An extreme magneto-ionic environment associated with the fast radio burst source FRB 121102.

Fast radio bursts are millisecond-duration, extragalactic radio flashes of unknown physical origin. The only known repeating fast radio burst source-FRB 121102-has been localized to a star-forming region in a dwarf galaxy at redshift 0.193 and is spatially coincident with a compact, persistent radio source. The origin of the bursts, the nature of the persistent source and the properties of the local environment are still unclear. Here we report observations of FRB 121102 that show almost 100 per cent linearly polarized emission at a very high and variable Faraday rotation measure in the source frame (varying from +1.46 × 105 radians per square metre to +1.33 × 105 radians per square metre at epochs separated by seven months) and narrow (below 30 microseconds) temporal structure. The large and variable rotation measure demonstrates that FRB 121102 is in an extreme and dynamic magneto-ionic environment, and the short durations of the bursts suggest a neutron star origin. Such large rotation measures have hitherto been observed only in the vicinities of massive black holes (larger than about 10,000 solar masses). Indeed, the properties of the persistent radio source are compatible with those of a low-luminosity, accreting massive black hole. The bursts may therefore come from a neutron star in such an environment or could be explained by other models, such as a highly magnetized wind nebula or supernova remnant surrounding a young neutron star.

A randomized controlled trial to study the effects of an automated premilking stimulation system on milking performance, teat tissue condition, and udder health in Holstein dairy cows.

The objectives were to examine the effect of an automated premilking stimulation (APS) by means of a high pulsation frequency (300 cycles/min) without a reduction of the vacuum in the pulsation chamber or claw piece on (1) milking performance, (2) teat tissue condition, and (3) udder health in dairy cows. In a randomized controlled field study, Holstein cows (n = 427) from 1 commercial dairy farm with a milking schedule of 3 times per day were assigned to treatment and control groups over a 90-d period. Treatments consisted of a maximum of 80 s (APS80) or 99 s (APS99) of mechanical stimulation at a pulsation rate of 300 pulses per minute and a ratio of 25:75 (no reduction of the pulsation chamber or milking vacuum). Cows in the control group (CON) received traditional premilking stimulation by means of manual forestripping for 8 s. Milking characteristics were documented with on-farm milk meters. Short- and long-term changes in teat tissue condition induced by machine milking were assessed visually on a weekly basis. Composite milk samples were analyzed once per month to determine somatic cell count. Generalized linear mixed models were used to study the effect of the treatment on the outcome variables. We observed no meaningful differences in milk yield or milking unit-on time. Least squares means and their 95% confidence intervals (95% CI) for cows in the APS80, APS99, and CON groups were 13.5 (13.1-14.0), 13.2 (12.8-13.7), and 13.2 (12.8-13.7) kg for milk yield and 222 (213-231), 219 (210-228), and 223 (214-232) s for milking unit-on time, respectively. The effect of treatment on bimodality was modified by milk yield such that the odds of bimodality increased in the treatment groups with increasing milk yield. Compared with cows in the CON group, the odds ratios (95% CI) of bimodality were 1.08 (0.62-1.89) in the APS80 group and 0.89 (0.55-1.42) in the APS99 group at a milk yield of 11 kg and 2.0 (1.24-3.22) in the APS80 group and 2.08 (1.29-3.35) in the APS99 group at a milk yield of 16 kg. We observed differences in short- and long-term changes in teat tissue condition between the treatment and control groups. Compared with cows in the CON group, the odds (95% CI) of short-term changes were 1.87 (1.35-2.58) for the APS80 group and 1.49 (1.08-2.07) for the APS99 group, and the odds of long-term changes were 1.52 (1.24-1.85) for cows in the APS80 group and 1.59 (1.31-1.94) for cows in the APS99 group. The least squares means (95% CI) for somatic cell counts (log10-transformed) were 4.74 (4.68-4.81) for the APS80 group, 4.77 (4.71-4.83) for the APS99 group, and 4.79 (4.73-4.86) for the CON group. We conclude that the APS system tested here had no negative effects on milk yield or milking unit-on time. However, differences in bimodality and teat tissue condition suggest that the APS system did not provide sufficient stimulation to facilitate a gentle milk harvest and adversely affects teat tissue condition.

Socio-cultural similarity with host population rather than ecological similarity predicts success and failure of human migrations.

