Intrinsic Low-Temperature Magnetism in SmB_{6}.

By means of new muon spin relaxation experiments, we disentangle extrinsic and intrinsic sources of low-temperature bulk magnetism in the candidate topological Kondo insulator (TKI) SmB_{6}. Results on Al-flux-grown SmB_{6} single crystals are compared to those on a large floating-zone-grown ^{154}Sm ^{11}B_{6} single crystal in which a 14 meV bulk spin exciton has been detected by inelastic neutron scattering. Below ∼10 K, we detect the gradual development of quasistatic magnetism due to rare-earth impurities and Sm vacancies. Our measurements also reveal two additional forms of intrinsic magnetism: (1) underlying low-energy (∼100 meV) weak magnetic moment (∼10^{-2} µ_{B}) fluctuations similar to those detected in the related candidate TKI YbB_{12} that persist down to millikelvin temperatures, and (2) magnetic fluctuations consistent with a 2.6 meV bulk magnetic excitation at zero magnetic field that appears to hinder surface conductivity above ∼4.5 K. We discuss potential origins of the magnetism.

DNA methylation reprogramming, TE derepression, and postzygotic isolation of nascent animal species.

The genomic shock hypothesis stipulates that the stress associated with divergent genome admixture can cause transposable element (TE) derepression, which could act as a postzygotic isolation mechanism. TEs affect gene structure, expression patterns, and chromosome organization and may have deleterious consequences when released. For these reasons, they are silenced by heterochromatin formation, which includes DNA methylation. Here, we show that a significant proportion of TEs are differentially methylated between the "dwarf" (limnetic) and the "normal" (benthic) whitefish, two nascent species that diverged some 15,000 generations ago within the Coregonus clupeaformis species complex. Moreover, TEs are overrepresented among loci that were demethylated in hybrids, indicative of their transcriptional derepression. These results are consistent with earlier studies in this system that revealed TE transcriptional derepression causes abnormal embryonic development and death of hybrids. Hence, this supports a role of DNA methylation reprogramming and TE derepression in postzygotic isolation of nascent animal species.

Coexistence of ferromagnetic fluctuations and superconductivity in the actinide superconductor UTe2.

We report low-temperature muon spin relaxation/rotation (µSR) measurements on single crystals of the actinide superconductor UTe2. Below 5 K we observe a continuous slowing down of magnetic fluctuations that persists through the superconducting transition temperature (T c = 1.6 K), but we find no evidence of long-range or local magnetic order down to 0.025 K. The temperature dependence of the dynamic relaxation rate down to 0.4 K agrees with the self-consistent renormalization theory of spin fluctuations for a three-dimensional weak itinerant ferromagnetic metal. Our µSR measurements also indicate that the superconductivity coexists with the magnetic fluctuations.

PP023. Unexpected random urinary protein: creatinine ratio results - Insightsfrom clinician-laboratory medicine collaboration.

INTRODUCTION: Proteinuria assessment is important in pregnancy, particularly in determining whether or not a woman has pre-eclampsia. The random protein to creatinine ratio (PrCr) has been recommended as a confirmatory test for dipstick proteinuria in pregnancy, defined as random PrCr ⩾30mg/mmol. However, it has been our clinical impression that women with normal pregnancy outcomes have fluctuating or persistently elevated PrCr values. OBJECTIVES: As the primary goal of proteinuria testing in pregnancy should be to identify women at increased risk of adverse outcomes, we sought to explore our clinical impression that an elevated PrCr is seen not infrequently in pregnancies with normal outcome. METHODS: In this prospective cohort study, consecutive inpatients or outpatients (attending high-risk maternity clinics) were evaluated at a tertiary care facility. Random midstream urine samples were obtained as part of normal clinical care. Urine protein was measured using a pyrocatechol violet molybdate dye-binding method, and urine creatinine by an enzymatic method, both on an automated analyser (Vitros® 5.1 FS or Vitros® 5600, Ortho-Clinical Diagnostics, Rochester, NY) followed by PrCr calculation. Maternal and perinatal outcomes were abstracted from the hospital case notes. RESULTS: 160 women (81.9% outpatients) were screened at one/more antenatal visits providing a total of 233 samples for analysis. Ninety one (39.1%) samples had a random PrCr ⩾30 mg/mmol. This result was more common when urinary creatinine concentration was <3mM [64 (94.1%)] compared with ⩾3mM [27 (16.4%)], even among the 32 (20.0%) women with known normal pregnancy outcome [(13 (92.9%) vs. 0 (0%), respectively] (Panel A). In dilution studies using the same automated analyser, urinary protein (at a concentration of 0.12g/L) was 'detected' in deionised, double-distilled water. Method-specific re-analysis of data from two other published cohorts from our centre revealed substantially less inflation of PrCr values in dilute 24h urine samples tested using a pyrogallol red dye-binding based protein assay. When results were categorized according to urinary creatinine <3mM vs. ⩾3mM, PrCr ⩾30mg/mmol occurred in 12 (66.7%) vs. 99 (55.3%) respectively (p=0.35) in a 24-h urine completeness cohort and 92 (73.6%) vs. 313 (64.9%) respectively (p=0.07) in a cohort of women hospitalised for pre-eclampsia (Panel B). CONCLUSION: Random urinary PrCr results may be inflated in dilute urines because of overestimation of proteinuria in a common pyrocatechol violet dye-based method. This inflation was reduced but not eliminated when the dye used was pyrogallol red. Analytical methods do matter in the assessment of proteinuria in pregnant women. It may be prudent to consider the potential for falsely positive PrCr ⩾30mg/mmol in dilute urine, and to order PrCr testing on first voided (concentrated) urines whenever possible.

