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Purpose: The 18-gene MyProstateScore 2.0 (MPS2) test was previously validated for detection of grade group ≥ 2 (GG ≥ 2) prostate cancer using post-digital rectal examination (DRE) urine. To improve ease of testing, we validated MPS2 using first-catch, non-DRE urine., Materials and Methods: Patients provided first-catch urine before biopsy. MPS2 values were calculated using previously validated models differing only by extent of clinical data included biomarkers alone (BA; no clinical data), biomarkers and clinical factors (BA + CF), and biomarkers, clinical factors, and prostate volume (BA + CF + PV). The primary outcome was GG ≥ 2 cancer on biopsy. MPS2 performance and clinical consequences of testing were compared with PSA and the Prostate Cancer Prevention Trial risk calculator (PCPTrc)., Results: The cohort included 266 men with median PSA 6.6 ng/mL (IQR, 4.9-9.1) of whom 103 (39%) had GG ≥ 2 cancer on biopsy. The AUC for GG ≥ 2 cancer was 57% for PSA, 62% for PCPTrc, and 71%, 74%, and 77% for MPS2 models. Under a testing approach detecting > 90% of GG ≥ 2 cancers, MPS2 testing would have avoided 36% to 42% of unnecessary biopsies, as compared with 13% using the PCPTrc. In patients with a prior negative biopsy, MPS2 testing would have avoided 44% to 53% of repeat biopsies, as compared with only 2.6% using PCPTrc., Conclusions: Using first-catch urine, MPS2 meaningfully improved the proportion of biopsies avoided relative to PCPTrc while maintaining highly sensitive detection of GG ≥ 2 cancer. Non-DRE testing provides a convenient, objective, and highly accurate testing option to reduce the need for imaging and biopsy in men with elevated PSA.

Aim: To investigate the role of family history, race/ethnicity, and genetics in prostate cancer (PCa) screening., Methods: We conducted a systematic review of articles from January 2013 through September 2023 that focused on the association of race/ethnicity and genetic factors on PCa detection. Of 10,815 studies, we identified 43 that fulfilled our pre-determined PICO (Patient, Intervention, Comparison and Outcome) criteria., Results: Men with ≥1 first-degree relative(s) with PCa are at increased risk of PCa, even with negative imaging and/or benign prostate biopsy. Black men have higher PCa risk, while Asian men have lower risk. Most of the differences in risks are attributable to environmental and socioeconomic factors; however, genetic differences may play a role. Among numerous pathogenic variants that increase PCa risk, BRCA2, MSH2, and HOXB13 mutations confer the highest risk of PCa. Polygenic risk score (PRS) models identify men at higher PCa risk for a given age and PSA; these models improve when considering other clinical factors and when the model population matches the study population's ancestry., Conclusions: Family history of PCa, race/ethnicity, pathogenic variants (particularly BRCA2, MSH2, and HOXB13), and PRS are associated with increased PCa risk and should be considered in shared decision-making to determine PCa screening regimens., Competing Interests: Declaration of competing interest No Competing Interest to Declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The study objective was to analyze long-term growth and outcomes of the distal aorta after open acute type A aortic dissection repair in patients with bicuspid aortic valves or tricuspid aortic valves without connective tissue disease., Methods: From 1996 to 2021, 60 patients with bicuspid aortic valves and 655 patients with tricuspid aortic valves without connective tissue disease underwent open repair for acute type A aortic dissection. Data were collected from the local Society of Thoracic Surgeons database, medical record review, surveys, and the National Death Index and Michigan Death Index (December 12, 2021)., Results: Compared with the tricuspid aortic valve group, the bicuspid aortic valve group was significantly younger, had more severe aortic insufficiency (33% vs 22%, P = .05), and had less hypertension (67% vs 78%, P = .05). Intraoperatively, patients with bicuspid aortic valves received more aortic root replacements (70% vs 26%, P < .001), less zone 2 aortic arch replacement (8.3% vs 20%, P = .03), and longer median cardiopulmonary bypass (233 vs 214 minutes, P = .05) and aortic crossclamp (184 vs 141 minutes, P < .001) times. The average annual aortic arch growth rate (0.23 mm/year vs 0.39 mm/year, P = .52) and descending aorta growth rate (0.61 mm/year vs 0.79 mm/year, P = .39) were similar between the bicuspid aortic valve and tricuspid aortic valve groups. The bicuspid aortic valve group had lower annual abdominal aorta growth (0.51 mm/year vs 0.68 mm/year, P = .03). The cumulative incidence of reoperation for the distal aorta (9.7% vs 16.0%, P = .77) was similar between the bicuspid aortic valve and tricuspid aortic valve groups. The 10-year survival was higher in the bicuspid aortic valve group (75.4% vs 66.0%, P = .03)., Conclusions: Patients with bicuspid aortic valves could be treated similarly as patients with tricuspid aortic valves without connective tissue disease in the setting of open acute type A aortic dissection repair., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Food deserts are low-income census tracts with poor access to supermarkets and are associated with worse outcomes in breast, colon, and a small number of esophageal cancer patients. This study investigated residency in food deserts on readmission rates in a multi-institutional cohort of esophageal cancer patients undergoing trimodality therapy., Methods: A retrospective review of patients who underwent trimodality therapy at 6 high-volume institutions from January 2015 to July 2019 was performed. Food desert status was defined by the United States Department of Agriculture by patient ZIP Code. The primary outcome was 30-day readmission after esophagectomy. Multilevel, multivariable logistic regression was used to model readmission on food desert status adjusted for diabetes, insurance type, length of stay, and any complication, treating the institution as a random factor., Results: Of the 453 records evaluated, 425 were included in the analysis. Seventy-three patients (17.4%) resided in a food desert. Univariate analysis demonstrated food desert patients had significantly increased 30-day readmission. No differences were seen in length of stay, complications, or 30-day mortality. In the adjusted logistic regression model, residing in a food desert remained a significant risk factor for readmission (odds ratio, 2.11; 95% CI, 1.07-4.15). There were no differences in 30-day, 90-day, or 1-year mortality based on food desert status, although readmission was associated with worse 90-day and 1-year mortality., Conclusions: Food desert residence was associated with 30-day readmission after esophagectomy in patients undergoing trimodality treatment for esophageal cancer in this multi-institutional population. Identification of patients residing in a food desert may allow surgeons to focus preventative interventions during treatment and postoperatively to improve outcomes., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Contrast-associated acute kidney injury (CA-AKI) after endovascular abdominal aortic aneurysm repair (EVAR) is associated with mortality and morbidity. Risk stratification remains a vital component of preoperative evaluation. We sought to generate and validate a preprocedure CA-AKI risk stratification tool for elective EVAR patients., Methods: We queried the Blue Cross Blue Shield of Michigan Cardiovascular Consortium database for elective EVAR patients and excluded those on dialysis, with a history of renal transplant, death during procedure, and without creatinine measures. Association with CA-AKI (rise in creatinine > 0.5 mg/dL) was tested using mixed-effects logistic regression. Variables associated with CA-AKI were used to generate a predictive model via a single classification tree. The variables selected by the classification tree were then validated by fitting a mixed-effects logistic regression model into the Vascular Quality Initiative dataset., Results: Our derivation cohort included 7,043 patients, 3.5% of whom developed CA-AKI. After multivariate analysis, age (odds ratio [OR] 1.021, 95% confidence interval [CI] 1.004-1.040), female sex (OR 1.393, CI 1.012-1.916), glomerular filtration rate (GFR) < 30 mL/min (OR 5.068, CI 3.255-7.891), current smoking (OR 1.942, CI 1.067-3.535), chronic obstructive pulmonary disease (OR 1.402, CI 1.066-1.843), maximum abdominal aortic aneurysm (AAA) diameter (OR 1.018, CI 1.006-1.029), and presence of iliac artery aneurysm (OR 1.352, CI 1.007-1.816) were associated with increased odds of CA-AKI. Our risk prediction calculator demonstrated that patients with a GFR < 30 mL/min, females, and patients with a maximum AAA diameter of > 6.9 cm are at a higher risk of CA-AKI after EVAR. Using the Vascular Quality Initiative dataset (N = 62,986), we found that GFR < 30 mL/min (OR 4.668, CI 4.007-5.85), female sex (OR 1.352, CI 1.213-1.507), and maximum AAA diameter > 6.9 cm (OR 1.824, CI 1.212-1.506) were associated with an increased risk of CA-AKI after EVAR., Conclusions: Herein, we present a simple and novel risk assessment tool that can be used preoperatively to identify patients at risk of CA-AKI after EVAR. Patients with a GFR < 30 mL/min, maximum AAA diameter > 6.9 cm, and females who are undergoing EVAR may be at risk for CA-AKI after EVAR. Prospective studies are needed to determine the efficacy of our model., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: There is debate regarding aortic arch repair extent for acute type A aortic dissection (ATAAD) patients., Methods: From 1996 to 2021, 756 ATAAD patients underwent open arch replacement. The cohort was divided into hemiarch (n = 481), zone 1 (n = 65), zone 2 (n = 148), and zone 3 (n = 62) arch replacement groups. Cross-group comparison of aortic growth was modeled using data from interval postoperative computed tomography or magnetic resonance imaging of the distal aorta., Results: Demographics were not significantly different except the hemiarch group had more coronary artery disease and less stroke. Intraoperatively, zones 1, 2, and 3 had greater cardiopulmonary bypass, cross-clamp, and hypothermic circulatory arrest times and required more intraoperative blood transfusion than the hemiarch group. Perioperative outcomes were similar among groups except zone 3 had more reoperation for bleeding. Ten-year cumulative incidence of reoperation was hemiarch, 16.7%; zone 1, 16.3%; zone 2, 21.5%; and zone 3, 17.6% (P = .70). Ten-year survival was similar: hemiarch, 66%; zone 1, 60.3%; zone 2, 68.0%); and zone 3 66.1% (P = .20). Aortic arch, descending aorta, and abdominal aorta growth rates were not significantly different among groups over 10 years. In the whole cohort, the growth rate over time for aortic arch was 0.38 mm per year (P < .001), descending aorta 0.84 mm per year (P < .001), and abdominal aorta 0.69 mm per year (P < .001)., Conclusions: There was no significant difference in long-term survival, distal aorta growth, or reoperation rate for distal aortic aneurysm after hemiarch or zones 1, 2, or 3 arch replacement. Patient-specific arch replacement strategies may be used rather than defaulting to aggressive arch replacement for all ATAAD patients., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Head and neck paragangliomas (HNPGLs) are slow-growing, vascular, typically benign tumors whose growth may induce significant lower cranial nerve deficits. While most tumors arise sporadically, a significant portion is associated with defined genetic syndromes. While surgical resection has historically been the gold standard, management strategies have evolved with acknowledgement of high surgical morbidity, slow tumor growth rates, and technological advances. Conservative management approaches via observation and newer radiation therapy techniques have become more common. This review seeks to provide an update on contemporary management strategies for HNPGLs and future directions., Competing Interests: Tobias Else is an associate editor on the editorial board of Endocrine Oncology. Tobias Else was not involved in the review or editorial process for this paper, on which he is listed as an author. No other conflicts of interest to declare., (© The authors.)

