Representation of Women in Contemporary Kidney Transplant Trials.

Women are often underrepresented in clinical trials. It is unclear if this applies to trials in kidney transplant (KT) and whether the intervention or trial focus influences this. In this study, the weighted participation-to-prevalence ratio (PPR) for women enrollees in KT trials was determined for leading medical transplant or kidney journals between 2018 and 2023 using meta-regression overall and in three sensitivity analyses by: 1) Whether the intervention involved immunosuppression; 2) Area of trial focus; rejection, cardiometabolic, infection, lifestyle, surgical; 3) Whether the intervention was medical/surgical or social/behavioral. Overall, 33.7% of participants in 24 trials were women. The overall pooled PPR for the included trials was 0.80, 95% CI 0.76-0.85, with significant heterogeneity between trials (I 2 56.6%, p-value < 0.001). Women had a lower PPR when the trial involved immunosuppression (PPR 0.77, 95% CI 0.72-0.82) than when it did not (PPR 0.86, 95% CI 0.80-0.94) and were less likely to participate in trials with a medical/surgical versus behavioral intervention; the lowest PPR for women was in studies examining rejection risk (PPR 0.75, 95% CI 0.70-0.81). There is better representation of women in KT trials compared to other medical disciplines, however women remain underrepresented in transplant trials examining immunosuppression and rejection.

Disparities in Deceased Donor Kidney Offer Acceptance: A Survey of Canadian Transplant Nephrologists, General Surgeons and Urologists.

Background: Significant variability in organ acceptance thresholds have been demonstrated across the United States, but data regarding the rate and rationale for kidney donor organ decline in Canada are lacking. Objective: To examine decision making regarding deceased kidney donor acceptance and non-acceptance in a population of Canadian transplant professionals. Design: A survey study of theoretical deceased donor kidney cases of increasing complexity. Setting: Canadian transplant nephrologists, urologists, and surgeons making donor call decisions responding to an electronic survey between July 22 and October 4, 2022. Participants: Invitations to participate were distributed to 179 Canadian transplant nephrologists, surgeons, and urologists through e-mail. Participants were identified by contacting each transplant program and requesting a list of physicians who take donor call. Measurements: Survey respondents were asked whether they would accept or decline a given donor, assuming there was a suitable recipient. They were also asked to cite reasons for donor non-acceptance. Methods: Donor scenario-specific acceptance rates (total acceptance divided by total number of respondents for a given scenario and overall) and reasons for decline were determined and presented as a percentage of the total cases declined. Results: In all, 72 respondents from 7 provinces completed at least one question of the survey, with considerable variability between acceptance rates for centers; the most conservative center declined 60.9% of donor cases, whereas the most aggressive center declined only 28.1%, P-value < .001. There was an increased risk of non-acceptance with advancing age, donation after cardiac death, acute kidney injury, chronic kidney disease, and comorbidities. Limitations: As with any survey, there is the potential for participation bias. In addition, this study examines donor characteristics in isolation, however, asks respondent to assume there is a suitable candidate available. In reality, whenever donor quality is considered, it should be considered in the context of the intended recipient. Conclusion: In a survey of increasingly medically complex deceased kidney donor cases, there was significant variability in donor decline among Canadian transplant specialists. Given relatively high rates of donor decline and apparent heterogeneity in acceptance decisions, Canadian transplant specialists may benefit from additional education regarding the benefits achieved from even medically complex kidney donors for appropriate candidates relative to remaining on dialysis on the transplant waitlist.

