An Effect of Gaze Direction in Cocktail Party Listening.

It is well established that gaze direction can influence auditory spatial perception, but the implications of this interaction for performance in complex listening tasks is unclear. In the current study, we investigated whether there is a measurable effect of gaze direction on speech intelligibility in a "cocktail party" listening situation. We presented sequences of digits from five loudspeakers positioned at 0°, ± 15°, and ± 30° azimuth, and asked participants to repeat back the digits presented from a designated target loudspeaker. In different blocks of trials, the participant visually fixated on a cue presented at the target location or at a nontarget location. Eye position was tracked continuously to monitor compliance. Performance was best when fixation was on-target (vs. off-target) and the size of this effect depended on the specific configuration. This result demonstrates an influence of gaze direction in multitalker mixtures, even in the absence of visual speech information.

Dynamic Survival Analysis for EHR Data with Personalized Parametric Distributions.

The widespread availability of high-dimensional electronic healthcare record (EHR) datasets has led to significant interest in using such data to derive clinical insights and make risk predictions. More specifically, techniques from machine learning are being increasingly applied to the problem of dynamic survival analysis, where updated time-to-event risk predictions are learned as a function of the full covariate trajectory from EHR datasets. EHR data presents unique challenges in the context of dynamic survival analysis, involving a variety of decisions about data representation, modeling, interpretability, and clinically meaningful evaluation. In this paper we propose a new approach to dynamic survival analysis which addresses some of these challenges. Our modeling approach is based on learning a global parametric distribution to represent population characteristics and then dynamically locating individuals on the time-axis of this distribution conditioned on their histories. For evaluation we also propose a new version of the dynamic C-Index for clinically meaningful evaluation of dynamic survival models. To validate our approach we conduct dynamic risk prediction on three real-world datasets, involving COVID-19 severe outcomes, cardiovascular disease (CVD) onset, and primary biliary cirrhosis (PBC) time-to-transplant. We find that our proposed modeling approach is competitive with other well-known statistical and machine learning approaches for dynamic risk prediction, while offering potential advantages in terms of interepretability of predictions at the individual level.

Rumination decreases parental problem-solving effectiveness in dysphoric postnatal mothers.

BACKGROUND: Postnatal depression is associated with poorer parenting quality, but there are few studies examining maternal-specific cognitive processes that may impact on parenting quality. In this study, we examined the impact of rumination on parental problem-solving effectiveness in dysphoric and non-dysphoric postnatal mothers. METHODS: Fifty-nine mothers with a infant aged 12 months and under, 20 of whom had a Beck Depression Score II (BDI-II) score ≥ 14, and 39 who scored less than 14 on the BDI-II were randomly assigned to either a rumination or distraction condition. Problem-solving effectiveness was assessed post-induction with the "Postnatal Parental Problem-Solving Task" (PPST), which was adapted from the Means Ends Problem-solving task. Parental problem-solving confidence was also assessed. RESULTS: Dysphoric ruminating mothers exhibited poorer problem-solving effectiveness and poorer confidence regarding their problem-solving compared to dysphoric distracting, non-dysphoric distracting, and non-dysphoric ruminating mothers. LIMITATIONS: A self-report measure of depressed mood was used. CONCLUSIONS: Rumination may be a key mechanism associated with both depressive mood and maternal parenting quality during the postnatal period.

Blastomyces dermatitidis Yeast Lysate Antigen Combinations: Antibody Detection in Dogs with Blastomycosis.