The integration of genomic data into genetic evaluations can facilitate the rapid selection of superior genotypes and accelerate the breeding cycle in trees. In this study, 390 trees from 74 control-pollinated families were genotyped using a 36K Axiom SNP array. A total of 15,624 high-quality SNPs were used to develop genomic prediction models for mammalian bark stripping, tree height, and selected primary and secondary chemical compounds in the bark. Genetic parameters from different genomic prediction methods-single-trait best linear unbiased prediction based on a marker-based relationship matrix (genomic best linear unbiased prediction), multitrait single-step genomic best linear unbiased prediction, which integrated the marker-based and pedigree-based relationship matrices (single-step genomic best linear unbiased prediction) and the single-trait generalized ridge regression-were compared to equivalent single- or multitrait pedigree-based approaches (ABLUP). The influence of the statistical distribution of data on the genetic parameters was assessed. Results indicated that the heritability estimates were increased nearly 2-fold with genomic models compared to the equivalent pedigree-based models. Predictive accuracy of the single-step genomic best linear unbiased prediction was higher than the ABLUP for most traits. Allowing for heterogeneity in marker effects through the use of generalized ridge regression did not markedly improve predictive ability over genomic best linear unbiased prediction, arguing that most of the chemical traits are modulated by many genes with small effects. Overall, the traits with low pedigree-based heritability benefited more from genomic models compared to the traits with high pedigree-based heritability. There was no evidence that data skewness or the presence of outliers affected the genomic or pedigree-based genetic estimates., (© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.)

Background: The growing availability of genomic resources in radiata pine paves the way for significant advances in fundamental and applied genomic research. We constructed robust high-density linkage maps based on exome-capture genotyping in two F 1 populations, and used these populations to perform quantitative trait locus (QTL) scans, genomic prediction and quantitative analyses of genetic architecture for key traits targeted by tree improvement programmes., Results: Our mapping approach used probabilistic error correction of the marker data, followed by an iterative approach based on stringent parameters. This approach proved highly effective in producing high-density maps with robust marker orders and realistic map lengths (1285-4674 markers per map, with sizes ranging from c. 1643-2292 cM, and mean marker intervals of 0.7-2.1 cM). Colinearity was high between parental linkage maps, although there was evidence for a large chromosomal rearrangement (affecting ~ 90 cM) in one of the parental maps. In total, 28 QTL were detected for growth (stem diameter) and wood properties (wood density and fibre properties measured by Silviscan) in the QTL discovery population, with 1-3 QTL of small to moderate effect size detected per trait in each parental map. Four of these QTL were validated in a second, unrelated F 1 population. Results from genomic prediction and analyses of genetic architecture were consistent with those from QTL scans, with wood properties generally having moderate to high genomic heritabilities and predictive abilities, as well as somewhat less complex genetic architectures, compared to growth traits., Conclusions: Despite the economic importance of radiata pine as a plantation forest tree, robust high-density linkage maps constructed from reproducible, sequence-anchored markers have not been published to date. The maps produced in this study will be a valuable resource for several applications, including the selection of marker panels for genomic prediction and anchoring a recently completed de novo whole genome assembly. We also provide the first map-based evidence for a large genomic rearrangement in radiata pine. Finally, results from our QTL scans, genomic prediction, and genetic architecture analyses are informative about the genomic basis of variation in important phenotypic traits., (© 2022. The Author(s).)

Global climate change introduces new combinations of environmental conditions, which is expected to increase stress on plants. This could affect many traits in multiple ways that are as yet unknown but will likely require the modification of existing genetic relationships among functional traits potentially involved in local adaptation. Theoretical evolutionary studies have determined that it is an advantage to have an excess of recombination events under heterogeneous environmental conditions. Our study, conducted on a population of radiata pine (Pinus radiata D. Don), was able to identify individuals that show high genetic recombination at genomic regions, which potentially include pleiotropic or collocating QTLs responsible for the studied traits, reaching a prediction accuracy of 0.80 in random cross-validation and 0.72 when whole family was removed from the training population and predicted. To identify these highly recombined individuals, a training population was constructed from correlation breakers, created through tandem selection of parents in the previous generation and their consequent mating. Although the correlation breakers showed lower observed heterogeneity possibly due to direct selection in both studied traits, the genomic regions with statistically significant differences in the linkage disequilibrium pattern showed higher level of heretozygosity, which has the effect of decomposing unfavourable genetic correlation. We propose undertaking selection of correlation breakers under current environmental conditions and using genomic predictions to increase the frequency of these 'recombined' individuals in future plantations, ensuring the resilience of planted forests to changing climates. The increased frequency of such individuals will decrease the strength of the population-level genetic correlations among traits, increasing the opportunity for new trait combinations to be developed in the future., (© 2022. The Author(s).)

Objective: To determine the long-term survival and rate of reoperation after surgical treatment of infective endocarditis (IE) in patients with a bicuspid aortic valve (BAV) and patients with a tricuspid aortic valve (TAV)., Methods: Between 1997 and 2017, 210 patients underwent surgical treatment for native aortic valve endocarditis, including 51 patients with BAV (24%) and 159 patients with TAV (76%). Data were obtained from the Society of Thoracic Surgeons data warehouse and hospital medical record review, supplemented with surveys and national death index data for more complete follow-up., Results: Compared with the TAV IE group, the BAV IE group was significantly younger (42 years vs 54 years) and had lower incidence rates of hypertension, coronary artery disease, and congestive heart failure (CHF). There were no significant between-group differences in postoperative stroke, sepsis, pacemaker requirement, or in-hospital mortality (2.0% vs 4.4%). Liver disease was a risk factor for operative mortality (odds ratio [OR], 13; 95% CI, 3.3-30; P  = .0002). The 10-year survival rate was 64% for the BAV group versus 46% for the TAV group ( P  = .0191). Significant risk factors for long-term mortality were intravenous drug use (hazard ratio [HR], 4.5; P  < .0001), preoperative renal failure requiring dialysis (HR, 4.13; P  < .0001), CHF (HR, 1.7; P  = .04), and liver disease (HR, 2.6; P  = .02). The HR for BAV was 0.67 (95% confidence interval [CI], 0.3-1.4). The 10-year postoperative cumulative incidence of reoperation was significantly higher in the BAV patients compared with the TAV patients (5.7% vs 4.5%; P  = .045) with an HR of 2.4 (95% CI, 0.8-7.1; P  = .11) for BAV., Conclusions: BAV patients develop IE requiring surgery at a younger age than TAV patients, but have significantly better long-term survival. Early detection of BAV is important to prevent IE and provide aggressive surgical treatment should IE occur., (© 2021 The Author(s).)