Contexte: Une importante variabilité a été observée aux États-Unis dans le seuil d'acceptation des organes. Au Canada, on manque de données sur le taux de refus des donneurs de reins et sur les raisons qui expliquent ce refus. Objectifs: Examiner la prise de décision quant à l'acceptation ou non d'un donneur de rein décédé dans une population de professionnels de la transplantation canadiens. Conception: Un sondage exposant des cas théoriques de plus en plus complexes de donneurs de reins décédés. Cadre: Des néphrologues, urologues et chirurgiens canadiens spécialisés en transplantation qui prennent des décisions relatives au don d'organes ont été invités à répondre à un sondage électronique entre le 22 juillet et le 4 octobre 2022. Participants: L'invitation à participer a été distribuée par courriel à 179 néphrologues, chirurgiens et urologues canadiens spécialisés en transplantation. Les participants ont été identifiés en communiquant avec chaque program de transplantation pour obtenir une liste des médecins recevant des offres d'organes. Mesures: Les répondants devaient indiquer s'ils accepteraient ou refuseraient un donneur donné, en supposant qu'un receveur approprié existait. Ils étaient également invités à citer les raisons justifiant le refus d'un donneur. Méthodologie: Les taux d'acceptation par scénario (acceptation totale divisée par le nombre total de répondants pour un scénario donné, et pour l'ensemble) et les raisons du refus ont été déterminés et présentés sous forme de pourcentage du nombre total de cas refusés. Résultats: En tout, 72 professionnels issus de 7 provinces avaient répondu à au moins une question du sondage. On a observé une grande variabilité du taux d'acceptation entre les différents centers; le plus conservateur avait refusé 60,9 % des donneurs présentés alors que le plus entreprenant n'avait refusé que de 28,1 % des cas (p < 0,001). Les donneurs d'âge avancé, ceux décédés d'un problème cardiaque et ceux qui souffraient d'insuffisance rénale aiguë, d'insuffisance rénale chronique et de comorbidités étaient plus susceptibles d'être refusés. Limites: Comme pour toute étude sous forme de sondage, celle-ci comporte un possible biais de participation. Cette étude examine les caractéristiques du donneur de manière isolée, mais demande aux répondants de supposer qu'un candidat approprié existe. Dans la réalité, chaque fois que la qualité d'un donneur est évaluée, elle doit être prise en compte dans le contexte du receveur visé. Conclusion: Dans cette étude présentant des cas théoriques de complexité croissante sur le plan médical de donneurs de reins décédés, une importante variabilité a été observée quant au refus des donneurs par les spécialistes de la transplantation canadiens. Les taux relativement élevés de refus et l'apparente hétérogénéité des décisions liées à l'acceptation justifient plus d'éducation auprès des spécialistes de la transplantation canadiens; notamment sur les avantages pour un candidat approprié de recevoir un organe, même si ce dernier provient d'un cas médicalement complexe, par rapport au fait de rester en dialyze sur la liste d'attente pour une transplantation.

Estimated Impact of Deemed Consent Legislation for Organ Donation on Individuals With Kidney Failure: A Dynamic Decision Analytic Model.

Background: There is little data modeling the impact of deemed consent legislation (eligible individuals who do not register their decision to decline to be a donor are presumed to consent after death) on outcomes for individuals with kidney failure. Objective: To estimate the change in life-years (LYs) and quality-adjusted life-years (QALYs) resulting from different changes in the rate of deceased donor kidney transplantation associated with deemed consent legislation and health system transformation. Design: Dynamic Decision Analytic Model. Setting: This modeling study included kidney failure patients in Atlantic Canada (all of whom receive their kidney transplants in Halifax, Nova Scotia). The adoption of deemed consent legislation was the intervention, and opt-in (the status quo) was the reference comparator. Patients: Prevalent kidney failure patients at the end of 2019 in all of Atlantic Canada (N = 3615) served as the starting population. Methods: We compared expected outcomes between the intervention and comparator. Changes in QALYs and total LYs were modeled under different changes to the proportion of patients receiving a deceased donor kidney transplant (from -10% to 20%) resulting from deemed consent relative to the status quo. Changes in QALYs and LYs were reported for 3 different time horizons (5, 10, and 30 years). Uncertainty around QALYs and total LYs was reported using 95% confidence intervals (CIs) constructed from a probabilistic sensitivity analysis using 1000 Monte Carlo Simulations. Results: The increase in QALYs ranged from 7 QALYs (95% CI: 5-10) with a 5% increase using a 5-year time frame to 882 QALYs (95% CI: 619-1144) with a 20% increase over a 30-year time frame. Parallel changes in total LYs were also observed. In contrast, decreases in deceased donor kidney transplantation resulted in a loss of QALYs (for example, -463 QALYs; 95% CI: -633 to -306 for a 10% decrease over a 30-year time frame). Using the most optimistic scenario (a 20% increase), there was an 18% increase in the cumulative number of deceased donor kidney transplant recipients over a 30-year observation period. Limitations: The results are subject to uncertainty depending on changes to the dialysis or transplant population that were not modeled and that may not be fully captured with probabilistic sensitivity analysis. Conclusions: Deemed consent legislation will lead to variable changes in QALYs and total LYs for the kidney failure population, depending on the degree to which deceased donor transplantation rates change and the time horizon of observation. This modeling study may serve as a baseline to monitor the future impact of deemed consent legislation.

