Air pollution accountability research: Moving from a chain to a web.

Air pollution accountability studies examine the relationship(s) between an intervention, regulation, or event and the resulting downstream impacts, if any, on emissions, exposure, and/or health. The sequence of events has been schematically described as an accountability chain. Here, we update the existing framework to capture real-life complexities and to highlight important factors that fall outside the linear chain. This new "accountability web" is intended to convey the intricacies associated with conducting an accountability study to various audiences, including researchers, policy makers, and stakeholders. We also identify data considerations for planning and completing a robust accountability study, including those relevant to novel and innovative air pollution and exposure data. Finally, we present a series of recommendations for the accountability research community that can serve as a guide for the next generation of accountability studies.

Improvements in the delivery of resuscitation and newborn care after Helping Babies Breathe training.

BACKGROUND: To evaluate changes in neonatal resuscitation and postnatal care following Helping Babies Breathe (HBB) training at a community hospital in rural Honduras. We hypothesized that HBB training would improve resuscitation and essential newborn care interventions. METHODS: Direct observation and video recording of delivery room care spanned before and after an initial HBB workshop held in August 2013. Rates of essential newborn care interventions were compared in resuscitations performed by individuals who had and had not received HBB training, and run charts recording performance of newborn care practices over time were developed. RESULTS: Ten percent of deliveries (N=250) were observed over the study period, with 156 newborn resuscitations performed by individuals without HBB training, compared to 94 resuscitations performed by HBB trainees. After HBB training, significant improvements were seen in skin-to-skin care, breastfeeding within 60 min of age, and delayed cord clamping after 1 min (all P<0.01). More babies cared for by HBB trainees received basic neonatal resuscitation such as drying and stimulation. Run charts tracking these practices over time showed significant improvements after HBB training that were sustained during the study period, but remained below ideal goals. With improvement in drying/stimulation practices, fewer babies required bag/mask ventilation. CONCLUSION: In a rural Honduran community hospital, improvements in basic neonatal resuscitation and postnatal essential newborn care practices can be seen after HBB training. Further improvements in newborn care practices may require focused quality improvement initiatives for hospitals to sustain high quality care.

Association of metabolic syndrome with kidney function and histology in living kidney donors.

The selection of living kidney donors is based on a formal evaluation of the state of health. However, this spectrum of health includes subtle metabolic derangements that can cluster as metabolic syndrome. We studied the association of metabolic syndrome with kidney function and histology in 410 donors from 2005 to 2012, of whom 178 donors were systematically followed after donation since 2009. Metabolic syndrome was defined as per the NCEP ATPIII criteria, but using a BMI > 25 kg/m(2) instead of waist circumference. Following donation, donors received counseling on lifestyle modification. Metabolic syndrome was present in 50 (12.2%) donors. Donors with metabolic syndrome were more likely to have chronic histological changes on implant biopsies than donors with no metabolic syndrome (29.0% vs. 9.3%, p < 0.001). This finding was associated with impaired kidney function recovery following donation. At last follow-up, reversal of metabolic syndrome was observed in 57.1% of donors with predonation metabolic syndrome, while only 10.8% of donors developed de novo metabolic syndrome (p < 0.001). In conclusion, metabolic syndrome in donors is associated with chronic histological changes, and nephrectomy in these donors was associated with subsequent protracted recovery of kidney function. Importantly, weight loss led to improvement of most abnormalities that define metabolic syndrome.

Urine high and low molecular weight proteins one-year post-kidney transplant: relationship to histology and graft survival.

Increased urinary protein excretion is common after renal transplantation and portends worse outcome. In this study we assessed the prognostic contribution of several urinary proteins. Urinary total protein, albumin, retinol binding protein (RBP), α-1-microglobulin, IgG and IgM were measured in banked urine samples from 221 individuals 1 year after renal transplantation (age 52 ± 13 years, 55% male, 93% Caucasian and 82% living donor). Levels of all proteins measured were higher than in normal nontransplant populations. Patients with glomerular lesions had higher urinary albumin than those with normal histology, while those with interstitial fibrosis and tubular atrophy plus inflammation (ci>0, cg = 0, i>0) had higher levels of IgG, IgM, α-1-microglobulin and RBP. Concomitant normal levels of urinary albumin, IgM and RBP identified normal histology (specificity 91%, sensitivity 15%,). Urinary levels of the specific proteins were highly correlated, could not differentiate among the histologic groups, and appeared to result from tubulointerstitial damage. Increased urinary excretion of the low molecular weight protein RBP was a sensitive marker of allografts at risk, predicting long-term graft loss independent of histology and urinary albumin. This study highlights the prognostic importance of tubulointerstitial disease for long-term graft loss.

Can we do better than a single estimated GFR threshold when screening for chronic kidney disease?

