Reduction In Survival Time Research Articles

Endogeneity of pedestrian survival time and emergency medical service response time: Variations across disadvantaged and non-disadvantaged communities

The Vision Zero-Safe Systems Approach prioritizes fast access to Emergency Medical Services (EMS) to improve the survivability of road users in transportation crashes, especially concerning the recent increase in pedestrian-involved crashes. Pedestrian crashes resulting in immediate or early death are considerably more severe than those taking longer. The time gap between injury and fatality is known as survival time, and it heavily relies on EMS response time. The characteristics of the crash location may be associated with EMS response and survival time. A US Department of Transportation initiative identifies communities often facing challenges. Six disadvantaged community (DAC) indicators, including economy, environment, equity, health, resilience, and transportation access, enable an analysis of how survival and EMS response times vary across DACs and non-DACs. To this end, this study created a unique and comprehensive database by linking DACs data with 2017–2021 pedestrian-involved fatal crashes. This study utilizes two-stage residual inclusion models with segmentation for DACs and non-DACs accounting for the endogenous relationship between EMS response and pedestrian survival time. The results indicate that EMS response time is higher and pedestrian survival time is lower in DACs than in non-DACs. A delayed EMS response time is associated with a greater reduction in survival time in DACs compared to non-DACs. Factors, e.g., nighttime and interstate crashes, contribute to higher EMS response time, while pedestrian drugs, driver speeding, and hit-and-run behaviors are associated with a greater reduction in survival time in DACs than non-DACs. The implications of the findings are discussed in the paper.

Association between echocardiographic features, troponin levels, and survival time in hospitalized COVID-19 patients with cardiovascular events

IntroductionThis study aims to explore the predictive roles of echocardiographic parameters and biomarkers in determining outcomes among hospitalized COVID-19 patients experiencing cardiovascular events. MethodsA retrospective cohort study was conducted involving 49 COVID-19 patients who encountered cardiovascular events during hospitalization and underwent echocardiography. Our findings revealed notable associations between echocardiographic parameters and survival time. ResultsA decrease in left ventricular ejection fraction (LVEF) of 10% was linked to a 20% reduction in survival time (TR: 0.80, 95% CI: 0.67 – 0.96, p = 0.017). Similarly, an increase in left ventricular (LV) volume by 10 mL was associated with a 9% decrease in survival time (TR: 0.91, 95% CI: 0.84 – 0.98, p = 0.011). Moreover, an increase in left atrial (LA) volume by 10 mL corresponded to an 8% decrease in survival time (TR: 0.92, 95% CI: 0.86 – 0.99, p = 0.026). Additionally, each 1 cm increase in right ventricular (RV) diameter was linked to a 22% reduction in survival time (TR: 0.78, 95% CI: 0.61 – 0.99, p = 0.043). Furthermore, a 10 mL increase in right atrial (RA) volume was associated with a 12% decrease in survival time (TR: 0.88, 95% CI: 0.78 – 0.98, p = 0.017). Notably, a tenfold rise in troponin levels was linked to a 33% decrease in survival time (TR: 0.67, 95% CI: 0.48 – 0.93, p = 0.014). ConclusionsOur study emphasizes the significant associations between various echocardiographic parameters and troponin levels with reduced survival time among COVID-19 patients experiencing cardiovascular events. These findings highlight the potential utility of echocardiography and troponin assessment in predicting outcomes and guiding management strategies in this patient population.

Analysis of the survival time of patients with heart failure with reduced ejection fraction: a Bayesian approach via a competing risk parametric model