The systemic fungal infection, blastomycosis, which infects both humans and animals has presented a diagnostic challenge for clinicians for many years. The aim of this study was to evaluate the diagnostic sensitivity of Blastomyces dermatitidis yeast lysate antigens with respect to antibody detection in dogs with blastomycosis. Lysate antigens were prepared from B. dermatitidis isolates T-58 and T-66 (dogs, Tennessee) and WI-R and WI-J (dogs, Wisconsin). Based on results obtained from a preliminary comparative study, five combinations of these isolates and one individual isolate were tested against 92 serum specimens from dogs with culture-proven or histologically-confirmed blastomycosis, using the indirect enzyme-linked immunosorbent assay (ELISA). Mean absorbance values obtained from the sera ranged from 0.905 with the individual T-58 antigen to 1.760 using an antigen combination (T-58 + T-66 + WI-R). All of the 6 antigenic preparations were able to detect antibody in the serum specimens, but the antigen combinations detected antibody to a higher degree than the individual antigen. This study provides evidence that combinations of the yeast lysate reagents seem to be more efficacious for antibody detection in dog sera, but our laboratory is continuing to evaluate antigen lysate combinations for detection of antibodies in blastomycosis.

The Paleozoic origin of enzymatic lignin decomposition reconstructed from 31 fungal genomes.

Wood is a major pool of organic carbon that is highly resistant to decay, owing largely to the presence of lignin. The only organisms capable of substantial lignin decay are white rot fungi in the Agaricomycetes, which also contains non-lignin-degrading brown rot and ectomycorrhizal species. Comparative analyses of 31 fungal genomes (12 generated for this study) suggest that lignin-degrading peroxidases expanded in the lineage leading to the ancestor of the Agaricomycetes, which is reconstructed as a white rot species, and then contracted in parallel lineages leading to brown rot and mycorrhizal species. Molecular clock analyses suggest that the origin of lignin degradation might have coincided with the sharp decrease in the rate of organic carbon burial around the end of the Carboniferous period.

The genome of the xerotolerant mold Wallemia sebi reveals adaptations to osmotic stress and suggests cryptic sexual reproduction.

Wallemia (Wallemiales, Wallemiomycetes) is a genus of xerophilic Fungi of uncertain phylogenetic position within Basidiomycota. Most commonly found as food contaminants, species of Wallemia have also been isolated from hypersaline environments. The ability to tolerate environments with reduced water activity is rare in Basidiomycota. We sequenced the genome of W. sebi in order to understand its adaptations for surviving in osmotically challenging environments, and we performed phylogenomic and ultrastructural analyses to address its systematic placement and reproductive biology. W. sebi has a compact genome (9.8 Mb), with few repeats and the largest fraction of genes with functional domains compared with other Basidiomycota. We applied several approaches to searching for osmotic stress-related proteins. In silico analyses identified 93 putative osmotic stress proteins; homology searches showed the HOG (High Osmolarity Glycerol) pathway to be mostly conserved. Despite the seemingly reduced genome, several gene family expansions and a high number of transporters (549) were found that also provide clues to the ability of W. sebi to colonize harsh environments. Phylogenetic analyses of a 71-protein dataset support the position of Wallemia as the earliest diverging lineage of Agaricomycotina, which is confirmed by septal pore ultrastructure that shows the septal pore apparatus as a variant of the Tremella-type. Mating type gene homologs were identified although we found no evidence of meiosis during conidiogenesis, suggesting there may be aspects of the life cycle of W. sebi that remain cryptic.

Hal: an automated pipeline for phylogenetic analyses of genomic data.

The rapid increase in genomic and genome-scale data is resulting in unprecedented levels of discrete sequence data available for phylogenetic analyses. Major analytical impasses exist, however, prior to analyzing these data with existing phylogenetic software. Obstacles include the management of large data sets without standardized naming conventions, identification and filtering of orthologous clusters of proteins or genes, and the assembly of alignments of orthologous sequence data into individual and concatenated super alignments. Here we report the production of an automated pipeline, Hal that produces multiple alignments and trees from genomic data. These alignments can be produced by a choice of four alignment programs and analyzed by a variety of phylogenetic programs. In short, the Hal pipeline connects the programs BLASTP, MCL, user specified alignment programs, GBlocks, ProtTest and user specified phylogenetic programs to produce species trees. The script is available at sourceforge (http://sourceforge.net/projects/bio-hal/). The results from an example analysis of Kingdom Fungi are briefly discussed.

Phylogenomic evidence for a common ancestor of mitochondria and the SAR11 clade.

