The impact of market integration on arranged marriages in Matlab, Bangladesh.

Success in marriage markets has lasting impacts on women's wellbeing. By arranging marriages, parents exert financial and social powers to influence spouse characteristics and ensure optimal marriages. While arranging marriages is a major focus of parental investment, marriage decisions are also a source of conflict between parents and daughters in which parents often have more power. The process of market integration may alter parental investment strategies, however, increasing children's bargaining power and reducing parents' influence over children's marriage decisions. We use data from a market integrating region of Bangladesh to (a) describe temporal changes in marriage types, (b) identify which women enter arranged marriages and (c) determine how market integration affects patterns of arranged marriage. Most women's marriages were arranged, with love marriages more recent. We found few predictors of who entered arranged vs. love marriages, and family-level market integration did not predict marriage type at the individual level. However, based on descriptive findings, and findings relating women's and fathers' education to groom characteristics, we argue that at the society-level market integration has opened a novel path in which daughters use their own status, gained via parental investments, to facilitate good marriages under conditions of reduced parental assistance or control.

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.

Religiosity is associated with greater size, kin density, and geographic dispersal of women's social networks in Bangladesh.

Human social relationships, often grounded in kinship, are being fundamentally altered by globalization as integration into geographically distant markets disrupts traditional kin based social networks. Religion plays a significant role in regulating social networks and may both stabilize extant networks as well as create new ones in ways that are under-recognized during the process of market integration. Here we use a detailed survey assessing the social networks of women in rural Bangladesh to examine whether religiosity preserves bonds among kin or broadens social networks to include fellow practitioners, thereby replacing genetic kin with unrelated co-religionists. Results show that the social networks of more religious women are larger and contain more kin but not more non-kin. More religious women's networks are also more geographically diffuse and differ from those of less religious women by providing more emotional support, but not helping more with childcare or offering more financial assistance. Overall, these results suggest that in some areas experiencing rapid social, economic, and demographic change, religion, in certain contexts, may not serve to broaden social networks to include non-kin, but may rather help to strengthen ties between relatives and promote family cohesion.

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.

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.

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.

A novel electron-microscopic method for measurement of mineral content in enamel lesions.

OBJECTIVE: To assess Scanning Electron Microscopy in Back-Scattered Emission mode (BSE-SEM) for measurement of lesion mineral content as a function of depth. Direct comparison is made with Transverse Micro-Radiography (TMR) and Surface Micro-Hardness (SMH) on carious and erosive lesions. DESIGN: Caries lesions prepared from sound bovine enamel at 37 °C and pH 4.6 in unsaturated (7d) or part-saturated (8d, 4.1 mM Ca2+, 8 mM Pi) lactic acid /methyl cellulose gel system, followed by TMR analysis. Erosive lesions prepared from sound bovine enamel (1% citric acid, pH3.8, room temperature) for 5, 10, 15 or 20 min at n = 10 per treatment group. SMH readings (Vickers diamond, 1.9 N, 20 s) were taken from acid-treated and reference areas of each sample. BSE-SEM performed on polished cross-sections of lesioned samples (Jeol JSM6490LV SEM; high vacuum, 10 keV beam voltage, magnification x500 with constant working distance of 10 mm). Under identical SEM conditions, polished standards i.e. MgF2, alumina, Mg, Al and Si provided a calibration plot of BSE-SEM signal vs. atomic number (z¯). Mineral content vs. depth plots were derived from the cross-sectional BSE-SEM data. RESULTS: Cross-sectional BSE-SEM images clearly differentiate between caries and erosive lesions. Comparison of caries lesion mineral loss from BSE-SEM with TMR data showed good correlation (R2 = 0.98). Similarly, comparison of BSE-SEM data from erosive lesions showed good correlation (R2 = 0.99) with hardness loss data from SMH. CONCLUSION: BSE-SEM provides a relatively rapid and cost-effective method for the assessment of mineral content in demineralised tooth enamel and is applicable to both caries and erosive lesions.

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.

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.

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.

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.

Effect of toothbrushing duration and dentifrice quantity on enamel remineralisation: An in situ randomized clinical trial.

