New Variations on the Theme of Multidimensional Geriatric Assessment.

Geriatric assessment-broadly defined-has become foundational to systems of care for frail elderly people at risk for functional decline, death, intensification of services, and long-term institutionalization [...].

Connecting Caregivers to Support: Lessons Learned From the VA Caregiver Support Program.

Development and evaluation of supportive caregiver interventions has become a national priority. This study's aim was to evaluate how caregivers participating in the Department of Veterans Affairs (VA) Caregiver Support Program (CSP) use and value supportive services. Qualitative semi-structured interviews (N = 50 caregivers) were the core of a mixed-methods design, and surveys (N = 160) were supplemental. Caregivers who had used CSP services valued emotional, functional, and health care navigational support, calling support groups and the program coordinator their "lifeline." However, many described a lack of connection with the program-not knowing about or successfully engaging in program services-and needed more information about available resources. Caregivers in rural areas or caring for individuals with specific diseases reported needing tailored services to meet their unique needs. Policy makers and practitioners should proactively promote supportive services for caregivers. Future research should explore strategies for reducing barriers to accessing tailored support to meet the needs of a diverse caregiver population.

Discharge Information and Support for Patients Discharged from the Emergency Department: Results from a Randomized Controlled Trial.

BACKGROUND: Little research has been done on primary care-based models to improve health care use after an emergency department (ED) visit. OBJECTIVE: To examine the effectiveness of a primary care-based, nurse telephone support intervention for Veterans treated and released from the ED. DESIGN: Randomized controlled trial with 1:1 assignment to telephone support intervention or usual care arms (ClinicalTrials.gov: NCT01717976). SETTING: Department of Veterans Affairs Health Care System (VAHCS) in Durham, NC. PARTICIPANTS: Five hundred thirteen Veterans who were at high risk for repeat ED visits. INTERVENTION: The telephone support intervention consisted of two core calls in the week following an ED visit. Call content focused on improving the ED to primary care transition, enhancing chronic disease management, and educating Veterans and family members about VHA and community services. MAIN MEASURES: The primary outcome was repeat ED use within 30 days. KEY RESULTS: Observed rates of repeat ED use at 30 days in usual care and intervention groups were 23.1% and 24.9%, respectively (OR = 1.1; 95% CI = 0.7, 1.7; P = 0.6). The intervention group had a higher rate of having at least 1 primary care visit at 30 days (OR = 1.6, 95% CI = 1.1-2.3). At 180 days, the intervention group had a higher rate of usage of a weight management program (OR = 3.5, 95% CI = 1.6-7.5), diabetes/nutrition (OR = 1.8, 95% CI = 1.0-3.0), and home telehealth services (OR = 1.7, 95% CI = 1.0-2.9) compared with usual care. CONCLUSIONS: A brief primary care-based nurse telephone support program after an ED visit did not reduce repeat ED visits within 30 days, despite intervention participants' increased engagement with primary care and some chronic disease management services. TRIALS REGISTRATION: ClinicalTrials.gov NCT01717976.

Invisible partners in care: Snapshot of well-being among caregivers receiving comprehensive support from Veterans Affairs.

BACKGROUND AND AIMS: Since May 2011, over 23 000 caregivers of Veterans seriously injured on or after September 11, 2001 have enrolled in the Program of Comprehensive Assistance for Family Caregivers (PCAFC). PCAFC provides caregivers training, a stipend, and access to health care. The aim of this study is to describe the characteristics of caregivers in PCAFC and examine associations between caregiver characteristics and caregiver well-being outcomes. METHODS: We sent a web survey invitation to 10 000 PCAFC caregivers enrolled as of September 2015. Using linear and logistic regressions, we examine associations between PCAFC caregiver characteristics and caregiver outcomes: perceived financial strain, depressive symptoms (Center for Epidemiologic Studies Depression Scale [CESD-10]), perceived quality of Veteran's Veterans Health Administration (VHA) care, and self-reported caregiver health. RESULTS: We had complete survey data for 899 respondents. Since becoming a caregiver, approximately 50% of respondents reported reducing or stopping work. Mean time spent providing care was 3.8 years (median 3, IQR 1-5) with an average of 4.9 weekdays (median 5, IQR 5-5) and 1.9 weekend days (median 2, IQR 2-2). The mean CESD-10 score was 8.2 (median 7, 4-12), at the cutoff for screening positive for depressive symptoms. A longer duration of caregiving was associated with having 0.08 increase in rating of financial strain (95% CI, 0.02-0.14). Caregiver rating of the Veteran's health status as "fair" or better was a strong predictor of better caregiver outcomes, ie, self-reported caregiver health. However, higher levels of education were associated with worse caregiver outcomes, ie, lower global satisfaction with VHA care, higher CESD-10 score, and higher rating of financial strain. CONCLUSIONS: Higher depressive symptoms among longer duration caregivers, coupled with high rates of reductions in hours worked, suggest interventions are needed to address the long-term emotional and financial needs of these caregivers of post-9/11 Veterans and identify subpopulations at risk for worse outcomes.

