Serial multi-omic analysis of proteome, phosphoproteome, and acetylome provides insights into changes in protein expression, cell signaling, cross-talk and epigenetic pathways involved in disease ...pathology and treatment. However, ubiquitylome and HLA peptidome data collection used to understand protein degradation and antigen presentation have not together been serialized, and instead require separate samples for parallel processing using distinct protocols. Here we present MONTE, a highly sensitive multi-omic native tissue enrichment workflow, that enables serial, deep-scale analysis of HLA-I and HLA-II immunopeptidome, ubiquitylome, proteome, phosphoproteome, and acetylome from the same tissue sample. We demonstrate that the depth of coverage and quantitative precision of each 'ome is not compromised by serialization, and the addition of HLA immunopeptidomics enables the identification of peptides derived from cancer/testis antigens and patient specific neoantigens. We evaluate the technical feasibility of the MONTE workflow using a small cohort of patient lung adenocarcinoma tumors.
Background The relationship of hyperglycemia to general surgery outcomes is not well-understood. We studied the association of operative day and postoperative day 1 (POD1) blood glucose (BG) with ...outcomes after open colectomy for cancer. Study Design We retrospectively analyzed the 2000-2005 Veterans Affairs Surgical Quality Improvement Program database, linked with Veterans Affairs Decision Support System BG values. Median BG was categorized as hypoglycemic (<80 mg/dL); normoglycemic (BG 80−120 mg/dL); or mildly (BG 121−160 mg/dL), moderately (BG 161−200 mg/dL), or severely (BG >200 mg/dL) hyperglycemic. The relationship of BG to postoperative outcomes was assessed with multivariable logistic regression. Results We identified 9,638 colectomies. We excluded 511 procedures for emergency status or preoperative coma, mechanical ventilation, or sepsis. After excluding patients without recorded BG, we analyzed operative day and POD1 BG in 7,576 and 5,773 procedures, respectively. On multivariable analysis, operative day moderate hyperglycemia was associated with surgical site infection (odds ratio = 1.44; 95% CI, 1.10−1.87). POD1 severe hyperglycemia was associated with cardiac arrest (odds ratio = 2.31; 95% CI, 1.08−4.98) and death (odds ratio = 1.97; 95% CI, 1.23−3.15). POD1 mild (odds ratio = 2.20; 95% CI, 1.05−4.60), moderate (odds ratio = 3.44; 95% CI, 1.51−7.84), and severe (odds ratio = 3.94; 95% CI, 1.64−9.58) hyperglycemia and hypoglycemia (odds ratio = 6.74; 95% CI, 1.75−25.97) were associated with myocardial infarction. Associations were similar in diabetic and nondiabetic patients. Conclusions Even mild hyperglycemia was associated with adverse outcomes after colectomy, suggesting that a perioperative BG target of 80 to 120 mg/dL, although avoiding hypoglycemia, might be appropriate. Randomized clinical trials are needed to confirm these findings.
Full text
Available for:
GEOZS, NUK, OILJ, SBJE, UL, UPUK
High river water temperature (Tw) extremes have been widely reported during drought conditions as extreme low‐flows often coincide with high atmospheric energy inputs. This has significant ...implications for freshwater ecosystem health and sustainable river management practices globally. However, the extent to which different meteorological and hydrological processes interact during droughts to govern Tw dynamics, and how this varies between environmental contexts, remains poorly understood. Here, we review the mechanisms controlling Tw dynamics during droughts across temperate, maritime environments, using the United Kingdom as a detailed case study. We evidence that Tw spikes have widely occurred during extreme low‐flow events observed within droughts, but such trends have been inconsistent due to varying hydroclimatic conditions and river basin controls. To better understand this, we re‐conceptualize the mechanisms governing drought‐induced Tw dynamics operating across three ‘process sets’: (i) ‘energy flux dynamics’ as non‐advective controls on Tw; (ii) the role of ‘reach‐scale habitat conditions’ in mediating non‐advective controls on Tw, including hydraulic properties (e.g., residence time) and physical conditions (e.g., riparian vegetation coverages, wetted perimeters); (iii) ‘water source contributions’ (surface water and groundwater) as advective heat and water flow controls. We review natural and anthropogenic influences affecting Tw controls within each process set and discuss how such mechanisms are likely to change under drought conditions. More systematic research (spanning various river environments and drought severities) is required to test such concepts, with existing scientific knowledge on drought‐induced Tw dynamics being largely gleaned from studies examining non‐extreme low‐flow conditions or with broader focuses (e.g., annual thermal dynamics). We conclude by highlighting critical future research questions that need to be answered to better model Tw dynamics during future droughts and for unmonitored sites. Such scientific advances would more effectively inform how high Tw extremes could be better managed through evidence‐based mitigation and adaptation strategies.
Changes in the relative influence of dominant heat fluxes governing drought‐induced river water temperature (Tw) variations. Thin, moderate and thick lines denote small, intermediate and large relative effects, respectively. Emboldened, italicized and underlined text denotes mechanisms comprising the ‘energy flux dynamics’, ‘reach‐scale habitat conditions’ and ‘water source contributions’ process sets, respectively.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We assessed cause specific and all cause survival in men with locally advanced prostate cancer after hormone therapy.
Between February 1991 and November 2000, 208 men with locally advanced prostate ...cancer were treated with gonadal androgen ablation or gonadal androgen ablation and an antiandrogen at a single medical center. Median PSA was 46 ng./ml. (range 2 to 748). Median potential followup was 78 months (range 4 to 122) and the median observation period was 46 months (range 3 to 122).