OBJECTIVES: The influence of toothbrushing duration and dentifrice quantity on fluoride efficacy against dental caries is poorly understood. This study investigated effects of these two oral hygiene factors on enamel remineralisation (measured as surface microhardness recovery [SMHR]), enamel fluoride uptake (EFU), and net acid resistance (NAR) post-remineralisation in a randomized clinical study using an in situ caries model. METHODS: Subjects (n=63) wore their partial dentures holding partially demineralised human enamel specimens and brushed twice-daily for two weeks, following each of five regimens: brushing for 120 or 45s with 1.5g of 1150ppm F (as NaF) dentifrice; for 120 or 45s with 0.5g of this dentifrice; and for 120s with 1.5g of 250ppm F (NaF) dentifrice. RESULTS: Comparing brushing for 120s against brushing for 45s, SMHR and EFU increased by 20.0% and 26.9% respectively when 1.5g dentifrice was used; and by 22.8% and 19.9% respectively when 0.5g dentifrice was used. Comparing brushing with 1.5g against brushing with 0.5g dentifrice, SMHR and EFU increased by 35.3% and 51.3% respectively when brushing for 120s, and by 38.4% and 43.0% respectively when brushing for 45s. Increasing brushing duration and dentifrice quantity also increased the NAR value. The effects of these two oral hygiene factors on SMHR, EFU, and NAR were statistically significant (p<0.05 in all cases). CONCLUSION: Brushing duration and dentifrice quantity have the potential to influence the anti-caries effectiveness of fluoride dentifrices. Study NCT01563172 on ClinicalTrials.gov. CLINICAL SIGNIFICANCE: The effect of two key oral hygiene regimen factors - toothbrushing duration and dentifrice quantity - on fluoride's anticaries effectiveness is unclear. This 2-week home-use in situ remineralisation clinical study showed both these factors can influence fluoride bioactivity, and so can potentially affect fluoride's ability to protect against caries.

Predicting outcome in acute severe ulcerative colitis: comparison of the Travis and Ho scores using UK IBD audit data.

BACKGROUND: Acute severe ulcerative colitis is categorised using the Truelove & Witts criteria. The Travis and the Ho scores are calculated following 72 h of steroid treatment to identify patients at risk of failing steroid therapy who require colectomy or second-line medical therapy. AIM: To compare the Travis and the Ho scores in a large unselected cohort to determine which might be more clinically relevant. METHODS: We analysed 3049 patients with ulcerative colitis from the 2010 round of the UK IBD audit of which 984 had acute severe ulcerative colitis. 420 patients had sufficient data for analysis. Patients were allocated into either a Travis high- or low-risk group and either a Ho high-, intermediate- or low-risk group. We assessed whether further medical or surgical intervention and outcomes varied between groups. RESULTS: High-risk patients in Travis and the Ho groups, when compared to lower risk groups, were more likely to fail steroid therapy: 64.5% (131/203) vs. 38.7% (84/217) (P < 0.0001) for Travis and 66.2% (96/145) vs. 46.7% (85/182) vs. 36.6% (34/93) (P < 0.0001) for Ho. They were also more likely to undergo surgery 34.0% (69/203) vs. 9.7% (21/217) for Travis and 33.1% (48/145) vs. 17.0% (31/182) vs. 11.8% (11/93) (P < 0.0001) for Ho. Travis high patients were more likely to be refractory to second-line medical therapy: 44.6% (37/83) vs. 20.0% (9/45) (P = 0.01). CONCLUSIONS: Patients identified as high risk using the Travis or the Ho scoring systems are more likely to be resistant to IV steroids and require surgery. Risk of surgery in both high-risk populations is lower than previously reported.

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.

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.

Dose-response effect of fluoride dentifrice on remineralisation and further demineralisation of erosive lesions: A randomised in situ clinical study.

