During 5 seconds of UB execution (stage 3), Vmean was higher than the baseline (stage 1), p &lt; 0.001, and also higher than VEA (stage 2), p &lt; 0.009. Against the background of free breathing (stage 1) and PEA (stage 2), the values of IP and were without significant differences compared to UB (stage 3).Conclusions: The UB breathing exercise increases the maximum linear blood flow velocity Vmax and the time-averaged maximum blood flow velocity Vmean in the MS, which may indicate activation of cerebral venous outflow during the exercise.

Cost effectiveness of colorectal cancer screening in the Dominican Republic.

e23033 Background: Colorectal cancer (CRC) incidence in the Dominican Republic (DR) is increasing, and CRC now ranks as the third-most prevalent cancer in the DR. There are no national CRC screening guidelines in the DR, and CRC screening is not routinely performed. We evaluated the impact of nationwide CRC screening by comparing the cost-effectiveness of four CRC screening strategies to the current practice of no screening. Methods: We developed a Markov model comparing four CRC screening strategies to the current practice of no screening, or natural history (NH): colonoscopy every ten years (Colo); sigmoidoscopy every five years (Sig); fecal immunochemical test biennially (FIT); and fecal occult blood test biennially (FOBT). Model inputs for screening arms were derived from international randomized controlled trials whenever possible. Data from The Rosa Emilia Sánchez Pérez de Tavares National Cancer Institute in the DR was used to estimate baseline CRC incidence, stage distribution and mortality. Screening was implemented from age 45 to 75. We assumed a 60.6% adherence rate for each screening arm. The model was cross validated by comparing the estimated lifetime impact of each screening arm on CRC incidence and mortality to estimates derived from the MIcrosimulation SCreening Analysis (MISCAN) Colorectal Cancer Model in the US. The primary outcome was the incremental cost-effectiveness ratio (ICER) of each screening strategy. Secondary outcomes included life expectancy, total cost, CRC incidence and CRC-related mortality. The willingness to pay threshold (WTP) was set to the 2022 DR gross domestic product per person ($10,111.20/life year gained). Results: In the NH strategy, 2.3% of the population developed CRC, and 1.2% died from CRC, with a lifetime cost of 203.47 per person. Compared to NH, FIT prevented 27% of CRCs and 37% of CRC deaths, with a lifetime cost of 244.76 per person. Colo was more effective than FIT, preventing 33% and 43% of CRC cases and deaths, respectively, compared to NH. However, the ICER for Colo exceeded the WTP threshold. One-way sensitivity analyses showed that the model is most sensitive to test performance characteristics and test costs. Conclusions: Among the evaluated CRC screening strategies, FIT is the cost-effective option, averting a significant number of CRC cases and deaths, at an incremental cost that is well within the WTP threshold for the DR. Inclusion of local data on the effectiveness and acceptability of the tested CRC screening modalities would improve this model, and strengthen the credibility of our findings. [Table: see text]

The cost-efficacy of a healthy food box for managing hypertension within a native American population: a group randomized controlled trial

BackgroundDietary interventions are used for the treatment of hypertension. We evaluated the cost-efficacy of delivering boxes of healthy, culturally tailored foods and checks that can only be spent on produce in a Native American population.MethodsWe conducted a group randomized controlled trial from 2018 to 2020 with N = 2 treatment counties and N = 2 control counties and a total of N = 160 Native American adults with baseline stage 1 or stage 2 hypertension. Participants in the intervention group received monthly boxes of food that adheres to the Dietary Approaches to Stop Hypertension diet as well as checks that could only be spent on produce for 6 months. We measured blood pressure and quality of life at baseline and at a 6-month follow-up in both intervention and control groups. We used ordered logistic regression to estimate the effect of treatment on probability of blood pressure improvements. We then conducted a cost-efficacy analysis.ResultsWe found that treatment was effective in reducing blood pressure in women with stage 1 hypertension at baseline. Based on this finding, we also estimate that this intervention satisfies normative cost-effectiveness thresholds, even when lifetime treatment is needed to preserve the impact, so long as treatment is only continued in those who respond to treatment.ConclusionsDirect delivery of healthy foods and checks that can only be spent on produce are a potentially cost-effective intervention for the management of hypertension among Native American women with stage 1 hypertension. Further research is needed to understand why we found an impact only for this group.

