Ventricular assist device implantation in the elderly

BACKGROUND: Dramatic advances in ventricular assist device (VAD) design and patient management have made mechanical circulatory support an attractive therapeutic option for the growing pool of elderly heart failure patients. METHODS: A literature review of all relevant studies was performed. No time or language restrictions were imposed, and references of the selected studies were checked for additional relevant citations. RESULTS: In concordance with the universal trend in mechanical circulatory support, continuous flow devices appear to have particular benefits in the elderly. In addition, the literature suggests that early intervention before the development of cardiogenic shock, important in all patients, is particularly paramount in older patients. CONCLUSIONS: The ongoing refinement of patient selection, surgical technique, and post-operative care will continue to improve surgical outcomes, and absolute age may become a less pivotal criterion for mechanical circulatory support. However, clear guidelines for the use of mechanical circulatory support in the elderly remain undefined

A dominant mutation within the DNA-binding domain of the bZIP transcription factor Maf causes murine cataract and results in selective alteration in DNA binding

The murine autosomal dominant cataract mutants created in mutagenesis experiments have proven to be a powerful resource for modelling the biological processes involved in cataractogenesis. We report a mutant which in the heterozygous state exhibits mild pulverulent cataract named ‘opaque flecks in lens', symbol Ofl. By molecular mapping, followed by a candidate gene approach, the mutant was shown to be allelic with a knockout of the bZIP transcription factor, Maf. Homozygotes for Ofl and for Maf null mutations are similar but a new effect, renal tubular nephritis, was found in Ofl homozygotes surviving beyond 4 weeks, which may contribute to early lethality. Sequencing identified the mutation as a G→A change, leading to the amino-acid substitution mutation R291Q in the basic region of the DNA-binding domain. Since mice heterozygous for knockouts of Maf show no cataracts, this suggests that the Ofl R291Q mutant protein has a dominant effect. We have demonstrated that this mutation results in a selective alteration in DNA binding affinities to target oligonucleotides containing variations in the core CRE and TRE elements. This implies that arginine 291 is important for core element binding and suggests that the mutant protein may exert a differential downstream effect amongst its binding targets. The cataracts seen in Ofl heterozygotes and human MAF mutations are similar to one another, implying that Ofl may be a model of human pulverulent cortical cataract. Furthermore, when bred onto a different genetic background Ofl heterozygotes also show anterior segment abnormalities. The Ofl mutant therefore provides a valuable model system for the study of Maf, and its interacting factors, in normal and abnormal lens and anterior segment developmen

Spatial clustering of filarial transmission before and after a Mass Drug Administration in a setting of low infection prevalence

BACKGROUND: In the global program for the elimination of lymphatic filariasis (LF) longitudinal assessment of the prevalence of microfilaremia and antigenemia is recommended to monitor the effect of mass treatment on transmission. Additional monitoring tools such as entomologic and antibody methods may be useful in identifying residual foci of infection. In this study, we characterized serologic markers of infection and exposure spatially both before and after mass treatment, in an area of initial low Wuchereria bancrofti infection prevalence. METHODS: Consenting persons in the sentinel community were tested for circulating microfilaria and antigen (by immunochromatographic test) before and after the 1(st )annual mass drug administration of diethylcarbamazine and albendazole. A cohort of 161 persons provided serum specimens both years that were tested for antifilarial IgG (1 and 4) antibody. Every house was mapped using a differential Global Positioning System; this information was linked to the serologic data. W. bancrofti infection in the mosquito vector was assessed with year-round collection. Multiple linear regression was used to investigate the influence of antigen-positive persons on the antifilarial antibody responses of antigen-negative neighbors. RESULTS: After mass treatment, decreases were observed in the sentinel site in the overall prevalence of antigen (10.4% to 6.3%) and microfilaremia (0.9 to 0.4%). Of the persons in the cohort that provided serum specimens both years, 79% received treatment. Antigen prevalence decreased from 15.0% to 8.7%. Among 126 persons who received treatment, antigen and antifilarial IgG1 prevalence decreased significantly (p = 0.002 and 0.001, respectively). Among 34 persons who did not receive treatment, antifilarial IgG1 prevalence increased significantly (p = 0.003). Average antifilarial IgG1 levels decreased in households with high treatment coverage and increased in households that refused treatment. Each 10-meter increase in distance from the residence of a person who was antigen-positive in 2000 was associated a 4.68 unit decrease in antifilarial IgG1 level in 2001, controlling for other factors (p = 0.04). DISCUSSION: Antifilarial antibody assays can be used as a measure of filarial exposure. Our results suggest that micro-scale spatial heterogeneity exists in LF exposure and infection. Treatment appeared to be associated with reduced exposure at the sub-community level, suggesting the need to achieve high and homogeneous coverage. Public health messages should note the benefits of having one's neighbors receive treatment with antifilarial drugs