PurposeHeart failure (HF) is a widespread ailment and is a primary contributor to hospital admissions. The focus of this study was to identify factors affecting the extended-term survival of patients with HF, anticipate patient outcomes through cause-of-death analysis, and identify risk elements for preventive measures.MethodsA total of 435 HF patients were enrolled from the medical records of the Rajaie Cardiovascular Medical and Research Center, covering data collected between March and August 2018. After a five-year follow-up (July 2023), patient outcomes were assessed based on the cause of death. The survival analysis was performed with the AFT method with the Bayesian approach in the presence of competing risks.ResultsBased on the results of the best model for HF-related mortality, age [time ratio = 0.98, confidence interval 95%: 0.96–0.99] and ADHF [TR = 0.11, 95% (CI): 0.01–0.44] were associated with a lower survival time. Chest pain in HF-related mortality [TR = 0.41, 95% (CI): 0.10–0.96] and in non-HF-related mortality [TR = 0.38, 95% (CI): 0.12–0.86] was associated with a lower survival time. The next significant variable in HF-related mortality was hyperlipidemia (yes): [TR = 0.34, 95% (CI): 0.13–0.64], and in non-HF-related mortality hyperlipidemia (yes): [TR = 0.60, 95% (CI): 0.37–0.90]. CAD [TR = 0.65, 95% (CI): 0.38–0.98], CKD [TR = 0.52, 95% (CI): 0.28–0.87], and AF [TR = 0.53, 95% (CI): 0.32–0.81] were other variables that were directly related to the reduction in survival time of patients with non-HF-related mortality.ConclusionThe study identified distinct predictive factors for overall survival among patients with HF-related mortality or non-HF-related mortality. This differentiated approach based on the cause of death contributes to the estimation of patient survival time and provides valuable insights for clinical decision-making.

Efficacy of binary mixtures and antagonistic effect of Azadirachta indica on Afranamum melegueta against helminth parasites of fish in Epe lagoon

This research aims to investigate the efficacy of binary mixtures and interaction of extracts of Azadirachta indica and Afranamum melegueta in reference with praziquantel at Fish Low Observed Effect Concentration (LOEC) on classes of fish parasite species. An in-vitro study was conducted using binary extract mixtures of A.melegueta and A.indica (ratios 1:3, 1:1 and 3:1) respectively on each of the classes of fish helminth parasites and saline solution was used as the control. Average Survival Time (AST) and percentage Reduction in Survival Time (%RST) as measure of sensitivity were estimated for the parasites at varying toxicities (fish 96 h LC5, LC10, LC50) with reference to praziquantel. Saponin and Terpenoid had the highest presence in ethanol mix (water) in A.indica and A.melegueta. The sensitivities of the parasites to the extracts and praziquantel in decreasing order is; A.melegueta (singly) > Praziquantel > 3:1 mix > 1:1 mix > 1:3 mix > A.indica (singly). Increase in the proportion of A. indica decreases the combined effect of the mixtures on the parasites, thereby, decreasing the effect of A. melegueta when acting singly. Tenuisentis sp, an acanthocephalan showed sensitivity of RST >80 % against A. melegueta (singly) similar to praziquantel, the sensitivity was reduced to RST <80 % with 3:1 mix, and significantly reduced to RST close to 60 % with 1:3 mix. Other parasite species had similar trend. There was significant correlation (r > 0.70) between parasite sensitivities to praziquantel and A.melegueta (singly) as well as its binary mixtures at the fish Low Observed Effect Concentration (LOEC). This indicates that the binary extract mixtures could serve as potential alternatives to the use of chemotherapy considering their potency and wide margin of fish host safety.

Ceruloplasmin is associated with the infiltration of immune cells and acts as a prognostic biomarker in patients suffering from glioma.

Glioma is regarded as a prevalent form of cancer that affects the Central Nervous System (CNS), with an aggressive growth pattern and a low clinical cure rate. Despite the advancement of the treatment strategy of surgical resection, chemoradiotherapy and immunotherapy in the last decade, the clinical outcome is still grim, which is ascribed to the low immunogenicity and tumor microenvironment (TME) of glioma. The multifunctional molecule, called ceruloplasmin (CP) is involved in iron metabolism. Its expression pattern, prognostic significance, and association with the immune cells in gliomas have not been thoroughly investigated. Studies using a variety of databases, including Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and Gliovis, showed that the mRNA and protein expression levels of CP in patients suffering from glioma increased significantly with an increasing glioma grade. Kaplan-Meier (KM) curves and statistical tests highlighted a significant reduction in survival time of patients with elevated CP expression levels. According to Cox regression analysis, CP can be utilized as a stand-alone predictive biomarker in patients suffering from glioma. A significant association between CP expression and numerous immune-related pathways was found after analyzing the data using the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). Tumor Immune Estimation Resource (TIMER) and CIBERSORT analyses indicated a substantial correlation between the CP expression and infiltration of immunocytes in the TME. Additionally, immune checkpoints and CP expression in gliomas showed a favorable correlation. According to these results, patients with glioma have better prognoses and levels of tumor immune cell infiltration when their CP expression is low. As a result, CP could be used as a probable therapeutic target for gliomas and potentially anticipate the effectiveness of immunotherapy.

