Comparison of structural differences between yeast ß-glucan sourced from different strains of saccharomyces cerevisiae and processed using proprietary manufacturing processes.

In this study, we explored structural differences of five commercial samples of yeast ß-glucan. Samples were assayed for their ß-glucan content and the yeast storage carbohydrate, glycogen. The ß-glucan content ranged from 74% to 86%, the glycogen content varied from 0 to 20%. The linkage pattern of each sample was measured by the partially methylated alditol acetate method. This method showed that the samples varied from 1.9% to 9.2% branching. The side chain length distribution for each sample was analyzed by an alkaline degradation assay followed by ion chromatography. The side length distributions of the samples were shown to be similar. The samples were also analyzed by FT-IR and 1HNMR spectroscopy but it was difficult to derive quantitative differences in the samples by these methods. Our findings confirm that each proprietary source of yeast ß-glucan has a unique purity profile, branching, and linkage patterns that determine the chemical structure and composition.

Paternal provisioning results from ecological change.

Paternal provisioning among humans is puzzling because it is rare among primates and absent in nonhuman apes and because emergent provisioning would have been subject to paternity theft. A provisioning "dad" loses fitness at the hands of nonprovisioning, mate-seeking "cads." Recent models require exacting interplay between male provisioning and female choice to overcome this social dilemma. We instead posit that ecological change favored widespread improvements in male provisioning incentives, and we show theoretically how social obstacles to male provisioning can be overcome. Greater availability of energetically rich, difficult-to-acquire foods enhances female-male and male-male complementarities, thus altering the fitness of dads versus cads. We identify a tipping point where gains from provisioning overcome costs from paternity uncertainty and the dad strategy becomes viable. Stable polymorphic states are possible, meaning that dads need not necessarily eliminate cads. Our simulations suggest that with sufficient complementarities, dads can emerge even in the face of high paternity uncertainty. Our theoretical focus on ecological change as a primary factor affecting the trade-off between male mating and parenting effort suggests different possibilities for using paleo-climatic, archaeological, and genomic evidence to establish the timing of and conditions associated with emergence of paternal provisioning in the hominin lineage.

Changes in Health Care Costs and Mortality Associated With Transitional Care Management Services After a Discharge Among Medicare Beneficiaries.

Importance: Medicare adopted transitional care management (TCM) payment codes in 2013 to encourage clinicians to furnish TCM services after beneficiaries were discharged to the community from medical facilities. To bill for the 30-day service, a care team member must communicate with the beneficiary or the caregiver within 2 business days after the discharge and the clinician must provide an office visit within 14 days. Objective: To investigate whether the receipt of TCM services was associated with the subsequent health care costs and mortality of the beneficiaries in the month after the service was provided. Design, Setting, and Participants: Retrospective cohort analysis of all Medicare fee-for-service claims for the period of January 1, 2013, through December 31, 2015, for 18 756 707 Medicare fee-for-service beneficiaries with discharges eligible for subsequent TCM services. Discharges from a hospital, an inpatient psychiatric facility, a long-term care hospital, a skilled nursing facility, an inpatient rehabilitation facility, or an outpatient facility for an observational stay were included. Data analysis was performed from July 2016 to March 2018. Exposure: Furnishing of TCM services for the 30 days following an eligible discharge for Medicare beneficiaries as reflected in Medicare fee-for-service claims. Main Outcomes and Measures: Total Medicare (Parts A, B, and D) health care costs and mortality in the 31 to 60 days after discharge, which is 30 days beyond the potential period for which the beneficiary could receive TCM services. Health care costs and mortality were adjusted for beneficiary age, sex, risk score, dual eligibility for Medicare and Medicaid, type of eligible discharge, year of discharge, and whether the eligible discharge to the community included home health care. Results: Of 18 756 707 eligible Medicare beneficiaries during the study period, 43.9% were male and had a mean (SD) age of 72.5 (13.8) years. Transitional care management services were billed following eligible discharges in 3.1% of cases in 2013, 5.5% in 2014, and 7.0% in 2015. The adjusted total Medicare costs ($3358; 95% CI, $3324-$3392 vs $3033; 95% CI, $3001-$3065; P < .001) and mortality (1.6%; 95% CI, 1.6%-1.6% vs 1.0%; 95% CI, 1.0%-1.1%; P < .001) were higher among those beneficiaries who did not receive TCM services compared with those who did receive TCM services in the 31 to 60 days following an eligible discharge. Conclusions and Relevance: Despite the apparent benefits of TCM services for Medicare beneficiaries, the use of this service remains low. An assessment should be made of interventions that can increase the appropriate use of this service.