Demographers argue that human migration patterns are shaped by people moving to better environments. More recently, however, evolutionary theorists have argued that people move to similar environments to which they are culturally adapted. While previous studies analysing which factors affect migration patterns have focused almost exclusively on successful migrations, here we take advantage of a natural experiment during World War II in which an entire population was forcibly displaced but were then allowed to return home to compare successful with unsuccessful migrations. We test two competing hypotheses: (1) individuals who relocate to environments that are superior to their place of origin will be more likely to remain-The Better Environment Hypothesis or (2) individuals who relocate to environments that are similar to their place of origin will be more likely to remain-The Similar Environment Hypothesis. Using detailed records recording the social, cultural, linguistic and ecological conditions of the origin and destination locations, we find that cultural similarity (e.g. linguistic similarity and marrying within one's own minority ethnic group)-rather than ecological differences-are the best predictors of successful migrations. These results suggest that social relationships, empowered by cultural similarity with the host population, play a critical role in successful migrations and provide limited support for the similar environment hypothesis. Overall, these results demonstrate the importance of comparing unsuccessful with successful migrations in efforts understand the engines of human dispersal and suggest that the primary obstacles to human migrations and successful range expansion are sociocultural rather than ecological.

A repeating fast radio burst.

Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

Partial budget analysis of culture- and algorithm-guided selective dry cow therapy.

The objectives of this study were to (1) use partial budget analysis to estimate the cash impact for herds that switch from blanket dry cow therapy (BDCT) to culture- or algorithm-guided selective dry cow therapy (SDCT) and (2) conduct a sensitivity analysis to investigate effects in situations where SDCT increased clinical and subclinical mastitis risk during the subsequent lactation. A partial budget model was created using Monte Carlo simulation with @Risk software. Expenditures associated with dry-off procedures and health outcomes (clinical and subclinical mastitis) during the first 30 d in milk were used to model herd-level effects, expressed in units of US dollars per cow dry-off. Values for each economic component were derived from findings from a recent multisite clinical trial, peer-reviewed journal articles, USDA databases, and our experiences in facilitating the implementation of SDCT on farms. Fixed values were used for variables expected to have minimal variation within the US dairy herd population (e.g., cost of rapid culture plates) and sampling distributions were used for variables that were hypothesized to vary enough to effect the herd net cash impact of one or more DCT approach(es). For Objective 1, herd-level udder health was assumed to be unaffected by the implementation of SDCT. For culture-guided SDCT, producers could expect to save an average of +$2.14 (-$2.31 to $7.23 for 5th and 95th percentiles) per cow dry-off as compared with BDCT, with 75.5% of iterations being ≥$0.00. For algorithm-guided SDCT, the mean net cash impact was +$7.85 ($3.39-12.90) per cow dry-off, with 100% of iterations being ≥$0.00. The major contributors to variance in cash impact for both SDCT approaches were percent of quarters treated at dry-off and the cost of dry cow antibiotics. For Objective 2, we repeated the partial budget model with the 30-d clinical and subclinical mastitis incidence increasing by 1, 2, and 5% (i.e., risk difference = 0.01, 0.02, and 0.05) in both SDCT groups compared with BDCT. For algorithm-guided SDCT, average net cash impacts were ≥$0.00 per cow dry-off (i.e., cost effective) when mastitis incidence increased slightly. However, as clinical mastitis incidence increased, economic returns for SDCT diminished. These findings indicate that when SDCT is implemented appropriately (i.e., no to little negative effect on health), it might be a cost-effective practice for US herds under a range of economic conditions.

A millisecond pulsar in a stellar triple system.

Gravitationally bound three-body systems have been studied for hundreds of years and are common in our Galaxy. They show complex orbital interactions, which can constrain the compositions, masses and interior structures of the bodies and test theories of gravity, if sufficiently precise measurements are available. A triple system containing a radio pulsar could provide such measurements, but the only previously known such system, PSR B1620-26 (refs 7, 8; with a millisecond pulsar, a white dwarf, and a planetary-mass object in an orbit of several decades), shows only weak interactions. Here we report precision timing and multiwavelength observations of PSR J0337+1715, a millisecond pulsar in a hierarchical triple system with two other stars. Strong gravitational interactions are apparent and provide the masses of the pulsar M[Symbol: see text](1.4378(13), where M[Symbol: see text]is the solar mass and the parentheses contain the uncertainty in the final decimal places) and the two white dwarf companions (0.19751(15)M[Symbol: see text] and 0.4101(3))M[Symbol: see text], as well as the inclinations of the orbits (both about 39.2°). The unexpectedly coplanar and nearly circular orbits indicate a complex and exotic evolutionary past that differs from those of known stellar systems. The gravitational field of the outer white dwarf strongly accelerates the inner binary containing the neutron star, and the system will thus provide an ideal laboratory in which to test the strong equivalence principle of general relativity.