PP024. Random urine albumin: Creatinine ratio in high-risk pregnancy - Is it clinically useful?

INTRODUCTION: The albumin:creatinine ratio (ACr) is the newest of available methods of proteinuria assessment in pregnancy. Published cut-offs for detection of ⩾0.3g/d proteinuria vary from 2mg/mmol to 8mg/mmol. Up to 20% of women have an elevated ACr in pregnancy but normal outcome. In addition, it is our impression that the urine albumin component of the ACr is frequently below the detection limit of the assay. OBJECTIVES: To evaluate the frequency with which a measurable ACr can be obtained in a high-risk outpatient maternity population. METHODS: In this prospective cohort study, consecutive inpatients or outpatients (attending primarily morning high-risk maternity clinics) were evaluated at a tertiary care facility. Random midstream urine samples were obtained as part of normal clinical care. In the hospital laboratory, urinary albumin was measured using an immunoturbidimetric method, and urinary creatinine by an enzymatic method, both on an automated analyser (Vitros® 5,1 FS or Vitros® 5600, Ortho-Clinical Diagnostics, Rochester NY). ACr was calculated for samples with measurable urine albumin, and for samples with albumin below the assay range, ACr was calculated using the assay cut-off for albumin of 6.00mg/L. RESULTS: One hundred and sixty women (81.9% outpatients) were screened at one/more antenatal visits, providing a total of 233 urine samples for analysis. 68 (29.2%) urine samples were dilute (i.e., had urinary creatinine <3mM); only 13 (19.1%) of these had measurable urinary albumin for calculation of the ACr. Overall, 117/233 samples (50.2%) had measurable urine albumin that could be used to calculate the ACr. 76 (65.0%) had ACr >2mg/mmol and 34 (29.1%) had ACr >8mg/mmol. For the 116/233 (49.8%) samples with urine albumin below the assay detection limit, ACr was calculated using 6.00mg/L as the value for urine albumin. All of the 55 dilute samples had an ACr >2mg/mmol and 3 (2.6%) had an ACr >8mg/mmol. If dilute samples were excluded, none of the remaining 61 samples had an ACr value >2mg/mmol. CONCLUSION: Among a population of pregnant women attending primarily morning high-risk maternity clinics, urine is often dilute and urine albumin is often below the assay detection limit. This combination may result in uninterpretable ACr values if an ACr cut-off of 2mg/mmol is used as the decision limit for proteinuria ⩾0.3g/d. ACr may be best performed on first voided (concentrated) urine if ACr is used to assess proteinuria in pregnancy.

PP025. Urinary dipstick proteinuria testing - Does automated strip analysis offer an advantage over visual testing?

INTRODUCTION: The visual urinary test strip is widely accepted for screening for proteinuria in pregnancy, given the convenience of the method and its low cost. However, test strips are known to lack sensitivity and specificity. The 2010 NICE (National Institute for Health and Clinical Excellence) guidelines for management of pregnancy hypertension have recommended the use of an automated test strip reader to confirm proteinuria (http://nice.org.uk/CG107). Superior diagnostic test performance of an automated (vs. visual) method has been proposed based on reduced subjectivity. OBJECTIVES: To compare the diagnostic test properties of automated vs. visual read urine dipstick testing for detection of a random protein:creatinine ratio (PrCr) of ⩾30mg/mmol. METHODS: In this prospective cohort study, consecutive inpatients or outpatients (obstetric medicine and high-risk maternity clinics) were evaluated at a tertiary care facility. Random midstream urine samples (obtained as part of normal clinical care) were split into two aliquots. The first underwent a point-of-care testing for proteinuria using both visual (Multistix 10SG, Siemens Healthcare Diagnostics, Inc., Tarrytown NY) and automated (Chemstrip 10A, Roche Diagnostics, Laval QC) test strips, the latter read by an analyser (Urisys 1100®, Roche Diagnostics, Laval QC). The second aliquot was sent to the hospital laboratory for analysis of urinary protein using a pyrocatechol violet molybdate dye-binding method, and urinary creatinine using an enzymatic method, both on an automated analyser (Vitros® 5,1 FS or Vitros® 5600, Ortho-Clinical Diagnostics, Rochester NY); random PrCr ratios were calculated in the laboratory. Following exclusion of dilute samples with urinary creatinine concentration <3mM (given inflation of PrCr values in dilute urine by our method), diagnostic test properties were determined for visual and automated dipstick proteinuria testing (⩾1+) for detection of a random PrCr ⩾30mg/mmol. RESULTS: 160 women (81.9% outpatients) were screened at one/more antenatal visits, providing a total of 233 urine samples for analysis. Both visual and automated read urinary dipstick testing showed low sensitivity (56.0% and 53.9%, respectively). Positive likelihood ratios (LR+) and 95% CI were 15.0 [5.9,37.9] and 24.6 [7.6,79.6], respectively. Negative LR (LR-) were 0.46 [0.29,0.71] and 0.47 [0.31,0.72], respectively. CONCLUSION: Automated dipstick urinalysis is not more sensitive than visual read urinalysis for detection of proteinuria in a primarily outpatient setting in pregnancy. Both have excellent LR+ but only fair to poor LR- as previously recognised for visual dipstick testing. Performance of automated strip analysis testing may vary with the test strips and analyser used.

