Continuous ambulatory and continuous cycling peritoneal dialysis in children. A report of the Southwest Pediatric Nephrology Study Group1

Continuous ambulatory and continuous cycling peritoneal dialysis in children. A report of the Southwest Pediatric Nephrology Study Group. Continuous ambulatory peritoneal dialysis (CAPD) and continuous cycling peritoneal dialysis (CCPD) have become acceptable methods of treatment for children with endstage renal disease (ESRD). In this study we have compared the effectiveness of these two modalities of prolonged dwell peritoneal dialysis in 82 children treated at home with CAPD and/or CCPD for a mean of 10.2 months. Forty variables were evaluated during 92 patient periods (63 CAPD, 29 CCPD). There was no difference between the two groups with regard to sex, race, original disease, duration of dialysis, or volume of dialysis fluid. The only difference in biochemical profiles between the two groups was a higher serum creatinine in CCPD patients due in part to this group's greater age. The rate of peritonitis was not different (CAPD 1/4.6, CCPD 1/5.2 months), but the number of patient periods devoid of peritonitis was greater in the CCPD group (14/29 vs. 17/63, P = 0.04). Growth velocity index (GVI) and standard deviation scores (SD scores) were used to evaluate growth in the total group and subsets according to age. Overall GVI was 88% of expected and did not differ between PD groups (CAPD 88% vs. CCPD 89%). There were no significant changes in SD scores for growth during the course of prolonged dwell peritoneal dialysis indicating that the children did not experience further deterioration in growth. Children less than 4 years of age also did not have significant changes in SD scores. We conclude that CAPD and CCPD provide acceptable and comparable modes of dialytic therapy for children with ESRD.Dialyse péritonéale continue ambulatoire et recyclage continu chez des enfants. Rapport du Southwest Pediatric Nephrology Study Group. La dialyse péritonéale continue ambulatoire (CAPD) et la dialyse péritonéale recyclage continu (CCPD) sont devenues des méthodes acceptables chez les enfants en ESRD. Dans cette étude, nous avons comparé l'efficacité de ces deux modalités de dialyse péritonéale à demeure prolongée chez 82 enfants traités à domicile par CAPD et/ou CCPD pendant 10,2 mois en moyenne. Quarante variables ont été évaluées pendant 92 périodes-malades (63 CAPD, 29 CCPD). Il n'y avait pas de différence entre les deux groupes quant au sexe, la race, la maladie initiale, la durée de dialyse ou le volume de liquide de dialyse. La seule différence dans les profils biochimiques entre les deux groupes était une créatininémie plus élevée chez les malades en CCPD, en partie à cause du plus grand âge de ce groupe. Le taux de péritonite n'était pas différent (CAPD 1/4,6, CCPD 1/5,2 mois), mais le nombre de malades sans épisode de péritonite était plus élevé dans le groupe CCPD (14/29 contre 17/62, P= 0,04). L'index de vitesse de croissance (GVI) et les scores de déviation standard (SD/scores) ont été utilisés pour évaluer la croissance chez les enfants et les sous-groupes en fonction de l'âge. Globalement, GVI était 84% de la valeur attendue, et ne différait pas entre les groupes PD (CAPD 88% contre CCPD 89%). Il n'existait pas de modification significative des scores de SD pour la croissance au cours de la dialyse péritonéale à demeure prolongée, indiquant que les enfants n'avaient pas eu de dégradation supplémentaire de leur croissance. Les enfants âgés de moins de 4 ans n'avaient pas non plus de changements significatifs des scores de SD. Nous concluons que la CAPD et la CCPD constituent des modes acceptables et comparables de traitement dialytique chez les enfants en ESRD

Finding, Characterizing, and Classifying Variable Sources in Multi-epoch Sky Surveys: QSOs and RR Lyrae in PS1 3π data