The Effect of Support and Training for Family Members on Access to Outpatient Services for Veterans with Posttraumatic Stress Disorder (PTSD).

The VA Program of Comprehensive Assistance for Family Caregivers (PCAFC) provides landmark support for family caregivers of post-9/11 veterans. This study examines PCAFC support for veterans with and without PTSD and assesses whether program effect differs by PTSD status using a pre-post, non-equivalent, propensity score weighted comparison group design (n = 24,280). Veterans with and without PTSD in PCAFC accessed more mental health, primary, and specialty care services than weighted comparisons. PCAFC participation had stronger effects on access to primary care for veterans with PTSD than for veterans without PTSD. For veterans with PTSD, PCAFC support might enhance health service use.

Wide dynamic range enrichment method of semiconducting single-walled carbon nanotubes with weak field centrifugation.

The potential of single-walled carbon nanotubes (SWCNTs) to outperform silicon in electronic application was finally enabled through selective separation of semiconducting nanotubes from the as-synthesized statistical mix with polymeric dispersants. Such separation methods provide typically high semiconducting purity samples with narrow diameter distribution, i.e. almost single chiralities. But for a wide range of applications high purity mixtures of small and large diameters are sufficient or even required. Here we proof that weak field centrifugation is a diameter independent method for enrichment of semiconducting nanotubes. We show that the non-selective and strong adsorption of polyarylether dispersants on nanostructured carbon surfaces enables simple separation of diverse raw materials with different SWCNT diameter. In addition and for the first time, we demonstrate that increased temperature enables higher purity separation. Furthermore we show that the mode of action behind this electronic enrichment is strongly connected to both colloidal stability and protonation. By giving simple access to electronically sorted SWCNTs of any diameter, the wide dynamic range of weak field centrifugation can provide economical relevance to SWCNTs.

Highly Efficient and Scalable Separation of Semiconducting Carbon Nanotubes via Weak Field Centrifugation.

The identification of scalable processes that transfer random mixtures of single-walled carbon nanotubes (SWCNTs) into fractions featuring a high content of semiconducting species is crucial for future application of SWCNTs in high-performance electronics. Herein we demonstrate a highly efficient and simple separation method that relies on selective interactions between tailor-made amphiphilic polymers and semiconducting SWCNTs in the presence of low viscosity separation media. High purity individualized semiconducting SWCNTs or even self-organized semiconducting sheets are separated from an as-produced SWCNT dispersion via a single weak field centrifugation run. Absorption and Raman spectroscopy are applied to verify the high purity of the obtained SWCNTs. Furthermore SWCNT - network field-effect transistors were fabricated, which exhibit high ON/OFF ratios (10(5)) and field-effect mobilities (17 cm(2)/Vs). In addition to demonstrating the feasibility of high purity separation by a novel low complexity process, our method can be readily transferred to large scale production.

Comprehensive primary care for older patients with multiple chronic conditions: "Nobody rushes you through".