Most Marketplace Plans Included At Least 25 Percent Of Local-Area Physicians, But Enrollment Disparities Remained.

The Affordable Care Act allows commercial insurers participating in the Marketplaces to vary the size of their provider networks as long as the providers are "sufficient" in numbers and types. Concerns have been growing over the increasing use of restricted-provider or narrow networks in Marketplace plans because of their implications for reduced access to care, but little is known about the breadth and stability of these networks over time or what types of enrollees choose such plans. Using national data, we found that in 2016, 60 percent of provider networks in plans offered in the federally facilitated Marketplaces included at least one-quarter of local-area physicians, and that consumers' access to broad-network plans remained stable between 2015 and 2016. Hispanic and low-income people made up a disproportionate share of enrollees in smaller-network plans (those with fewer than one-quarter of local-area physicians). It will be important to monitor the impact of narrow networks on access to and quality of care as well as on health outcomes.

Efficient and accurate whole genome assembly and methylome profiling of E. coli.

BACKGROUND: With the price of next generation sequencing steadily decreasing, bacterial genome assembly is now accessible to a wide range of researchers. It is therefore necessary to understand the best methods for generating a genome assembly, specifically, which combination of sequencing and bioinformatics strategies result in the most accurate assemblies. Here, we sequence three E. coli strains on the Illumina MiSeq, Life Technologies Ion Torrent PGM, and Pacific Biosciences RS. We then perform genome assemblies on all three datasets alone or in combination to determine the best methods for the assembly of bacterial genomes. RESULTS: Three E. coli strains - BL21(DE3), Bal225, and DH5α - were sequenced to a depth of 100× on the MiSeq and Ion Torrent machines and to at least 125× on the PacBio RS. Four assembly methods were examined and compared. The previously published BL21(DE3) genome [GenBank:AM946981.2], allowed us to evaluate the accuracy of each of the BL21(DE3) assemblies. BL21(DE3) PacBio-only assemblies resulted in a 90% reduction in contigs versus short read only assemblies, while N50 numbers increased by over 7-fold. Strikingly, the number of SNPs in PacBio-only assemblies were less than half that seen with short read assemblies (~20 SNPs vs. ~50 SNPs) and indels also saw dramatic reductions (~2 indel >5 bp in PacBio-only assemblies vs. ~12 for short-read only assemblies). Assemblies that used a mixture of PacBio and short read data generally fell in between these two extremes. Use of PacBio sequencing reads also allowed us to call covalent base modifications for the three strains. Each of the strains used here had a known covalent base modification genotype, which was confirmed by PacBio sequencing. CONCLUSION: Using data generated solely from the Pacific Biosciences RS, we were able to generate the most complete and accurate de novo assemblies of E. coli strains. We found that the addition of other sequencing technology data offered no improvements over use of PacBio data alone. In addition, the sequencing data from the PacBio RS allowed for sensitive and specific calling of covalent base modifications.

The Evolution of Altruistic Preferences: Mothers versus Fathers.

What can evolutionary biology tell us about male-female differences in preferences concerning family matters? Might mothers be more solicitous toward offspring than fathers, for example? The economics literature has documented gender differences-children benefit more from money put in the hands of mothers rather than fathers, for example-and these differences are thought to be partly due to preferences. Yet for good reason family economics is mostly concerned with how prices and incomes affect behavior against a backdrop of exogenous preferences. Evolutionary biology complements this approach by treating preferences as the outcome of natural selection. We mine the well-developed biological literature to make a prima facie case for evolutionary roots of parental preferences. We consider the most rudimentary of traits-sex differences in gamete size and internal fertilization-and explain how they have been thought to generate male-female differences in altruism toward children and other preferences related to family behavior. The evolutionary approach to the family illuminates connections between issues typically thought distinct in family economics, such as parental care and marriage markets.

Whole-genome gene expression profiling of formalin-fixed, paraffin-embedded tissue samples.