A generalizable data-driven model of atrophy heterogeneity and progression in memory clinic settings.

Memory clinic patients are a heterogeneous population representing various aetiologies of pathological ageing. It is not known whether divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer's disease patients, are prevalent and clinically meaningful in this group of older adults. To uncover distinct atrophy subtypes, we applied the Subtype and Stage Inference (SuStaIn) algorithm to baseline structural MRI data from 813 participants enrolled in the DELCODE cohort (mean ± standard deviation, age = 70.67 ± 6.07 years, 52% females). Participants were cognitively unimpaired (n = 285) or fulfilled diagnostic criteria for subjective cognitive decline (n = 342), mild cognitive impairment (n = 118) or dementia of the Alzheimer's type (n = 68). Atrophy subtypes were compared in baseline demographics, fluid Alzheimer's disease biomarker levels, the Preclinical Alzheimer Cognitive Composite (PACC-5) as well as episodic memory and executive functioning. PACC-5 trajectories over up to 240 weeks were examined. To test whether baseline atrophy subtype and stage predicted clinical trajectories before manifest cognitive impairment, we analysed PACC-5 trajectories and mild cognitive impairment conversion rates of cognitively unimpaired participants and those with subjective cognitive decline. Limbic-predominant and hippocampal-sparing atrophy subtypes were identified. Limbic-predominant atrophy initially affected the medial temporal lobes, followed by further temporal regions and, finally, the remaining cortical regions. At baseline, this subtype was related to older age, more pathological Alzheimer's disease biomarker levels, APOE ε4 carriership and an amnestic cognitive impairment. Hippocampal-sparing atrophy initially occurred outside the temporal lobe, with the medial temporal lobe spared up to advanced atrophy stages. This atrophy pattern also affected individuals with positive Alzheimer's disease biomarkers and was associated with more generalized cognitive impairment. Limbic-predominant atrophy, in all participants and in only unimpaired participants, was linked to more negative longitudinal PACC-5 slopes than observed in participants without or with hippocampal-sparing atrophy and increased the risk of mild cognitive impairment conversion. SuStaIn modelling was repeated in a sample from the Swedish BioFINDER-2 cohort. Highly similar atrophy progression patterns and associated cognitive profiles were identified. Cross-cohort model generalizability, at both the subject and the group level, was excellent, indicating reliable performance in previously unseen data. The proposed model is a promising tool for capturing heterogeneity among older adults at early at-risk states for Alzheimer's disease in applied settings. The implementation of atrophy subtype- and stage-specific end points might increase the statistical power of pharmacological trials targeting early Alzheimer's disease.

A New Global Gas Dynamics Performance Optimization Method for Refrigeration Centrifugal Compressor Stage Based on the Immune Algorithm

Abstract This study proposes a new global gas dynamics optimization method, which was applied to a multi-objective optimization task of centrifugal compressor performance with the aim of determining the improvement probability for achieving high efficiency across a wide operating range. Initially, the original nondominated neighbor immune algorithm (NNIA) was extended to solve constrained multi-objective optimization problems for the first time, which mainly incorporated a procedure for handling inequality and equality constraints without additional parameters. Subsequently, an adaptive topological back-propagation multilayer feed-forward artificial neural network (BP-MLFANN) was trained using the modified NNIA to quickly evaluate the fitness value of the centrifugal compressor stage performance during the optimization. The feasibility of the method was validated using the first stage of a refrigeration centrifugal compressor. The results indicated a substantial enhancement in the stage efficiency of the optimized impeller at the Near-stall, Design, and Near-choke operating points, with increasement of 1.8%, 1.9%, and 4%, respectively, as compared to the baseline stage. The flow field analysis shows that the impact loss at impeller leading edge and flow separation in the passage reduced greatly, the mixing process between the leakage flow and mainstream in the channel is significantly weakened, thus the flow field becomes more uniform after optimization. The new global gas dynamics optimization method provides a reference for the development of efficient and rapid optimization techniques for centrifugal compressor.