The effect of 2 different premilking stimulation regimens, with and without manual forestripping, on teat tissue condition and milking performance in Holstein dairy cows milked 3 times daily.

The objectives were to study the effect of 2 different premilking stimulation regimens, with and without manual forestripping, on teat tissue condition and milking characteristics in dairy cows. In a randomized controlled crossover study, 130 Holstein cows milked 3 times daily were assigned to treatment and control groups. Premilking udder preparation for the treatment group consisted of: (1) predipping with 1% iodine, (2) sequential forestripping of 3 streams of milk per quarter, (3) wiping of teats, and (4) attachment of the milking unit. Premilking udder preparation for the control group was identical except that the forestripping step was omitted. The mean tactile stimulation durations were 16 s and 7 s for the treatment and control group, respectively. The time spent from first tactile stimulus (either forestripping or wiping of teats) to milking unit attachment was kept consistent at 90 s for both groups. The study lasted for 14 d with 2 periods, each consisting of a 2-d adjustment time followed by 5 d of data collection. Machine milking-induced short-term changes to the teat tissue were assessed by palpation and visually. The following milking characteristics were assessed with electronic on-farm milk meters: milk yield (MY), milking unit-on time (MUOT), 2-min MY (2MIN), and time spent in low milk flow rate (LMF). Generalized linear mixed models were used to describe the effect of treatment on the outcome variables. The odds of machine milking-induced short-term changes to the teat tissue were lower for cows that received forestripping compared with cows that were not forestripped (odds ratio = 0.31; 95% confidence interval = 0.22-0.42). Least squares means (95% confidence interval) for cows that were forestripped and animals that were not forestripped, respectively, were 12.7 (12.2-13.2) and 12.7 (12.2-13.2) kg for MY and 6.1 (5.8-6.4) and 5.6 (5.3-5.9) kg for 2MIN. There was an interaction between treatment and MY for LMF. Time spent in LMF for cows that were forestripped and received no forestripping, respectively, were 18 (17-20) and 24 (23-26) s for a MY level of 10 kg; and 13 (12-14) and 15 (14-16) s for a MY level of 15 kg. The effect of treatment on MUOT was modified by parity. Milking unit-on times for animals in first, second and third or greater lactation, respectively, were 230 (219-243), 249 (236-262), and 260 (249-272) s for cows that were forestripped, and 245 (232-258), 252 (239-266), and 268 (257-281) s for cows that received no forestripping. In this study, cows that were forestripped had shorter MUOT, higher 2MIN, lower LMF, and lower odds of exhibiting changes to the teat tissue after machine milking. We conclude that wiping of teats during premilking udder preparation alone and omitting forestripping of teats without compensating for the loss in stimulation time may not provide sufficient tactile stimulation to elicit the cows' maximum physiological milk-ejection capacity. This can aggravate the adverse effects of vacuum-induced forces on teat tissue during machine milking, diminish animal well-being, and possibly affect udder health.

Donor understandings of blood and the body in relation to more frequent donation.

BACKGROUND AND OBJECTIVES: The INTERVAL trial aimed to find the optimum frequency of blood donation to enhance blood supplies and maintain donor health. This not only requires biological knowledge, but also an appreciation of donor perspectives, and how their experiences and beliefs might be central if any changes are ever to be made. To address this, trial participants were interviewed about their ideas of blood and the body in relation to their experiences of increased donation frequency. MATERIALS AND METHODS: Thirty in depth face-to-face interviews conducted with blood donors participating in the trial. RESULTS: Three key themes emerged: ideas about how blood and iron reserves are replenished, and what people did to facilitate this; beliefs about physiological differences relating to age and gender; and practical issues that affected the experience of donation. Overall, participants interviewed welcomed more frequent donation, despite a range of pragmatic concerns. CONCLUSION: Despite some practical obstacles, increased donation frequency aligned with participant's ideas about bodily replenishment, the value of donation, and their identity as enduring blood donors. They therefore supported the idea of increasing frequency of donation, independently of the biomedical evidence from the trial itself.