Mitochondria share a common ancestor with the Alphaproteobacteria, but determining their precise origins is challenging due to inherent difficulties in phylogenetically reconstructing ancient evolutionary events. Nonetheless, phylogenetic accuracy improves with more refined tools and expanded taxon sampling. We investigated mitochondrial origins with the benefit of new, deeply branching genome sequences from the ancient and prolific SAR11 clade of Alphaproteobacteria and publicly available alphaproteobacterial and mitochondrial genome sequences. Using the automated phylogenomic pipeline Hal, we systematically studied the effect of taxon sampling and missing data to accommodate small mitochondrial genomes. The evidence supports a common origin of mitochondria and SAR11 as a sister group to the Rickettsiales. The simplest explanation of these data is that mitochondria evolved from a planktonic marine alphaproteobacterial lineage that participated in multiple inter-specific cell colonization events, in some cases yielding parasitic relationships, but in at least one case producing a symbiosis that characterizes modern eukaryotic life.

Reduced drug use and hospitalization rates in patients undergoing hemodialysis who received pharmaceutical care: a 2-year, randomized, controlled study.

STUDY OBJECTIVE: To investigate the impact of a pharmaceutical care program managed by clinical pharmacists on drug use, drug costs, hospitalization rates, and drug-related problems (DRPs) in ambulatory patients undergoing hemodialysis. DESIGN: Prospective, randomized, controlled, longitudinal, 2-year pilot study. SETTING: Nonprofit university-affiliated dialysis clinic. PATIENTS: One hundred four patients older than 18 years with end-stage renal disease (ESRD) who were undergoing a stable hemodialysis regimen for at least 3 months. INTERVENTION: Patients were randomly assigned to receive either pharmaceutical care, consisting of one-on-one care, with in-depth drug therapy reviews conducted by a clinical pharmacist (57 patients), or standard of care, consisting of brief drug therapy reviews conducted by a nurse (47 patients). MEASUREMENTS AND MAIN RESULTS: Baseline data on demographic and clinical characteristics were collected. Mean numbers of concomitant drugs, drug costs, hospitalization rates, and lengths of stay were compared between the groups. In the pharmaceutical care group, DRPs were identified and recorded. Baseline age, length of time receiving hemodialysis, and etiology of ESRD were not significantly different between the groups. Mean number of concomitant drugs at baseline was similar between the groups. At the end of the 2-year follow-up, pharmaceutical care was associated with a significant decrease of 14% fewer drugs compared with standard of care, as documented during each drug therapy review (p<0.05). There were significantly fewer all-cause hospitalizations among patients assigned to pharmaceutical care compared with those receiving standard of care (mean +/- SD 1.8 +/- 2.4 vs 3.1 +/- 3 hospitalizations, p=0.02), and the cumulative time hospitalized was shorter in the pharmaceutical care group compared with the standard of care group (9.7 +/- 14.7 vs 15.5 +/- 16.3 days, p=0.06). During the study period, 530 DRPs were identified and resolved. CONCLUSION: Identification and resolution of DRPs through pharmaceutical care resulted in decreased drug use and costs for patients undergoing hemodialysis. Hospitalization rates were significantly lower in the pharmaceutical care group, with a trend toward shorter duration. Provision of pharmaceutical care is associated with tangible benefits on outcomes in ambulatory patients undergoing hemodialysis and should be considered in health care policy decisions.

Health-related quality of life is maintained in hemodialysis patients receiving pharmaceutical care: a 2-year randomized, controlled study.