Epicardial adipose excision slows the progression of porcine coronary atherosclerosis

BACKGROUND: In humans there is a positive association between epicardial adipose tissue (EAT) volume and coronary atherosclerosis (CAD) burden. We tested the hypothesis that EAT contributes locally to CAD in a pig model. METHODS: Ossabaw miniature swine (n = 9) were fed an atherogenic diet for 6 months to produce CAD. A 15 mm length by 3–5 mm width coronary EAT (cEAT) resection was performed over the middle segment of the left anterior descending artery (LAD) 15 mm distal to the left main bifurcation. Pigs recovered for 3 months on atherogenic diet. Intravascular ultrasound (IVUS) was performed in the LAD to quantify atheroma immediately after adipectomy and was repeated after recovery before sacrifice. Coronary wall biopsies were stained immunohistochemically for atherosclerosis markers and cytokines and cEAT was assayed for atherosclerosis-related genes by RT-PCR. Total EAT volume was measured by non-contrast CT before each IVUS. RESULTS: Circumferential plaque length increased (p < 0.05) in the proximal and distal LAD segments from baseline until sacrifice whereas plaque length in the middle LAD segment underneath the adipectomy site did not increase. T-cadherin, scavenger receptor A and adiponectin were reduced in the intramural middle LAD. Relative to control pigs without CAD, 11β-hydroxysteroid dehydrogenase (11βHSD-1), CCL19, CCL21, prostaglandin D(2) synthase, gp91phox [NADPH oxidase], VEGF, VEGFGR1, and angiotensinogen mRNAs were up-regulated in cEAT. EAT volume increased over 3 months. CONCLUSION: In pigs used as their own controls, resection of cEAT decreased the progression of CAD, suggesting that cEAT may exacerbate coronary atherosclerosis

The Hugging Team: The Role of Technology in Business Networking Practices

Abstract. Technological devices for social networking are produced in droves and networking through media seems to be the way of getting ahead in business. We examine what role technology plays in the creation, development and maintenance of business relationships among entrepreneurs in Copenhagen. We find that mediated communication is useful in all stages of relational maintenance but only in a supportive role in relational development where co-presence and shared personal experiences take center-stage, generating trust necessary for business relationships to work. These trust-developing experiences take effort and hard work and although they can be successfully supported and even facilitated through the use of communication technologies, they need not be replaced or made simpler. The difficulties of creating these experiences make working business relationships viable in the uncertain and risky world of entrepreneurship

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A randomised clinical trial on a comprehensive geriatric assessment and intensive home follow-up after hospital discharge: the Transitional Care Bridge

<p>Abstract</p> <p>Background</p> <p>Older patients are at high risk for poor outcomes after acute hospital admission. The mortality rate in these patients is approximately 20%, whereas 30% of the survivors decline in their level of activities of daily living (ADL) functioning three months after hospital discharge. Most diseases and geriatric conditions that contribute to poor outcomes could be subject to pro-active intervention; not only during hospitalization, but also after discharge. This paper presents the design of a randomised controlled clinical trial concerning the effect of a pro-active, multi-component, nurse-led transitional care program following patients for six months after hospital admission.</p> <p>Methods/Design</p> <p>Three hospitals in the Netherlands will participate in the multi-centre, double-blind, randomised clinical trial comparing a pro-active multi-component nurse-led transitional care program to usual care after discharge. All patients acutely admitted to the Department of Internal Medicine who are 65 years and older, hospitalised for at least 48 hours and are at risk for functional decline are invited to participate in the study. All patients will receive integrated geriatric care by a geriatric consultation team during hospital admission. Randomization, which will be stratified by study site and cognitive impairment, will be conducted during admission. The intervention group will receive the transitional care bridge program, consisting of a handover moment with a community care Care Nurse (CN) during hospital admission and five home visits after discharge. The control group will receive 'care as usual' after discharge. The main outcome is the level of ADL functioning six months after discharge compared to premorbid functioning measured with the Katz ADL index. Secondary outcomes include; survival, cognitive functioning, quality of life, and health care utilization, satisfaction of the patient and primary care giver with the transitional care bridge program. All outcomes will be measured at three, six and twelve months after discharge. Approximately 674 patients will be enrolled to either the intervention or control group.</p> <p>Discussion</p> <p>The study will provide new knowledge on a combined intervention of integrated care during hospital admission, a proactive handover moment before discharge and intensive home visits after discharge.</p> <p>Trial registration</p> <p><b>Trial registration number: NTR 2384</b></p

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure