Development and evaluation of a specifically designed website for haematopoietic stem cell transplant patients in Leeds.

The purpose of this project was to develop and evaluate a specifically designed website (ALLograft INformation EXchange - ALLINEX) for adult allogeneic haematopoietic stem cell transplant (allo-HSCT) patients in Leeds. Specifications included information on the transplant journey and supportive care services, discussion forum and patient-clinical team electronic messaging service. The method followed a participatory action research approach in a five-phase project involving stakeholders. Phase 1 involved information gathering; Phase 2 development of content; Phase 3 building of website and usability testing; Phase 4 preliminary evaluation; and Phase 5 clinical implementation. Results concluded that Phase 1 patients were unaware of all services and reported unmet needs; gaps in support services were identified from a service evaluation; Phase 2 content was collected from experts, collated and synthesised; Phase 3 patient and staff feedback was positive and constructive resulting in more than 50 changes; Phase 4 ALLINEX evaluation demonstrated acceptable usability with good layout, content and aesthetics reported; Phase 5, over 15 weeks, ALLINEX had 6630 page hits, 9 new forum topics posted and received 3 clinical messages. The clinical team embraced responsibility for reviewing and monitoring ALLINEX. Financial and indemnity cover was secured for 3 years. ALLINEX, adopted locally, is sustainable and has functionality to roll-out to other UK allo-HSCT centres.

Psychosocial supportive care services for haematopoietic stem cell transplant patients; a service evaluation of three UK transplant centres.

Following haematopoietic stem cell transplant (HSCT) some patients experience long-term physical and psychosocial problems which impact on everyday life. The aim of this service evaluation was to investigate the psychosocial supportive care available for HSCT patients in three UK centres, particularly related to five identified areas of concern: fatigue; psychological distress; vocational and financial issues; sexuality, and fertility. HSCT health professionals were invited to audio-recorded semi-structured interviews. Enquiry was made into supportive care provided routinely (proactive), provided in response to a need (reactive) and missing (gaps in service) from pre-transplant to 18 months post transplant. Information gathered was transcribed and subjected to framework analysis. Interviews were conducted with 84 staff including nurses, doctors, psychologists, social workers, physiotherapists, dieticians and occupational therapists. Support for the five main areas of concern was variable across centres particularly with limitation of services for psychology; sexual dysfunction and fertility. Pro-active interventions such as psychological screening were rare with support being more commonly provided in response to an identified need. Support provided reactively for the areas of concern was comprehensive across professional groups and centres. Further work explores patients' psychosocial issues and other ways of providing adjuvant support.

Randomized cross-over trial of short-term water-only fasting: metabolic and cardiovascular consequences.

BACKGROUND AND AIMS: Routine, periodic fasting is associated with a lower prevalence of coronary artery disease (CAD). Animal studies show that fasting may increase longevity and alter biological parameters related to longevity. We evaluated whether fasting initiates acute changes in biomarker expression in humans that may impact short- and long-term health. METHODS AND RESULTS: Apparently-healthy volunteers (N = 30) without a recent history of fasting were enrolled in a randomized cross-over trial. A one-day water-only fast was the intervention and changes in biomarkers were the study endpoints. Bonferroni correction required p ≤ 0.00167 for significance (p < 0.05 was a trend that was only suggestively significant). The one-day fasting intervention acutely increased human growth hormone (p = 1.1 × 10⁻4), hemoglobin (p = 4.8 × 10⁻7), red blood cell count (p = 2.5 × 10⁻6), hematocrit (p = 3.0 × 10⁻6), total cholesterol (p = 5.8 × 10⁻5), and high-density lipoprotein cholesterol (p = 0.0015), and decreased triglycerides (p = 1.3 × 10⁻4), bicarbonate (p = 3.9 × 10⁻4), and weight (p = 1.0 × 10⁻7), compared to a day of usual eating. For those randomized to fast the first day (n = 16), most factors including human growth hormone and cholesterol returned to baseline after the full 48 h, with the exception of weight (p = 2.5 × 10⁻4) and (suggestively significant) triglycerides (p = 0.028). CONCLUSION: Fasting induced acute changes in biomarkers of metabolic, cardiovascular, and general health. The long-term consequences of these short-term changes are unknown but repeated episodes of periodic short-term fasting should be evaluated as a preventive treatment with the potential to reduce metabolic disease risk. Clinical trial registration (ClinicalTrials.gov): NCT01059760 (Expression of Longevity Genes in Response to Extended Fasting [The Fasting and Expression of Longevity Genes during Food abstinence {FEELGOOD} Trial]).