The Modification of Diet in Renal Disease (MDRD) equation has been used to screen for and diagnose chronic kidney disease (CKD). A fixed estimated glomerular filtration rate cutoff point has been advocated by the National Kidney Foundation to diagnose CKD. However, data derived from healthy individuals challenge this approach and suggest that age- and gender-specific reference values may be more useful in the screening setting.

Assessment of changes in kidney allograft function using creatinine-based estimates of glomerular filtration rate.

These analyses assessed whether creatinine based estimates of glomerular filtration rate (eGFR) accurately represent (1) graft function at different times post-transplant and (2) changes in function over time. These analyses compared iothalamate GFR to eGFR in 684 kidney allograft recipients. Changes in graft function over time (GFR slope) were measured in 360 of 459 recipients (78%) who were followed for at least 3 years. Ninety-five percent of the patients were Caucasians and 72% received kidneys from living donors. All eGFR calculations correlated significantly with GFR at all time points. However, eGFR were less precise and less accurate during the first-year post-transplant than thereafter. The average rate of GFR change (slope) was -2.93 +/- 11.3%/year (-1.06 +/- 5.3 mL/min/1.73 m(2)/year). Fifty-four percent of patients had stable or positive GFR slopes. The GFR and eGFR slopes were highly correlated. However, eGFR slope, particularly when calculated by MDRD, significantly underestimated the number of patients with declining graft function. For example, 165 out of 360 patients (46%) lost GFR faster than -1 mL/min/1.73 m(2)/year. eMDRD identified only 83 of these patients (50%) while the eMayo formula identified 134 (81%). In conclusion, eGFR correlate with GFR but they have relatively low precision and accuracy particularly early post-transplant. eGFR slopes underestimate graft functional loss although some formulas are significantly better than others for this calculation.

Hyperoxaluric nephrolithiasis is a complication of Roux-en-Y gastric bypass surgery.

Roux-en-Y bypass surgery is the most common bariatric procedure currently performed in the United States for medically complicated obesity. Although this leads to a marked and sustained weight loss, we have identified an increasing number of patients with episodes of nephrolithiasis afterwards. We describe a case series of 60 patients seen at Mayo Clinic-Rochester that developed nephrolithiasis after Roux-en-Y gastric bypass (RYGB), including a subset of 31 patients who had undergone metabolic evaluation in the Mayo Stone Clinic. The mean body mass index of the patients before procedure was 57 kg/m(2) with a mean decrease of 20 kg/m(2) at the time of the stone event, which averaged 2.2 years post-procedure. When analyzed, calcium oxalate stones were found in 19 and mixed calcium oxalate/uric acid stones in two patients. Hyperoxaluria was a prevalent factor even in patients without a prior history of nephrolithiasis, and usually presented more than 6 months after the procedure. Calcium oxalate supersaturation, however, was equally high in patients less than 6 months post-procedure due to lower urine volumes. In a small random sampling of patients undergoing this bypass procedure, hyperoxaluria was rare preoperatively but common 12 months after surgery. We conclude that hyperoxaluria is a potential complicating factor of RYGB surgery manifested as a risk for calcium oxalate stones.

Kidney transplant function and histological clearance of virus following diagnosis of polyomavirus-associated nephropathy (PVAN).

Polyomavirus-associated nephropathy (PVAN) is managed by reduced immunosuppression with or without antiviral therapy. Data from 55 patients with biopsy-proven PVAN were analyzed for adverse outcomes and influence of baseline variables and interventions. During 20+/-11 months follow-up, the frequencies of graft loss, major and any functional decline were 15%, 24% and 38%, respectively. Repeat biopsies were performed in 45 patients with persistent PVAN in 47%. Low-dose cidofovir, IVIG and cyclosporine conversion were used in 55%, 20% and 55% of patients. No single intervention was associated with improved outcome. Of the variables examined, only degree of interstitial fibrosis at diagnosis was associated with kidney function decline. In contrast, donor source, interstitial fibrosis, proportion of BKV positive tubules and plasma viral load at diagnosis were all associated with failure of histological viral clearance. This retrospective, nonrandomized analysis suggests that: (i) Graft loss within 2 years of PVAN diagnosis is now uncommon, but ongoing functional decline and persistent infection occur frequently. (ii) Low-dose cidofovir, IVIG and conversion to cyclosporine do not abrogate adverse outcomes following diagnosis. (iii) Fibrosis at the time of diagnosis predicts subsequent functional decline. Further elucidation of the natural history of PVAN and its response to individual interventions will require prospective clinical trials.

Glomerular filtration rate estimated by cystatin C among different clinical presentations.