MODL-39. CHARACTERIZING NON-ENHANCING TUMOR USING MULTI-SHELL DIFFUSION MRI

Abstract Characterizing infiltration in the non-enhancing tumor (NET) is clinically crucial as infiltration leads to progression, and a reduction in survival times. As voxel-wise biopsy of these regions is infeasible, a non-invasive MRI-based identification of infiltration would be a significant contribution. Diffusion MRI (dMRI), with its ability to model different levels of water restriction, as is caused by infiltration and edema, is well positioned to model the NET. This is achieved via multicomparment modeling (MCM) of the dMRI where infiltration, vasogenic edema and healthy tissue (with complex fibers) form the different compartments. Current MCM approaches are either not designed for NET or rely on advanced MRI scans currently not feasible in the clinic. The simplest ball-tensor models, including Hoy 2014 using multi-shell data and FERNET 2020 for single-shell data, consists of a free water compartment that models vasogenic edema and a tensor modeling underlying tissue. These single-tensor methods cannot model complex WM fibers. Our proposed model consists of two steps. First, two bundles are fit: an isotropic bundle with two balls that model isotropic free diffusivity and restricted diffusivity, and a bundle containing stick and zeppelin, corresponding to intra-cellular and extra-cellular diffusion of axons, respectively. Next, a fiber orientation distribution (FOD) is estimated from the fitted parameters. We applied our modeling to multi-shell data from eight patients with glioblastoma, and one patient with a metastatic brain tumor. Our method produces maps corresponding to free water (CSF), restricted diffusion, intra-cellular, and extra-cellular volume fractions. Preliminary results show that restricted diffusivity map of NET comprises 46% of vasogenic metastatic edema compare to 15% of infiltrated GBM edema. In conclusion, we demonstrate that our proposed model shows promise to characterize the NET region of various brain tumors, and distinguishing tumor types. These compartments will provide invaluable radiomic features that no other modality can capture.

Oral Health and Mortality Among Older Adults: A Doubly Robust Survival Analysis

Evidence on the association between oral health and mortality is inconclusive, and few studies have accounted for the nonrandom selection bias in estimating their relationship. This study aims to investigate the link between oral health and mortality in community-dwelling older adults by adjusting for confounding factors with a doubly robust survival estimation. Data came from the third National Health and Nutrition Examination Survey (1988-1994) and were linked to the National Death Index mortality data through December 2015. The analytic sample consisted of 4,880 adults aged ≥60 years. Oral health measures included objective clinical indicators (edentulism, periodontitis, and untreated dental caries) and self-rated oral health. Cox proportional hazards regression models and inverse probability weighting with regression adjustment for observational survival-time estimation were utilized to assess the relationship between oral health and mortality. Analyses were conducted in 2021. Edentulism (average treatment effect= -26.13, 95% CI= -48.69, -3.57) was associated with a reduction in survival time. Periodontal conditions and dental caries were related to all-cause mortality in Cox models but became nonsignificant when inverse probability weighting with regression adjustment survival estimation was applied. Good self-rated oral health was significantly related to an increase in survival time (average treatment effect=21.50; 95% CI= 4.92, 38.07). Both objective and subjective oral health are risk factors for mortality among older adults. Improving access to dental screening and treatment among community-dwelling older adults has the potential to reduce oral health‒related risks of mortality.