Can Pediatric Primary Care Practices Afford Integrated Behavioral Health? A Comparison of 5 Pediatric Practices.

Licensed behavioral health providers (LBHPs) were integrated into 5 pediatric primary care practices in southeast and east Texas from October 2018 through March 2020. LBHPs Licensed behavioral health providers across the sites were 3 licensed clinical social workers (LCSW), 1 psychologist, and 1 nurse practitioner (NP). Practices provided data for 6 to 15 months. Overall, 2769 units of behavioral health services were provided to 746 children over 2243 hours. Across 4 sites, 44.3% of behavioral health patients were diagnosed with trauma disorders, 22.1% with anxiety, 19.3% with attention-deficit hyperactivity disorder, 15.1% with depression, and 10.9% with disruptive behavior disorders. Overall, the model was financially successful at 2 sites (LCSWs) and unsuccessful at 1 site (NP). The other 2 sites demonstrated potential for financial sustainability with increased behavioral health patient volume. Overall, this model is a financially viable option for pediatric primary care practices with adequate patient volumes to provide integrated behavioral health services.

The Hsp40 J-domain stimulates Hsp70 when tethered by the client to the ATPase domain.

The Escherichia coli Hsp40 DnaJ uses its J-domain (Jd) to couple ATP hydrolysis and client protein capture in Hsp70 DnaK. Fusion of the Jd to peptide p5 (as in Jdp5) dramatically increases the apparent affinity of the p5 moiety for DnaK in the presence of ATP, and Jdp5 stimulates ATP hydrolysis in DnaK by several orders of magnitude. NMR experiments with [(15)N]Jdp5 demonstrated that the peptide tethers the Jd to the ATPase domain. Thus, ATP hydrolysis and client protein binding in DnaK are coupled principally through the association of the client with DnaJ. Overexpression of a recombinant Jd was specifically toxic to cells that simultaneously expressed DnaK. No toxicity was observed when overexpressing Jdp5 or mutant Jd or when co-overexpressing the Jd and the nucleotide exchange factor GrpE. The results suggest that the Jd shifts DnaK to a client-bound form by stimulating the DnaK ATPase but only when the Jd is brought to DnaK by a client-Hsp40 complex.

Under-ice noise generated from diamond exploration in a Canadian sub-arctic lake and potential impacts on fishes.

Mineral exploration is increasing in Canada, particularly in the north where extensive diamond mining and exploration are occurring. This study measured the under-ice noise produced by a variety of anthropogenic sources (drilling rigs, helicopters, aircraft landing and takeoff, ice-road traffic, augers, snowmobiles, and chisels) at a winter-based diamond exploration project on Kennady Lake in the Northwest Territories, Canada to infer the potential impact of noise on fishes in the lake. The root-mean-square noise level measured 5 m from a small diameter drill was approximately 46 dB greater (22 kHz bandwidth) than ambient noise, while the acoustic particle velocity was approximately 40 dB higher than ambient levels. The loudest sounds at the exploration site were produced by ice cracking, both natural and during landing and takeoff of a C130 Hercules aircraft. However, even walking on the snow above the ice raised ambient sound levels by approximately 30 dB. Most of the anthropogenic sounds are likely detectable by fishes with hearing specializations, such as chubs and suckers. Other species without specialized hearing adaptations will detect these sounds only close to the source. The greatest potential impact of noise from diamond exploration is likely to be the masking of sounds for fishes with sensitive hearing.