Contexte: Il existe peu de données modélisant l'impact d'une loi sur le consentement présumé (les personnes admissibles qui n'enregistrent pas leur décision de refuser d'être un donneur sont présumées consentir après leur décès) sur les résultats des personnes atteintes d'insuffisance rénale. Objectif: Estimer les variations dans les années de vie (AV) et les années de vie corrigées en fonction de leur qualité (AVCQ) résultant de changements dans les taux de transplantation rénale provenant d'un donneur décédé; changements qui seraient associés à la loi sur le consentement présumé et à la transformation du système de santé. Conception: Modèle dynamique d'analyse décisionnelle. Cadre: L'étude a été modélisée avec des patients du Canada atlantique atteints d'insuffisance rénale terminale (tous avaient reçu leur greffe de rein à Halifax, en Nouvelle-Écosse). L'intervention consistait en l'adoption d'une loi sur le consentement présumé, alors que le statu quo représentait le comparateur de référence. Sujets: La population de départ était constituée des patients atteints d'insuffisance rénale terminale à la fin de 2019 dans l'ensemble du Canada atlantique (N=3615). Méthodologie: Nous avons comparé les résultats attendus pour l'intervention et le comparateur. Les variations dans les AVCQ et les AV totales ont été modélisées en fonction de divers changements résultant du consentement présumé par rapport au statu quo dans la proportion de patients recevant une transplantation rénale d'un donneur décédé (de -10 à 20 %). Les variations dans les AVCQ et les AV ont été rapportées pour trois horizons temporels (5, 10 et 30 ans). L'incertitude entourant les AVCQ et les années de vie totales a été rapportée avec des intervalles de confiance à 95 % établis à partir d'une analyse de sensibilité probabiliste réalisée par la méthode de Monte Carlo. Résultats: En ce qui concerne les AVCQ, la variation passait de 7 AVCQ (IC 95 % : 5, 10), avec une augmentation de 5 % sur une période de 5 ans, à 882 AVCQ (IC 95 % : 619, 1 144) avec une augmentation de 20 % sur une période de 30 ans. Des variations parallèles ont été observées pour les AV totales. En revanche, la diminution du taux de transplantations rénales provenant d'un donneur décédé a entraîné une perte d'AVCQ (par ex. - 463 AVQ; IC à 95 % : -633, -306 pour une diminution de 10 % sur une période de 30 ans). Dans le scénario le plus optimiste (augmentation de 20 %), on a observé une augmentation de 18 % du nombre cumulatif de transplantations rénales provenant de donneurs décédés au cours d'une période d'observation de 30 ans. Limites: Les résultats sont sujets à des incertitudes en fonction de variations dans la population de patients sous dialyse ou greffés qui n'auraient pas été modélisées et qui pourraient ne pas être entièrement prises en compte par une analyse de sensibilité probabiliste. Conclusion: La loi sur le consentement présumé entraînera des changements variables dans les AV totales et les AVCQ des patients atteints d'insuffisance rénale terminale, selon le degré d'évolution des taux de transplantation provenant de donneurs décédés et de l'horizon d'observation. Cette étude de modélisation peut servir de référence pour surveiller les impacts futurs d'une loi sur le consentement présumé.

No Guts About It: Captivity, But Not Neophobia Phenotype, Influences the Cloacal Microbiome of House Sparrows (Passer domesticus).