Differing effects of parental and natal hosts on the preference and performance of the stored product pests Callosobruchus maculatus and C. analis

Bean beetles (Bruchinae) are a taxon of seed predators and several species are economically significant stored product pests. Seed quality may affect adult life history traits, with consequences for their population dynamics. We investigated if variation in host quality (poor quality: lentil; high quality: mung bean) as experienced by the parental (i.e. the individuals ovipositing) generation and the natal (i.e. the study individuals emerging from the host) generation influenced the preference and performance of Callosobruchus maculatus and C. analis. Both species preferred ovipositing on mung bean regardless of experience. Emergence rate was high for all treatments except for C. maculatus reared on mung, whose offspring did poorly when developing in lentil. The sex ratio of emerging offspring was 1:1 except for C. analis emerging from lentil, which was female biased if the parents were reared on lentil, but male biased if reared on mung. In C. analis, lentil parental host resulted in larger offspring irrespective of natal host, while in C. maculatus larger offspring emerged from mung as natal host. Overall, males emerging from lentils obtained more matings, except with C. maculatus where females had emerged from mung, where there was no preference. Development time for beetles was increased for those with parents reared on mung and for those with lentil natal hosts. For C. analis there was no difference in survival time for those where the parental host was lentil, but when the parental host was mung, then there was a significant reduction in survival time for those whose natal host was also mung, compared to those emerging from lentils. This work shows that predicting the effect of host quality on traits requires more than single-species, single-generation studies, as transgenerational effects can influence the performance and preference of closely related stored product pest species in quite different ways.

Cognitive impairment three months after surgery is an independent predictor of survival time in glioblastoma patients

PurposeCognitive functioning is increasingly investigated for its prognostic value in glioblastoma (GBM) patients, but the association of cognitive status during early adjuvant treatment with survival time is unclear. The aim of this study was to determine whether cognitive performance three months after surgical resection predicted survival time, while using a clinically intuitive time ratio (TR) statistic.MethodsNewly diagnosed patients with GBM undergoing resection between November 2010 and February 2018 completed computerized cognitive assessment 3 months after surgery with the CNS Vital Signs battery (8 measures). The association of cognitive performance (continuous Z scores and dichotomous impairment status; impaired vs. unimpaired) with survival time was assessed with multivariate Accelerated Failure Time (AFT) models that also included clinical prognostic factors and covariates related to cognitive performances.Results114 patients were included in the analyses (median survival time 16.4 months). Of the clinical factors, postoperative Karnofsky Performance Status (TR 1.51), surgical (TR 2.20) and non-surgical (TR 1.94) salvage treatment, and pre-surgical tumor volume (cm3, TR 1.003) were significant independent predictors of survival time. Independently of the base model factors and covariates, impairment on Stroop test I and Stroop test III estimated 23% and 26% reduction of survival time (TR 0.77, TR 0.74) respectively, as compared to unimpaired performance.ConclusionThese findings suggest that impaired performances on tests of executive control and processing speed in the early phase of adjuvant treatment can reflect a worse prognostic outlook rather than an early treatment effect, and their assessment might allow for early refinement of current prognostic stratification.

Disease-modifying effects of an SCAF4 structural variant in a predominantly SOD1 ALS cohort.

ObjectiveTo test the hypothesis that rs573116164 will have disease-modifying effects in patients with superoxide dismutase 1 (SOD1) familial amyotrophic lateral sclerosis (fALS), we characterized rs573116164 within a cohort of 190 patients with fALS and 560 healthy age-matched controls to assess the variant for association with various measures of disease.MethodsUsing a previously described bioinformatics evaluation algorithm, a polymorphic short structural variant associated with SOD1 was identified according to its theoretical effect on gene expression. An 12–18 poly-T repeat (rs573116164) within the 3′ untranslated region of serine and arginine rich proteins-related carboxy terminal domain associated factor 4 (SCAF4), a gene that is adjacent to SOD1, was assessed for disease association and influence on survival and age at onset in an fALS cohort using PCR, Sanger sequencing, and capillary separation techniques for allele detection.ResultsIn a North American cohort of predominantly SOD1 fALS patients (n =190) and age-matched healthy controls (n = 560), we showed that carriage of an 18T SCAF4 allele was associated with disease within this cohort (odds ratio [OR] 6.6; 95% confidence interval [CI] 3.9–11.2; p = 4.0e-11), but also within non-SOD1 cases (n = 27; OR 5.3; 95% CI 1.9–14.5; p = 0.0014). This finding suggests genetically SOD1-independent effects of SCAF4 on fALS susceptibility. Furthermore, carriage of an 18T allele was associated with a 26-month reduction in survival time (95% CI 6.6–40.8; p = 0.014), but did not affect age at onset of disease.ConclusionsThe findings in this fALS cohort suggest that rs573116164 could have SOD1-independent and broader relevance in ALS, warranting further investigation in other fALS and sporadic ALS cohorts, as well as studies of functional effects of the 18T variant on gene expression.