Both initial red cell distribution width (RDW) and change in RDW during heart failure hospitalization are associated with length of hospital stay and 30-day outcomes.

INTRODUCTION: We examined the predictive ability of red cell distribution width (RDW) and the change in RDW during hospitalization (ΔRDW) for length of stay (LOS) and 30-day outcomes after heart failure (HF) inpatient stay. METHODS: Electronic query of Intermountain Healthcare medical records identified patients (N = 6414) with a primary diagnosis of HF who were discharged between 2004 and 2013, had RDW measured within 24 h after admission, and had RDW tested at least once more during the same hospitalization. ΔRDW was defined as the last RDW within 24 h prior to discharge minus the first RDW. RESULTS: Median LOS by initial RDW quartiles was Q1: 3.0, Q2: 3.1, Q3: 3.7, and Q4: 4.0 days (P-trend<0.001), and by ΔRDW quartiles was Q1: 4.1, Q2: 3.4, Q3: 3.6, and Q4: 4.7 days (P-trend<0.001). Both initial RDW (16.8 ± 2.8% vs. 16.3 ± 2.7%, P < 0.001) and ΔRDW (0.21 ± 1.09% vs. 0.14 ± 1.04%, P = 0.039) predicted 30-day readmission vs. no readmit. For 30-day decedents vs. survivors, initial RDW was 17.3 ± 3.0% vs. 16.3 ± 2.6% (P < 0.001), while ΔRDW was +0.20 ± 1.14% vs. +0.14 ± 1.04% (P = 0.15). CONCLUSIONS: Greater initial RDW and ΔRDW during HF hospitalization were associated with 30-day mortality, longer LOS, and 30-day all-cause readmission, suggesting both ΔRDW and initial RDW may aid in personalizing prognosis and treatment.

Prospective study of pathogen burden and risk of myocardial infarction or death.

BACKGROUND: We previously demonstrated that the risk of coronary artery disease (CAD) increased in relation to the number of pathogens (the "pathogen burden") in a cross-sectional study. In the present prospective study with a different patient cohort, we evaluated the effect of pathogen burden on the risk of myocardial infarction (MI) or death among CAD patients. METHODS AND RESULTS: IgG antibodies to cytomegalovirus (CMV), hepatitis A virus (HAV), herpes simplex virus type 1 (HSV1), HSV type 2 (HSV2), Chlamydia pneumoniae and Helicobacter pylori, and C-reactive protein (CRP) levels were tested in baseline blood samples from 890 patients who had significant CAD on angiography. The mean follow-up period was 3 years. The baseline prevalence of antibodies directed against CMV, HAV, HSV1, or HSV2, but not C pneumoniae and H pylori, was significantly higher among patients who subsequently developed MI or death than among control subjects. After adjustment for traditional risk factors, number of diseased vessels, and clinical presentation, relative hazards (95% confidence limits) for MI or death were 2.0 (1. 4 to 3.2) for CMV, 1.6 (1.1 to 2.3) for HAV, and 1.5 (1.0 to 2.2) for HSV2. Increasing pathogen burden was significantly associated with increasing risk of MI or death in a dose-response fashion. Adjusted relative hazards of MI or death associated with pathogen burden were significant among individuals with low or high CRP levels. CONCLUSIONS: The results suggest that infection plays an important role in incident MI or death and that the risk posed by infection is independently related to the pathogen burden.

Plasma homocysteine predicts mortality independently of traditional risk factors and C-reactive protein in patients with angiographically defined coronary artery disease.

BACKGROUND: Plasma homocysteine (tHCY) has been associated with coronary artery disease (CAD). We tested whether tHCY also increases secondary risk, after initial CAD diagnosis, and whether it is independent of traditional risk factors, C-reactive protein (CRP), and methylenetetrahydrofolate reductase (MTHFR) genotype. METHODS AND RESULTS: Blood samples were collected from 1412 patients with severe angiographically defined CAD (stenosis >/=70%). Plasma tHCY was measured by fluorescence polarization immunoassay. The study cohort was evaluated for survival after a mean of 3.0+/-1.0 years of follow-up (minimum 1.5 years, maximum 5.0 years). The average age of the patients was 65+/-11 years, 77% were males, and 166 died during follow-up. Mortality was greater in patients with tHCY in tertile 3 than in tertiles 1 and 2 (mortality 15.7% versus 9.6%, P:=0.001 [log-rank test], hazard ratio [HR] 1.63). The relative hazard increased 16% for each 5-micromol/L increase in tHCY (P:<0.001). In multivariate Cox regression analysis, controlling for univariate clinical and laboratory predictors, elevated tHCY remained predictive of mortality (HR 1.64, P:=0.009), together with age (HR 1. 72 per 10-year increment, P:<0.0001), ejection fraction (HR 0.84 per 10% increment, P:=0.0001), diabetes (HR 1.98, P:=0.001), CRP (HR 1. 42 per tertile, P:=0.004), and hyperlipidemia. Homozygosity for the MTHFR variant was weakly predictive of tHCY levels but not mortality. CONCLUSIONS: In patients with angiographically defined CAD, tHCY is a significant predictor of mortality, independent of traditional risk factors, CRP, and MTHFR genotype. These findings increase interest in tHCY as a secondary risk marker and in secondary prevention trials (ie, with folate/B vitamins) to determine whether reduction in tHCY will reduce risk.

Randomized secondary prevention trial of azithromycin in patients with coronary artery disease: primary clinical results of the ACADEMIC study.

BACKGROUND: Chlamydia pneumoniae is associated with coronary artery disease (CAD), although its causal role is uncertain. A small preliminary study reported a >50% reduction in ischemic events by azithromycin, an antibiotic effective against C pneumoniae, in seropositive CAD patients. We tested this prospectively in a larger, randomized, double-blind study. METHODS AND RESULTS: CAD patients (n=302) seropositive to C pneumoniae (IgG titers >/=1:16) were randomized to placebo or azithromycin 500 mg/d for 3 days and then 500 mg/wk for 3 months. The primary clinical end point included cardiovascular death, resuscitated cardiac arrest, nonfatal myocardial infarction (MI), stroke, unstable angina, and unplanned coronary revascularization at 2 years. Treatment groups were balanced, and azithromycin was generally well tolerated. During the trial, 47 first primary events occurred (cardiovascular death, 9; resuscitated cardiac arrest, 1; MI, 11; stroke, 3; unstable angina, 4; and unplanned coronary revascularization, 19), with 22 events in the azithromycin group and 25 in the placebo group. There was no significant difference in the 1 primary end point between the 2 groups (hazard ratio for azithromycin, 0.89; 95% CI, 0.51 to 1.61; P:=0.74). Events included 9 versus 7 occurring within 6 months and 13 versus 18 between 6 and 24 months in the azithromycin and placebo groups, respectively. CONCLUSIONS: This study suggests that antibiotic therapy with azithromycin is not associated with marked early reductions (>/=50%) in ischemic events as suggested by an initial published report. However, a clinically worthwhile benefit (ie, 20% to 30%) is still possible, although it may be delayed. Larger (several thousand patient), longer-term (>/=3 to 5 years) antibiotic studies are therefore indicated.

Cytomegalovirus seropositivity and C-reactive protein have independent and combined predictive value for mortality in patients with angiographically demonstrated coronary artery disease.

BACKGROUND: The role of inflammation in coronary artery disease (CAD) is being increasingly recognized. Markers of inflammation (eg, C-reactive protein [CRP]) and infection (eg, seropositivity to Chlamydia pneumoniae, cytomegalovirus [CMV], and Helicobacter pylori) have been proposed as risk factors for CAD, but these associations require further evaluation. METHODS AND RESULTS: We prospectively tested whether CRP levels and IgG seropositivity to C pneumoniae, CMV, and H pylori are predictors of subsequent mortality in 985 consecutive patients with angiographically demonstrated CAD (stenosis >/=70%). Patients were followed for an average of 2.7 years (range 1.5 to 4.0 years). Patients averaged 65 years of age; 77% were men; and 110 (11.2%) died during follow-up. CRP levels were significantly elevated in nonsurvivors compared with survivors (mean CRP 3.1 mg/dL versus 1.5 mg/dL, P:=0.003). After controlling for all known baseline variables, the 2nd and 3rd tertiles of CRP compared with the 1st produced a Cox hazard ratio (HR) for mortality of 2.4 (P:=0.001). Of the 3 infectious markers tested, only seropositivity to CMV (HR=1.9, P:<0.05) was predictive of mortality. The majority of mortality risk associated with elevated CRP or CMV seropositivity occurred when both risk factors were present (P: for trend <0.0001). Other independent predictors of increased risk of mortality were age (HR=1.07 per year, P:<0.0001), left ventricular ejection fraction (HR=0.97 per percent, P:<0.0001), and diabetes mellitus (HR=1.7, P:=0.02). CONCLUSIONS: CMV seropositivity and elevated CRP, especially when in combination, are strong, independent predictors of mortality in patients with CAD. This suggests an interesting hypothesis that a chronic, smoldering infection (CMV) might have the capacity to accelerate the atherothrombotic process.

Evaluation of C-reactive protein, an inflammatory marker, and infectious serology as risk factors for coronary artery disease and myocardial infarction.

OBJECTIVES: We sought to test whether C-reactive protein (CRP) and seropositivity to any of three infectious agents are associated with angiographic coronary artery disease (CAD) and clinical myocardial infarction (MI). BACKGROUND: CRP, an inflammatory marker, is reported to predict risk of MI. The stimulus for CRP is unknown but might include infection. Chlamydia pneumoniae, cytomegalovirus and Helicobacter pylori have been linked to risk of MI or CAD. METHODS: Blood samples were collected from 363 patients undergoing coronary arteriography and tested for CRP and IgG titers to the infectious agents. RESULTS: CRP was higher in patients with CAD (1.32 mg/dl [SE 0.22, n = 80] vs. 0.58 mg/dl [SE 0.11 mg/dl, n = 109], p = 0.004) and in those with MI (2.05 mg/dl [SE 0.36, n = 47] vs. 0.54 mg/dl [SE 0.08, n = 133], p = 0.0002) than in respective control subjects. Seropositivity for each agent was present in a high proportion of patients with CAD (58% to 77%) or MI (54% to 75%) as well as in control subjects (no CAD: 46% to 74%; no MI: 50% to 77%). However, subjects seropositive to both C. pneumoniae and H. pylori had an increased prevalence of CAD (odds ratio [OR] 2.6, p = 0.02) and MI (OR 2.0, p = 0.15) and tended to have higher CRP levels (1.07 mg/dl [SE 0.16]) than those seronegative to both infectious agents (0.53 mg/dl [SE 0.10], p = 0.06). CONCLUSIONS: CRP is elevated in patients with CAD (more than twofold) and in those with MI (fourfold). Infectious serology is highly prevalent in both patients and control subjects. Seropositivity to both C. pneumoniae and H. pylori (but not one agent alone) may predict increased risk and may be associated with higher CRP levels. Infectious serology may be less predictive than previously suggested, but the cause of inflammation in CAD and MI deserves further study.

A common variant of the AMPD1 gene predicts improved cardiovascular survival in patients with coronary artery disease.