Https://oaskpublishers.com/assets/article-pdf/kenscoff-its-development-of-tourism-from-forts-jacques-and-alexandre-in-a-dynamic-of-local-development.pdf

This research is interested in carrying out research on the effects of Monitoring and Evaluation on the Performance of Diary Community Processing Centre in Rwanda. In order to assess the relationship between Industrial development projects monitoring and evaluation for projects performance, an assessment conducted demonstrated that Monitoring is being done on monthly, Quarterly, semi-annually and annually and evaluation is done during baseline stage, mid-way of the project, End term of project and ex post of the project. The results showed that 67.9% were strongly agreed that the developed indicators were being monitored and evaluated regularly, 89.3% of them were also strongly agreed that the developed Performance indicators track project/program changes and provided the details information on the Performance of the program at Burera Diary Ltd while 75% of the reported that there is an appropriate way to monitor and evaluate the project/program progress made along its implementations. The result from interview guide for NIRDA staffs showed that RMMF and M&amp;E manuals were most useful M&amp;E tools used by NIRDA M&amp;E team to monitor and evaluate Burera Diary Ltd projects. They highlighted the aggregates and disaggregates indicators to be monitored and evaluated include, number of new jobs created, changes in sales and productions, changes in technologies used, changes in profits, changes in exports and assess how these listed indicators shall impact the lives of communities. Finally, the beneficiaries responded that their lives improved and more changes happened in their families like most of them bought land, built the houses and pay the tuition fees of their children.

Multicentre validation of CT grey-level co-occurrence matrix features for overall survival in primary oesophageal adenocarcinoma

BackgroundPersonalising management of primary oesophageal adenocarcinoma requires better risk stratification. Lack of independent validation of proposed imaging biomarkers has hampered clinical translation. We aimed to prospectively validate previously identified prognostic grey-level co-occurrence matrix (GLCM) CT features for 3-year overall survival.MethodsFollowing ethical approval, clinical and contrast-enhanced CT data were acquired from participants from five institutions. Data from three institutions were used for training and two for testing. Survival classifiers were modelled on prespecified variables (‘Clinical’ model: age, clinical T-stage, clinical N-stage; ‘ClinVol’ model: clinical features + CT tumour volume; ‘ClinRad’ model: ClinVol features + GLCM_Correlation and GLCM_Contrast). To reflect current clinical practice, baseline stage was also modelled as a univariate predictor (‘Stage’). Discrimination was assessed by area under the receiver operating curve (AUC) analysis; calibration by Brier scores; and clinical relevance by thresholding risk scores to achieve 90% sensitivity for 3-year mortality.ResultsA total of 162 participants were included (144 male; median 67 years [IQR 59, 72]; training, 95 participants; testing, 67 participants). Median survival was 998 days [IQR 486, 1594]. The ClinRad model yielded the greatest test discrimination (AUC, 0.68 [95% CI 0.54, 0.81]) that outperformed Stage (ΔAUC, 0.12 [95% CI 0.01, 0.23]; p = .04). The Clinical and ClinVol models yielded comparable test discrimination (AUC, 0.66 [95% CI 0.51, 0.80] vs. 0.65 [95% CI 0.50, 0.79]; p > .05). Test sensitivity of 90% was achieved by ClinRad and Stage models only.ConclusionsCompared to Stage, multivariable models of prespecified clinical and radiomic variables yielded improved prediction of 3-year overall survival.Clinical relevance statementPreviously identified radiomic features are prognostic but may not substantially improve risk stratification on their own.Key Points• Better risk stratification is needed in primary oesophageal cancer to personalise management.• Previously identified CT features—GLCM_Correlation and GLCM_Contrast—contain incremental prognostic information to age and clinical stage.• Compared to staging, multivariable clinicoradiomic models improve discrimination of 3-year overall survival.