Micropapillary pattern is associated with the development of brain metastases and the reduction of survival time in EGFR-mutation lung adenocarcinoma patients with surgery

ObjectiveThe role of micropapillary pattern (MIP) in EGFR-mutated NSCLC patients with brain metastases (BM) after complete surgical resection still remains unclear. Therefore, a retrospective study was conducted to evaluate the role of MIP in those patients. MethodsThis study included 332 stage I-III patients with EGFR-mutant lung adenocarcinoma and complete resection. Patients were classified in four groups: the MIP-positive patients without BM development, the MIP-negative patients without BM development, the MIP-positive patients with BM development and the MIP-negative patients with BM development. Intracranial disease-free survival (iDFS), systemic disease-free survival (DFS) and overall survival (OS) were evaluated. ResultsThe median OS in the whole group was 70 months. The patients with MIP show inferior DFS (13 months vs. 22 months; P < 0.001) and OS (56 months vs. 74 months; P < 0.001). Furthermore, BM development was more likely to be found in patients with MIP (P = 0.001). In addition, the MIP-positive patients showed a significantly shorter iDFS compared with MIP-negative patients (14.5 months vs. 26 months; P < 0.001). Furthermore, the MIP-positive patients had significantly inferior iDFS in both BM as first line development groups (13 months vs. 19 months; P < 0.001) and BM as non-first line development groups (18 months vs. 33 months; P = 0.007). ConclusionsMIP was related to the earlier recurrence and shortened survival time. In addition, MIP was an independent poor prognostic factor for the increase of BM rate and the shortened time of BM development after surgery.

Optimization of irradiation dose to Aedes aegypti and Ae. albopictus in a sterile insect technique program.

The sterile insect technique (SIT) may offer a means to control the transmission of mosquito borne diseases. SIT involves the release of male insects that have been sterilized by exposure to ionizing radiation. We determined the effects of different doses of radiation on the survival and reproductive capacity of local strains of Aedes aegypti and Ae. albopictus in southern Mexico. The survival of irradiated pupae was invariably greater than 90% and did not differ significantly in either sex for either species. Irradiation had no significant adverse effects on the flight ability (capacity to fly out of a test device) of male mosquitoes, which consistently exceeded 91% in Ae. aegypti and 96% in Ae. albopictus. The average number of eggs laid per female was significantly reduced in Ae. aegypti at doses of 15 and 30 Gy and no eggs were laid by females that had been exposed to 50 Gy. Similarly, in Ae. albopictus, egg production was reduced at doses of 15 and 25 Gy and was eliminated at 35 Gy. In Ae. aegypti, fertility in males was eliminated at 70 Gy and was eliminated at 30 Gy in females, whereas in Ae. albopictus, the fertility of males that mated with untreated females was almost zero (0.1%) in the 50 Gy treatment and female fertility was eliminated at 35 Gy. Irradiation treatments resulted in reduced ovary length and fewer follicles in both species. The adult median survival time of both species was reduced by irradiation in a dose-dependent manner. However, sterilizing doses of 35 Gy and 50 Gy resulted in little reduction in survival times of males of Ae. albopictus and Ae. aegypti, respectively, indicating that these doses should be suitable for future evaluations of SIT-based control of these species. The results of the present study will be applied to studies of male sexual competitiveness and to stepwise evaluations of the sterile insect technique for population suppression of these vectors in Mexico.

