736–3 Costs and Complications of Non-thoracotomy Defibrillator Systems: Impact of Health Care Financing Administration Guidelines

Non-thoracotomy implantable defibrillator (ICD) systems have been shown to have lower costs and fewer complications than thoracotomy systems. Recent interpretation of Health Care Financing Administration regulations has challenged reimbursement for investigational devices or combinations of components not approved by the Food and Drug Administration (“off-label”). We compared the costs and complications associated with approved pulse generator/lead systems (CPI 1600/Endotak, CPl 1705/Endotak and Medtronic 7217/Transvene, n=136) with investigational and “off-label” systems (CPI 1625/Endotak, CPI 1715/Endotak, Medtronic 7219/Transvene and Ventritex V100 or V110/TVL and Vl00/Endotak, n=79). Age [63±12 years versus 63±11 years (mean±SD)] and ejection fraction (31±15% versus 31±11%) were similar for patients with approved and investigational systems, respectively. However, total hospital charges including preoperative care and evaluation, implant procedure and hardware, postoperative testing and revisions were $64±19,000 for approved devices versus$57±16,000 for non-approved devices (p=0.02) despite higher overall costs of newer pulse generators and leads. Total length of stay was 17±10 days versus 14±8 days (p=0.03) and complications including lead dislodgement, increased defibrillation threshold, hematoma and infection were 25/136 versus 4/77 (p<0.005) for approved and investigational or “off-label” systems, respectively. Based on data provided by the manufacturers, anticipated average battery longevity is 3.8 years for approved systems and 5.5 years for investigational or “off-label” systems.ConclusionsThe prudent use of current investigational or “off-label” nonthoracotomy ICD systems is more cost-effective and is associated with fewer complications than approved ICD systems. When increased battery longevity is considered, long term costs of non-thoracotomy ICD therapy may be improved dramatically with the use of investigational or “off-label” systems. Review of reimbursement regulations may be warranted

Cloud microphysical effects of turbulent mixing and entrainment

Turbulent mixing and entrainment at the boundary of a cloud is studied by means of direct numerical simulations that couple the Eulerian description of the turbulent velocity and water vapor fields with a Lagrangian ensemble of cloud water droplets that can grow and shrink by condensation and evaporation, respectively. The focus is on detailed analysis of the relaxation process of the droplet ensemble during the entrainment of subsaturated air, in particular the dependence on turbulence time scales, droplet number density, initial droplet radius and particle inertia. We find that the droplet evolution during the entrainment process is captured best by a phase relaxation time that is based on the droplet number density with respect to the entire simulation domain and the initial droplet radius. Even under conditions favoring homogeneous mixing, the probability density function of supersaturation at droplet locations exhibits initially strong negative skewness, consistent with droplets near the cloud boundary being suddenly mixed into clear air, but rapidly approaches a narrower, symmetric shape. The droplet size distribution, which is initialized as perfectly monodisperse, broadens and also becomes somewhat negatively skewed. Particle inertia and gravitational settling lead to a more rapid initial evaporation, but ultimately only to slight depletion of both tails of the droplet size distribution. The Reynolds number dependence of the mixing process remained weak over the parameter range studied, most probably due to the fact that the inhomogeneous mixing regime could not be fully accessed when phase relaxation times based on global number density are considered.Comment: 17 pages, 10 Postscript figures (figures 3,4,6,7,8 and 10 are in reduced quality), to appear in Theoretical Computational Fluid Dynamic

Mapping the Constrained Coding Regions in the human genome to their corresponding proteins