Glomerular filtration rate (GFR) estimates from serum creatinine has not been generalizable across all populations. Cystatin C has been proposed as an alternative marker for estimating GFR. The objective of this study was to compare cystatin C with serum creatinine for estimating GFR among different clinical presentations. Cystatin C and serum creatinine levels were obtained from adult patients (n=460) during an evaluation that included a GFR measurement by iothalamate clearance. Medical records were abstracted for clinical presentation (healthy, native chronic kidney disease or transplant recipient) at the time of GFR measurement. GFR was modeled using the following variables: cystatin C (or serum creatinine), age, gender and clinical presentation. The relationship between cystatin C and GFR differed across clinical presentations. At the same cystatin C level, GFR was 19% higher in transplant recipients than in patients with native kidney disease (P<0.001). The association between cystatin C and GFR was stronger among native kidney disease patients than in healthy persons (P<0.001 for statistical interaction). Thus, a cystatin C equation was derived using only patients with native kidney disease (n=204). The correlation with GFR (r(2)=0.853) was slightly higher than a serum creatinine equation using the same sample (r(2)=0.827), the Modification of Diet in Renal Disease equation (r(2)=0.825) or the Cockcroft-Gault equation (r(2)=0.796). Averaged estimates between cystatin C and serum creatinine equations further improved correlation (r(2)=0.891). Cystatin C should not be interpreted as purely a marker of GFR. Other factors, possibly inflammation or immunosuppression therapy, affect cystatin C levels. While recognizing this limitation, cystatin C may improve GFR estimates in chronic kidney disease patients.

Immunofluorescent localization of an androgen-dependent isoenzyme of prostatic acid phosphatase in rat ventral prostate.

Isoenzymes of rat ventral prostate (RVP) acid phosphatase were isolated and partially purified by ultracentrifugation, Sephadex G-100 column chromatography, and isoelectric focusing. Antisera were raised to the isoenzymes of prostatic acid phosphatase by immunization of New Zealand white rabbits. Rabbit antisera reacting specifically to homologous but not heterologous isoenzymes of acid phosphatase were then reacted with a variety of tissues using indirect immunofluorescence. The tissues included prostate, spleen, bone marrow, liver, kidney, salivary gland complex, small intestine, and adrenal glands. An antiserum against a RVP acid phosphatase isoenzyme with a pI of 4.5 (A-PAP) localized acid phosphatase only in the supranuclear region of rat ventral prostate epithelial cells, and did not react with acid phosphatase in any of the other organs tested. A-PAP did not localize acid phosphatase in the ventral prostate from rats 14 days after castration. A-PAP did localize acid phosphatase in the ventral prostate from castrated animals that were treated with testosterone. These results indicate the A-PAP localized an androgen-dependent isoenzyme of acid phosphatase in RVP epithelial cells that may be secretory in nature. This antiserum should prove to be an ideal marker for studies involving hormonal regulation of prostatic epithelial function in vivo and in vitro.

Use of beta-human chorionic gonadotropin in gestational aging.

Quantitative radioimmunoassay (RIA) of the beta chain of human chorionic gonadotropin (B-hCG) in serum has been used to evaluate the gestational status of 99 normal early pregnancies in contrast to 29 ectopic, threatened, aborted and/or terminated cases. Quantitative measurement of serum B-hCG-RIA standardized against the second international standard (2dIS) accurately established age of normal pregnancies in utero up to but not after three weeks postconception and with an accuracy of plus or minus four days between the third and eighth week of gestation. Quantitative urinary hCG-RIA standardized against the 2dIS were not useful for gestational aging. Useful serum hCG-RIA were identically linear and parallel with the 2dIS, had negligible crossreactivity with LH, FSH and/or TSH, and had low nonspecific binding. Of 13 hCG-RIA evaluated, only assays having these latter characteristics were able to detect ectopic pregnancies, spontaneous abortions, and/or threatened pregnancies with up to 90 percent accuracy. However, some assays not standardized to the 2dIS gave over 200 percent error in hCG serum values. Thus, correct choice of quantitative B-hCG reagents is necessary for early pregnancy assessment.

Complete duplication of the uterus and cervix with a unilaterally imperforate vagina.

Complete duplication of the uterus and cervix with a unilaterally imperforate vagina must be suspected when a unilateral pelvic mass terminates in a purpuric bulge of the lateral vaginal wall in a young woman with severely progressive dysmenorrhea. Intravenous pyelography will reveal renal agenesis ipsilateral to the imperforate vagina. The prompt and accurate diagnosis of this unusual anomaly should lead to transvaginal drainage of the retained menstrual fluids prior to irreversible damage of the pelvic viscera from chronic cryptomenorrhea.

[Mechanism of the decrease in free plasma calcium produced by the administration of inorganic phosphates]. / Mecanismo de la disminución de calcio libre plasmático producida por la administración de fosfatos inorgánicos.

