Cost Savings of Whole Blood Versus Component Therapy at a Community Level 1 Trauma Center.

BACKGROUND: Blood product component-only resuscitation (CORe) has been the standard of practice in both military and civilian trauma care with a 1:1:1 ratio used in attempt to recreate whole blood (WB) until recent data demonstrated WB to confer a survival advantage, leading to the emergence of WB as the contemporary resuscitation strategy of choice. Little is known about the cost and waste reduction associated with WB vs CORe. METHODS: This study is a retrospective single-center review of adult trauma patients admitted to a community trauma center who received WB or CORe as part of their massive transfusion protocol (MTP) resuscitation from 2017 to 2021. The WB group received a minimum of one unit WB while CORe received no WB. Univariate and multivariate analyses were completed. Statistical analysis was conducted using a 95% confidence level. Non-normally distributed, continuous data were analyzed using the Wilcoxon rank sum test. RESULTS: 576 patients were included (201 in WB and 375 in CORe). Whole blood conveyed a survival benefit vs CORe (OR 1.49 P < .05, 1.02-2.17). Whole blood use resulted in an overall reduction in products prepared (25.8%), volumes transfused (16.5%), product waste (38.7%), and MTP activation (56.3%). Cost savings were $849 923 annually and $3 399 693 over the study period. DISCUSSION: Despite increased patient volumes over the study period (43.7%), the utilization of WB as compared to CORe resulted in an overall $3.39 million cost savings while improving mortality. As such, we propose WB should be utilized in all resuscitation strategies for the exsanguinating trauma patient.

Interpersonal Violence and Social Determinants of Health.

Social determinants of health (SDOH) influence patient outcomes and risk assessment. This study focuses on interpersonal violence, trauma outcomes, and SDOH. We hypothesized patients with lower SDOH experience worse trauma outcomes and present from higher-risk communities. Demographics, SDOH, and outcomes for patients admitted to surgical trauma suffering interpersonal violence were collected and analyzed. Home addresses were plotted, identifying areas of need compared with Area Deprivation Index (ADI). Only 18.8% of patients had documented SDOH, yielding small sample size. Analysis revealed no statistically significant associations (P < .05) between SDOH and trauma outcomes, including ICU length of stay and stress concern (P = .0804). Heat mapping revealed several hot spots across our catchment area, correlating with higher-ranked ADIs and increased deprivation. This study demonstrated SDOH can bring value in determining patient risk, emphasizing resource dedication to documenting these factors. Home addresses in conjunction with ADIs can ascertain areas for resource allocation within communities.

Identification and apportionment of groundwater nitrate sources in Chakari Plain (Afghanistan).

The Chakari alluvial aquifer is the primary source of water for human, animal, and irrigation applications. In this study, the geochemistry of major ions and stable isotope ratios (δ2H-H2O, δ18O-H2O, δ15N-NO3̄, and δ18O-NO3̄) of groundwater and river water samples from the Chakari Plain were analyzed to better understand characteristics of nitrate. Herein, we employed nitrate isotopic ratios and BSIMM modeling to quantify the proportional contributions of major sources of nitrate pollution in the Chakari Plain. The cross-plot diagram of δ15N-NO3̄ against δ18O-NO3̄ suggests that manure and sewage are the main source of nitrate in the plain. Nitrification is the primary biogeochemical process, whereas denitrification did not have a significant influence on biogeochemical nitrogen dynamics in the plain. The results of this study revealed that the natural attenuation of nitrate in groundwater of Chakari aquifer is negligible. The BSIMM results indicate that nitrate originated mainly from sewage and manure (S&M, 75‰), followed by soil nitrogen (SN, 13‰), and chemical fertilizers (CF, 9.5‰). Large uncertainties were shown in the UI90 values for S&M (0.6) and SN (0.47), whereas moderate uncertainty was exhibited in the UI90 value for CF (0.29). The findings provide useful insights for decision makers to verify groundwater pollution and develop a sustainable groundwater management strategy.

Activated granulocytes and inflammatory cytokine signaling drive T-cell lymphoma progression and disease symptoms.