Older patients with multiple chronic health conditions and complex health care needs often receive care that is fragmented, incomplete, inefficient, and ineffective. This article describes the case of an older woman whose case cannot be managed effectively through the customary approach of simply diagnosing and treating her individual diseases. Based on expert consensus about the available evidence, this article identifies 4 proactive, continuous processes that can substantially improve the primary care of community-dwelling older patients who have multiple chronic conditions: comprehensive assessment, evidence-based care planning and monitoring, promotion of patients' and (family caregivers') active engagement in care, and coordination of professionals in care of the patient--all tailored to the patient's goals and preferences. Three models of chronic care that include these processes and that appear to improve some aspects of the effectiveness and the efficiency of complex primary care--the Geriatric Resources for Assessment and Care of Elders (GRACE) model, Guided Care, and the Program of All-inclusive Care for the Elderly (PACE)--are described briefly, and steps toward their implementation are discussed.

The national evaluation of senior mentor programs: older adults in medical education.

OBJECTIVES: To identify models for senior mentor programs (SMPs), critical factors in program development, achievement of goals and objectives, effect on medical school environment, and future of programs. DESIGN: Ten SMPs were systematically selected to represent a variety of medical schools, geographic regions, and program types. The National Senior Mentor Program Evaluation relied upon archived data within the programs and new data collected during site visits. Archived data included internally conducted program evaluations, student course evaluations, and survey and focus group results. Site visit data were collected from key informant interviews with program staff and faculty, medical school leadership and students, and older adults serving as mentors. SETTING: Ten U.S. medical schools with SMPs. PARTICIPANTS: Evaluation participants at each site included program faculty, key medical school administrators, participating students, and mentors. MEASUREMENTS: Program evaluation. RESULTS: All 10 programs demonstrated a positive effect on student attitudes toward older adults. Student acceptance of the programs was strong, and mentor acceptance and support were extraordinary. Eight of the 10 programs were operating in 2008 and having considerable effect on medical school environments. Most of the operating programs expect to be continuing for 5 or more years into the future. CONCLUSIONS: The findings of the national evaluation point toward continuation and likely growth of the senior mentor phenomenon in U.S. medical education.

The middle of the road: results from the aging semantic differential with four cohorts of medical students.

OBJECTIVES: To explore the presence of negative stereotypical attitudes among medical students and the extent to which attitudes changed over time. DESIGN: Analysis of pre- and postexperience administration of attitude measures to four cohorts of medical students (two cohorts as quasi-controls and two cohorts as curriculum "treatment" groups). SETTING: The curriculum of a community-based medical school in the United States. PARTICIPANTS: Four sequential cohorts of medical students. INTERVENTION: Experience in a required comprehensive vertically integrated curriculum. MEASUREMENTS: The Aging Semantic Differential (ASD), using an 85-year-old woman as the cue image. RESULTS: The reliability scores for all administrations were acceptable. The two control cohorts demonstrated no change in attitude scores, whereas the treatment cohorts reflected a slight shift toward more-positive scores. However, all cohorts had scores for all sittings that were in the neutral range; on average students routinely scored 70% of the 32 items neither positively nor negatively. CONCLUSION: These students seemed not to hold negative stereotypes as measured using the ASD. Although two of the 32 items prompted negative stereotyping, and six items elicited positive stereotyping, attitudes were neutral about older adults. Characteristics of the ASD itself or of the response set used in this study may have affected the results.

From bedside to bench: research in comorbidity and aging.

As their patients age, clinicians are increasingly confronted with diseases, impairments, or conditions that complicate the diagnosis and treatment of index diseases and with the management challenge of the overall burden of morbidity in their patients. Nevertheless, there has been little applicable conceptual work and empirical research on the nature, impact, and management of comorbid and multiple morbid conditions. Advancing research in this area has been the goal of a recent National Institute on Aging Task Force on Comorbidity Research Issues, as well as a working conference of the American Geriatrics Society. Both efforts highlighted current knowledge and thinking about comorbidity in the context of caring for an aging population, in preparation for research ultimately leading to better understanding of comorbidity and improvement in clinical practice. This Perspective provides a brief overview of these developments.

Phase I clinical trial of the bispecific antibody MDX-H210 (anti-FcgammaRI x anti-HER-2/neu) in combination with Filgrastim (G-CSF) for treatment of advanced breast cancer.