Multivariate analysis using mixed models allows for the exploration of genetic correlations between traits. Additionally, the transition to a genomic based approach is simplified by substituting classic pedigrees with a marker-based relationship matrix. It also enables the investigation of correlated responses to selection, trait integration and modularity in different kinds of populations. This study investigated a strategy for the construction of a marker-based relationship matrix that prioritized markers using Partial Least Squares. The efficiency of this strategy was found to depend on the correlation structure between investigated traits. In terms of accuracy, we found no benefit of this strategy compared with the all-marker-based multivariate model for the primary trait of diameter at breast height (DBH) in a radiata pine ( Pinus radiata ) population, possibly due to the presence of strong and well-estimated correlation with other highly heritable traits. Conversely, we did see benefit in a shining gum ( Eucalyptus nitens ) population, where the primary trait had low or only moderate genetic correlation with other low/moderately heritable traits. Marker selection in multivariate analysis can therefore be an efficient strategy to improve prediction accuracy for low heritability traits due to improved precision in poorly estimated low/moderate genetic correlations. Additionally, our study identified the genetic diversity as a factor contributing to the efficiency of marker selection in multivariate approaches due to higher precision of genetic correlation estimates., (Copyright © 2020 Klápště, Dungey, Telfer, Suontama, Graham, Li and McKinley.)

Background: Many conifer breeding programs are paying increasing attention to breeding for resistance to needle disease due to the increasing importance of climate change. Phenotyping of traits related to resistance has many biological and temporal constraints that can often confound the ability to achieve reliable phenotypes and consequently, reliable genetic progress. The development of next generation sequencing platforms has also enabled implementation of genomic approaches in species lacking robust reference genomes. Genomic selection is, therefore, a promising strategy to overcome the constraints of needle disease phenotyping., Results: We found high accuracy in the prediction of genomic breeding values in the disease-related traits that were well characterized, reaching 0.975 for genotyped individuals and 0.587 for non-genotyped individuals. This compared well with pedigree-based accuracies of up to 0.746. Surprisingly, poorly phenotyped disease traits also showed very high accuracy in terms of correlation of predicted genomic breeding values with pedigree-based counterparts. However, this was likely caused by the fact that both were clustered around the population mean, while deviations from the population mean caused by genetic effects did not appear to be well described. Caution should therefore be taken with the interpretation of results in poorly phenotyped traits., Conclusions: Implementation of genomic selection in this test population of Pinus radiata resulted in a relatively high prediction accuracy of needle loss due to Dothistroma septosporum compared with a pedigree-based approach. Using genomics to avoid biological/temporal constraints where phenotyping is reliable appears promising. Unsurprisingly, reliable phenotyping, resulting in good heritability estimates, is a fundamental requirement for the development of a reliable prediction model. Furthermore, our results are also specific to the single pathogen mating-type that is present in New Zealand, and may change with future incursion of other pathogen varieties. There is no doubt, however, that once a robust genomic prediction model is built, it will be invaluable to not only select for host tolerance, but for other economically important traits simultaneously. This tool will thus future-proof our forests by mitigating the risk of disease outbreaks induced by future changes in climate.

Background: Administration of human mesenchymal stem cell (MSC)-derived exosomes can enhance neurorestoration in models of traumatic brain injury (TBI) and hemorrhagic shock (HS). The impact of early treatment with MSC-derived exosomes on brain injury in a large animal model remains unknown. We sought to evaluate the impact of early single-dose exosome treatment on brain swelling and lesion size, blood-based cerebral biomarkers, and blood-brain barrier (BBB) integrity., Methods: Female Yorkshire swine were subjected to a severe TBI (12-mm cortical impact) and HS (40% estimated total blood volume). One hour into shock, animals were randomized (n = 5/cohort) to receive either lactated Ringer's (LR; 5 mL) or LR + exosomes (1 × 10 exosome particles in 5 mL LR). Animals then underwent additional shock (1 hour) followed by normal saline resuscitation. After 6 hours of observation, brain swelling (% increase compared with the uninjured side) and lesion size (mm) were assessed. Cerebral hemodynamics and blood-based biomarkers of brain injury were compared. Immunofluorescence and RNA sequencing with differential gene expression and pathway analysis were used to assess the integrity of the perilesion BBB., Results: Exosome-treated animals had significantly less (p < 0.05) brain swelling and smaller lesion size. They also had significantly decreased (p < 0.05) intracranial pressures and increased cerebral perfusion pressures. Exosome-treated animals had significantly decreased (p < 0.05) albumin extravasation and significantly higher (p < 0.05) laminin, claudin-5, and zonula occludens 1 levels. Differential gene expression and pathway analysis confirmed these findings. Serum glial fibrillary acidic protein levels were also significantly lower (p < 0.05) in the exosome-treated cohort at the end of the experiment., Conclusion: In a large animal model of TBI and HS, early treatment with a single dose of MSC-derived exosomes significantly attenuates brain swelling and lesion size, decreases levels of blood-based cerebral biomarkers, and improves BBB integrity.

Background: Trauma is a leading cause of death, and traumatic brain injury is one of the hallmark injuries of current military conflicts. Valproic acid (VPA) administration in high doses (300-400 mg/kg) improves survival in lethal trauma models, but effectiveness of lower doses on survival is unknown. This information is essential for properly designing the upcoming clinical trials. We, therefore, performed the current study to determine the lowest dose at which VPA administration improves survival in a model of lethal injuries., Methods: Swine were subjected to traumatic brain injury (10-mm cortical impact), 40% blood volume hemorrhage, and multiple trauma (femur fracture, rectus crush, and Grade V liver laceration). After 1 hour of shock, animals were randomized (n = 6/group) to four groups: normal saline (NS) resuscitation; or NS with VPA doses of 150 mg/kg (VPA 150) or 100 mg/kg (VPA 100) administered over 3 hours or 100 mg/kg over 2 hours (VPA 100 over 2 hours). Three hours after shock, packed red blood cells were given, and animals were monitored for another 4 hours. Survival was assessed using Kaplan-Meier and log-rank test., Results: Without resuscitation, all of the injured animals died within 5 hours. Similar survival rates were observed in the NS (17%) and VPA 100 (0%) resuscitation groups. Survival rates in the 100-mg/kg VPA groups were significantly (p < 0.05) better when it was given over 2 hours (67%) compared to 3 hours (0%). 83% of the animals in the VPA 150 group survived, which was significantly higher than the NS and VPA 100 over 3 hours groups (p < 0.05)., Conclusion: A single dose of VPA (150 mg/kg) significantly improves survival in an otherwise lethal model of multiple injuries. This is a much lower dose than previously shown to have a survival benefit and matches the dose that is tolerated by healthy human subjects with minimal adverse effects., Level of Evidence: Therapeutic, level V.

Trauma remains a leading cause of morbidity and mortality among all age groups in the United States. Hemorrhagic shock and traumatic brain injury (TBI) are major causes of preventable death in trauma. Initial treatment involves fluid resuscitation to improve the intravascular volume. Although crystalloids may provide volume expansion, they do not have any pro-survival properties. Furthermore, aggressive fluid resuscitation can provoke a severe inflammatory response and worsen clinical outcomes. Due to logistical constraints, however, definitive resuscitation with blood products is often not feasible in the prehospital setting-highlighting the importance of adjunctive therapies. In recent years, histone deacetylase inhibitors (HDACis) have shown promise as pharmacologic agents for use in both trauma and sepsis. In this review, we discuss the role of histone deacetylases (HDACs) and pharmacologic agents that inhibit them (HDACis). We also highlight the therapeutic effects and mechanisms of action of HDACis in hemorrhagic shock, TBI, polytrauma, and sepsis. With further investigation and translation, HDACis have the potential to be a high-impact adjunctive therapy to traditional resuscitation.

Background: Although damage control resuscitation (DCR) is routinely performed for short durations, prolonged DCR may be required in military conflicts as a component of prolonged field care. Valproic acid (VPA) has been shown to have beneficial properties in lethal hemorrhage/trauma models. We sought to investigate whether the addition of a single dose of VPA to a 72-hour prolonged DCR protocol would improve clinical outcomes., Methods: Fifteen Yorkshire swine (40-45 kg) were subjected to lethal (50% estimated total blood volume) hemorrhagic shock (HS) and randomized to three groups: (1) HS, (2) HS-DCR, (3) HS-DCR-VPA (150 mg/kg over 3 hours) (n = 5/cohort). In groups assigned to receive DCR, Tactical Combat Casualty Care guidelines were applied (1 hour into the shock period), targeting a systolic blood pressure of 80 mm Hg. At 72 hours, surviving animals were given transfusion of packed red blood cells, simulating evacuation to higher echelons of care. Survival rates, physiologic parameters, resuscitative fluid requirements, and laboratory profiles were used to compare the clinical outcomes., Results: This model was 100% lethal in the untreated animals. DCR improved survival to 20%, although this was not statistically significant. The addition of VPA to DCR significantly improved survival to 80% (p < 0.01). The VPA-treated animals also had significantly (p < 0.05) higher systolic blood pressures, lower fluid resuscitation requirements, higher hemoglobin levels, and lower creatinine and potassium levels., Conclusion: VPA administration improves survival, decreases resuscitation requirements, and improves hemodynamic and laboratory parameters when added to prolonged DCR in a lethal hemorrhage model.