Constrained Coding Regions (CCRs) in the human genome have been derived from DNA sequencing data of large cohorts of healthy control populations, available in the Genome Aggregation Database (gnomAD) [1]. They identify regions depleted of protein-changing variants and thus identify segments of the genome that have been constrained during human evolution. By mapping these DNA-defined regions from genomic coordinates onto the corresponding protein positions and combining this information with protein annotations, we have explored the distribution of CCRs and compared their co-occurrence with different protein functional features, previously annotated at the amino acid level in public databases. As expected, our results reveal that functional amino acids involved in interactions with DNA/RNA, protein-protein contacts and catalytic sites are the protein features most likely to be highly constrained for variation in the control population. More surprisingly, we also found that linear motifs, linear interacting peptides (LIPs), disorder-order transitions upon binding with other protein partners and liquid-liquid phase separating (LLPS) regions are also strongly associated with high constraint for variability. We also compared intra-species constraints in the human CCRs with inter-species conservation and functional residues to explore how such CCRs may contribute to the analysis of protein variants. As has been previously observed, CCRs are only weakly correlated with conservation, suggesting that intraspecies constraints complement interspecies conservation and can provide more information to interpret variant effects

The Palmer LTER: A Long-Term Ecological Research Program at Palmer Station, Antarctica

THE ANTARCTIC marine ecosystem-the assemblage of plants, animals, ocean, sea ice, and island components south of the Antarctic Convergence is among the largest readily defined ecosystems on Earth (36 X 106 km2 ) (Hedgpeth, 1977; Petit et al., 1991). This ecosystem is composed of an interconnected system of functionally distinct hydrographic and biogeochemical subdivisions (Treguer and Jacques, 1992) and includes open ocean, frontal regions, shelf-slope waters, sea ice, and marginal ice zones. Oceanic, atmospheric, and biogeochemical processes within this system are thought to be globally significant, have been infrequently studied, and are poorly understood relative to more accessible marine ecosystems (Harris and Stonehouse, 1991; Johannessen et al., 1994). The Palmer Long-Term Ecological Research (Palmer LTER) area west of the Antarctic Peninsula (Fig. la) is a complex combination of a coastal/continental shelf zone and a seasonal sea ice zone, because this area is swept by the yearly advance and retreat of sea ice. The Palmer LTER program is a multidisciplinary program established to study this polar marine ecosystem

A cluster randomized controlled trial of the effectiveness and cost-effectiveness of Intermediate Care Clinics for Diabetes (ICCD) : study protocol for a randomized controlled trial

Background World-wide healthcare systems are faced with an epidemic of type 2 diabetes. In the United Kingdom, clinical care is primarily provided by general practitioners (GPs) rather than hospital specialists. Intermediate care clinics for diabetes (ICCD) potentially provide a model for supporting GPs in their care of people with poorly controlled type 2 diabetes and in their management of cardiovascular risk factors. This study aims to (1) compare patients with type 2 diabetes registered with practices that have access to an ICCD service with those that have access only to usual hospital care; (2) assess the cost-effectiveness of the intervention; and (3) explore the views and experiences of patients, health professionals and other stakeholders. Methods/Design This two-arm cluster randomized controlled trial (with integral economic evaluation and qualitative study) is set in general practices in three UK Primary Care Trusts. Practices are randomized to one of two groups with patients referred to either an ICCD (intervention) or to hospital care (control). Intervention group: GP practices in the intervention arm have the opportunity to refer patients to an ICCD - a multidisciplinary team led by a specialist nurse and a diabetologist. Patients are reviewed and managed in the ICCD for a short period with a goal of improving diabetes and cardiovascular risk factor control and are then referred back to practice. or Control group: Standard GP care, with referral to secondary care as required, but no access to ICCD. Participants are adults aged 18 years or older who have type 2 diabetes that is difficult for their GPs to control. The primary outcome is the proportion of participants reaching three risk factor targets: HbA1c (≤7.0%); blood pressure (<140/80); and cholesterol (<4 mmol/l), at the end of the 18-month intervention period. The main secondary outcomes are the proportion of participants reaching individual risk factor targets and the overall 10-year risks for coronary heart disease(CHD) and stroke assessed by the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Other secondary outcomes include body mass index and waist circumference, use of medication, reported smoking, emotional adjustment, patient satisfaction and views on continuity, costs and health related quality of life. We aimed to randomize 50 practices and recruit 2,555 patients

Mother Knows Best: Dominant Females Determine Offspring Dispersal in Red Foxes (Vulpes vulpes)