Use of a culture-independent on-farm algorithm to guide the use of selective dry-cow antibiotic therapy.

An algorithm using only computer-based records to guide selective dry-cow therapy was evaluated at a New York State dairy farm via a randomized field trial. DairyComp 305 (Valley Ag Software, Tulare, CA) and Dairy Herd Improvement Association test-day data were used to identify cows as low risk (cows that might not benefit from dry-cow antibiotics) or high risk (cows that will likely benefit). Low-risk cows were those that had all of the following: somatic cell count (SCC) ≤200,000 cells/mL at last test, an average SCC ≤200,000 cells/mL over the last 3 tests, no signs of clinical mastitis at dry-off, and no more than 1 clinical mastitis event in the current lactation. Low-risk cows were randomly assigned to receive intramammary antibiotics and external teat sealant (ABXTS) or external teat sealant only (TS) at dry-off. Using pre-dry-off and postcalving quarter-level culture results, low-risk quarters were assessed for microbiological cure risk and new infection risk. Groups were also assessed for differences in first-test milk yield and linear scores, individual milk weights for the first 30 d, and culling and mastitis events before 30 d in milk. A total of 304 cows and 1,040 quarters in the ABXTS group and 307 cows and 1,058 quarters in the TS group were enrolled. Among cows to be dried, the proportion of cows that met low-risk criteria was 64% (n = 611/953). Of cultures eligible for bacteriological cure analysis (n = 171), 93% of ABXTS cured, whereas 88% of TS cured. Of the non-cures, 95% were contributed by the minor pathogens coagulase-negative staphylococci (n = 19/20). These organisms also accounted for 57.5% of new infections (n = 77/134). We found no statistical differences between treatment groups for new infection risk (TS = 7.3% quarters experiencing new infections; ABXTS = 5.5%), milk production (ABXTS = 40.5 kg; TS = 41.2 kg), linear scores (ABXTS = 2.5; TS = 2.7), culling events (ABXTS, n = 18; TS, n = 15), or clinical mastitis events (ABXTS, n = 9; TS, n = 5). Results suggest that the algorithm used decreased dry-cow antibiotic use by approximately 60% without adversely affecting production or health outcomes.

Sociodemographic Determinants of Waitlist and Posttransplant Survival Among End-Stage Liver Disease Patients.

While regional organ availability dominates discussions of distribution policy, community-level disparities remain poorly understood. We studied micro-geographic determinants of survival risk and their distribution across Donor Service Areas (DSAs). Scientific Registry of Transplant Recipients records for all adults waitlisted for liver transplantation 2002-2014 were reviewed. The primary exposure variables were county-level sociodemographic risk, as measured by the Community Health Score (CHS), a previously-validated composite index local health conditions, and distance to listing transplant center. Among 114 347 patients, the median CHS was 19.4 (range: 0-40). Compared the lowest risk counties (CHS 1-10), highest-risk counties (CHS 31-40) had more black (14.6% vs. 5.4%), publicly insured (44.9% vs. 33.0), and remote candidates (34.0% vs. 15.1% living >100 miles away). Higher-CHS candidates had greater waitlist mortality in Cox multivariable (HR 1.16 for CHS 31-40, 95% CI 1.11-1.21) and competing risks analysis (sHR 1.07, 95% CI 0.99-1.14). Post-transplant survival was similar across CHS quartiles. Living >25 miles from the transplant center conferred excess mortality risk (sHR 1.08, 95% CI 1.03-1.12). Proposed distribution changes would disproportionately impact DSAs with more high-CHS or distant candidates. Low-income, rural and minority patients experience excess mortality while awaiting transplant, and risk disproportionately worse outcomes with reduced organ availability under current proposals.

First-Year Waitlist Hospitalization and Subsequent Waitlist and Transplant Outcome.