Background: The use of partial resuscitative endovascular balloon occlusion of the aorta (pREBOA) in combined hemorrhagic shock (HS) and traumatic brain injury (TBI) has not been well studied. We hypothesized that the use of pREBOA in the setting of TBI would be associated with worse clinical outcomes., Methods: Female Yorkshire swine were randomized to the following groups: HS-TBI, HS-TBI-pREBOA, and HS-pREBOA (n = 5/cohort). Animals in the HS-TBI group were left in shock for a total of 2 hours, whereas animals assigned to pREBOA groups were treated with supraceliac pREBOA deployment (60 minutes) 1 hour into the shock period. All animals were then resuscitated, and physiologic parameters were monitored for 6 hours. Further fluid resuscitation and vasopressors were administered as needed. At the end of the observation period, brain hemispheric swelling (%) and lesion size (mm) were assessed., Results: Mortality was highest in the HS-TBI-pREBOA group (40% [2/5] vs. 0% [0/5] in the other groups, p = 0.1). Severity of shock was greatest in the HS-TBI-pREBOA group, as defined by peak lactate levels and pH nadir (p < 0.05). Fluid resuscitation and norepinephrine requirements were significantly higher in the HS-TBI-pREBOA group (p < 0.05). No significant differences were noted in brain hemispheric swelling and lesion size between the groups., Conclusion: Prolonged application of pREBOA in the setting of TBI does not contribute to early worsening of brain lesion size and edema. However, the addition of TBI to HS-pREBOA may worsen the severity of shock. Providers should be aware of the potential physiologic sequelae induced by TBI.

Open-pollinated (OP) mating is frequently used in forest tree breeding due to the relative temporal and financial efficiency of the approach. The trade-off is the lower precision of the estimated genetic parameters. Pedigree/sib-ship reconstruction has been proven as a tool to correct and complete pedigree information and to improve the precision of genetic parameter estimates. Our study analyzed an advanced generation Eucalyptus population from an OP breeding program using single-step genetic evaluation. The relationship matrix inferred from sib-ship reconstruction was used to rescale the marker-based relationship matrix (G matrix). This was compared with a second scenario that used rescaling based on the documented pedigree. The proposed single-step model performed better with respect to both model fit and the theoretical accuracy of breeding values. We found that the prediction accuracy was superior when using the pedigree information only when compared with using a combination of the pedigree and genomic information. This pattern appeared to be mainly a result of accumulated unrecognized relatedness over several breeding cycles, resulting in breeding values being shrunk toward the population mean. Using biased, pedigree-based breeding values as the base with which to correlate predicted GEBVs, resulted in the underestimation of prediction accuracies. Using breeding values estimated on the basis of sib-ship reconstruction resulted in increased prediction accuracies of the genotyped individuals. Therefore, selection of the correct base for estimation of prediction accuracy is critical. The beneficial impact of sib-ship reconstruction using G matrix rescaling was profound, especially in traits with inbreeding depression, such as stem diameter.

Hemorrhage remains the leading cause of preventable deaths in trauma. Endovascular management of non-compressible torso hemorrhage has been at the forefront of trauma care in recent years. Since complete aortic occlusion presents serious concerns, the concept of partial aortic occlusion has gained a growing attention. Here, we present a large animal model of hemorrhagic shock to investigate the effects of a novel partial aortic balloon occlusion catheter and compare it with a catheter that works on the principles of complete aortic occlusion. Swine are anesthetized and instrumented in order to conduct controlled fixed-volume hemorrhage, and hemodynamic and physiological parameters are monitored. Following hemorrhage, aortic balloon occlusion catheters are inserted and inflated in the supraceliac aorta for 60 min, during which the animals receive whole-blood resuscitation as 20% of the total blood volume (TBV). Following balloon deflation, the animals are monitored in a critical care setting for 4 h, during which they receive fluid resuscitation and vasopressors as needed. The partial aortic balloon occlusion demonstrated improved distal mean arterial pressures (MAPs) during the balloon inflation, decreased markers of ischemia, and decreased fluid resuscitation and vasopressor use. As swine physiology and homeostatic responses following hemorrhage have been well-documented and are like those in humans, a swine hemorrhagic shock model can be used to test various treatment strategies. In addition to treating hemorrhage, aortic balloon occlusion catheters have become popular for their role in cardiac arrest, cardiac and vascular surgery, and other high-risk elective surgical procedures.

Context: Single-nucleotide polymorphisms (SNPs) in genes related to vitamin D metabolism have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentration, but these relationships have not been examined following antenatal cholecalciferol supplementation., Objective: To determine whether SNPs in DHCR7, CYP2R1, CYP24A1, and GC are associated with the response to gestational cholecalciferol supplementation., Design: Within-randomization group analysis of the Maternal Vitamin D Osteoporosis Study trial of antenatal cholecalciferol supplementation., Setting: Hospital antenatal clinics., Participants: In total, 682 women of white ethnicity (351 placebo, 331 cholecalciferol) were included. SNPs at rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1), and rs2282679 (GC) were genotyped., Interventions: 1000 IU/d cholecalciferol from 14 weeks of gestation until delivery., Main Outcome Measure: 25(OH)D at randomization and 34 weeks of gestation were measured in a single batch (Liaison; Diasorin, Dartford, UK). Associations between 25(OH)D and the SNPs were assessed by linear regression using an additive model [β represents the change in 25(OH)D per additional common allele]., Results: Only rs12785878 (DHCR7) was associated with baseline 25(OH)D [β = 3.1 nmol/L; 95% confidence interval (CI), 1.0 to 5.2 nmol/L; P < 0.004]. In contrast, rs10741657 (CYP2R1) (β = -5.2 nmol/L; 95% CI, -8.2 to -2.2 nmol/L; P = 0.001) and rs2282679 (GC) (β = 4.2 nmol/L; 95% CI, 0.9 to 7.5 nmol/L; P = 0.01) were associated with achieved 25(OH)D status following supplementation, whereas rs12785878 and rs6013897 (CYP24A1) were not., Conclusions: Genetic variation in DHCR7, which encodes 7-dehyrocholesterol reductase in the epidermal vitamin D biosynthesis pathway, appears to modify baseline 25(OH)D. In contrast, the response to antenatal cholecalciferol supplementation was associated with SNPs in CYP2R1, which may alter 25-hydroxylase activity, and GC, which may affect vitamin D binding protein synthesis or metabolite affinity., (Copyright © 2017 Endocrine Society)

Bioretention systems have been recommended as one of the best management practices for low impact development for water recycling/reuse systems. Although improvement of the stormwater quality has been reported regarding pollutants eliminations such as suspended solids and heavy metals, a substantial removal of indicator bacteria is required for possible non-potable reuse. This study investigated the efficiency of wood biochar with H 2 SO 4 -, H 3 PO 4 -, KOH-, and amino-modifications for E. coli removal from synthetic stormwater under intermittent flow. The H 2 SO 4 -modified biochar showed a specific surface area of 234.7 m 2  g -1 (approximately double the area of original biochar), whereas a substantial reduction in surface area was found with amino-modified biochar. The E. coli removal (initial concentration of 0.3-3.2 × 10 6  CFU mL -1 ) by modified biochars as filter media was very promising with, for example, over 98% removal efficiency in the first 20 pore volumes of stormwater infiltration and over 92% removal by the end of the second infiltration cycle. Only a small portion of E. coli attached on the modified biochars (<0.3%, except KOH- and amino-modified biochars) was remobilized during the drainage phase of intermittent flow. The high removal capacity and stability against drainage were attributed to the high surface area, porous structure, and surface characteristics (e.g. hydrophobicity and O-containing functional groups) of the biochars. Thus, the H 2 SO 4 -modified biochar appeared to give the best treatment performance., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Peatland ecosystem services include drinking water provision, flood mitigation, habitat provision and carbon sequestration. Dissolved organic carbon (DOC) removal is a key treatment process for the supply of potable water downstream from peat-dominated catchments. A transition from peat-forming Sphagnum moss to vascular plants has been observed in peatlands degraded by (a) land management, (b) atmospheric deposition and (c) climate change. Here within we show that the presence of vascular plants with higher annual above-ground biomass production leads to a seasonal addition of labile plant material into the peatland ecosystem as litter recalcitrance is lower. The net effect will be a smaller litter carbon pool due to higher rates of decomposition, and a greater seasonal pattern of DOC flux. Conventional water treatment involving coagulation-flocculation-sedimentation may be impeded by vascular plant-derived DOC. It has been shown that vascular plant-derived DOC is more difficult to remove via these methods than DOC derived from Sphagnum, whilst also being less susceptible to microbial mineralisation before reaching the treatment works. These results provide evidence that practices aimed at re-establishing Sphagnum moss on degraded peatlands could reduce costs and improve efficacy at water treatment works, offering an alternative to 'end-of-pipe' solutions through management of ecosystem service provision.

Pre-treatment is normally required to reduce or control the fouling of ultrafiltration (UF) membranes in drinking water treatment process. Current pre-treatment methods, such as coagulation, are only partially effective to prevent long-term fouling. Since biological activities are a major contributor to accumulated fouling, the application of an oxidation/disinfection step can be an effective complement to coagulation. In this study, a novel pre-treatment method has been evaluated at laboratory scale consisting of the addition of low dose ozone into the UF membrane tank after coagulation and the use of a hollow-fibre membrane coated with/without MnO2 nanoparticles over a test period of 70 days. The results showed that there was minimal fouling of the MnO2 coated membrane (0.5 kPa for 70 days), while the uncoated membrane experienced both reversible and irreversible fouling. The difference was attributed to the greatly reduced presence of bacteria and organic matter because of the catalytic decomposition of ozone to hydroxyl radicals and increase of the hydrophilicity of the membrane surface. In particular, the MnO2 coated membrane had a much thinner cake layer, with significantly less polysaccharides and proteins, and much less accumulated organic matter within the membrane pores.

Coagulation prior to ultrafiltration (UF) is widely applied for treating contaminated surface water sources for potable supply. While beneficial, coagulation alone is unable to control membrane fouling effectively in many cases, and there is continuing interest in the use of additional, complementary methods such as oxidation in the pre-treatment of raw water prior to UF. In this study, the application of ozone at low dose in the membrane tank immediately following coagulation has been evaluated at laboratory-scale employing model raw water. In parallel tests with and without the application of ozone, the impact of applied ozone doses of 0.5 mg L(-1) and 1.5 mg L(-1) (approximately 0.18 mg L(-1) and 0.54 mg L(-1) consumed ozone, respectively) on the increase of trans-membrane pressure (TMP) was evaluated and correlated with the quantity and nature of membrane deposits, both as a cake layer and within membrane pores. The results showed that a dose of 0.5 mgO3 L(-1) gave a membrane fouling rate that was substantially lower than without ozone addition, while a dose of 1.5 mgO3 L(-1) was able to prevent fouling effects significantly (no increase in TMP). Ozone was found to decrease the concentration of bacteria (especially the concentration of bacteria per suspended solid) in the membrane tank, and to alter the nature of dissolved organic matter by increasing the proportion of hydrophilic substances. Ozone decreased the concentration of extracellular polymeric substances (EPS), such as polysaccharides and proteins, in the membrane cake layer; the reduced EPS and bacterial concentrations resulted in a much thinner cake layer, although the suspended solids concentration was much higher in the ozone added membrane tank. Ozone also decreased the accumulation and hydrophobicity of organic matter within the membrane pores, leading to minimal irreversible fouling. Therefore, the application of low-dose ozone within the UF membrane tank is a potentially important approach for fully mitigating membrane fouling., (Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.)

The degradation kinetics of three pesticides - metaldehyde, clopyralid and mecoprop - by ultraviolet photolysis and hydroxyl radical oxidation by low pressure ultraviolet hydrogen peroxide (LP-UV/H2O2) advanced oxidation was determined. Mecoprop was susceptible to both LP-UV photolysis and hydroxyl radical oxidation, and exhibited the fastest degradation kinetics, achieving 99.6% (2.4-log) degradation with a UV fluence of 800 mJ/cm(2) and 5 mg/L hydrogen peroxide. Metaldehyde was poorly degraded by LP-UV photolysis while 97.7% (1.6-log) degradation was achieved with LP-UV/H2O2 treatment at the maximum tested UV fluence of 1000 mJ/cm(2) and 15 mg/L hydrogen peroxide. Clopyralid was hardly susceptible to LP-UV photolysis and exhibited the lowest degradation by LP-UV/H2O2 among the three pesticides. The second-order reaction rate constants for the reactions between the pesticides and OH-radicals were calculated applying a kinetic model for LP-UV/H2O2 treatment to be 3.6 × 10(8), 2.0 × 10(8) and 1.1 × 10(9) M(-1) s(-1) for metaldehyde, clopyralid and mecoprop, respectively. The main LP-UV photolysis reaction product from mecoprop was 2-(4-hydroxy-2-methylphenoxy) propanoic acid, while photo-oxidation by LP-UV/H2O2 treatment formed several oxidation products. The photo-oxidation of clopyralid involved either hydroxylation or dechlorination of the ring, while metaldehyde underwent hydroxylation and produced acetic acid as a major end product. Based on the findings, degradation pathways for the three pesticides by LP-UV/H2O2 treatment were proposed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Uncertainty regarding changes in dissolved organic carbon (DOC) quantity and quality has created interest in managing peatlands for their ecosystem services such as drinking water provision. The evidence base for such interventions is, however, sometimes contradictory. We performed a laboratory climate manipulation using a factorial design on two dominant peatland vegetation types (Calluna vulgaris and Sphagnum Spp.) and a peat soil collected from a drinking water catchment in Exmoor National Park, UK. Temperature and rainfall were set to represent baseline and future conditions under the UKCP09 2080s high emissions scenario for July and August. DOC leachate then underwent standard water treatment of coagulation/flocculation before chlorination. C. vulgaris leached more DOC than Sphagnum Spp. (7.17 versus 3.00 mg g(-1)) with higher specific ultraviolet (SUVA) values and a greater sensitivity to climate, leaching more DOC under simulated future conditions. The peat soil leached less DOC (0.37 mg g(-1)) than the vegetation and was less sensitive to climate. Differences in coagulation removal efficiency between the DOC sources appears to be driven by relative solubilisation of protein-like DOC, observed through the fluorescence peak C/T. Post-coagulation only differences between vegetation types were detected for the regulated disinfection by-products (DBPs), suggesting climate change influence at this scale can be removed via coagulation. Our results suggest current biodiversity restoration programmes to encourage Sphagnum Spp. will result in lower DOC concentrations and SUVA values, particularly with warmer and drier summers., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Ozonation before chlorination is associated with enhanced formation of chloropicrin, a halonitromethane disinfection by-product (DBP), during drinking water treatment. In order to elucidate reasons for this, five natural organic matter (NOM) surrogates were treated using both chlorination and ozonation-chlorination under controlled laboratory conditions. Selected surrogates comprised two phenolic compounds, two free amino acids and one dipeptide; these were resorcinol, 3-aminophenol, L-aspartic acid, β-alanine and ala-ala, respectively. Quantified DBPs included chloropicrin, chloroform, dichloroacetonitrile and trichloroacetonitrile. Relative to chlorination alone, increases in the formation of chloropicrin from ozonation-chlorination varied from 138% for 3-aminophenol to 3740% for ala-ala for the four amine surrogates. This indicates that ozone is more effective than chlorine in mediating a rate-limiting oxidation step in chloropicrin formation, most plausibly involving conversion of an amine group to a nitro group. While both hydrophilic and hydrophobic surrogates acted as chloropicrin precursors, ala-ala was the most reactive precursor following ozonation-chlorination. Since peptides are far commoner in drinking water sources than free amino acids, further research into chemical oxidation of these species by ozone and chlorine is recommended. In contrast, oxidation with ozone prior to chlorination reduced chloroform formation moderately for the two phenolic compounds., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Climate change in the UK is expected to cause increases in temperatures, altered precipitation patterns and more frequent and extreme weather events. In this review we discuss climate effects on dissolved organic matter (DOM), how altered DOM and water physico-chemical properties will affect treatment processes and assess the utility of techniques used to remove DOM and monitor water quality. A critical analysis of the literature has been undertaken with a focus on catchment drivers of DOM character, removal of DOM via coagulation and the formation of disinfectant by-products (DBPs). We suggest that: (1) upland catchments recovering from acidification will continue to produce more DOM with a greater hydrophobic fraction as solubility controls decrease; (2) greater seasonality in DOM export is likely in future due to altered precipitation patterns; (3) changes in species diversity and water properties could encourage algal blooms; and (4) that land management and vegetative changes may have significant effects on DOM export and treatability but require further research. Increases in DBPs may occur where catchments have high influence from peatlands or where algal blooms become an issue. To increase resilience to variable DOM quantity and character we suggest that one or more of the following steps are undertaken at the treatment works: a) 'enhanced coagulation' optimised for DOM removal; b) switching from aluminium to ferric coagulants and/or incorporating coagulant aids; c) use of magnetic ion-exchange (MIEX) pre-coagulation; and d) activated carbon filtration post-coagulation. Fluorescence and UV absorbance techniques are highlighted as potential methods for low-cost, rapid on-line process optimisation to improve DOM removal and minimise DBPs., (Copyright © 2013 Elsevier B.V. All rights reserved.)