Abstract 2533: In-depth multi-omic profiling of immune cells in cancer patients developing immune-related adverse events

Abstract Background: The clinical efficacy of immune-checkpoint inhibitors is complicated by the risk for immune-related adverse events (irAEs) that can involve any organ systems. To date, (1) we cannot predict irAE risk reliably at patient level and (2) irAEs remain a diagnosis of exclusion as there are no specific clinical or biological markers. The goal of this study was to elucidate intricate transcriptomic and proteomic signatures of immune cells in patients evolving irAEs. Methods: This pilot trial was conducted as part of a prospective multicenter cohort study (NCT04631731). The study cohort consisted of n=71 patients who were treated with ICIs across Blacktown and Westmead Hospitals, NSW, Australia. Peripheral blood mononuclear cells (PBMCs) were collected from both pre-treatment and after 6-8 weeks post-ICI commencement. Samples were further utilized for RNA sequencing, flow cytometry and Chromium 3’ gene expression analysis (10x Genomics). Results: The median age was 67 years old with the 78% (n=56) of Caucasian origin. The predominant number of patients were treated with dual ICIs. N=21 patients experienced irAEs. Firstly, a differential analysis established a set of genes which were significantly (FDR&amp;lt;0.01) dysregulated between patients with (group A) and without irAEs (group B) and were mostly related to cell cycle and regulation. Notably, phospholipase D signaling pathway was exclusively upregulated in group A and is known to be linked to B cell expansion. Secondly, a cell enrichment analysis within the group A revealed a significant increase of CD4+ and CD8+ T central memory (Tcm) cells upon the toxicity onset as compared to baseline stage. Thirdly, the flow cytometry data established that group A had (1) higher expression of CD27 on CD4+ T cells, a member of Traf-linked tumor necrosis factor receptor family essential for T cells’ maturation and (2) lower expression of inhibitory receptor LAG3 (CD223) which is crucial for maintaining homeostasis of immune system through suppression of T cell proliferation. Finally, we sequenced CD45+ cells from n=4 patients from group A and n=4 from group B at both pre- and post-treatment stages. The unsupervised clustering established 17 different clusters in our single cell dataset with cluster 11 was unique only to patients from group A. The differential analysis established that a set of n=62 genes was significantly upregulated (p&amp;lt;0.05) in cluster 11. Functional annotation established that B cell activation and proliferation pathways were enriched by those genes further stressing B cells’ role in irAEs development. Conclusions: Our real-world cohort study established significant molecular and cellular differences between patients with and without irAEs. Further research in larger cohorts is imperative to validate the established findings and to elucidate the precise mechanisms contributing to the development of irAEs. Citation Format: Dmitrii Shek, Bo Gao, Joey Lai, Brian Gloss, Adnan Nagrial, Ines Pires da Silva, Matteo S. Carlino, Scott A. Read, Golo Ahlenstiel. In-depth multi-omic profiling of immune cells in cancer patients developing immune-related adverse events [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2533.

Risk Factors for Worsening Morphology and Visual Acuity in Eyes with Adult-Onset Foveomacular Vitelliform Dystrophy