End-stage renal disease and initiation of hemodialysis (HD) adversely affect health-related quality of life (HRQOL). There are currently no data evaluating the effect of pharmaceutical care (PC) on HRQOL in HD patients. HD patients were randomized to receive PC; one-on-one, in-depth medication reviews conducted by a clinical pharmacist or Standard of Care (SOC); and brief medication reviews conducted by dialysis nurses. The renal quality of life profile (RQLP) was administered at baseline and then at 1 and 2 years after study initiation. The RQLP is a 43-item questionnaire that has 5 dimensions: Eating/Drinking, Physical Activities, Leisure Time, Psychosocial Activities, and Impact of Treatment, where increasing scores reflect worsening of HRQOL. A total of 107 patients were enrolled (SOC: n=46; PC: n=61). Besides gender, there were no differences in the demographics or the baseline total RQLP scores. The mean+/-SD total RQLP scores at Year 1 were significantly worse in SOC compared with PC (88+/-31 vs. 71+/-34, respectively; P=0.03). Significant worsening of Eating and Drinking (5.9+/-3.3 vs. 4.4+/-3.1, respectively; P=0.04), Physical Activities (37+/-13.6 vs. 30+/-16.3, respectively; P=0.04), and Leisure Time scores (8.3+/-3.4 vs. 5.9+/-3.6, respectively; P=0.03) was also observed in the SOC group. After 2 years, only the SOC patients had worsening of Leisure Time (7.5+/-3.0 vs. 5.2+/-3.9, respectively; P=0.04). No other parameters were different between the groups after 2 years. These data indicate that patients who have clinical care provided by pharmacists do not have worsened HRQOL after 1 year and are able to maintain HRQOL for an additional year.

Metformin use in decompensated heart failure.

Metformin is associated with decreased mortality and morbidity in stable heart failure patients with diabetes mellitus type II. Diabetic heart failure patients with elevated systolic blood pressure are at increased risk for developing acute decompensated heart failure, which is often associated with decreased kidney function. Metformin-associated lactic acidosis is a rare but fatal side effect that may occur when kidney function is decreased. During acute decompensated heart failure, timely treatment may prevent the decrease in kidney function to the threshold associated with an increased risk of metformin-associated lactic acidosis. Metformin should not be withheld in diabetic patients with stable heart failure who do not have other risk factors for acute decompensated heart failure or lactic acidosis.

Comparison of oxidative stress markers after intravenous administration of iron dextran, sodium ferric gluconate, and iron sucrose in patients undergoing hemodialysis.

STUDY OBJECTIVE: To compare non-transferrin-bound iron and markers of oxidative stress after single intravenous doses of iron dextran, sodium ferric gluconate, and iron sucrose. DESIGN: Prospective, open-label, crossover study. SETTING: University-affiliated general clinical research center. PATIENTS: Twelve ambulatory patients undergoing hemodialysis. INTERVENTION: Patients received 100 mg of intravenous iron dextran, sodium ferric gluconate, and iron sucrose in random sequence, with a 2-week washout period between treatments. MEASUREMENTS AND MAIN RESULTS: Serum samples for transferrin saturation, non-transferrin-bound iron, and malondialdehyde (MDA; marker of lipid peroxidation) were obtained before (baseline) and 30, 60, 120, and 360 minutes and 2 weeks after each iron infusion. A serum sample for hemeoxygenase-1 (HO-1) RNA was obtained at baseline and 360 minutes after infusion. Non-transferrin-bound iron values were significantly higher 30 minutes after administration of sodium ferric gluconate and iron sucrose compared with iron dextran (mean +/- SEM 10.1 +/- 2.2, 3.8 +/- 0.8, and 0.23 +/-0.1 microM, respectively, p<0.001 for sodium ferric gluconate vs iron dextran, p = 0.002 for iron sucrose vs iron dextran). A significant positive correlation was noted between transferrin saturation and the presence of non-transferrin-bound iron for sodium ferric gluconate and iron sucrose (r2 = 0.37 and 0.45, respectively, p<0.001) but not for iron dextran (r2 = 0.09). After sodium ferric gluconate, significantly more samples showed increases in MDA levels from baseline compared with iron sucrose and iron dextran (p = 0.006); these increased levels were associated with the presence of non-transferrin-bound iron, baseline transferrin saturation above 30%, baseline transferrin levels below 180 mg/dl, and ferritin levels above 500 ng/ml (p<0.05). However, only a transferrin level below 180 mg/dl was independently associated (odds ratio 4.8, 95% confidence interval 1.2-15.3). CONCLUSION: Iron sucrose and sodium ferric gluconate were associated with greater non-transferrin-bound iron appearance compared with iron dextran. However, only sodium ferric gluconate showed significant increases in lipid peroxidation. The relationship between non-transferrin-bound iron from intravenous iron and oxidative stress warrants further exploration.