During drinking water treatment aqueous chlorine and bromine compete to react with natural organic matter (NOM). Among the products of these reactions are potentially harmful halogenated disinfection by-products, notably four trihalomethanes (THM4) and nine haloacetic acids (HAAs). Previous research has concentrated on the role of bromide in chlorination reactions under conditions of a given NOM type and/or concentration. In this study different concentrations of dissolved organic carbon (DOC) from U.K. lowland water were reacted with varying amounts of bromide and chlorine in order to examine the interrelationship between the three reactants in the formation of THM4, dihaloacetic acids (DHAAs) and trihaloacetic acids (THAAs). Results showed that, in general, molar yields of THM4 increased with DOC, bromide and chlorine concentrations, although yields did fluctuate versus chlorine dose. In contrast both DHAA and THAA yields were mainly independent of changes in bromide and chlorine dose at low DOC (1 mg·L(-1)), but increased with chlorine dose at higher DOC concentrations (4 mg·L(-1)). Bromine substitution factors reached maxima of 0.80, 0.67 and 0.65 for the THM4, DHAAs and THAAs, respectively, at the highest bromide/chlorine ratio studied. These results suggest that THM4 formation kinetics depend on both oxidation and halogenation steps, whereas for DHAAs and THAAs oxidation steps are more important. Furthermore, they indicate that high bromide waters may prove more problematic for water utilities with respect to THM4 formation than for THAAs or DHAAs. While mass concentrations of all three groups increased in response to increased bromide incorporation, only the THMs also showed an increase in molar yield. Overall, the formation behaviour of DHAA and THAA was more similar than that of THM4 and THAA., (© 2013.)

In metal machining processes, the regulation of heat generation and lubrication at the contact point are achieved by application of a fluid referred to as metalworking fluid (MWF). MWFs inevitably become operationally exhausted with age and intensive use, which leads to compromised properties, thereby necessitating their safe disposal. Disposal of this waste through a biological route is an increasingly attractive option, since it is effective with relatively low energy demands. However, successful biological treatment is challenging since MWFs are chemically complex, and include biocides specifically to retard microbial deterioration whilst the fluids are operational. In this study remediation of the recalcitrant component of a semi-synthetic MWF by a novel hybrid ozone-bacteriological treatment, was investigated. The hybrid treatment proved to be effective and reduced the chemical oxygen demand by 72% (26.9% and 44.9% reduction after ozonation and biological oxidation respectively). Furthermore, a near-complete degradation of three non-biodegradable compounds (viz. benzotriazole, monoethanolamine, triethanolamine), commonly added as biocides and corrosion inhibitors in MWF formulations, under ozonation was observed., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for ∼8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ∼70,000 cases and ∼68,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 × 10(-35)), 12q24 (rs1292011; P = 4.3 × 10(-19)) and 21q21 (rs2823093; P = 1.1 × 10(-12)). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.

Monitoring the quality of drinking water from the treatment plant to the consumers tap is critical to ensure compliance with national standards and/or WHO guideline levels. There are a number of processes and factors affecting the water quality during transmission and distribution which are little understood. A significant obstacle for gaining a detailed knowledge of various physical and chemical processes and the effect of the hydraulic conditions on the water quality deterioration within water supply systems is the lack of reliable and low-cost (both capital and O & M) water quality sensors for continuous monitoring. This paper has two objectives. The first one is to present a detailed evaluation of the performance of a novel in-pipe multi-parameter sensor probe for reagent- and membrane-free continuous water quality monitoring in water supply systems. The second objective is to describe the results from experimental research which was conducted to acquire continuous water quality and high-frequency hydraulic data for the quantitative assessment of the water quality changes occurring under steady and unsteady-state flow conditions. The laboratory and field evaluation of the multi-parameter sensor probe showed that the sensors have a rapid dynamic response, average repeatability and unreliable accuracy. The uncertainties in the sensor data present significant challenges for the analysis and interpretation of the acquired data and their use for water quality modelling, decision support and control in operational systems. Notwithstanding these uncertainties, the unique data sets acquired from transmission and distribution systems demonstrated the deleterious effect of unsteady state flow conditions on various water quality parameters. These studies demonstrate: (i) the significant impact of the unsteady-state hydraulic conditions on the disinfectant residual, turbidity and colour caused by the re-suspension of sediments, scouring of biofilms and tubercles from the pipe and increased mixing, and the need for further experimental research to investigate these interactions; (ii) important advances in sensor technologies which provide unique opportunities to study both the dynamic hydraulic conditions and water quality changes in operational systems. The research in these two areas is critical to better understand and manage the water quality deterioration in ageing water transmission and distribution systems., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

This paper describes a preliminary evaluation of the performance of carbonaceous materials prepared from sewage sludges (SBCMs) in a hybrid water treatment process based on adsorption and catalytic wet air oxidation; phenol was used as the model pollutant. Three different sewage sludges were treated by either carbonisation or steam activation, and the physico-chemical properties of the resultant carbonaceous materials (e.g. hardness, BET surface area, ash and elemental content, surface chemistry) were evaluated and compared with a commercial reference activated carbon (PICA F22). The adsorption capacity for phenol of the SBCMs was greater than suggested by their BET surface area, but less than F22; a steam activated, dewatered raw sludge (SA&#95;DRAW) had the greatest adsorption capacity of the SBCMs in the investigated range of concentrations (<0.05 mol L(-1)). In batch oxidation tests, the SBCMs demonstrated catalytic behaviour arising from their substrate adsorptivity and metal content. Recycling of SA&#95;DRAW in successive oxidations led to significant structural attrition and a hardened SA&#95;DRAW was evaluated, but found to be unsatisfactory during the oxidation step. In a combined adsorption-oxidation sequence, both the PICA carbon and a selected SBCM showed deterioration in phenol adsorption after oxidative regeneration, but a steady state performance was reached after 2 or 3 cycles., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The aqueous degradation of iopromide, an iodinated X-ray contrast media (ICM) compound, by the combination of UV(254) irradiation and potassium peroxydisulfate (K(2)S(2)O(8)) has been studied in laboratory scale experiments. The influence of various parameters on the performance of the treatment process has been considered, namely the UV irradiation light intensity, the initial concentrations of iopromide and peroxydisulfate, and the initial solution pH. Iopromide degradation increased with UV light intensity and peroxydisulfate concentration, but decreased with initial pH. Under specific conditions complete removal of iopromide was achieved within 30 min, and near-complete mineralisation (loss of solution TOC) within 80 min. Degradation was believed to be caused by a combination of direct photolysis, sulphate radical attack, and, to a minor degree, direct oxidation by peroxydisulfate. Approximate values for the reaction rate constants have been determined and found to be equal to 1-2x10(4) M(-1) s(-1) for sulfate radicals, and 1-2 M(-2) s(-1) for S(2)O(8)(2-). Overall compound degradation was observed to follow first-order kinetics where the rate constant decreased with initial solution pH. During the reaction, the solution pH decreased as a consequence of sulfate radical scavenging., (Copyright 2010 Elsevier B.V. All rights reserved.)

Solid waste management in developing countries is often unsustainable, relying on uncontrolled disposal in waste dumps. Particular problems arise from the disposal of treatment residues generated by removing arsenic (As) from drinking water because As can be highly mobile and has the potential to leach back to ground and surface waters. This paper reviews the disposal of water treatment wastes containing As, with a particular emphasis on stabilisation/solidification (S/S) technologies which are currently used to treat industrial wastes containing As. These have been assessed for their appropriateness for treating As containing water treatment wastes. Portland cement/lime mixes are expected (at least in part) to be appropriate for wastes from sorptive filters, but may not be appropriate for precipitative sludges, because ferric flocs often used to sorb As can retard cement hydration. Brine resulting from the regeneration of activated alumina filters is likely to accelerate cement hydration. Portland cement can immobilize soluble arsenites and has been successfully used to stabilise As-rich sludges and it may also be suitable for treating sludges generated from precipitative removal units. Oxidation of As(III) to As(V) and the formation of calcium-arsenic compounds are important immobilisation mechanisms for As in cements. Geopolymers are alternative binder systems that are effective for treating wastes rich in alumina and metal hydroxides and may have potential for As wastes generated using activated alumina. The long-term stability of cemented, arsenic-bearing wastes is however uncertain, as like many cements, they are susceptible to carbonation effects which may result in the subsequent re-release of As.