Abstract P6-05-06: Estrogen induced miR-489 acts as a negative feedback to confine uncontrolled estrogen signaling and cell proliferation in breast cancer

Abstract Estrogen induced miR-489 acts as a negative feedback to confine uncontrolled estrogen signaling and cell proliferation in breast cancer. Mithil Soni1,2, Yogin Patel1,2,3, Ryann Shealy1, Hexin Chen1,2,4. 1Dept. of Biological Sciences, University of South Carolina, 2Center for colon cancer research, 3current location, National cancer institute, surgery branch, 4corrosponding author. Approximately 75% of diagnosed breast cancer tumors are Estrogen receptor positive tumors and are associated with better prognosis due to response to hormonal therapies. However, around 40% of patients relapse after hormonal therapies. Identification of novel molecular targets is necessary to combat such resistant tumors. In the current study, using microarray, qRT-PCR, western blot, luciferase reporter assay and immunofluorescence, we found that miR-489 is an estrogen regulated miRNA that negatively regulates estrogen signaling. Depletion of miR-489 using Anti-miR-489 siRNA or CRISPR-Cas9 significantly increased estrogen induced proliferation, colony formation ability and stem like cell population. Loss of miR-489 also induced estrogen independent proliferation. Mechanistically we found that depletion of miR-489 enhanced nuclear localization of estrogen receptor while restoration of miR-489 increased cytosolic ER and inhibited estrogen induced transcription. Furthermore, we found that miR-489 depletion also increases estrogen independent growth through activation of MAPK and PI3K-AKT pathway. We also observed loss of miR-489 in tamoxifen resistance breast cancer cell line and found increased resistance to tamoxifen upon miR-489 inhibition while miR-489 restoration sensitized Tamoxifen resistant cell lines. Clinical analysis of estrogen receptor positive breast cancer patient showed that ER+ve breast cancers with low miR-489 expression represents aggressive cancers with significant reduction in survival time. In summary, these results indicate potential role of miR-489 as a biomarker to predict aggressiveness of ER+ve breast cancer and response to tamoxifen therapy and can potentially be used as a therapeutic agent to treat or sensitize tamoxifen resistant tumors. Citation Format: Soni M, Patel Y, Shealy R, Chen H. Estrogen induced miR-489 acts as a negative feedback to confine uncontrolled estrogen signaling and cell proliferation in breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-05-06.

N-Linked Glycan Branching and Fucosylation Are Increased Directly in Hcc Tissue As Determined through in Situ Glycan Imaging.

Hepatocellular carcinoma (HCC) remains as the fifth most common cancer in the world and accounts for more than 700,000 deaths annually. Changes in serum glycosylation have long been associated with this cancer but the source of that material is unknown and direct glycan analysis of HCC tissues has been limited. Our laboratory previously developed a method of in situ tissue based N-linked glycan imaging that bypasses the need for microdissection and solubilization of tissue prior to analysis. We used this methodology in the analysis of 138 HCC tissue samples and compared the N-linked glycans in cancer tissue with either adjacent untransformed or tissue from patients with liver cirrhosis but no cancer. Ten glycans were found significantly elevated in HCC tissues as compared to cirrhotic or adjacent tissue. These glycans fell into two major classes, those with increased levels of fucosylation and those with increased levels of branching with or without any fucose modifications. In addition, increased levels of fucosylated glycoforms were associated with a reduction in survival time. This work supports the hypothesis that the increased levels of fucosylated N-linked glycans in HCC serum are produced directly from the cancer tissue.

Plasma cholesterol level determines in vivo prion propagation

Transmissible spongiform encephalopathies are fatal neurodegenerative diseases with an urgent need for therapeutic and prophylactic strategies. At the time when the blood-mediated transmission of prions was demonstrated, in vitro studies indicated a high binding affinity of the scrapie prion protein (PrPSc) with apoB-containing lipoproteins, i.e., the main carriers of cholesterol in human blood. The aim of the present study was to explore the relationship between circulating cholesterol-containing lipoproteins and the pathogenicity of prions in vivo. We showed that, in mice with a genetically engineered deficiency for the plasma lipid transporter, phospholipid transfer protein (PLTP), abnormally low circulating cholesterol concentrations were associated with a significant prolongation of survival time after intraperitoneal inoculation of the 22L prion strain. Moreover, when circulating cholesterol levels rose after feeding PLTP-deficient mice a lipid-enriched diet, a significant reduction in survival time of mice together with a marked increase in the accumulation rate of PrPSc deposits in their brain were observed. Our results suggest that the circulating cholesterol level is a determinant of prion propagation in vivo and that cholesterol-lowering strategies might be a successful therapeutic approach for patients suffering from prion diseases.