Behavioral traits such as anxiety and depression have been linked to diversity of the gut microbiome in humans, domesticated animals, and lab-bred model species, but the extent to which this link exists in wild animals, and thus its ecological relevance, is poorly understood. We examined the relationship between a behavioral trait (neophobia) and the cloacal microbiome in wild house sparrows (Passer domesticus, n = 22) to determine whether gut microbial diversity is related to personality in a wild animal. We swabbed the cloaca immediately upon capture, assessed neophobia phenotypes in the lab, and then swabbed the cloaca again after several weeks in captivity to additionally test whether the microbiome of different personality types is affected disparately by captivity, and characterized gut microbiomes using 16S rRNA gene amplicon sequencing. We did not detect differences in cloacal alpha or beta microbial diversity between neophobic and non-neophobic house sparrows, and diversity for both phenotypes was negatively impacted by captivity. Although our results suggest that the adult cloacal microbiome and neophobia are not strongly linked in wild sparrows, we did detect specific OTUs that appeared more frequently and at higher abundances in neophobic sparrows, suggesting that links between the gut microbiome and behavior may occur at the level of specific taxa. Further investigations of personality and the gut microbiome are needed in more wild species to reveal how the microbiome-gut-brain axis and behavior interact in an ecological context.

Donor-Recipient Matching in Kidney Transplant: We're Not There Yet.

BACKGROUND: Strategic organ allocation is expected to prolong patient and graft survival after transplant. This study explored differences in graft survival when kidneys are allocated based on strategic donor-recipient (D-R) pairing vs with the existing Kidney Allocation System (KAS). METHODS: Using the Scientific Registry of Transplant Recipients from 2000 to 2014, we used a multivariable Cox model to assess the hazard ratios (HRs) for death or graft failure among 3 hypothetical donor kidneys transplanted into 3 hypothetical recipients, relative to an ideally matched D-R pair. Median predicted survival for each of the 9 possible D-R pairing combinations was determined, and outcomes for strategic D-R pairing were compared with those obtained using the KAS for allocation. RESULTS: A total of 31,607 patients (29.7%) died or developed graft loss over the study period. Strategic allocation of kidneys resulted in HRs for graft loss of 1.74 (95% confidence interval [CI], 1.41-2.14), 1.82 (95% CI, 1.46-2.26), and 1.74 (95% CI 1.38-2.19) for recipients 1, 2 and 3 respectively, whereas by following the KAS, HRs were 1.93 (95%, CI 1.63-2.28), 2.06 (95% CI, 1.74-2.44), and 1.93 (95% CI, 1.58-2.37); corresponding to 3.84, 11.39, and 7.40 months longer predicted patient or graft survival for recipients 1, 2 and 3 with strategic D-R pairing compared with the KAS. CONCLUSIONS: Allocation of kidneys by strategic D-R pairing may improve graft survival relative to allocation using the KAS.

Predictors of Need for First and Recurrent Emergency Medical Service Transport to Emergency Department after Dialysis Initiation.

Background: Dialysis patients are frequently transported to the emergency department (ED) by Emergency Medical Services (EMS) due to acute and severe illness. However, little is known about predictors of first and recurrent transport to the ED (EMS-ED), based on characteristics at the time of dialysis initiation.Methods: We analyzed a cohort of adult (≥18 years) patients affiliated with a large quaternary care center who initiated chronic dialysis from 2009 to 2013 (last follow-up: 2015). Data on patient characteristics at the time of dialysis initiation were linked to regional EMS data. Candidate predictors of first and recurrent EMS-ED transport included comorbid conditions, dialysis characteristics and frailty severity (using the first version of the clinical frailty scale score; CFS). Time to first EMS-ED was analyzed using a multivariable sub-hazards regression model accounting for competing events (transplantation or death). Time to recurrent EMS-ED was analyzed using the Anderson-Gill counting approach, accounting for competing risks.Results: A total of 455 patients were included in the study, 243 (53%) had 1+ EMS-ED events, 90 (20%) never required an EMS-ED at last follow-up, and 69 (15%) and 53 (12%) experienced transplant or death as their first event, respectively. The mean age of the cohort was 62 ± 15 years, 89% were Caucasian, and 35% were female sex. Patients were highly comorbid and 97/381 (25.5%) with available data on frailty severity had a CFS score of ≥5, inclusive of CFS scores ranging from mildly to severely frail. After adjustment, a CFS score of ≥5 (relative to 1-2) was associated with a > 2-fold increase in the risk of first EMS-ED (subdistribution relative hazard; SHR 2.28, 95% confidence interval; CI 1.30-3.98). A history of peripheral vascular disease (SHR 1.43, 95% CI 1.00-2.03) and rheumatologic disease (SHR 1.84, 95% CI 1.00-3.38) was also associated with first EMS-ED. Frailty severity was the only factor associated with recurrent EMS-ED.Conclusion: Patients are at a high risk of EMS-ED after dialysis initiation. Frailty severity (at the time of dialysis initiation) is a strong predictor of first and recurrent EMS-ED and this may be important to guide informed decision making and resource planning for dialysis patients who require EMS.