Background, Aim and Scope: Photocatalytic oxidation using UV irradiation of TiO(2) has been studied extensively and has many potential industrial applications, including the degradation of recalcitrant contaminants in water and wastewater treatment. A limiting factor in the oxidation process is the recombination of conduction band electrons (e(-)(cb)) with electron holes (h(vb)(+)) on the irradiated TiO(2) surface; thus, in aqueous conditions, the presence of an effective electron scavenger will be beneficial to the efficiency of the oxidation process. Ferrate (FeO(4)(2-)) has received much recent attention as a water treatment chemical since it behaves simultaneously as an oxidant and coagulant. The combination of ferrate [Fe(VI)] with UV/TiO(2) photocatalysis offers an oxidation synergism arising from the Fe(VI) scavenging of e(-)(cb) and the corresponding beneficial formation of Fe(V) from the Fe(VI) reduction. This paper reviews recent studies concerning the photocatalytic oxidation of problematic pollutants with and without ferrate., Materials and Methods: The paper reviews the published results of laboratory experiments designed to follow the photocatalytic degradation of selected contaminants of environmental significance and the influence of the experimental conditions (e.g. pH, reactant concentrations and dissolved oxygen). The specific compounds are as follows: ammonia, cyanate, formic acid, bisphenol-A, dibutyl- and dimethyl-phthalate and microcystin-LR. The principal focus in these studies has been on the rates of reaction rather than on reaction pathways and products., Results: The presence of UV/TiO(2) accelerates the chemical reduction of ferrate, and the reduction rate decreases with pH owing to deprotonation of ferrate ion. For all the selected contaminant substances, the photocatalytic oxidation rate was greater in the presence of ferrate, and this was believed to be synergistic rather than additive. The presence of dissolved oxygen in solution reduced the degradation rate of dimethyl phthalate in the ferrate/photocatalysis system. In the study of microcystin-LR, it was evident that an optimal ferrate concentration exists, whereby higher Fe(VI) concentrations above the optimum leads to a reduction in microcystin-LR degradation. In addition, the rate of microcystin-LR degradation was found to be strongly dependent on pH and was greatest at pH 6., Discussion: The initial rate of photocatalytic reduction under different conditions was analysed using a Langmuirian form. Decrease in rates in the presence of dissolved oxygen may be due to competition between oxygen and ferrate as electron scavengers and to non-productive radical species interactions. The reaction between ferrate(VI) and microcystins-LR in the pH range of 6.0-10.0 is most likely controlled by the protonated Fe(VI) species, HFeO(4)(-)., Conclusions: The photocatalytic oxidation of selected, recalcitrant contaminants was found to be significantly greater in the presence of ferrate, arising from the role of ferrate in inhibiting the h(vb)(+)-e(-)(cb) pair recombination on TiO(2) surfaces and the corresponding generation of highly oxidative Fe(V) species. The performance of the ferrate/photocatalysis system is strongly influenced by the reaction conditions, particularly the pH and dissolved oxygen concentration, arising from the complex nature of the interactions between the catalyst and the solution. Overall, the treatment performance of the Fe(VI)-TiO(2)-UV system is generally superior to alternative chemical oxidation methods., Recommendations and Perspectives: The formation of intermediate Fe(V) species in the photocatalytic reduction of ferrate(VI) requires confirmation, and a method involving electron paramagnetic resonance spectroscopy could be applied for this. The reactivity of Fe(V) with the selected contaminants is required in order to better understand the role of ferrate in the Fe(VI)-TiO(2)-UV oxidation system. To increase the practical utility of the system, it is recommended that future studies involving the photocatalytic oxidation of pollutants in the presence of ferrate(VI) should focus on developing modified TiO(2) surfaces that are photocatalytic under visible light conditions.

Ferrate (FeO₄²⁻) is believed to have a dual role in water treatment, both as oxidant and coagulant. Few studies have considered the coagulation effect in detail, mainly because of the difficulty of separating the oxidation and coagulation effects. This paper summarises some preliminary results from laboratory-based experiments that are investigating the coagulation reaction dynamically via a PDA instrument, between ferrate and humic acid (HA) at different doses and pH values, and comparing the observations with the use of ferric chloride. The PDA output gives a comparative measure of the rate of floc growth and the magnitude of floc formation. The results of the tests show some significant differences in the pattern of behaviour between ferrate and ferric chloride. At pH 5 the chemical dose range (as Fe) corresponding to HA coagulation was much broader for ferrate than ferric chloride, and the optimal Fe dose was greater. Ferrate oxidation appears to increase the hydrophilic and electronegative nature of the HA leading to an extended region of charge neutralisation. A consequence of the ferrate oxidation is that the extent of HA removal was slightly lower ( approximately 5%) than with ferric chloride. At pH 7, in the sweep flocculation domain, ferrate achieved much greater floc formation than ferric chloride, but a substantially lower degree of HA removal.

The influence of natural organic matter on contaminant removal by Fe(0) systems has been of increasing concern. Recent studies have shown that, in addition to direct sorption on the Fe(0) surfaces, humic acid complexation with dissolved iron released from corrosion results in the formation of colloids and aggregates in solution that may affect contaminant removal. High-pressure size-exclusion chromatographic analyses revealed increasing molecular weights of dissolved humic acids with reaction time. Humic acid aggregation occurred across a wide range of molecular weight fractions. Fourier transform infrared spectroscopic analysis of humic acid aggregates suggested the presence of inner-sphere complexation involving different oxygen-containing functional groups; hydrophobic interactions also probably contributed to aggregation as the humic acid of more aromatic and hydrophobic character was aggregated at a faster rate. Because of multiple underlying processes, a variety of cross-correlated physicochemical properties of humic acids contributed to their aggregation. The presence of humic acid aggregates provided an additional hydrophobic domain for partitioning that enhanced trichloroethylene removal, although steric blocking of the Fe(0) surfaces may inhibit its reduction to some extent. Comparable effects were demonstrated for various types of humic acids.

The imposition of more stringent legislation governing the disposal and utilisation of sewage sludge, coupled with the growth in its generation and the loss of traditionally accepted disposal routes, has prompted a drive for alternative uses for sewage sludge. One option that exhibits special promise, due to its potential to valorise the sludge, is the conversion of the sludge into adsorbents. This paper seeks to review the published research in this field: it covers the means of production, the characteristics and the potential applications of sewage sludge-based adsorbents (SBAs). The literature has indicated that chemical activation utilising alkali metal hydroxides is the most effective technique for producing high surface area SBAs. In addition, acid washing is highly effective at raising the BET surface area of SBAs, especially when coupled with physical activation. Due to their relatively low microporosity, the phenol uptake of SBAs produced by physical activation is low, but through a combination of their favourable surface chemistry and relatively high mesoporosity, the best of these adsorbents can attain high uptakes of organic dyes. The SBAs produced by carbonisation, through their high cation exchange capacity, generally exhibit a high metal cation capacity. For further research, the following investigations are recommended: the utilisation of alternative chemical activation reagents; the optimisation of the most effective chemical activation techniques; the combined utilisation of different activation and surface chemistry modification techniques to produce application-specific adsorbents.

The degradation of specific iodinated X-ray contrast media (ICM) compounds (viz: diatrizoate, iomeprol, iopromide, and iopamidol) by ultrasound irradiation in aqueous solution, with and without the presence of hydrogen peroxide or ozone, has been studied. Experiments were carried out at a constant ultrasound frequency of 20 kHz, at two power intensity values of 17.6 and 200.1 W cm(-2), and at five power densities up to 0.235 W ml(-1). Zero-order kinetic rate constants for the ICM degradation by ultrasound alone were calculated under certain sonication conditions. Pyrolysis appeared to contribute approximately 30%, and radical attack 70%, of the overall ICM degradation performance. The effect of ultrasound intensity on compound degradation (at a given power density) was found to play a negligible role, whereas ultrasound power density was found to be a major factor controlling the overall oxidation process under these conditions. The compound degradation by ultrasound alone was relatively minor, but the addition of hydrogen peroxide in the sonication process gave some improvement with a doubling in the degradation performance at the greatest applied peroxide concentration. The combination of gaseous ozone and ultrasound was found to be very effective in degrading ICM compounds and an almost complete compound removal could be achieved.

The remediation of the Thala Valley landfill, Casey Station, East Antarctica, is part of efforts to clean-up contaminated sites associated with the Australian Antarctic Program. These sites, ranging from abandoned rubbish dumps to fuel spills, are contaminated principally with metals and petroleum hydrocarbons. Remediation success depends on accurate, cost-effective and timely--fit-for-purpose--chemical analysis of soil and water samples from the site, which is required to guide excavation, the in situ or off-site treatment and disposal of contaminated material, and to validate satisfactory remediation. Owing to the remote location of Antarctica, it is necessary to carry out chemical analyses on-site. Waste and soil contaminated with Pb, Zn, Cd, and Cu were excavated from Thala Valley for removal to Australia, treatment and disposal. Analysis of total metal concentrations in soil was performed at Casey Station with a transportable energy dispersive X-ray fluorescence (EDXRF) spectrometer. Soil samples were prepared using a simple size-fractionation method to expedite sample throughput. A method for assessing contaminant mobility in solid waste (toxicity characteristic leaching procedure, TCLP) was also used to characterise soil. Although this was more labour-intensive and time-consuming than the total metals analysis, it was of great utility because leachable metals were often significant determinants in the assessment of contaminated soil. The combined data helped managers during remediation, directing excavation and allowing waste to be classified for treatment and disposal before its return to Australia.