Neural predictors of substance use disorders in Young adulthood

Offspring from multiplex, alcohol-dependent families are at heightened risk for substance use disorders (SUDs) in adolescence and young adulthood. These high-risk offspring have also been shown to have atypical structure and function of brain regions implicated in emotion regulation, social cognition, and reward processing. This study assessed the relationship between amygdala and orbitofrontal cortex (OFC) volumes obtained in adolescence and SUD outcomes in young adulthood among high-risk offspring and low-risk controls. A total of 78 participants (40 high-risk; 38 low-risk) from a longitudinal family study, ages 8–19, underwent magnetic resonance imaging; volumes of the amygdala and OFC were obtained with manual tracing. SUD outcomes were assessed at approximately yearly intervals. Cox regression survival analyses were used to assess the effect of regional brain volumes on SUD outcomes. The ratio of OFC to amygdala volume significantly predicted SUD survival time across the sample; reduction in survival time was seen in those with smaller ratios for both high-risk and low-risk groups. Morphology of prefrontal relative to limbic regions in adolescence prospectively predicts age of onset for substance use disorders.

Survival of teeth treated with cast post and cores: A retrospective analysis over an observation period of up to 19.5 years

Statement of ProblemScientific data about the long-term survival of teeth treated with cast post and cores are scarce. Retrospective studies often use different target events for their analyses. A comparison is therefore complicated. For associated tooth-, jaw-, and patient-related factors little evidence exists as to their effect on survival. PurposeThe purpose of this study was to extend the knowledge on the survival of teeth treated with cast post and cores for observation periods of more than 10 years. A decrease or increase in survival times according to the presence or absence of associated parameters needs to be evaluated. Material and MethodsA retrospective evaluation was conducted of all cast post and cores inserted in 1 university clinic between January 1992 and June 2011. A Kaplan-Meier survival analysis was carried out by using extraction as the target event. The survival curves for different tooth types, the presence or absence of adjacent teeth, and the prosthetic restoration of the respective jaws were compared by using the log-rank test (α=.05). A Cox regression model was calculated for multivariate analyses. ResultsA total of 717 cast post and cores for 343 patients were recorded. The mean survival time was 13.5 years. A statistically significant decrease in survival times was found for canines (11.9 years) and premolars (13.4 years) versus molars (14.1 years), no adjacent teeth (10.6 years) versus at least 1 adjacent tooth (13.8 years), and the restoration with removable dental prostheses (12.5 years) versus fixed dental prostheses and single crowns (13.9 years). The largest reduction in survival time was found for teeth being used as an abutment for a double crown-retained removable partial dental prosthesis (telescopic denture) (9.8 years). Tooth type and adjacent tooth status remained as significant variables within the multivariate Cox regression model. ConclusionsCast post and cores have an acceptable long-term survival time. Because different factors may influence survival, considering these factors in treatment planning may increase the long-term success of these restorations.

Survival and weight change among adult individuals of Periplaneta americana (Linnaeus, 1758) (Blattaria, Blattidae) subject to various stress conditions

Periplaneta americana is a species of great importance to public health, since it can act as a vector of many pathogens and it reaches large populations in urban environments. This is probably due to its ability to resist starvation and desiccation. This study aimed to evaluate the effects of absence of water and food on survival and weight change among adult P. americana individuals and check whether the initial weight of individuals influences on their survival. Four groups having twenty P. americana couples were formed and subject to: I) no water or food; II) no food; III) no water; and IV) control group. Insects were isolated according to the groups, which were weighed at the beginning and end of the stress conditions. They remained under these conditions until all individuals in each test group were dead. Stress conditions caused reduction in survival time when compared to the control group. Adults with higher body mass survived longer when deprived only of food, while among those lacking water, weight had no influence on survival. Total weight loss was greater among individuals deprived of water than those deprived only of food.