PurposeTo explore clinical risk factors and optical coherence tomography (OCT) features associated with worse visual acuity (VA), progression of disease, choroidal neovascularization (CNV), and atrophy in eyes with adult-onset foveomacular vitelliform dystrophy (AOFVD). DesignSingle-center, retrospective, observational cohort study ParticipantsPatients seen at Duke Eye Center between January 2012 and May 2023 with a diagnosis of AOFVD confirmed via OCT and fundus autofluorescence. MethodsBaseline and final visit images from eyes with AOFVD were examined. Disease stage was assigned, and presence of atrophy or CNV was determined. Clinical and OCT features associated with progression to atrophy and CNV were determined using t-tests and chi-square analysis. Correlation with lower VA was determined using linear regression. Outcome MeasuresAssociation of clinical characteristics and OCT features with worse VA, progression of disease, CNV, and atrophy as determined by independent t-tests, chi-square analysis, and linear regression (p<0.05). Results101 eyes (63 patients) met inclusion criteria for this study, with mean follow-up duration of 48 months (SD 31 months). 51% of eyes progressed beyond baseline staging during follow-up; among baseline stage 1 eyes, incidence of atrophy was 0.068/person-year; incidence of CNV was 0.022/person-year. Risk factors for worse final VA were baseline presence of vitreomacular traction (VMT) (p=0.006), ellipsoid zone attenuation (p=0.024), increased lesion height and width (p<0.001). Predictors of progression include diabetes mellitus (p=0.012), statin use (p=0.031), presence of hyperreflective foci (p=0.012), and increased lesion width and volume (p=0.034, p=0.040). Predictors of atrophy include the baseline presence of VMT (p=0.018), decreased choroidal thickness (p=0.027), and greater maximal height, width, and volume of the lesion (p=0.031, p=0.020, p=0.009, respectively). Lower baseline VA (p=0.031) and increased lesion volume (p=0.042) were associated with CNV. ConclusionsClinical and OCT imaging features at baseline may prove useful in stratifying patient risk for progression, atrophy, CNV, and worse VA. Features such as statin use, diabetes, baseline VA, and laterality should be accounted for. OCT features such as lesion size, VMT, ellipsoid zone attenuation, choroidal thickness and hyperreflective foci may impart greater risk of poor outcomes. Future prospective analysis accounting for the time to development of atrophy and CNV is needed.

Early radiologic and metabolic tumour response assessment during combined chemo-radiotherapy for locally advanced NSCLC

BackgroundThe role of early treatment response for patients with locally advanced non-small cell lung cancer (LA-NSCLC) treated with concurrent chemo-radiotherapy (cCRT) is unclear. The study aims to investigate the predictive value of response to induction chemotherapy (iCX) and the correlation with pattern of failure (PoF). Materials and methodsPatients with LA-NSCLC treated with cCRT were included for analyses (n = 276). Target delineations were registered from radiotherapy planning PET/CT to diagnostic PET/CT, in between which patients received iCX. Volume, sphericity, and SUVpeak were extracted from each scan. First site of failure was categorised as loco-regional (LR), distant (DM), or simultaneous LR+M (LR+M). Fine and Gray models for PoF were performed: a baseline model (including performance status (PS), stage, and histology), an image model for squamous cell carcinoma (SCC), and an image model for non-SCC. Parameters included PS, volume (VOL) of tumour, VOL of lymph nodes, ΔVOL, sphericity, SUVpeak, ΔSUVpeak, and oligometastatic disease. ResultsMedian follow-up was 7.6 years. SCC had higher sub-distribution hazard ratio (sHR) for LRF (sHR = 2.771 [1.577:4.87], p < 0.01) and decreased sHR for DM (sHR = 0.247 [0.125:0.485], p < 0.01). For both image models, high diagnostic SUVpeak increased risk of LRF (sHR = 1.059 [1.05:1.106], p < 0.01 for SCC, sHR = 1.12 [1.03:1.21], p < 0.01 for non-SCC). Patients with SCC and less decrease in VOL had higher sHR for DM (sHR = 1.025[1.001:1.048] pr. % increase, p = 0.038). ConclusionPoor response in disease volume was correlated with higher sHR of DM for SCC, no other clear correlation of response and PoF was observed. Histology significantly correlated with PoF with SCC prone to LRF and non-SCC prone to DM as first site of failure. High SUVpeak at diagnosis increased the risk of LRF for both histologies.

Maintenance therapy for chronic lymphocytic leukaemia.

Maintenance therapy for chronic lymphocytic leukaemia.