OBJECTIVE: We tested whether a common AMPD1 gene variant is associated with improved cardiovascular (CV) survival in patients with coronary artery disease (CAD). BACKGROUND: Reduced activity of adenosine monophosphate deaminase (AMPD) may increase production of adenosine, a cardioprotective agent. A common, nonsense, point variant of the AMPD1 gene (C34T) results in enzymatic inactivity and has been associated with prolonged survival in heart failure. METHODS: Blood was collected from 367 patients undergoing coronary angiography. Genotyping was done by polymerase chain reaction amplification and restriction enzyme digestion, resulting in allele-specific fragments. Coronary artery disease was defined as > or =70% stenosis of > or =1 coronary artery. Patients were followed prospectively for up to 4.8 years. Survival statistics compared hetero- (+/-) or homozygotic (-/-) carriers with noncarriers. RESULTS: Patients were 66 +/- 10 years old; 79% were men; 22.6% were heterozygous and 1.9% homozygous for the variant AMPD1(-) allele. During a mean of 3.5 +/- 1.0 years, 52 patients (14.2%) died, 37 (10.1%) of CV causes. Cardiovascular mortality was 4.4% (4/90) in AMPD1(-) allele carriers compared with 11.9% (33/277) in noncarriers (p = 0.046). In multiple variable regression analysis, only age (hazard ratio, 1.11/year, p < 0.001) and AMPD1(-) carriage (hazard ratio, 0.36, p = 0.053) were independent predictors of CV mortality. CONCLUSIONS: Carriage of a common variant of the AMPD1 gene was associated with improved CV survival in patients with angiographically documented CAD. The dysfunctional AMPD1(-) allele may lead to increased cardiac adenosine and increased cardioprotection during ischemic events. Adenosine monophosphate deaminase-1 genotyping should be further explored in CAD for prognostic, mechanistic and therapeutic insights.

Statin therapy, lipid levels, C-reactive protein and the survival of patients with angiographically severe coronary artery disease.

OBJECTIVES: The joint predictive value of lipid and C-reactive protein (CRP) levels, as well as a possible interaction between statin therapy and CRP, were evaluated for survival after angiographic diagnosis of coronary artery disease (CAD). BACKGROUND: Hyperlipidemia increases risk of CAD and myocardial infarction. For first myocardial infarction, the combination of lipid and CRP levels may be prognostically more powerful. Although lipid levels are often measured at angiography to guide therapy, their prognostic value is unclear. METHODS: Blood samples were collected from a prospective cohort of 985 patients diagnosed angiographically with severe CAD (stenosis > or =70%) and tested for total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and CRP levels. Key risk factors, including initiation of statin therapy, were recorded, and subjects were followed for an average of 3.0 years (range: 1.8 to 4.3 years) to assess survival. RESULTS: Mortality was confirmed for 109 subjects (11%). In multiple variable Cox regression, levels of TC, LDL, HDL and the TC:HDL ratio did not predict survival, but statin therapy was protective (adjusted hazard ratio [HR] = 0.49, p = 0.04). C-reactive protein levels, age, left ventricular ejection fraction and diabetes were also independently predictive. Statins primarily benefited subjects with elevated CRP by eliminating the increased mortality across increasing CRP tertiles (statins: HR = 0.97 per tertile, p-trend = 0.94; no statins: HR = 1.8 per tertile, p-trend < 0.0001). CONCLUSIONS: Lipid levels drawn at angiography were not predictive of survival in this population, but initiation of statin therapy was associated with improved survival regardless of the lipid levels. The benefit of statin therapy occurred primarily in patients with elevated CRP.

Usefulness of in-hospital prescription of statin agents after angiographic diagnosis of coronary artery disease in improving continued compliance and reduced mortality.