In area and depth, the Pan-STARRS1 (PS1) 3π survey is unique among many-epoch, multi-band surveys and has enormous potential for the all-sky identification of variable sources. PS1 has observed the sky typically seven times in each of its five bands (grizy) over 3.5 years, but unlike SDSS, not simultaneously across the bands. Here we develop a new approach for quantifying statistical properties of non-simultaneous, sparse, multi-color light curves through light curve structure functions, effectively turning PS1 into a ~35-epoch survey. We use this approach to estimate variability amplitudes and timescales (ωr, τ) for all point sources brighter than rP1 = 21.5 mag in the survey. With PS1 data on SDSS Stripe 82 as "ground truth," we use a Random Forest Classifier to identify QSOs and RR Lyrae based on their variability and their mean PS1 and WISE colors. We find that, aside from the Galactic plane, QSO and RR Lyrae samples of purity ~75% and completeness ~92% can be selected. On this basis we have identified a sample of ~1,000,000 QSO candidates, as well as an unprecedentedly large and deep sample of ~150,000 RR Lyrae candidates with distances from ~10 to ~120 kpc. Within the Draco dwarf spheroidal, we demonstrate a distance precision of 6% for RR Lyrae candidates. We provide a catalog of all likely variable point sources and likely QSOs in PS1, a total of 25.8 × 106 sources

Brief Report: No Evidence for an Association between Statin Use and Lower Biomarkers of HIV Persistence or Immune Activation/Inflammation during Effective ART

Background: Statins exert pleiotropic anti-inflammatory and immune-modulatory effects, which might translate into antiviral activity. We evaluated whether reported current statin exposure is associated with lower levels of markers of HIV persistence and immune activation/inflammation. Methods: We compared levels of markers of HIV viral persistence [cell-associated HIV RNA (CA-RNA), CA-DNA, and single copy assay plasma HIV RNA] and immune activation/inflammation (IL-6, IP-10, neopterin, sCD14, sCD163, and TNF-alpha) between statin users and nonusers among participants of ACTG A5321 who initiated antiretroviral therapy (ART) during chronic infection and maintained virologic suppression (HIV-1 RNA levels ≤50 copies/mL) for ≥3 years. Results: A total of 303 participants were analyzed. Median time on the current statin was 2.9 years (1.2-5.1). There were no differences between statin users and nonusers in levels of CA-DNA (median 650 vs. 540 copies/106 CD4+ T cells; P = 0.58), CA-RNA (53 vs. 37 copies/106 CD4+ T cells; P = 0.12), or single copy assay (0.4 vs. 0.4 copies/mL; P = 0.45). Similarly, there were no significant differences between statin users and nonusers in markers of inflammation/activation, except for IP-10 (137 vs. 118 pg/mL; P = 0.028). Findings were unchanged after adjustment for factors including pre-ART CD4 and HIV RNA, and years on ART. Conclusions: In this cohort of persons on long-term suppressive ART, current statin use was not associated with lower levels of HIV persistence or immune activation/inflammation. These results do not support a major role for statins in reducing HIV persistence, although an early transient effect cannot be excluded. Prospective, randomized studies are needed to confirm these findings

Gravitational Lensing at Millimeter Wavelengths

With today's millimeter and submillimeter instruments observers use gravitational lensing mostly as a tool to boost the sensitivity when observing distant objects. This is evident through the dominance of gravitationally lensed objects among those detected in CO rotational lines at z>1. It is also evident in the use of lensing magnification by galaxy clusters in order to reach faint submm/mm continuum sources. There are, however, a few cases where millimeter lines have been directly involved in understanding lensing configurations. Future mm/submm instruments, such as the ALMA interferometer, will have both the sensitivity and the angular resolution to allow detailed observations of gravitational lenses. The almost constant sensitivity to dust emission over the redshift range z=1-10 means that the likelihood for strong lensing of dust continuum sources is much higher than for optically selected sources. A large number of new strong lenses are therefore likely to be discovered with ALMA, allowing a direct assessment of cosmological parameters through lens statistics. Combined with an angular resolution <0.1", ALMA will also be efficient for probing the gravitational potential of galaxy clusters, where we will be able to study both the sources and the lenses themselves, free of obscuration and extinction corrections, derive rotation curves for the lenses, their orientation and, thus, greatly constrain lens models.Comment: 69 pages, Review on quasar lensing. Part of a LNP Topical Volume on "Dark matter and gravitational lensing", eds. F. Courbin, D. Minniti. To be published by Springer-Verlag 2002. Paper with full resolution figures can be found at ftp://oden.oso.chalmers.se/pub/tommy/mmviews.ps.g

Adding tree rings to North America's National Forest Inventories: an essential tool to guide drawdown of atmospheric CO2