A phase I study of the bispecific antibody MDX-H210 in combination with granulocyte colony-stimulating factor (G-CSF) was performed in stage IV breast carcinoma patients, overexpressing HER-2/neu. MDX-H210, constructed by crosslinking antigen binding fragments (F(ab') fragments) of monoclonal antibody (mAb) H22 to Fc gamma receptor I (FcgammaRI), and mAb 520C9 to HER-2/neu, respectively, mediates the lysis of tumour cells in vitro, and in human FcgammaRI transgenic mouse models. The proto-oncogene HER-2/neu is overexpressed in approximately 30% of breast cancer patients, and represents a promising target for antibody-based immunotherapy. Fc gamma receptor I (CD64) is an effective trigger molecule, which is expressed on monocytes/macrophages, immature dendritic cells, and G-CSF-primed polymorphonuclear cells (PMN). Patients received G-CSF (Filgrastim) for 8 consecutive days, and cohorts of three patients were treated on day 4 with escalating, single doses of MDX-H210. A total of 30 patients were included, and treatment was generally well tolerated, without reaching dose-limiting toxicity. Side effects consisted mainly of fever and short periods of chills, which were timely related to elevated plasma levels of interleukin 6 and tumour necrosis factor alpha. In the last two cohorts, MDX-H210 plasma levels exceeded 1 microg ml(-1), and on circulating myeloid cells >50% saturation of FcgammaRI was found until day 4. These effector cells were highly effective in antibody-dependent cell-mediated cytotoxicity. Immunohistochemical analyses of tumour biopsies in individual patients documented infiltration of monocytes and PMN after MDX-H210 infusion. Although the clinical course of the disease was not altered by the single dose of MDX-H210, a favourable toxicity profile--even at high doses--and remarkable biological effects were seen when combined with G-CSF. Therefore, the combination of G-CSF and MDX-H210 should be evaluated in further immunotherapeutical strategies.

Variation of microbial communities in soil, rhizosphere, and rhizoplane in response to crop species, soil type, and crop development.

We investigated the influence of plant species, soil type, and plant development time on the shaping of microbial communities in soil and in association with roots. The sample group consisted of a total of 32 microcosms in three habitats: soil, rhizosphere, and rhizoplane. Communities were represented by the patterns of a sequence-specific separation of rRNA target sequences. Effects of experimental parameters were classified by a cluster analysis of pattern similarities. The type of plant species (clover, bean, or alfalfa) had the greatest effect in plant-associated habitats and also affected soil patterns. Plant development had a minor habitat-dependent effect that was partly obscured by replicate variation. The results stress the applicability of biased community representations in an analysis of induced variation.

Bulk and rhizosphere soil bacterial communities studied by denaturing gradient gel electrophoresis: plant-dependent enrichment and seasonal shifts revealed.

The bacterial rhizosphere communities of three host plants of the pathogenic fungus Verticillium dahliae, field-grown strawberry (Fragaria ananassa Duch.), oilseed rape (Brassica napus L.), and potato (Solanum tuberosum L.), were analyzed. We aimed to determine the degree to which the rhizosphere effect is plant dependent and whether this effect would be increased by growing the same crops in two consecutive years. Rhizosphere or soil samples were taken five times over the vegetation periods. To allow a cultivation-independent analysis, total community DNA was extracted from the microbial pellet recovered from root or soil samples. 16S rDNA fragments amplified by PCR from soil or rhizosphere bacterium DNA were analyzed by denaturing gradient gel electrophoresis (DGGE). The DGGE fingerprints showed plant-dependent shifts in the relative abundance of bacterial populations in the rhizosphere which became more pronounced in the second year. DGGE patterns of oilseed rape and potato rhizosphere communities were more similar to each other than to the strawberry patterns. In both years seasonal shifts in the abundance and composition of the bacterial rhizosphere populations were observed. Independent of the plant species, the patterns of the first sampling times for both years were characterized by the absence of some of the bands which became dominant at the following sampling times. Bacillus megaterium and Arthrobacter sp. were found as predominant populations in bulk soils. Sequencing of dominant bands excised from the rhizosphere patterns revealed that 6 out of 10 bands resembled gram-positive bacteria. Nocardia populations were identified as strawberry-specific bands.

Determination of the binding constants of the centromere protein Cbf1 to all 16 centromere DNAs of Saccharomyces cerevisiae.