Despite well-documented clinical benefit of the use of statins in patients with coronary artery disease (CAD) and even mild lipid elevations, studies have documented the presence of a significant "treatment gap" between those patients in whom treatment is indicated and those patients who actually receive it. It has been proposed that a prescription for statin therapy given to indicated patients at the time of initial angiographic diagnosis of CAD has the potential to improve long-term medication compliance, but this requires further evaluation. We prospectively followed 600 patients with angiographically demonstrated CAD (diameter stenosis > or = 70%) who met the National Cholesterol Education Project (NCEP) guidelines for statin therapy for an average of 3.0 years (range 2.0 to 4.6). Patients were an average of 65 years of age, 78% were men, 77% presented initially with acute ischemic syndrome, and 64 (10.7%) died during follow-up. Overall, 105 patients (18%) were discharged from the initial hospitalization with a statin prescription. At long-term follow-up, the number of patients taking statins had increased to 47%. However, long-term statin compliance was significantly higher among patients initially discharged with a statin prescription than those who were not (77% vs 40%; p < 0.0001). Additionally, those patients discharged with a statin prescription had significantly reduced mortality rate at long-term follow-up (5.7% vs 11.7%; p = 0.05). Cox hazard regression analysis, controlling for all known clinical baseline variables, confirmed the absence of a prehospital discharge statin prescription to be an independent predictor of increased mortality (hazard ratio 2.4) with a statistical trend (p = 0.06). Thus, this study demonstrates that after angiographic diagnosis of CAD, prescription of appropriate statin therapy at the time of hospital discharge improves long-term statin compliance and may significantly enhance survival.

Temporal and spatial variations in the behavior of shrubsteppe birds.

We documented patterns of activity and microhabitat use by breeding male Sage Sparrows (Amphispiza belli) and Brewer's Sparrows (Spizella breweri) in the semiarid shrubsteppe of northwestern U.S.A. to determine how their behavior varies in space and time and how these variations relate to environmental features. In analyses of several sites with multiple plots that were studied for 2-4 yr, the frequencies of activities and substrate use varied significantly with year, plot, and location. The major activities, foraging and singing, varied inversely with one another. Thus, although the general structure of the activity budgets of these species was stable (i.e. foraging and singing were always the most frequent activities), there was considerable variation in the quantitative details of their behavior in space and time. Using stepwise regression, we related these variations in behavior to variations in environmental features such as the densities of the same or other species, the number of species in the community, and coverages of the different substrate types. Few patterns emerged, and those that did were generally not in accord with our expectations. In particular, patterns of substrate use were not related to variations in coverages of those substrates. Sage Sparrows, for example, increased their use of sagebrush and grass with increasing grass coverage and with increasing densities of Sage Sparrows. Responses to both variables suggested nonlinear threshold patterns.We interpret the variations in behavior as indicating a loose coupling between behavior and proximate environmental conditions for these species. In such situations, the variability of behavior complicates attempts to test ecological hypotheses (e.g. behavioral niche partitioning) with data from a limited number of locations or years.

Femoral arterial puncture management after percutaneous coronary procedures: a comparison of clinical outcomes and patient satisfaction between manual compression and two different vascular closure devices.