Of the patients 14 (7%) died of causes related to cancer and 71 (34%) died of competing co-morbid disease. Actuarial cause specific survival at 5 and 8 years was 92% and 80%, respectively. The only demographic or tumor related variable that influenced cause specific survival was Gleason score less than 8 versus 8 or greater (p = 0.02). Actuarial all cause survival at 5 and 8 years was 59% and 41%, respectively. The only variable that influenced all cause survival was a Charlson weighted co-morbidity score of less than 2 versus 2 or greater (p <0.0001). Major morbidity from the primary tumor, including bothersome obstructive voiding symptoms requiring transurethral prostate resection, ureteral obstruction or persistent hematuria, developed in 13 patients (6%), while major treatment related morbidity, including flutamide hepatotoxicity and hip fracture, developed in 4.
Hormone therapy for locally advanced prostate cancer is associated with minimal morbidity from the primary tumor and from treatment. All cause survival parallels that reported for integrated hormone and radiation therapy.
ABSTRACT
This paper presents data about the emotional, behavioural and substance abuse disorders of youth in foster care and former recipients of foster care (‘alumni’) in the USA. The prevalence ...rates of these groups are compared to those of the youth and young adults in the US general population. The implications of these data for policy and program design are discussed.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
There is evidence across several species for genetic control of phenotypic variation of complex traits, such that the variance among phenotypes is genotype dependent. Understanding genetic control of ...variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using ∼170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype), is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of ∼0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI, possibly mediated by DNA methylation. Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.
Full text
Available for:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The mesopredator release hypothesis (MRH) has been suggested as a reason why many mammalian generalist mesopredators flourish and become abundant. However, the MRH has only been examined in a limited ...number of field studies. Some studies have argued that coyotes (Canis latrans) act as top predators in fragmented forest systems and coyote presence has a positive effect on song bird diversity and abundance by controlling mesopredator abundance. We integrated camera trap data and occupancy modeling to determine the factors that affect coyote detection probability and habitat use in a fragmented suburban landscape in central Missouri. We then examined the influence of coyote presence and other habitat variables on mesopredator detection probability and habitat use in the same system. Coyote detection was negatively related to increasing forest cover, whereas red fox (Vulpes vulpes) detection was positively related to increasing urbanization. Coyote occurrence models suggested little habitat selection, while the mesopredator occurrence models suggested an affinity for urbanization. Although there was a slight negative effect of coyote presence on site use by other mesopredators, we suggest that the smaller species are better adapted to coexisting with humans and thus have increased in abundance.
Full text
Available for:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A rapid, sensitive, and accurate method for the screening and determination of polycyclic aromatic hydrocarbons (PAHs) in edible seafood is described. The method uses quick, easy, cheap, effective, ...rugged, and safe (QuEChERS)-based extraction and HPLC with fluorescence detection (FLD). The method was developed and validated in response to the massive Deepwater Horizon oil spill in the Gulf of Mexico. Rapid and highly sensitive PAH screening methods are critical tools needed for oil spill response; they help to assess when seafood is safe for harvesting and consumption. Sample preparation involves SPE of edible seafood portions with acetonitrile, followed by the addition of salts to induce water partitioning. After centrifugation, a portion of the acetonitrile layer is filtered prior to analysis via HPLC-FLD. The chromatographic method uses a polymeric C18 stationary phase designed for PAH analysis with gradient elution, and it resolves 15 U.S. Environmental Protection Agency priority parent PAHs in fewer than 20 min. The procedure was validated in three laboratories for the parent PAHs using spike recovery experiments at PAH fortification levels ranging from 25 to 10 000 microg/kg in oysters, shrimp, crab, and finfish, with recoveries ranging from 78 to 99%. Additional validation was conducted for a series of alkylated homologs of naphthalene, dibenzothiophene, and phenanthrene, with recoveries ranging from 87 to 128%. Method accuracy was further assessed based on analysis of National Institute of Standards and Technology Standard Reference Material 1974b. The method provides method detection limits in the sub to low ppb (microg/kg) range, and practical LOQs in the low ppb (microg/kg) range for most of the PAH compounds studied.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
C. W. White, J. H. Jackson, A. Abuchowski, G. M. Kazo, R. F. Mimmack, E. M. Berger, B. A. Freeman, J. M. McCord and J. E. Repine
Department of Pediatrics, University of Colorado School of Medicine, ...Denver 80262.
When exposed continuously to hyperoxia (100% O2, 760 Torr barometric
pressure), rats pretreated with polyethylene glycol (PEG)-attached
superoxide dismutase and catalase (PEG-SOD + PEG-CAT) lived longer (79.1 +
7.6 h) than rats pretreated with saline (60.7 +/- 2.1 h) or
PEG-inactivated-SOD + PEG-inactivated-CAT (62.3 +/- 1.6 h). Rats pretreated
with PEG-SOD + PEG-CAT also had less hyperoxia-induced acute oxidative
edematous lung injury, as assessed by increases in lung oxidized
glutathione (GSSG) contents, pleural effusions, and lung lavage albumin
concentrations than saline-pretreated rats. Rats pretreated with the
long-lived conjugates PEG-inactivated-SOD + PEG-inactivated-CAT or
PEG-albumin also had decreased acute oxidative edematous lung injury
compared with rats pretreated with PEG, SOD + CAT + PEG, SOD + CAT, or
saline. In vitro studies suggested that PEG itself may have contributed to
protection by scavenging hydroxyl radical (.OH) but not superoxide (O2-.)
or H2O2. Compared with more effective endogenous (via preexposure to
hypoxia) or exogenous (via liposomes) means for increasing lung antioxidant
enzymes, PEG enzymes are less protective against lung injury from
continuous hyperoxia.
PDF