Hepatitis C virus-infected kidney waitlist patients: Treat now or treat later?

Currently many but not all centers transplant hepatitis C virus (HCV) viremic positive (+) donor kidneys into HCV+ recipients. Directed donation of HCV+ organs reduces the wait time to transplantation for HCV+ patients. Direct-acting antiviral (DAA) therapy can cure HCV in virtually all who are infected. Some have suggested that treatment of HCV+ waitlisted patients be deferred with the hope that earlier transplantation will provide better outcomes than early DAA therapy. However, there are not enough organs to guarantee prompt transplantation for the current waitlist of infected candidates. A Markov medical decision analysis model was created to compare the overall outcomes of delayed DAA therapy (Option 1) to immediate DAA therapy (Option 2) in waitlisted HCV+ patients. Option 1 patients were modeled to be transplanted 1 year earlier, with a higher cumulative transplant incidence (54% at 5 years post-listing vs 45% for Option 2). Despite this, Option 2 provided 0.43 (95% confidence interval [CI] 0.38-0.49) more life years than Option 1. However, Option 1 was preferred for regions with much greater access to HCV+ organs or in patients with very low HCV+-associated mortality. The best option from an individual patient's perspective will differ by region and candidate.

Genetical genomics of Th1 and Th2 immune response in a baboon model of atherosclerosis risk factors.

OBJECTIVE: CD4(+) T-cells mediate inflammation in atherosclerosis, but additive genetic effects on associated pathways of Th1 and Th2 immune response have not been described. We sought to characterize heritability, pleiotropy, and QTL effects on the expression of genes implicated in Th1 and Th2 immune response in a baboon model of risk factors for atherosclerosis. METHODS: We employed a maximum likelihood-based variance decomposition approach to estimate additive genetic effects on transcript levels generated from a gene expression profile of lymphocytes in 499 pedigreed baboons maintained on a basal diet. Transcript levels for 57 genes implicated in Th1 and Th2 immune response were selected for analysis based on significant heritability in this profile. Multipoint whole genome scans were conducted on heritable transcript levels to localize QTLs influencing these measures. To evaluate pleiotropic effects on transcript levels, we estimated genetic and phenotypic correlations among transcript measures, and assessed their correspondence using a Mantel test. Network analysis using GeneGo's MetaCore™ software was conducted to characterize known interaction among coded proteins. RESULTS: Heritabilities for candidate gene transcript levels ranged from 0.092-0.786 (median h(2)=0.278, P=4.72×10(-4)). Linkage analyses yielded significant evidence (LOD≥2.73) for 14 eQTLs (LOD score range 2.76-14.87, genome-wide P=4.9×10(-2)-1.03×10(-14)). Estimates of genetic correlation supported shared additive genetic effects incorporating all 57 transcripts (null hypothesis of ρ(G)=0 rejected at FDR≤0.05 for 522 of 1596 estimates), and accounted for most of the observed phenotypic correlation among transcripts (Mantel test, r([ρP],)([ρG])=0.781, P<0.0001). Network analysis revealed direct interactions among 54 of the 57 coded proteins. CONCLUSIONS: We conclude that major genetic effects influence expression levels of multiple genes implicated in Th1 and Th2 immune response. Additionally, we find that expression levels of these candidate genes are characterized by extensive pleiotropy, consistent with known interaction among their coded proteins, many of which are independently associated with atherosclerosis.

A pleiotropic QTL on 2p influences serum Lp-PLA2 activity and LDL cholesterol concentration in a baboon model for the genetics of atherosclerosis risk factors.