The preceding paper (published in the issue) demonstrated that the administration of sodium phosphates exerted a marked antiarrhythmic effect on several models of digitalis intoxication; this action being due to a decrease in the free calcium fraction. THe purpose of the present paper is to analyze the effects that several concentrations of phosphates have on the different calcium fractions and determine the fate of the ions that are disappearing from the calcium pool. This study was done using two models of digitalis intoxication, one in the intact dog and the other in the heart-lung preparation and two protocols in which the experiments were carried out using blood in vitro. The results show: 1) the administration of phosphates into the intact dog produces a small decrease in the total calcium content of plasma and blood. 2) the increase in phosphate concentration runs parallel to an important decrease in free calcium. 3) In the heart-lung preparation, phosphate administration markedly decreases free calcium but does not lower total calcium in plasma or blood. 4) An increase in phosphate concentration of plasma in in vitro conditions does not alter total calcium and decreases free calcium in a linear relationship with the levels of phosphates. 5) A fraction of the phosphates added to the plasma and the ions that are disappearing from the free calcium pool are binding to a plasmatic macromolecule (most probably a protein) which prevents them from precipitating.

Partial vaginal agenesis with a urinary-vaginal fistula.

A patient with partial vaginal agenesis and a urinary-vaginal fistula is presented together with a review of the 12 cases reported previously. This unusual anomaly presents with cyclically recurrent hematuria; hypothetically, it results from failure of formation or canalization of the primitive vaginal plate together with partial persistence of the urogenital sinus. Surgical correction, ideally performed after puberty, requires resection of the fistula and mobilization of the apical vaginal segment for its anastomosis to the inferior vaginal pouch.

Asymmetric hyperthecosis ovarii.

Testosterone and delta4-androstenedione concentrations, in venous blood obtained by percutaneous retrograde femoral catheterization of the ovarian and adrenal veins bilaterally, demonstrated the left ovary to be the predominant secretory source of androgens in an 18-year-old virilized female. Histologic examination of the excised ovarian tissue revealed asymmetric hyperthecosis ovarii and confirmed the biochemical data. This study demonstrates the accuracy of the venous catheterization method in locating preoperatively the hypersecretory source of androgens in virilized women. The favorable postoperative clinical result emphasizes the importance of an accurate preoperative diagnosis in virilized women even in the absence of ovarian neoplasia.

Relation of glucose to alpha-fetoprotein in amniotic fluid.

A direct relationship between amniotic fluid glucose and alpha-fetoprotein (AFP) has been found between the 16th and 22nd weeks of pregnancy. This relationship is statistically significant (P less than .001) in each of the 6 gestational weeks tested, the coefficients of correlation vary from .74 to .91. The relationship between amniotic fluid AFP and another metabolite, urea nitrogen, was not significant (r = -.34), suggesting that the AFP-glucose relationship was not spurious. Absence of pregnancy-associated macroglobulins in the samples indicates that they were not contaminated by maternal serum. These data reflect an aspect of fetal metabolism or transport that should be investigated more thoroughly.

Complement fixation for study of placental-type alkaline phosphatase.

Preparations of human placental alkaline phosphatase differing in specific enzyme activities were compared by microcomplement fixation assays using monospecific antisera. While both specific enzyme activity and complement fixation units increased 15,000-fold upon purification, the ratio between these units remained constant. Separation of an alkaline phosphatase preparation into 'A' and 'B' forms by ampholine isoelectric focusing indicated that these forms also possessed the same ratio of immunoreactive enzyme protein to enzyme activity. The correspondence of complement fixation units with specific enzyme activity indicates that complement fixation with monospecific antisera can be used to analyze structural differences among alkaline phosphatase isoenzymes.

Partial purification of pemphigus-related epidermal antigens.

Epidermal antigens partially purified by either isoelectric focusing (the pH 5.2 peak) or concanavalin A (Con A) affinity chromatography react with Con A in tube precipitation reactions. Bands of identity between crude skin antigens, the Con A affinity antigens eluted with alpha-methyl glucoside and the pH 5.2 peak are formed in Ouchterlony gel with rabbit antisera (Rab) to the pH 5.2 antigen. Absorption of Rab or pemphigus antibodies (Pab) with A+ erythrocytes does not affect complement fixation reactions of Rab with the skin antigen nor abolish the ability of Pab to interact with the intercellular cement. The pH 5.2 epidermal antigens react weakly with Pab in tube precipitation reactions and only weakly, if at all, to inhibit Pab reactions in the region of the intercellular cement. High concentrations of Con A inhibit the Pab, peroxidase-anti-IgG tissue reaction whereas the converse inhibition does not occur. Simultaneous use of both Pab and Con A-perodixase reactions at Con A concentrations which do not inhibit Pab, causes enhanced tissue peroxidase reactions in the region of the intercellular cement. These preliminary data indicate that the Pab and Con A-reacting sites are localized on different molecules or antigenic determinants in the intercellular cement. They exclude the possibility that A-blood substances are involved in either site.