Direct and indirect effects of development temperature on adult water balance traits of Eldana saccharina (Lepidoptera: Pyralidae)

For water balance physiology, prior thermal history may pre-condition individuals to be more sparing in their water consumption at a given temperature upon subsequent exposure, or alternatively, may relax constraints on water economy leading to more frivolous use of water at a later stage. Here we test these two major alternative hypotheses on the adult life stage of Eldana saccharina Walker (Lepidoptera: Pyralidae) by exposing them to different rearing temperatures (acclimation treatments) during immature stage development and comparing adult physiological performance (water loss rates, time to death) and water-balance related traits (body size, water content). Developmental acclimation at 20°C, 25°C or 30°C throughout the larval and pupal stage resulted in significant effects on water balance traits of two-day old adult male and female E. saccharina. In summary, lower developmental acclimation resulted in a 61% increase in water loss rate (range: 0.78mg/h) and a 26% reduction in survival time (6.8h). Initial body water content and initial body mass generally remained similar across male acclimation groups while higher developmental acclimation reduced female body mass significantly. High developmental acclimation resulted in significantly higher (∼23%) body water content at death possibly indicating a better overall ability to withstand desiccating conditions, although there was no difference in time to death compared to the intermediate group. The relationship between time to death and body mass was altered from negative at 25°C and 30°C acclimation, to positive at 20°C acclimation. These results show pervasive effects of rearing temperature on adult physiological performance, with low temperature relaxing what appear to be substantial constraints on water economy at higher temperatures for E. saccharina. Furthermore, they are significant for understanding the recent range expansion of E. saccharina into cooler environments in southern Africa and for management of the species.

A High-Fat Diet Activates Oncogenic Kras and COX2 to Induce Development of Pancreatic Ductal Adenocarcinoma in Mice

Obesity is a risk factor for pancreatic ductal adenocarcinoma (PDAC), but it is not clear how obesity contributes to pancreatic carcinogenesis. The oncogenic form of KRAS is expressed during early stages of PDAC development and is detected in almost all of these tumors. However, there is evidence that mutant KRAS requires an additional stimulus to activate its full oncogenic activity and that this stimulus involves the inflammatory response. We investigated whether the inflammation induced by a high-fat diet, and the accompanying up-regulation of cyclooxygenase-2 (COX2), increases Kras activity during pancreatic carcinogenesis in mice. We studied mice with acinar cell-specific expression of KrasG12D (LSL-Kras/Ela-CreERT mice) alone or crossed with COX2 conditional knockout mice (COXKO/LSL-Kras/Ela-CreERT). We also studied LSL-Kras/PDX1-Cre mice. All mice were fed isocaloric diets with different amounts of fat, and a COX2 inhibitor was administered to some LSL-Kras/Ela-CreERT mice. Pancreata were collected from mice and analyzed for Kras activity, levels of phosphorylated extracellular-regulated kinase, inflammation, fibrosis, pancreatic intraepithelial neoplasia (PanIN), and PDACs. Pancreatic tissues from LSL-Kras/Ela-CreERT mice fed high-fat diets (HFDs) had increased Kras activity, fibrotic stroma, and numbers of PanINs and PDACs than LSL-Kras/Ela-CreERT mice fed control diets; the mice fed the HFDs also had shorter survival times than mice fed control diets. Administration of a COX2 inhibitor to LSL-Kras/Ela-CreERT mice prevented these effects of HFDs. We also observed a significant reduction in survival times of mice fed HFDs. COXKO/LSL-Kras/Ela-CreERT mice fed HFDs had no evidence for increased numbers of PanIN lesions, inflammation, or fibrosis, as opposed to the increases observed in LSL-Kras/Ela-CreERT mice fed HFDs. In mice, an HFD can activate oncogenic Kras via COX2, leading to pancreatic inflammation and fibrosis and development of PanINs and PDAC. This mechanism might be involved in the association between risk for PDAC and HFDs.