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), the major portion of which is bound to low-density lipoprotein, is an independent biomarker of cardiovascular disease risk. To search for common genetic determinants of variation in both Lp-PLA(2) activity and LDL cholesterol (LDL-C) concentration, we assayed these substances in serum from 679 pedigreed baboons. Using a maximum likelihood-based variance components approach, we detected significant evidence for a QTL affecting Lp-PLA(2) activity (LOD=2.79, genome-wide P=0.039) and suggestive evidence for a QTL affecting LDL-C levels (LOD=2.16) at the same location on the baboon ortholog of human chromosome 2p. Because we also found a significant genetic correlation between the two traits (rho(G)=0.50, P<0.00001), we conducted bivariate linkage analyses of Lp-PLA(2) activity and LDL-C concentration. These bivariate analyses improved the evidence (LOD=3.19, genome-wide P=0.015) for a QTL at the same location on 2p, corresponding to the human cytogenetic region 2p24.3-p23.2. The QTL-specific correlation between the traits (rho(Q)=0.62) was significantly different from both zero and 1 (P[rho(Q)=0]=0.047; P[rho(Q)=1]=0.022), rejecting the hypothesis of co-incident linkage and consistent with incomplete pleiotropy at this locus. We conclude that polymorphisms at the QTL described in this study exert some genetic effects that are shared between Lp-PLA(2) activity and LDL-C concentration.

Treatment of pediatric both-bone forearm fractures: a comparison of operative techniques.

Both-bone forearm fractures of the radius and ulna are a common injury in children. Closed reduction and casting has historically been the primary means of treatment in over 90% of these fractures. Unstable and irreducible fractures, however, often pose a therapeutic challenge, with little data available to compare outcomes. The authors performed a retrospective review of 50 children with both-bones fractures treated with closed reduction and cast immobilization, open reduction and internal fixation (ORIF), or intramedullary (IM) nailing. Complications were tabulated and separated by treatment modality and subdivided into minor/major complications. Statistical regression was performed. There were 54 operations in 50 patients with both-bones fractures. All fractures healed within 8 to 10 weeks, except for two delayed unions and one nonunion. The complication rate was 5% for closed treatment, 33% for ORIF, and 42% for IM nailing. Complication rates were significantly different between the closed and operative groups. When comparing treatments in pediatric both-bones fractures, there are significantly more complications with operative techniques. Patients with ORIF had more major complications, often requiring a return to the operating room. IM nailing, when done correctly, is as acceptable and safe a form of treatment.

Adult scoliosis: a quantitative radiographic and clinical analysis.

STUDY DESIGN: Prospective analysis of a consecutive series of adult patients with adolescent idiopathic scoliosis of the adult and de novo degenerative scoliosis. OBJECTIVES: To clinically and radiographically study two populations of adult patients with either adolescent idiopathic scoliosis of the adult or de novo degenerative scoliosis in a quantitative manner to identify reliable radiographic parameters that correlate with clinical symptoms. SUMMARY AND BACKGROUND: Although there are many causes of spinal deformity in the adult, there are two main categories of adult scoliosis: adolescent idiopathic scoliosis of the adult and de novo degenerative scoliosis. Unlike pediatric scoliosis, in adults there are no established radiographic parameters or classification systems that reliably provide a clinical correlation or offer a useful language for communication among specialists. This study gathered complete clinical and radiographic information on 95 patients with adult scoliosis and established several radiographic parameters that correlated with clinical symptoms. METHODS: Each of the 95 patients completed a clinical questionnaire that included a self-reported visual analog scale and underwent full-length standing anteroposterior and lateral radiography. Radiographic analysis was performed by use of digital analysis and included measurement of the Cobb angle, the number of vertebrae in each curve, plumbline offset from T1 to the midsacral line, the upper endplate obliquities of L3 and L4, and maximal lateral olisthy between two adjacent lumbar vertebrae. Sagittal plane measurements included lumbar lordosis, thoracolumbar kyphosis, and the Sagittal Pelvic Tilt Index. Statistical analysis of both radiographic and clinical parameters of pain was performed to determine any significant correlations between the two. RESULTS: This study showed that lateral vertebral olisthy, L3 and L4 endplate obliquity angles, lumbar lordosis, and thoracolumbar kyphosis were significantly correlated with pain. CONCLUSION: This quantitative analysis identified several clinically relevant radiographic parameters in adult scoliosis patients. Additionally, excellent predictive formulas for self-reported pain levels were obtained.