Peripheral T-cell lymphomas (PTCLs), especially angioimmunoblastic and follicular TCLs, have a dismal prognosis because of the lack of efficient therapies, and patients' symptoms are often dominated by an inflammatory phenotype, including fever, night sweats, weight loss, and skin rash. In this study, we investigated the role of inflammatory granulocytes and activated cytokine signaling on T-cell follicular helper-type PTCL (TFH-PTCL) disease progression and symptoms. We showed that ITK-SYK-driven murine PTCLs and primary human TFH-PTCL xenografts both induced inflammation in mice, including murine neutrophil expansion and massive cytokine release. Granulocyte/lymphoma interactions were mediated by positive autoregulatory cytokine loops involving interferon gamma (CD4+ malignant T cells) and interleukin 6 (IL-6; activated granulocytes), ultimately inducing broad JAK activation (JAK1/2/3 and TYK2) in both cell types. Inflammatory granulocyte depletion via antibodies (Ly6G), genetic granulocyte depletion (LyzM-Cre/MCL1flox/flox), or IL-6 deletion within microenvironmental cells blocked inflammatory symptoms, reduced lymphoma infiltration, and enhanced mouse survival. Furthermore, unselective JAK inhibitors (ruxolitinib) inhibited both TCL progression and granulocyte activation in various PTCL mouse models. Our results support the important role of granulocyte-driven inflammation, cytokine-induced granulocyte/CD4+ TCL interactions, and an intact JAK/STAT signaling pathway for TFH-PTCL development and also support broad JAK inhibition as an effective treatment strategy in early disease stages.

Lymphoma-Associated Biomarkers Are Increased in Current Smokers in Twin Pairs Discordant for Smoking.

Smoking is associated with a moderate increased risk of Hodgkin and follicular lymphoma. To understand why, we examined lymphoma-related biomarker levels among 134 smoking and non-smoking twins (67 pairs) ascertained from the Finnish Twin Cohort. Previously collected frozen serum samples were tested for cotinine to validate self-reported smoking history. In total, 27 immune biomarkers were assayed using the Luminex Multiplex platform (R & D Systems). Current and non-current smokers were defined by a serum cotinine concentration of >3.08 ng/mL and ≤3.08 ng/mL, respectively. Associations between biomarkers and smoking were assessed using linear mixed models to estimate beta coefficients and standard errors, adjusting for age, sex and twin pair as a random effect. There were 55 never smokers, 43 current smokers and 36 former smokers. CCL17/TARC, sgp130, haptoglobin, B-cell activating factor (BAFF) and monocyte chemoattractant protein-1 (MCP1) were significantly (p < 0.05) associated with current smoking and correlated with increasing cotinine concentrations (Ptrend < 0.05). The strongest association was observed for CCL17/TARC (Ptrend = 0.0001). Immune biomarker levels were similar in former and never smokers. Current smoking is associated with increased levels of lymphoma-associated biomarkers, suggesting a possible mechanism for the link between smoking and risk of these two B-cell lymphomas.

Educational attainment of same-sex and opposite-sex dizygotic twins: An individual-level pooled study of 19 twin cohorts.

Comparing twins from same- and opposite-sex pairs can provide information on potential sex differences in a variety of outcomes, including socioeconomic-related outcomes such as educational attainment. It has been suggested that this design can be applied to examine the putative role of intrauterine exposure to testosterone for educational attainment, but the evidence is still disputed. Thus, we established an international database of twin data from 11 countries with 88,290 individual dizygotic twins born over 100 years and tested for differences between twins from same- and opposite-sex dizygotic pairs in educational attainment. Effect sizes with 95% confidence intervals (CI) were estimated by linear regression models after adjusting for birth year and twin study cohort. In contrast to the hypothesis, no difference was found in women (ß = -0.05 educational years, 95% CI -0.11, 0.02). However, men with a same-sex co-twin were slightly more educated than men having an opposite-sex co-twin (ß = 0.14 educational years, 95% CI 0.07, 0.21). No consistent differences in effect sizes were found between individual twin study cohorts representing Europe, the USA, and Australia or over the cohorts born during the 20th century, during which period the sex differences in education reversed favoring women in the latest birth cohorts. Further, no interaction was found with maternal or paternal education. Our results contradict the hypothesis that there would be differences in the intrauterine testosterone levels between same-sex and opposite-sex female twins affecting education. Our findings in men may point to social dynamics within same-sex twin pairs that may benefit men in their educational careers.