Cbf1p is a Saccharomyces cerevisiae chromatin protein belonging to the basic region helix-loop-helix leucine zipper (bHLHzip) family of DNA binding proteins. Cbf1p binds to a conserved element in the 5'-flanking region of methionine biosynthetic genes and to centromere DNA element I (CDEI) of S.cerevisiae centromeric DNA. We have determined the apparent equilibrium dissociation constants of Cbf1p binding to all 16 CDEI DNAs in gel retardation assays. Binding constants of full-length Cbf1p vary between 1.7 and 3.8 nM. However, the dissociation constants of a Cbf1p deletion variant that has been shown to be fully sufficient for Cbf1p function in vivo vary in a range between 3.2 and 12 nM. In addition, native polyacrylamide gel electrophoresis revealed distinct changes in the 3D structure of the Cbf1p/CEN complexes. We also show that the previously reported DNA binding stimulation activity of the centromere protein p64 functions on both the Cbf1 full-length protein and a deletion variant containing only the bHLHzip domain of Cbf1p. Our results suggest that centromeric DNA outside the consensus CDEI sequence and interaction of Cbf1p with adjacent centromere proteins contribute to the complex formation between Cbf1p and CEN DNA.

Interaction of yeast kinetochore proteins with centromere-protein/transcription factor Cbf1.

The centromere-kinetochore complex of Saccharomyces cerevisiae is a specialized chromosomal substructure that mediates attachment of duplicated chromosomes to the mitotic spindle by a regulated network of protein-DNA and protein-protein interactions. We have used in vitro assays to analyze putative molecular interactions between components of the yeast centromerekinetochore complex. Glutathione S-transferase pull-down experiments showed the direct interaction of in vitro translated p110, p64, and p58 of the essential CBF3 kinetochore protein complex with Cbf1p, a basic region helix-loop-helix zipper protein (bHLHzip) that specifically binds to the CDEI region on the centromere DNA. Furthermore, recombinant p64 and p23 each stimulated the in vitro DNA binding activity of Cbf1p. The N-terminal 70 amino acids of p23 were sufficient to mediate this effect. P64 could also promote the multimerization activity of Cbf1p in the presence of centromere DNA in vitro. These results show the direct physical interaction of Cbf1p and CBF3 subunits and provide evidence that CBF3 components can promote the binding of Cbf1p to its binding site in the yeast kinetochore. A functional comparison of the centromere binding proteins with transcription factors binding at MET16 promoters reveals the strong analogy between centromeres and the MET16 promoter.

Variation of Microbial Rhizosphere Communities in Response to Crop Species, Soil Origin, and Inoculation with Sinorhizobium meliloti L33.

A greenhouse study with soil-plant microcosms was conducted in order to compare the effect of crop species, soil origin, and a bacterial inoculant on the establishment of microbial communities colonizing plant roots. Two crop species, alfalfa (Medicago sativa) and rye (Secale cereale), were grown separately in two soils collected from agricultural fields at different locations and with differing histories of leguminous crop rotation. A subset of microcosms was inoculated at 10(6) cfu g(-1) soil with the luciferase marker gene-tagged Sinorhizobium meliloti strain L33, a symbiotic partner of M. sativa. Microbial consortia were collected from the rhizospheres of alfalfa after 10 weeks of incubation and from rye after 11 weeks. S. meliloti L33 populations were one to two orders of magnitude higher in the rhizospheres of alfalfa than of rye. In soil with previous alfalfa cultivation, 80% of the alfalfa nodules were colonized by indigenous bacteria, while in the other soil alfalfa was colonized almost exclusively (>90%) with S. meliloti L33. Three community-level targeting approaches were used to characterize the variation of the extracted microbial rhizosphere consortia: (1) Community level physiological profiles (CLPP), (2) fatty acid methyl ester analysis (FAME), and (3) diversity of PCR amplified 16S rRNA target sequences from directly extracted ribosomes, determined by temperature gradient gel electrophoresis (TGGE). All approaches identified the crop species as the major determinant of microbial community characteristics. Consistently, the influence of soil was of minor importance, while a modification of the alfalfa-associated microbial community structure after inoculation with S. meliloti L33 was only consistently observed by using TGGE.