Frailty is associated with inferior survival and increased resource requirements among kidney transplant candidates, but assessments are time-intensive and costly and require direct patient interaction. Waitlist hospitalization may be a proxy for patient fitness and could help those at risk of poor outcomes. We examined United States Renal Data System data from 51 111 adult end-stage renal disease patients with continuous Medicare coverage who were waitlisted for transplant from January 2000 to December 2011. Heavily admitted patients had higher subsequent resource requirements, increased waitlist mortality and decreased likelihood of transplant (death after listing: 1-7 days: hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.20-1.28; 8-14 days: HR 1.49, 95% CI 1.42-1.56; ≥15 days: HR 2.07, 95% CI 1.99-2.15; vs. 0 days). Graft and recipient survival was inferior, with higher admissions, although survival benefit was preserved. A model including waitlist admissions alone performed better (C statistic 0.76, 95% CI 0.74-0.80) in predicting postlisting mortality than estimated posttransplant survival (C statistic 0.69, 95% CI 0.67-0.73). Although those with a heavy burden of admissions may still benefit from kidney transplant, less utility is derived from allografts placed in this population. Current kidney allocation policy, which is based in part on longevity matching, could be significantly improved by consideration of hospitalization records of transplant candidates.

Safety, pharmacokinetics and neutralization of the broadly neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults.

VRC-HIVMAB060-00-AB (VRC01) is a broadly neutralizing HIV-1 monoclonal antibody (mAb) isolated from the B cells of an HIV-infected patient. It is directed against the HIV-1 CD4 binding site and is capable of potently neutralizing the majority of diverse HIV-1 strains. This Phase I dose-escalation study in healthy adults was conducted at the National Institutes of Health (NIH) Clinical Center (Bethesda, MD, USA). Primary objectives were the safety, tolerability and pharmacokinetics (PK) of VRC01 intravenous (i.v.) infusion at 5, 20 or 40 mg/kg, given either once (20 mg/kg) or twice 28 days apart (all doses), and of subcutaneous (s.c.) delivery at 5 mg/kg compared to s.c. placebo given twice, 28 days apart. Cumulatively, 28 subjects received 43 VRC01 and nine received placebo administrations. There were no serious adverse events or dose-limiting toxicities. Mean 28-day serum trough concentrations after the first infusion were 35 and 57 µg/ml for groups infused with 20 mg/kg (n = 8) and 40 mg/kg (n = 5) doses, respectively. Mean 28-day trough concentrations after the second infusion were 56 and 89 µg/ml for the same two doses. Over the 5-40 mg/kg i.v. dose range (n = 18), the clearance was 0.016 l/h and terminal half-life was 15 days. After infusion VRC01 retained expected neutralizing activity in serum, and anti-VRC01 antibody responses were not detected. The human monoclonal antibody (mAb) VRC01 was well tolerated when delivered i.v. or s.c. The mAb demonstrated expected half-life and pharmacokinetics for a human immunoglobulin G. The safety and PK results support and inform VRC01 dosing schedules for planning HIV-1 prevention efficacy studies.

Development of a novel antibody to calcitonin gene-related peptide for the treatment of osteoarthritis-related pain.

OBJECTIVE: Investigate a role for calcitonin gene-related peptide (CGRP) in osteoarthritis (OA)-related pain. DESIGN: Neutralizing antibodies to CGRP were generated de novo. One of these antibodies, LY2951742, was characterized in vitro and tested in pre-clinical in vivo models of OA pain. RESULTS: LY2951742 exhibited high affinity to both human and rat CGRP (KD of 31 and 246 pM, respectively). The antibody neutralized CGRP-mediated induction of cAMP in SK-N-MC cells in vitro and capsaicin-induced dermal blood flow in the rat. Neutralization of CGRP significantly reduced pain behavior as measured by weight bearing differential in the rat monoiodoacetate model of OA pain in a dose-dependent manner. Moreover, pain reduction with neutralization of CGRP occurred independently of prostaglandins, since LY2951742 and NSAIDs worked additively in the NSAID-responsive version of the model and CGRP neutralization remained effective in the NSAID non-responsive version of the model. Neutralization of CGRP also provided dose-dependent and prolonged (>60 days) pain reduction in the rat meniscal tear model of OA after only a single injection of LY2951742. CONCLUSIONS: LY2951742 is a high affinity, neutralizing antibody to CGRP. Neutralization of CGRP is efficacious in several OA pain models and works independently of NSAID mechanisms of action. LY2951742 holds promise for the treatment of pain in OA patients.

Do bacterial and fungal communities assemble differently during primary succession?