Increased burden of familial-associated early-onset cancer risk among minority Americans compared to non-Latino Whites.

Background: The role of race/ethnicity in genetic predisposition of early-onset cancers can be estimated by comparing family-based cancer concordance rates among ethnic groups. Methods: We used linked California health registries to evaluate the relative cancer risks for first-degree relatives of patients diagnosed between ages 0 and 26, and the relative risks of developing distinct second primary malignancies (SPMs). From 1989 to 2015, we identified 29,631 cancer patients and 62,863 healthy family members. We calculated the standardized incident ratios (SIRs) of early-onset primary cancers diagnosed in proband siblings and mothers, as well as SPMs detected among early-onset patients. Analyses were stratified by self-identified race/ethnicity. Results: Given probands with cancer, there were increased relative risks of any cancer for siblings and mothers (SIR = 3.32; 95% confidence interval [CI]: 2.85-3.85) and of SPMs (SIR = 7.27; 95% CI: 6.56-8.03). Given a proband with solid cancer, both Latinos (SIR = 4.98; 95% CI: 3.82-6.39) and non-Latino Blacks (SIR = 7.35; 95% CI: 3.36-13.95) exhibited significantly higher relative risk of any cancer in siblings and mothers when compared to non-Latino White subjects (SIR = 3.02; 95% CI: 2.12-4.16). For hematologic cancers, higher familial risk was evident for Asian/Pacific Islanders (SIR = 7.56; 95% CI: 3.26-14.90) compared to non-Latino whites (SIR = 2.69; 95% CI: 1.62-4.20). Conclusions: The data support a need for increased attention to the genetics of early-onset cancer predisposition and environmental factors in race/ethnic minority families in the United States. Funding: This work was supported by the V Foundation for funding this work (Grant FP067172).

Dietary glycemic index, glycemic load, and lung cancer risk: A case-control study in Los Angeles County.

BACKGROUND: Although there is some evidence of positive associations between both the glycemic index (GI) and glycemic load (GL) with cancer risk, the relationships with lung cancer risk remain largely unexplored. We evaluated the associations between GI and GL with lung cancer. METHODS: The analyses were performed using data from a population-based case-control study recruited between 1999 and 2004 in Los Angeles County. Dietary factors were collected from 593 incident lung cancer cases and 1026 controls using a modified food frequency questionnaire. GI and GL were estimated using a food composition table. Adjusted odds ratios (ORs) and 95 % confidence intervals (CI) were estimated using unconditional logistic regression adjusting for potential confounders. RESULTS: Dietary GI was positively associated with lung cancer (OR for upper vs. lower tertile = 1.62; 95 % CI: 1.17, 2.25). For histologic subtypes, positive associations were observed between GI and adenocarcinoma (OR for upper vs. lower tertile = 1.82; 95 % CI: 1.22, 2.70) and small cell carcinoma (OR for upper vs. lower tertile = 2.68; 95 % CI: 1.25, 5.74). No clear association between GL and lung cancer was observed. CONCLUSION: These findings suggest that high dietary GI was associated with increased lung cancer risk, and the positive associations were observed for both lung adenocarcinoma and small cell lung carcinoma. Replication in an independent dataset is merited for a broader interpretation of our results.

Genetic and environmental variation in educational attainment: an individual-based analysis of 28 twin cohorts.

We investigated the heritability of educational attainment and how it differed between birth cohorts and cultural-geographic regions. A classical twin design was applied to pooled data from 28 cohorts representing 16 countries and including 193,518 twins with information on educational attainment at 25 years of age or older. Genetic factors explained the major part of individual differences in educational attainment (heritability: a2 = 0.43; 0.41-0.44), but also environmental variation shared by co-twins was substantial (c2 = 0.31; 0.30-0.33). The proportions of educational variation explained by genetic and shared environmental factors did not differ between Europe, North America and Australia, and East Asia. When restricted to twins 30 years or older to confirm finalized education, the heritability was higher in the older cohorts born in 1900-1949 (a2 = 0.44; 0.41-0.46) than in the later cohorts born in 1950-1989 (a2 = 0.38; 0.36-0.40), with a corresponding lower influence of common environmental factors (c2 = 0.31; 0.29-0.33 and c2 = 0.34; 0.32-0.36, respectively). In conclusion, both genetic and environmental factors shared by co-twins have an important influence on individual differences in educational attainment. The effect of genetic factors on educational attainment has decreased from the cohorts born before to those born after the 1950s.