The aqueous degradation of iodinated X-ray contrast media (ICM) by the combination of ozone and ultrasound has been studied. Experiments were conducted at a constant ultrasound frequency of 20 kHz, at five power densities up to 0.235 W/mL, and various ozone centrations. In experiments involving dissolved ozone in solution, the addition of ultrasound significantly decreased the oxidation performance of the dissolved ozone, while the combination of dissolved oxygen and ultrasound gave a greater oxidation performance than ultrasound alone. However, the combination of gaseous ozone and ultrasound was found to give a higher degree of compound degradation than either ozone or ultrasound alone. In the experiments with final effluent, the degradation of ICM compounds by gaseous ozone and ultrasound was found to depend on the ozone dose applied. The degradation of ICM compounds in final effluent was modeled, which was found to moderately overestimate the observed compound degradation.

The indirect reaction of octylphenol (OP) and nonylphenol (NP) with hydroxyl radicals (*OH) during ozonation was investigated at pH values ranging from 6 to 9. A parameter Rct, representing the ratio of the *OH-exposure to the ozone-exposure, was measured using a method involving a low concentration of p-chlorobenzoic acid as a *OH-probe compound during the ozonation. By assuming that Rct is a constant value at a given pH, the second order rate constants of the alkylphenol reaction with hydroxyl radicals were determined as 1.4(+/-0.2) x 10(10) and 1.1(+/-0.2) x 10(10) M(-1) s(-1) for OP and NP, respectively. The proportions of each alkylphenol degraded by direct molecular ozone reaction and indirect hydroxyl radical reaction were predicted at different pH values. The contribution of indirect *OH reactions with each AP was found to represent over 50% of the total degradation for pH approximately 7, and the contribution increases substantially with pH>7.

This aqueous reaction between ozone and two alkylphenols (APs), namely octylphenol (OP) and nonylphenol (NP), has been investigated. Both compounds are important endocrine disrupting chemicals, which arise from the biodegradation of alkylphenol ethoxylates and are often found at relatively high concentrations in wastewater effluents. In this paper the results of an experimental study are presented which provide values for the reaction rate constants between molecular ozone and undissociated OP and NP, and overall reaction rate constants for the degradation of the two APs at pH values in the range of 7-9. The kinetic rate constants for OP and NP degradation by molecular ozone were 4.33(+/-0.18) x 10(4) and 3.90(+/-0.10) x 10(4) M(-1) s(-1), and the reaction stoichiometry was similar in both cases and equal to approximately 1.3:1 ([O3]:[AP]). The overall second order reaction rate constants for the two APs increased significantly with increasing pH, which is believed to be mainly due to the increasing influence of indirect radical reaction with increasing pH; this aspect is considered in more detail in a companion paper. A preliminary investigation of the reaction mechanism suggests that an initial product of ozonation is hydroxyl-alkyl phenol.

Three distinctive phases of BHA reactivity toward UV/ S2O8(2-) at acidic, neutral, and basic pH range were examined, where 80-100% mineralization has been observed within an hour of irradiation under 254 nm. A reduction in solution pH during the reaction was observed mainly due to the complete conversion of S2O8(2-) to sulfate ion together with proton generation. Seven measurable intermediates were found via an oxidation and dimerization process at all tested pH levels. The BHA decay mechanisms are quite different in acidic condition and at other pH levels. There are three unique intermediates that are only detectable at pH 3 via two additional pathways. This is due to the generation of weaker oxidants or radicals which results in a slower degradation of the BHA, and therefore, the accumulation of these intermediates to detectable levels. The rate of BHA decay generally increases from low to high pH levels; however, the corresponding mineralization at higher pH is retarded due to the futile process of recombining radicals and involvement of intermediates. Therefore, neutral pH was suggested to be the optimum condition in terms of mineralization and moderate efficiency in removing BHA.

Purpose: To conduct a phase I clinical trial with a second-generation oncolytic herpes simplex virus (HSV) expressing granulocyte macrophage colony-stimulating factor (Onco VEXGM-CSF) to determine the safety profile of the virus, look for evidence of biological activity, and identify a dosing schedule for later studies., Experimental Design: The virus was administered by intratumoral injection in patients with cutaneous or s.c. deposits of breast, head and neck and gastrointestinal cancers, and malignant melanoma who had failed prior therapy. Thirteen patients were in a single-dose group, where doses of 10(6), 10(7), and 10(8) plaque-forming units (pfu)/mL were tested, and 17 patients were in a multidose group testing a number of dose regimens., Results: The virus was generally well tolerated with local inflammation, erythema, and febrile responses being the main side effects. The local reaction to injection was dose limiting in HSV-seronegative patients at 10(7) pfu/mL. The multidosing phase thus tested seroconverting HSV-seronegative patients with 10(6) pfu/mL followed by multiple higher doses (up to 10(8) pfu/mL), which was well tolerated by all patients. Biological activity (virus replication, local reactions, granulocyte macrophage colony-stimulating factor expression, and HSV antigen-associated tumor necrosis), was observed. The duration of local reactions and virus replication suggested that dosing every 2 to 3 weeks was appropriate. Nineteen of 26 patient posttreatment biopsies contained residual tumor of which 14 showed tumor necrosis, which in some cases was extensive, or apoptosis. In all cases, areas of necrosis also strongly stained for HSV. The overall responses to treatment were that three patients had stable disease, six patients had tumors flattened (injected and/or uninjected lesions), and four patients showed inflammation of uninjected as well as the injected tumor, which, in nearly all cases, became inflamed., Conclusions: Onco VEXGM-CSF is well tolerated and can be safely administered using the multidosing protocol described. Evidence of an antitumor effect was seen.

In this study, the degradation of atrazine (ATZ) by ozone (O3) oxidation and its associated processes (i.e. UV, UV/O3) in the presence and absence of surfactant was investigated and compared. A non-ionic surfactant, Brij 35, was selected. It was found that the presence of a low concentration of surfactant could improve the removal of ATZ by increasing the dissolution of ozone and the indirect generation of hydroxyl radicals. The saturated ozone level and the reaction rate constants were increased with increasing the concentration of surfactant and then decreased at higher surfactant doses at pH level of 2.5. A similar trend was observed at pH level of 7.0 in the presence of bicarbonate ion, because it is capable of deactivating the hydroxyl radicals generating at higher pH level. However, when the radical reactions become dominant in the ozonation (at pH 7.0 without bicarbonate), the saturated ozone level was higher than that with bicarbonate and the kinetic rate constants were increased first and levelled off with increasing of the dose of surfactant. Through the examining of a proposed unit performance index, the low concentration of surfactant is surely beneficial to the ozonation process. Besides, the direct photolysis and photo-assisted ozonation were compared to the ozonation. A significant enhancement on the decay rate of ATZ was resulted exclusively by adding the surfactant. An enhancement index for quantifying the improvement of the various processes was developed.

We have developed a mutation-scanning approach suitable for whole population screening for unknown mutations. The method, meltMADGE, combines thermal ramp electrophoresis with MADGE to achieve suitable cost efficiency and throughput. The sensitivity was tested in blind trials using 54 amplicons representing the BRCA1 coding region and a panel of 94 unrelated family breast cancer risk consultands previously screened in a clinical diagnostic laboratory. All 10 common polymorphisms, 15/15 previously identified disease-causing mutations, and three previously untested single base changes were identified. Assays of LDLR exons 3 and 8 were validated in 460 familial hypercholesteremics and detected 8/9 known variants. We then applied the exon 3 assay in several DNA banks representing approximately 8000 subjects with known cholesterol values and applied both assays in one DNA bank (n = 3600). In exon 3 we identified one previously reported moderate mutation, P84S (n = 1), also associated with moderate hypercholesteremia in this subject; an unreported silent variant, N76N (n = 1); and known severe hypercholesteremia splice mutation 313+1G-->A (n = 2). Around exon 8 we identified a paucimorphism (n = 35) at the splice site 1061-8T-->C (known to be in complete linkage disequilibrium with T705I) and unreported sequence variants 1186+11G-->A (n = 1) and D335N G-->A (n = 1). The cholesterol value for D335N was on the 96.2 percentile and for T705I, 2/35 carriers were above the 99th percentile. Thus, variants with predicted severe, moderate, and no effect were identified at the population level. In contrast with case collections, CpG mutations predominated. MeltMADGE will enable definition of the full population spectrum of rare, paucimorphic, severe, moderate (forme fruste), and silent mutations and effects.

Background: Most obstetricians and gynecologists order serum levels of thyroid stimulating hormone (TSH) and prolactin (PRL) in every female patient undergoing an infertility evaluation (regardless of their menstrual rhythm)., Methods: Patients were recruited from the clinical practice of the named authors in a prospective manner. Serum TSH and PRL were ordered at the time of the couple's initial consult., Results: 2.48% of patients (21 out of 846 patients) had abnormal levels of TSH, and 1.77% (15 of 844 patients) had elevated levels of PRL., Conclusions: The practice of routinely ordering serum levels of TSH and PRL in infertility patients having normal periods is questioned.