Photoactivated fluorescence from individual silver nanoclusters.

Fluorescence microscopy of nanoscale silver oxide (Ag2O) reveals strong photoactivated emission for excitation wavelengths shorter than 520 nanometers. Although blinking and characteristic emission patterns demonstrate single-nanoparticle observation, large-scale dynamic color changes were also observed, even from the same nanoparticle. Identical behavior was observed in oxidized thin silver films that enable Ag2O particles to grow at high density from silver islands. Data were readily written to these films with blue excitation; stored data could be nondestructively read with the strong red fluorescence resulting from green (wavelengths longer than 520 nanometers) excitation. The individual luminescent species are thought to be silver nanoclusters that are photochemically generated from the oxide.

Neutron and X-ray reflectivity studies of human serum albumin adsorption onto functionalized surfaces of self-assembled monolayers.

Neutron and X-ray reflectivity (NR and XR) have been widely used for the investigation of the structure of thin organic films. Here we demonstrate how these sensitive techniques may be applied to the study of protein adsorption to well-characterized self-assembled monolayers (SAMs) with different chemical functionalities. NR can be used for in situ study, while XR provides complementary information on the initial surfaces and dried layers measured in air after protein has been adsorbed. In situ measurements of adsorption of human serum albumin onto a hydrophilic NH2-terminated monolayer clearly show the presence of a thin layer of adsorbed protein next to the SAM. Adsorption of albumin onto a hydrophobic, deuterated, CD3-terminated SAM causes even bigger changes in the NR. Upon replacing the protein solution with protein-free buffer solution, the reflectivities from both kinds of monolayers do not change, demonstrating that the albumin adsorption is irreversible after several hours of contact with the protein solution. X-ray reflectivity measurements of dried substrates performed ex situ in air provide a lower bound estimate of the amount of protein which must be at the interface in situ. This combination of techniques provides a uniquely sensitive approach for studying changes that occur upon protein adsorption at an interface.

Quantitative microdialysis of serotonin and norepinephrine: pharmacological influences on in vivo extraction fraction.

The present study was designed to investigate the potential influence of various neuronal processes including uptake, release and metabolism, on the in vivo microdialysis extraction fraction (Ed) of serotonin (5HT) and norepinephrine (NE). Paroxetine administration decreased the Ed of 5HT in the nucleus accumbens from 24 +/- 3 to 18 +/- 0.2% (p < 0.05). Similarly, desipramine infusion reduced the NE Ed from 35 +/- 2 to 26 +/- 1% (p < 0.05). However, perfusion with pargyline or tetrodotoxin had no effect on the Ed of either 5HT or NE. Perfusion with agonists for the 5HT, alpha-adrenergic, D2 and histamine receptors had no effect on the Ed of 5HT. In the same manner, perfusion with the alpha-adrenergic agonists, methoxamine or clonidine, did not affect the Ed of NE. These data are in agreement with experimental results obtained for dopamine in the nucleus accumbens and the theory of quantitative microdialysis which predicts that only changes in the rate of clearance will change Ed of monoamines. These results suggest that, like DA, changes in the Ed for 5HT or NE are indicative of changes in the reuptake of these neurotransmitters. The results also indicate that pharmacological agents which do not affect uptake have no effect on the extraction fraction.

Absolute ethanol embolization for peripheral arteriovenous malformation: report of two cures.

We have reported two patients in whom absolute ethanol was used to sclerose arteriovenous malformations. Because of its low viscosity, liquid form, and devastating effect when injected intra-arterially, absolute ethanol is effective in treating AVMs, and it has been proven to have curative potential. For these same reasons it is also potentially harmful, particularly to nerves and possibly to skin.

The management of clotted angiographic catheters.

In our experience, clotted angiographic catheters pulled back to near the puncture site and severed near the skin will spontaneously clear, facilitating insertion of a guidewire and catheter exchange without repuncture or other manipulation.

Replacement of dislodged biliary catheters using angiographic techniques and the fiberoptic bronchoscope.

A method for replacing biliary tract catheters with angiographic techniques is described, along with clinical experience in its use. Situations which at first seem hopeless may in fact be simply resolved as in the first instance. We found the fiberoptic scope to be useful when the cannulation tract involves a segment of bowel.