Tree-ring time series provide long-term, annually resolved information on the growth of trees. When sampled in a systematic context, tree-ring data can be scaled to estimate the forest carbon capture and storage of landscapes, biomes, and-ultimately-the globe. A systematic effort to sample tree rings in national forest inventories would yield unprecedented temporal and spatial resolution of forest carbon dynamics and help resolve key scientific uncertainties, which we highlight in terms of evidence for forest greening (enhanced growth) versus browning (reduced growth, increased mortality). We describe jump-starting a tree-ring collection across the continent of North America, given the commitments of Canada, the United States, and Mexico to visit forest inventory plots, along with existing legacy collections. Failing to do so would be a missed opportunity to help chart an evidence-based path toward meeting national commitments to reduce net greenhouse gas emissions, urgently needed for climate stabilization and repair.Published versio

T cells with high PD-1 expression are associated with lower HIV-specific immune responses despite long-term antiretroviral therapy

Objective: We evaluated frequencies of T cells with high PD-1 expression (PD-1HI) before and after long-term effective antiretroviral therapy (ART), and determined if frequencies on-ART correlated positively with measures of HIV persistence and negatively with HIV-specific responses.Methods:We enrolled individuals who started ART during chronic infection and had durable suppression of viremia for at least 4 years (N=99). We assessed PD-1HI T-cell frequencies at timepoints pre-ART and on-ART using flow cytometry, and evaluated how frequencies on-ART are associated with measures of HIV persistence, HIV-specific immune responses, and immune activation levels.Results:Pre-ART, PD-1HI CD4+ T cells correlated positively with viremia and negatively with CD4+ T-cell count. At year 1 on-ART, %PD-1HI CD4+ T cells decreased but then remained stable at 4 and 6-15 years on-ART, whereas %PD-1HI CD8+ T cells on-ART remained similar to pre-ART. PD-1HI CD4+ T cells correlated positively with HIV DNA pre-ART and on-ART, and with CD4+ T-cell activation on-ART. PD-1HI CD4+ T cells negatively correlated with HIV Gag-specific and Env-specific T-cell responses but not with CMV-specific or EBV-specific responses. PD-1HI CD8+ T cells trended towards a negative correlation with responses to Gag and Env, but not to CMV and EBV.Conclusion:PD-1HI T cells persist in blood despite prolonged suppression on ART, correlate with HIV DNA levels, and are associated with lower HIV-specific T-cell responses but not CMV-specific or EBV-specific responses, suggesting that these cells are HIV-specific. The findings support evaluating PD-1 blockade strategies for their effect on HIV persistence and HIV-specific immunity

Cumulative antiretroviral exposure measured in hair is not associated with measures of HIV persistence or inflammation among individuals on suppressive ART

Data on the relationship of antiretroviral exposure to measures of human immunodeficiency virus (HIV) persistence are limited. To address this gap, multiple viral, immunologic, and pharmacologic measures were analyzed from individuals with sustained virologic suppression on therapy (median 7 years) in the AIDS Clinical Trials Group A5321 cohort. Among 110 participants on tenofovir-(TFV)-disoproxil-fumarate (TDF)/emtricitabine (FTC)-containing regimens, we found no significant correlation between hair concentrations of individual antiretrovirals (ARVs) in the regimen and measures of HIV persistence (plasma HIV-1 RNA by single copy assay, cell-associated-DNA, cell-associated RNA) or soluble markers of inflammation. These findings suggest that higher systemic ARV exposure may not impact HIV persistence or inflammation

Persistent HIV-infected cells in cerebrospinal fluid are associated with poorer neurocognitive performance

BACKGROUND. Persistence of HIV in sanctuary sites despite antiretroviral therapy (ART) presents a barrier to HIV remission and may affect neurocognitive function. We assessed HIV persistence in cerebrospinal fluid (CSF) and associations with inflammation and neurocognitive performance during long-term ART. METHODS. Participants enrolled in the AIDS Clinical Trials Group (ACTG) HIV Reservoirs Cohort Study (A5321) underwent concurrent lumbar puncture, phlebotomy, and neurocognitive assessment. Cell-associated HIV DNA and HIV RNA (CA-DNA, CA-RNA) were measured by quantitative PCR (qPCR). in peripheral blood mononuclear cells (PBMCs) and in cell pellets from CSF. In CSF supernatant and blood plasma, cell-free HIV RNA was quantified by qPCR with single copy sensitivity, and inflammatory biomarkers were measured by enzyme immunoassay. RESULTS. Sixty-nine participants (97% male, median age 50 years, CD4 696 cells/mm3, plasma HIV RNA &lt;100 copies/mL) were assessed after a median 8.6 years of ART. In CSF, cell-free RNA was detected in 4%, CA-RNA in 9%, and CA-DNA in 48% of participants (median level 2.1 copies/103 cells). Detection of cell-free CSF HIV RNA was associated with higher plasma HIV RNA (P = 0.007). CSF inflammatory biomarkers did not correlate with HIV persistence measures. Detection of CSF CA-DNA HIV was associated with worse neurocognitive outcomes including global deficit score (P = 0.005), even after adjusting for age and nadir CD4 count. CONCLUSION. HIV-infected cells persist in CSF in almost half of individuals on long-term ART, and their detection is associated with poorer neurocognitive performance