Genetic and environmental influences on human height from infancy through adulthood at different levels of parental education.

Genetic factors explain a major proportion of human height variation, but differences in mean stature have also been found between socio-economic categories suggesting a possible effect of environment. By utilizing a classical twin design which allows decomposing the variation of height into genetic and environmental components, we tested the hypothesis that environmental variation in height is greater in offspring of lower educated parents. Twin data from 29 cohorts including 65,978 complete twin pairs with information on height at ages 1 to 69 years and on parental education were pooled allowing the analyses at different ages and in three geographic-cultural regions (Europe, North America and Australia, and East Asia). Parental education mostly showed a positive association with offspring height, with significant associations in mid-childhood and from adolescence onwards. In variance decomposition modeling, the genetic and environmental variance components of height did not show a consistent relation to parental education. A random-effects meta-regression analysis of the aggregate-level data showed a trend towards greater shared environmental variation of height in low parental education families. In conclusion, in our very large dataset from twin cohorts around the globe, these results provide only weak evidence for the study hypothesis.

Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.

Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.

Parental Education and Genetics of BMI from Infancy to Old Age: A Pooled Analysis of 29 Twin Cohorts.

OBJECTIVE: The objective of this study was to analyze how parental education modifies the genetic and environmental variances of BMI from infancy to old age in three geographic-cultural regions. METHODS: A pooled sample of 29 cohorts including 143,499 twin individuals with information on parental education and BMI from age 1 to 79 years (299,201 BMI measures) was analyzed by genetic twin modeling. RESULTS: Until 4 years of age, parental education was not consistently associated with BMI. Thereafter, higher parental education level was associated with lower BMI in males and females. Total and additive genetic variances of BMI were smaller in the offspring of highly educated parents than in those whose parents had low education levels. Especially in North American and Australian children, environmental factors shared by co-twins also contributed to the higher BMI variation in the low education level category. In Europe and East Asia, the associations of parental education with mean BMI and BMI variance were weaker than in North America and Australia. CONCLUSIONS: Lower parental education level is associated with higher mean BMI and larger genetic variance of BMI after early childhood, especially in the obesogenic macro-environment. The interplay among genetic predisposition, childhood social environment, and macro-social context is important for socioeconomic differences in BMI.

DNA methylation patterns of adult survivors of adolescent/young adult Hodgkin lymphoma compared to their unaffected monozygotic twin.

DNA methylation (DNAm) silences gene expression and may play a role in immune dysregulation that is characteristic of adolescent/young adult Hodgkin lymphoma (AYAHL). We used the Infinium HumanMethylation27 BeadChip to quantify DNAm in blood (N = 9 pairs, mean age 57.4 y) or saliva (N = 36 pairs, mean age 50.0 y) from long-term AYAHL survivors and their unaffected co-twins. Epigenetic aging (DNAm age) was calculated using previously described methods and compared between survivors and co-twins using paired t-tests and analyses were stratified by sample type, histology, sex, age at sample collection and time since diagnosis. Differences in blood DNAm age were observed between survivors and unaffected co-twins (64.1 vs. 61.3 years, respectively, p = .04), especially in females (p = .01); no differences in saliva DNAm age were observed. Survivors and co-twins had 74 (in blood DNA) and 6 (in saliva DNA) differentially methylated loci. Our results suggest persistent epigenetic aging in AYAHL survivors long after HL cure.

Birth Anomalies in Monozygotic and Dizygotic Twins: Results From the California Twin Registry.