Effect of intravenous iron supplementation on hepatic cytochrome P450 3A4 activity in hemodialysis patients: a prospective, open-label study.

BACKGROUND: Cytochrome P450 (CYP) 3A4 is an enzyme with activity dependent on the reduction of heme iron that is responsible for the metabolism of many drugs. CYP3A4 activity is reduced in hemodialysis (HD) patients and thus may be related to functional iron deficiency. OBJECTIVE: The purpose of this study was to investigate the effect of IV iron supplementation on hepatic is CYP3A4 activity in HD patients. METHODS: This prospective, open-label study was conducted in 12 iron-deficient (transferrin saturation <20% or ferritin <100 ng/L) HD patients on stable medication regimens. To probe for hepatic CYP3A4 activity, an erythromycin breath test (ERMBT) was administered before and after 1 g IV iron sucrose (administered as a 100-mg dose [20 mg/mL]), at each of 10 consecutive HD sessions). CYP3A4 activity was estimated by the percentage of administered (14)C exhaled in a single-breath collection after the test dose of erythromycin underwent demethylation by CYP3A4. The ERMBT was also administered to 7 age-, sex-, and race-matched healthy controls. RESULTS: Twelve HD patients (6 Hispanic, 3 white, 3 Native American; 8 men, 4 women; mean [SEM] age, 56.2 [5.0] years; mean [SEM] weight, 77.0 [5.6] kg; and 7 controls (4 men, 3 women; mean [SEM] age, 51.3 [5.0] years; mean [SEM] weight, 77.5 [7.4] kg) were enrolled in the study. In the total HD population studied, mean (SEM) CYP3A4 activity did not change significantly after IV iron replacement (1.46 [0.27] vs 1.57 [0.24] (14)C exhaled/h). A subgroup of 7 HD patients had significantly lower CYP3A4 activity before IV iron replacement compared with the other 5 HD patients and controls (mean [SEM] 0.86 [0.24] vs 2.30 [0.26] and 2.10 [0.26] (14)C exhaled/h; P < 0.01). After IV iron replacement, mean (SEM) CYP3A4 activity increased in these 7 HD patients (120.1% [67.1%]); P = 0.04) and it was not statistically different from that of controls (1.50 [0.36] vs 2.10 [0.26]). CONCLUSIONS: Overall, IV iron administration had no significant effect on hepatic CYP3A4 activity. However, in a subset of HD patients with low baseline CYP3A4 activity indicated by low ERMBT values, IV iron supplementation was associated with a potentially clinically relevant increase in hepatic CYP3A4 activity. Further studies are needed to clarify mechanisms and clinical implications of this interaction.

Sampling for international normalized ratios in patients on hemodialysis with central venous catheters.

The primary objectives of this study were to evaluate the effect of varying heparin concentrations on International Normalized Ratio values and to assess the accuracy of these values deter mined through the arterial line of the dialysis circuit Twenty-two patients on hemodialysis with central venous catheters were studied After a peripheral venipuncture, timed samples from the arterial line of the hemodialysis circuit were obtained after dialysis was initiated and prior to initiating heparin. Assays for coagulation parameters were performed. There was no signifcant difference in any coagulation parameter measured from the arterial line samples compared to the venipuncture samples. Serial heparin dilutions in vitro demonstrated that residual amounts of heparin in the central venous catheter may falsely elevate International Normalized Ratio values. This study demonstrates that accurate International Normalized Ratio values in patients on hemodialysis with heparinized central venous catheters can be obtained ericiently and cost-effectively from the arterial line within 1 minute of dialysis initiation.