BACKGROUND: Vascular access site management is crucial to safe, efficient and comfortable diagnostic or interventional transfemoral percutaneous coronary procedures. Two new femoral access site closure devices, Perclose and Angio-Seal , have been proposed as alternative methods to manual compression (MC). We compared these two devices and tested them in reference to standard MC for safety, effectiveness and patient preference. METHODS: Prospective demographic, peri-procedural, and late follow-up data for 1,500 patients undergoing percutaneous coronary procedures were collected from patients receiving femoral artery closure by MC (n = 469), Perclose (n = 492), or Angio-Seal (n = 539). Peri-procedural, post-procedural, and post-hospitalization endpoints were: 1) safety of closure method; 2) efficacy of closure method; and 3) patient satisfaction. RESULTS: Patients treated with Angio-Seal experienced shorter times to hemostasis (p < 0.0001, diagnostic and interventional) and ambulation (diagnostic, p = 0.05; interventional, p < 0.0001) than those treated with Perclose. Those treated with Perclose experienced greater access site complications (Perclose vs. Angio-Seal, p = 0.008; Perclose vs. MC, p = 0.06). Patients treated with Angio-Seal reported greater overall satisfaction, better wound healing and lower discomfort (each vs. Perclose or vs. MC, all p < or = 0.0001). For diagnostic cath only, median post-procedural length of stay was reduced by Angio-Seal (Angio-Seal vs. MC, p < 0.0001; Angio-Seal vs. Perclose, p = 0.009). No difference was seen in length of stay for interventional cases. CONCLUSIONS: Overall, Angio-Seal performed better than Perclose or MC in reducing time to ambulation and length of stay among patients undergoing diagnostic procedures. There was a higher rate of successful deployment and shorter time to hemostasis for Angio-Seal, and this was accomplished with no increase in bleeding complications throughout the follow-up. Additionally, Angio-Seal performed better than Perclose in exhibiting a superior 30-day patient satisfaction and patient assessment of wound healing with less discomfort.

Efficient algorithms for function approximation with piecewise linear sigmoidal networks.

This paper presents a computationally efficient algorithm for function approximation with piecewise linear sigmoidal nodes. A one hidden layer network is constructed one node at a time using the well-known method of fitting the residual. The task of fitting an individual node is accomplished using a new algorithm that searches for the best fit by solving a sequence of quadratic programming problems. This approach offers significant advantages over derivative-based search algorithms (e.g., backpropagation and its extensions). Unique characteristics of this algorithm include: finite step convergence, a simple stopping criterion, solutions that are independent of initial conditions, good scaling properties and a robust numerical implementation. Empirical results are included to illustrate these characteristics.

Learning long-term dependencies in NARX recurrent neural networks.

It has previously been shown that gradient-descent learning algorithms for recurrent neural networks can perform poorly on tasks that involve long-term dependencies, i.e. those problems for which the desired output depends on inputs presented at times far in the past. We show that the long-term dependencies problem is lessened for a class of architectures called nonlinear autoregressive models with exogenous (NARX) recurrent neural networks, which have powerful representational capabilities. We have previously reported that gradient descent learning can be more effective in NARX networks than in recurrent neural network architectures that have "hidden states" on problems including grammatical inference and nonlinear system identification. Typically, the network converges much faster and generalizes better than other networks. The results in this paper are consistent with this phenomenon. We present some experimental results which show that NARX networks can often retain information for two to three times as long as conventional recurrent neural networks. We show that although NARX networks do not circumvent the problem of long-term dependencies, they can greatly improve performance on long-term dependency problems. We also describe in detail some of the assumptions regarding what it means to latch information robustly and suggest possible ways to loosen these assumptions.

An analysis of noise in recurrent neural networks: convergence and generalization.

Concerns the effect of noise on the performance of feedforward neural nets. We introduce and analyze various methods of injecting synaptic noise into dynamically driven recurrent nets during training. Theoretical results show that applying a controlled amount of noise during training may improve convergence and generalization performance. We analyze the effects of various noise parameters and predict that best overall performance can be achieved by injecting additive noise at each time step. Noise contributes a second-order gradient term to the error function which can be viewed as an anticipatory agent to aid convergence. This term appears to find promising regions of weight space in the beginning stages of training when the training error is large and should improve convergence on error surfaces with local minima. The first-order term is a regularization term that can improve generalization. Specifically, it can encourage internal representations where the state nodes operate in the saturated regions of the sigmoid discriminant function. While this effect can improve performance on automata inference problems with binary inputs and target outputs, it is unclear what effect it will have on other types of problems. To substantiate these predictions, we present simulations on learning the dual parity grammar from temporal strings for all noise models, and present simulations on learning a randomly generated six-state grammar using the predicted best noise model.