High-throughput sequencing technologies are now allowing us to study patterns of community assembly for diverse microbial assemblages across environmental gradients and during succession. Here we discuss potential explanations for similarities and differences in bacterial and fungal community assembly patterns along a soil chronosequence in the foreland of a receding glacier. Although the data are not entirely conclusive, they do indicate that successional trajectories for bacteria and fungi may be quite different. Recent empirical and theoretical studies indicate that smaller microbes (like most bacteria) are less likely to be dispersal limited than are larger microbes - which could result in a more deterministic community assembly pattern for bacteria during primary succession. Many bacteria are also better adapted (than are fungi) to life in barren, early-successional sediments in that some can fix nitrogen and carbon from the atmosphere - traits not possessed by any fungi. Other differences between bacteria and fungi are discussed, but it is apparent from this and other recent studies of microbial succession that we are a long way from understanding the mechanistic underpinnings of microbial community assembly during ecosystem succession. We especially need a better understanding of global and regional patterns of microbial dispersal and what environmental factors control the development of microbial communities in complex natural systems.

Effect of gallium on growth of Streptococcus mutans NCTC 10449 and dental tissues.

Gallium-doped phosphate-based glasses (Ga-PBG) were assessed for their impact on Streptococcus mutans and dental mineralisation, firstly by disc diffusion assays followed by biofilms grown on nitrocellulose filter membrane (NFM) and constant-depth film fermentor (CDFF). Short-time exposure (10 min) effects of Ga-PBG on S. mutans biofilm were compared with that of 0.2% chlorhexidine. The effects of Ga-PBG on bovine enamel (which was investigated under pH-cycling condition) and dentine were analysed using transverse microradiography (TMR), profilometry and inductively coupled plasma optical-emission spectrometry (ICP-OES). The disc diffusion assays showed inhibition zones of 24.5 ± 0.5 mm for Ga-PBG compared with controls (C-PBG). Ga-PBG showed statistically significant growth inhibition of S. mutans biofilms on NFM (p = 0.001) and CDFF (p < 0.046) compared with hydroxyapatite (HA) and C-PBG. The CDFF assay revealed a maximum of 2.11 log colony-forming unit (CFU) reduction at 48 h, but short-time exposure effects were comparable with that of 0.2% chlorhexidine only on older biofilms (maximum of 0.59 vs. 0.69 log CFU reduction at 120 h). TMR analyses of the enamel revealed non-significant mineral loss (p = 0.37) only in the case of Ga-PBG samples compared with controls including sodium fluoride. ICP-OES analyses indicated transient gallium adsorption into dentine by calcium displacement. The results confirmed that gallium inhibited S. mutans growth and appears to have the potential to protect the enamel surface under conditions representative of the oral environment. Further work is needed to establish whether it has an application in daily oral hygiene procedures to prevent or reduce caries.

Cryptic B cell response to renal transplantation.

Transplantation reliably evokes allo-specific B cell and T cell responses in mice. Yet, human recipients of kidney transplants with normal function usually exhibit little or no antibody specific for the transplant donor during the early weeks and months after transplantation. Indeed, the absence of antidonor antibodies is taken to reflect effective immunosuppressive therapy and to predict a favorable outcome. Whether the absence of donor-specific antibodies reflects absence of a B cell response to the donor, tolerance to the donor or immunity masked by binding of donor-specific antibodies to the graft is not known. To distinguish between these possibilities, we devised a novel ELISPOT, using cultured donor, recipient and third-party fibroblasts as targets. We enumerated donor-specific antibody-secreting cells in the blood of nine renal allograft recipients with normal kidney function before and after transplantation. Although none of the nine subjects had detectable donor-specific antibodies before or after transplantation, all exhibited increases in the frequency of donor-specific antibody-secreting cells eight weeks after transplantation. The responses were directed against the donor HLA-class I antigens. The increase in frequency of donor-specific antibody-secreting cells after renal transplantation indicates that B cells respond specifically to the transplant donor more often than previously thought.

Characteristics of methylcellulose acid gel lesions created in human and bovine enamel.

Acid gel caries lesions were created in 3,100 human and bovine enamel specimens and studied with transverse microradiography. Small, significant differences were found. Human enamel lesions were found to be less demineralized, shallower, had a higher ratio of integrated mineral loss (ΔZ) to lesion depth (L), a lower degree of surface zone mineralization (SZ(max)) and showed less variability than those in bovine enamel. SZ(max) showed the highest variability. Between tissues, L differed the most, ΔZ the least. Biological variation within bovine enamel is perhaps not only bigger than previously assumed, it may also overshadow any structural and chemical differences between tissues.