BACKGROUND: We have developed a gene expression assay (Whole-Genome DASL), capable of generating whole-genome gene expression profiles from degraded samples such as formalin-fixed, paraffin-embedded (FFPE) specimens. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated a similar level of sensitivity in gene detection between matched fresh-frozen (FF) and FFPE samples, with the number and overlap of probes detected in the FFPE samples being approximately 88% and 95% of that in the corresponding FF samples, respectively; 74% of the differentially expressed probes overlapped between the FF and FFPE pairs. The WG-DASL assay is also able to detect 1.3-1.5 and 1.5-2 -fold changes in intact and FFPE samples, respectively. The dynamic range for the assay is approximately 3 logs. Comparing the WG-DASL assay with an in vitro transcription-based labeling method yielded fold-change correlations of R(2) approximately 0.83, while fold-change comparisons with quantitative RT-PCR assays yielded R(2) approximately 0.86 and R(2) approximately 0.55 for intact and FFPE samples, respectively. Additionally, the WG-DASL assay yielded high self-correlations (R(2)>0.98) with low intact RNA inputs ranging from 1 ng to 100 ng; reproducible expression profiles were also obtained with 250 pg total RNA (R(2) approximately 0.92), with approximately 71% of the probes detected in 100 ng total RNA also detected at the 250 pg level. When FFPE samples were assayed, 1 ng total RNA yielded self-correlations of R(2) approximately 0.80, while still maintaining a correlation of R(2) approximately 0.75 with standard FFPE inputs (200 ng). CONCLUSIONS/SIGNIFICANCE: Taken together, these results show that WG-DASL assay provides a reliable platform for genome-wide expression profiling in archived materials. It also possesses utility within clinical settings where only limited quantities of samples may be available (e.g. microdissected material) or when minimally invasive procedures are performed (e.g. biopsied specimens).

Oxazole- and imidazole-based Ser-Leu dipeptide mimetics in potent inhibitors of antigen presentation by MHC class II DR molecules.

Imidazole and oxazole derivatives 1 to 4 were designed and prepared as dipeptide mimetics to replace the Ser-Leu dipeptide sequence of Ro-25-9980 (Ac-(Cha)-RAMA-S-L-NH2), a peptidic inhibitor of antigen binding to major histocompatibility complex (MHC) class II DR molecules linked to rheumatoid arthritis (RA). The most potent analog in binding assays (IC50 = 30 nM in DRB1*0401 binding; 1.6 times as potent as Ro 25-9980) was 16, Ac-(Cha)RAMA-(S)S-psi(oxazole)-L-NH2. The SAR of peptide hybrids 10 to 24, prepared by incorporating the dipeptide mimetics 1 to 4 is discussed. Of these hybrids, 23 and 24, analogs that incorporated the imidazole and oxazole mimetics as well as optimized variants at positions 3 to 5, were found to have 70 to 80 nM binding affinity comparable to the parent peptide in DRB 1*0401 binding and were also active in DRB1*0101 binding, while being resistant to proteolysis by cathepsin B. Both of these compounds showed inhibitory activity in an antigen-stimulated T-cell proliferation assay, indicating their potential to suppress autoimmune responses and as leads for therapeutic agents to treat RA.

Assessing Medicare Health Plan Performance in Serving Beneficiary Subpopulations.

In this analysis, the authors examined differences in managed care health plan performance ratings between selected subgroups of the Medicare population who may have exceptional health care needs (EHCNs) or may require special plan efforts to facilitate effective service use compared with the residual enrolled population. Findings indicated that disabled enrollees have lower plan ratings across all dimensions of performance than do other enrollees. Aged enrollees in self-reported fair/poor health and those with limited independence have lower ratings for most dimensions of performance. Finally, although Hispanic persons and persons other than white were more satisfied with their health plans, overall, they had lower ratings for dimensions of the process of care and access to services.

Electron Impact Excitation of Hydrogen Lyman- α Radiation.

An experimental investigation of electron impact excitation of the 2p state of atomic hydrogen is described. A beam of electrons was passed through a chopped beam of hydrogen atoms in a high vacuum apparatus. The modulated flux of Lyman-α photons emitted in the radiative decay of the 2p state was taken as a measurement of the excitation probability resulting from direct excitation plus indirect excitation resulting from cascading. The region surrounding the intersection of the two beams was electrically and magnetically shielded to prevent quenching of metastable 2s atoms and thereby to ensure that the observed Lyman-α flux resulted from decay of the short-lived 2p state. The experimental results are consistent with those obtained by Fite, Stebbings, and Brackmann [1959], and confirm the existence of a large discrepancy between theoretical and experimental results in the electron energy range below 50 eV.