PIERS proteinuria: relationship with adverse maternal and perinatal outcome.

OBJECTIVE: To examine the ability of three different proteinuria assessment methods (urinary dipstick, spot urine protein:creatinine ratio [Pr/Cr], and 24-hour urine collection) to predict adverse pregnancy outcomes. METHODS: We performed a prospective multicentre cohort study, PIERS (Preeclampsia Integrated Estimate of RiSk), in seven academic tertiary maternity centres practising expectant management of preeclampsia remote from term in Canada, New Zealand, and Australia. Eligible women were those admitted with preeclampsia who had at least one antenatal proteinuria assessment by urinary dipstick, spot urine Pr/Cr ratio, and/or 24-hour urine collection. Proteinuria assessment was done either visually at the bedside (by dipstick) or by hospital clinical laboratories for spot urine Pr/Cr and 24-hour urine collection. We calculated receiver operating characteristic area under the curve (95% CI) for each proteinuria method and each of the combined adverse maternal outcomes (within 48 hours) or adverse perinatal outcomes (at any time). Models with AUC ≥ 0.70 were considered of interest. Analyses were run for all women who had each type of proteinuria assessment and for a cohort of women ("ALL measures") who had all three proteinuria assessments. RESULTS: More women were proteinuric by urinary dipstick (≥ 2+, 61.4%) than by spot urine Pr/Cr (≥ 30 g/mol, 50.4%) or 24-hour urine collection (≥ 0.3g/d, 34.7%). Each proteinuria measure evaluated had some discriminative power, and dipstick proteinuria (categorical) performed as well as other methods. No single method was predictive of adverse perinatal outcome. CONCLUSION: The measured amount of proteinuria should not be used in isolation for decision-making in women with preeclampsia. Dipstick proteinuria performs as well as other methods of assessing proteinuria for prediction of adverse events.

Expectant management of severe preeclampsia remote from term: a structured systematic review.

OBJECTIVE: To compare outcomes associated with expectant vs. interventionist care of severe preeclampsia in observational studies. DATA SOURCES: Medline (01/1980-07/2007), bibliographies of retrieved papers, personal files, Cochrane Database of Systematic Reviews. STUDY SELECTION: Expectant or interventionist care of preeclampsia at <34 wk. TABULATION, INTEGRATION, RESULTS: Data abstraction independently by two reviewers. Median [IQR] of clinical maternal/perinatal outcomes presented. RESULTS: 72 publications, primarily from tertiary care centres in Dutch and developed world sites. Expectant care of severe preeclampsia <34 wk (39 cohorts, 4,650 women), for which 40% of women are eligible, is associated with pregnancy prolongation of 7-14 d, and few serious maternal complications (median <5%), similar to interventionist care (2 studies, 42 women). Complication rates are higher with HELLP <34wk (12 cohorts, 438 women) and severe preeclampsia <28wk (6 cohorts, 305 women), similar to interventionist care (6 cohorts, 467 women and 2 cohorts, 70 women, respectively). Expectant care of HELLP <34 wk (12 cohorts, 438 women) is associated with fewer days gained (median 5), but more serious maternal morbidity (e.g., eclampsia, median 15%). More than half of women have at least temporary improvement of HELLP. In the developed world, expectant (vs. interventionist) care of severe preeclampsia or HELLP <34 wk is associated with reduced neonatal death and complications. Stillbirth is higher in Dutch and developing world sites where viability thresholds are higher. For preeclampsia <24wk (4 cohorts), perinatal mortality is >80%. No predictors of adverse maternal/perinatal outcomes were identified (13 studies). CONCLUSIONS: Future research should establish the best maternal/fetal monito regimen and indications for delivery with expectant care. A definitive RCT is needed.

Needle muscle biopsy with the automatic Biopty instrument.

Needle muscle biopsies are less traumatic and easier to do than open biopsies, but their main disadvantage is the small specimen size. One hundred and five patients underwent needle biopsies with a 14-gauge spring-loaded device that guillotines the muscle automatically (Bard Radiology). Fifty patients had more than one muscle biopsy. One hundred and forty-six of 155 specimens contained over 200 muscle fibers, some as many as 500 fibers. Having evaluated various needles, we found the Bard Biopty instrument more efficient than manual needles and open biopsy techniques, and it provides muscle specimens for pathologic interpretation that are comparable with open surgical procedures.