Background: Relatedness between group members is central to understanding the causes of animal dispersal. In many group-living mammals this can be complicated as extra-pair copulations result in offspring having varying levels of relatedness to the dominant animals, leading to a potential conflict between male and female dominants over offspring dispersal strategies. To avoid resource competition and inbreeding, dominant males might be expected to evict unrelated males and related females, whereas the reverse strategy would be expected for dominant females. Methodology/Principal Findings: We used microsatellites and long-term data from an urban fox (Vulpes vulpes) population to compare dispersal strategies between offspring with intra- and extra-group fathers and mothers of differing social status in red foxes. Relatedness to the dominant male had no effect on dispersal in offspring of either sex, whereas there was a strong effect of relatedness to resident females on offspring dispersal independent of population density. Males with dominant mothers dispersed significantly more often than males with subordinate mothers, whereas dispersing females were significantly more likely to have subordinate mothers compared to philopatric females. Conclusions/Significance: This is the first study to demonstrate that relatedness to resident females is important in juvenile dispersal in group-living mammals. Male dispersal may be driven by inbreeding avoidance, whereas female dispersal appears to be influenced by the fitness advantages associated with residing with the same-sex dominant parent. Selection pressure for paternal influence on offspring dispersal is low due to the limited costs associated with retaining unrelated males and the need for alternative inbreeding avoidance mechanisms between the dominant male and his female offspring. These findings have important implications for the evolution of dispersal and group living in social mammals, and our understanding of a key biological process.peerReviewe

Allocoprobacillus halotolerans gen. nov., sp. nov and Coprobacter tertius sp. nov., isolated from human gut microbiota

Two novel bacterial isolates were cultured from faecal samples of patients attending the Breast Care clinic at the Norwich and Norfolk University Hospital. Strain LH1062T was isolated from a 58-year-old female diagnosed with invasive adenocarcinoma with ductal carcinoma in situ. Strain LH1063T was isolated from a healthy 51-year-old female. Isolate LH1062T was predicted to be a potential novel genus most closely related to Coprobacillus , whilst LH1063T was predicted to be a novel species belonging to Coprobacter . Both strains were characterized by polyphasic approaches including 16S rRNA gene analysis, core-genome analysis, average nucleotide identity (ANI) comparisons and phenotypic analysis. Initial screening of the 16S rRNA gene of LH1062T returned a nucleotide identity of 93.4 % to Longibaculum muris . For LH1063T, nucleotide identity was a 92.6 % to Coprobacter secundus . Further investigations showed that LH1062T had a genome size of 2.9 Mb and G+C content of 31.3 mol %. LH1063T had a genome size of 3.3Mb and G+C content of 39.2 mol %. Digital DNA-DNA hybridization (dDDH) and ANI values of LH1062T with its closest relative, Coprobacillus cateniformis JCM 10604T, were 20.9 and 79.54 %, respectively. For LH1063T, the dDDH and ANI values with its closest relative, Coprobacter secundus 177T, were 19.3 and 77.81 %, respectively. Phenotypic testing confirmed that LH1062T could not be matched to a known validly published isolate in any database; thereby indicating a novel genus for which the name Allocoprobacillus gen. nov. is now proposed with LH1062T (=DSM 114537T=NCTC 14686T) being the type strain of the proposed novel species Allocoprobacillus halotolerans sp. nov. Strain LH1063T (=DSM 114538T=NCTC 14698T) fits within the genus Coprobacter and, it being the third species within this genus, the name Coprobacter tertius sp. nov. is proposed

Status of NINJA: the Numerical INJection Analysis project

The 2008 NRDA conference introduced the Numerical INJection Analysis project (NINJA), a new collaborative effort between the numerical relativity community and the data analysis community. NINJA focuses on modeling and searching for gravitational wave signatures from the coalescence of binary system of compact objects. We review the scope of this collaboration and the components of the first NINJA project, where numerical relativity groups shared waveforms and data analysis teams applied various techniques to detect them when embedded in colored Gaussian noise

TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 1