BACKGROUND: Inherited factors and maternal behaviors are thought to play an important role in the etiology of several congenital malformations. Twin studies can offer additional evidence regarding the contribution of genetic and lifestyle factors to common birth anomalies, but few large-scale studies have been reported. METHODS: We included data from twins (20,803 pairs) from the population-based California Twin Program. We compared concordance in monozygotic (MZ) to dizygotic (DZ) twins for the following birth anomalies: clubfoot, oral cleft, spina bifida, muscular dystrophy, deafness, cerebral palsy, strabismus, and congenital heart defects. Each birth anomaly was also examined for the associations with birth characteristics (birthweight and birth order) and parental exposures (age, smoking, and parental education). RESULTS: The overall prevalence of any selected birth anomaly in California twins was 38 per 1,000 persons, with a slightly decreasing trend from 1957-1982. For pairwise concordance in 6,752 MZ and 7,326 like-sex DZ twin pairs, high MZ:DZ concordance ratios were observed for clubfoot (CR 5.91; P = 0.043) and strabismus (CR 2.52; P = 0.001). Among the total 20,803 pairs, parental smoking was significantly associated with risk of spina bifida (OR 3.48; 95% CI, 1.48-8.18) and strabismus (OR 1.61; 95% CI, 1.28-2.03). A significant quadratic trend of increasing risk for clubfoot, spina bifida, and strabismus was found when examining whether father smoked, mother smoked, or both parents smoked relative to non-smoking parents (P = 0.029, 0.026, and 0.0005, respectively). CONCLUSIONS: Our results provide evidence for a multifactorial etiology underlying selected birth anomalies. Further research is needed to understand the biological mechanisms.

Water-Dispersible Polydopamine-Coated Nanofibers for Stimulation of Neuronal Growth and Adhesion.

Hybrid nanomaterials have shown great potential in regenerative medicine due to the unique opportunities to customize materials properties for effectively controlling cellular growth. The peptide nanofiber-mediated auto-oxidative polymerization of dopamine, resulting in stable aqueous dispersions of polydopamine-coated peptide hybrid nanofibers, is demonstrated. The catechol residues of the polydopamine coating on the hybrid nanofibers are accessible and provide a platform for introducing functionalities in a pH-responsive polymer analogous reaction, which is demonstrated using a boronic acid modified fluorophore. The resulting hybrid nanofibers exhibit attractive properties in their cellular interactions: they enhance neuronal cell adhesion, nerve fiber growth, and growth cone area, thus providing great potential in regenerative medicine. Furthermore, the facile modification by pH-responsive supramolecular polymer analog reactions allows tailoring the functional properties of the hybrid nanofibers in a reversible fashion.

Education in Twins and Their Parents Across Birth Cohorts Over 100 years: An Individual-Level Pooled Analysis of 42-Twin Cohorts.

Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990-1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.

Differences in genetic and environmental variation in adult BMI by sex, age, time period, and region: an individual-based pooled analysis of 40 twin cohorts.

Background: Genes and the environment contribute to variation in adult body mass index [BMI (in kg/m2)], but factors modifying these variance components are poorly understood.Objective: We analyzed genetic and environmental variation in BMI between men and women from young adulthood to old age from the 1940s to the 2000s and between cultural-geographic regions representing high (North America and Australia), moderate (Europe), and low (East Asia) prevalence of obesity.Design: We used genetic structural equation modeling to analyze BMI in twins ≥20 y of age from 40 cohorts representing 20 countries (140,379 complete twin pairs).Results: The heritability of BMI decreased from 0.77 (95% CI: 0.77, 0.78) and 0.75 (95% CI: 0.74, 0.75) in men and women 20-29 y of age to 0.57 (95% CI: 0.54, 0.60) and 0.59 (95% CI: 0.53, 0.65) in men 70-79 y of age and women 80 y of age, respectively. The relative influence of unique environmental factors correspondingly increased. Differences in the sets of genes affecting BMI in men and women increased from 20-29 to 60-69 y of age. Mean BMI and variances in BMI increased from the 1940s to the 2000s and were greatest in North America and Australia, followed by Europe and East Asia. However, heritability estimates were largely similar over measurement years and between regions. There was no evidence of environmental factors shared by co-twins affecting BMI.Conclusions: The heritability of BMI decreased and differences in the sets of genes affecting BMI in men and women increased from young adulthood to old age. The heritability of BMI was largely similar between cultural-geographic regions and measurement years, despite large differences in mean BMI and variances in BMI. Our results show a strong influence of genetic factors on BMI, especially in early adulthood, regardless of the obesity level in the population.