Single-nuclei and bulk-tissue gene-expression analysis of pheochromocytoma and paraganglioma links disease subtypes with tumor microenvironment

Pheochromocytomas (PC) and paragangliomas (PG) are rare neuroendocrine tumors associated with autonomic nerves. Here we use single-nuclei RNA-seq and bulk-tissue gene-expression data to characterize the cellular composition of PCPG and normal adrenal tissues, refine tumor gene-expression subtypes and make clinical and genotypic associations. We confirm seven PCPG gene-expression subtypes with significant genotype and clinical associations. Tumors with mutations in VHL, SDH-encoding genes (SDHx) or MAML3-fusions are characterized by hypoxia-inducible factor signaling and neoangiogenesis. PCPG have few infiltrating lymphocytes but abundant macrophages. While neoplastic cells transcriptionally resemble mature chromaffin cells, early chromaffin and neuroblast markers are also features of some PCPG subtypes. The gene-expression profile of metastatic SDHx-related PCPG indicates these tumors have elevated cellular proliferation and a lower number of non-neoplastic Schwann-cell-like cells, while GPR139 is a potential theranostic target. Our findings therefore clarify the diverse transcriptional programs and cellular composition of PCPG and identify biomarkers of potential clinical significance.Magnus Zethoven, Luciano Martelotto, Andrew Pattison, Blake Bowen, Shiva Balachander, Aidan Flynn, Fernando J. Rossello, Annette Hogg, Julie A.Miller, Zdenek Frysak, Sean Grimmond, Lauren Fishbein, Arthur S. Tischler, Anthony J. Gill, Rodney J. Hicks, Patricia L. M. Dahia, Roderick Clifton-Bligh, Karel Pacak, Richard W. Tothil

Prognostic importance of anaemia in HIV type-1-infected patients starting antiretroviral therapy: collaborative analysis of prospective cohort studies

Background: In HIV type-1-infected patients starting highly active antiretroviral therapy (HAART), the prognostic value of haemoglobin when starting HAART, and of changes in haemoglobin levels, are not well defined. Methods: We combined data from 10 prospective studies of 12,100 previously untreated individuals (25% women). A total of 4,222 patients (35%) were anaemic: 131 patients (1.1%) had severe (<8.0 g/dl), 1,120 (9%) had moderate (male 8.0-<11.0 g/dl and female 8.0-<10.0g/dl) and 2,971 (25%) had mild (male 11.0-<13.0g/dl and female 10.0-<12.0 g/dl) anaemia. We separately analysed progression to AIDS or death from baseline and from 6 months using Weibull models, adjusting for CD4+ T-cell count, age, sex and other variables. Results: During 48,420 person-years of follow-up 1,448 patients developed at least one AIDS event and 857 patients died. Anaemia at baseline was independently associated with higher mortality: the adjusted hazard ratio (95% confidence interval) for mild anaemia was 1.42 (1.17-1.73), for moderate anaemia 2.56 (2.07-3.18) and for severe anaemia 5.26 (3.55-7.81). Corresponding figures for progression to AIDS were 1.60 (1.37-1.86), 2.00 (1.66-2.40) and 2.24 (1.46-3.42). At 6 months the prevalence of anaemia declined to 26%. Baseline anaemia continued to predict mortality (and to a lesser extent progression to AIDS) in patients with normal haemoglobin or mild anaemia at 6 months. Conclusions: Anaemia at the start of HAART is an important factor for short- and long-term prognosis, including in patients whose haemoglobin levels improved or normalized during the first 6 months of HAART