OBJECTIVE: The objective was to evaluate the ability of fluoride in a conventional, non-specialised sodium fluoride-silica dentifrice to promote tooth remineralisation and enamel fluoride uptake (EFU), and assess the resistance of the newly formed mineral to attack by dietary acid, across the concentration range used in mass-market dentifrices. METHODS: Subjects wore a palatal appliance containing eight polished bovine enamel specimens, each including an early erosive lesion. In a randomised full-crossover sequence, 62 healthy subjects were treated with dentifrices containing four different fluoride concentrations: no fluoride; 250ppm, 1150ppm and 1426ppm fluoride. At each treatment visit, under supervision, subjects brushed with 1.5g dentifrice and rinsed once while wearing the appliance; the appliance was removed after a 4-h remineralisation period and effects on the enamel specimens determined. The primary efficacy variable was surface microhardness recovery (SMHR); others included EFU, relative erosion resistance (RER) and comparative erosion resistance. RESULTS: Highly significant linear and, with the exception of SMHR, quadratic dose-response relationships were observed between all efficacy variables and fluoride concentration. For SMHR, EFU and RER, values for the different fluoride concentrations were statistically resolved from one another, with the exception of the two highest fluoride concentrations. The degree of remineralisation and the acid resistance of enamel after treatment were closely related to EFU. CONCLUSION: After a single brushing, conventional non-specialised sodium fluoride-silica dentifrices promoted remineralisation of early enamel lesions, and imparted increased acid-resistance to the enamel surface, in a dose-dependent manner at least up to 1500ppm fluoride. CLINICAL SIGNIFICANCE: Enamel erosive tissue loss is an increasing concern, associated with modern diets. This study demonstrated that sodium fluoride, in a conventional non-specialised dentifrice formulation, can promote repair of the earliest stages of enamel erosion after a single application, in a dose-dependent fashion across the fluoride concentration range used in mass-market dentifrices. This study is registered in the GlaxoSmithKline Study Register (ID RH01299), available at: www.gsk-clinicalstudyregister.com/study/RH01299.

Comparison of Knoop and Vickers surface microhardness and transverse microradiography for the study of early caries lesion formation in human and bovine enamel.

OBJECTIVE: The aims of the present laboratory study were twofold: a) to investigate the suitability of Knoop and Vickers surface microhardness (SMH) in comparison to transverse microradiography (TMR) to investigate early enamel caries lesion formation; b) to compare the kinetics of caries lesion initiation and progression between human and bovine enamel. DESIGN: Specimens (90×bovine and 90×human enamel) were divided into six groups (demineralization times of 8/16/24/32/40/48h) of 15 per enamel type and demineralized using a partially saturated lactic acid solution. SMH was measured before and after demineralization and changes in indentation length (ΔIL) calculated. Lesions were characterized using TMR. Data were analyzed (two-way ANOVA) and Pearson correlation coefficients calculated. RESULTS: ΔIL increased with increasing demineralization times but plateaued after 40h, whereas lesion depth (L) and integrated mineral loss (ΔZ) increased almost linearly throughout. No differences between Knoop and Vickers SMH in their ability to measure enamel demineralization were observed as both correlated strongly. Overall, ΔIL correlated strongly with ΔZ and L but only moderately with the degree of surface zone mineralization, whereas ΔZ and L correlated strongly. Bovine demineralized faster than human enamel (all techniques). CONCLUSIONS: Lesions in bovine formed faster than in human enamel, although the resulting lesions were almost indistinguishable in their mineral distribution characteristics. Early caries lesion demineralization can be sufficiently studied by SMH, but its limitations on the assessment of the mineral status of more demineralized lesions must be considered. Ideally, complementary techniques to assess changes in both physical and chemical lesion characteristics would be employed.

Physical chemical effects of zinc on in vitro enamel demineralization.

OBJECTIVES: Zinc salts are formulated into oral health products as antibacterial agents, yet their interaction with enamel is not clearly understood. The aim was to investigate the effect of zinc concentration [Zn(2+)] on the in vitro demineralization of enamel during exposure to caries-simulating conditions. Furthermore, the possible mechanism of zinc's action for reducing demineralization was determined. METHODS: Enamel blocks and synthetic hydroxyapatite (HAp) were demineralized in a range of zinc-containing acidic solutions (0-3565ppm [Zn(2+)]) at pH 4.0 and 37°C. Inductively coupled-plasma optical emission spectroscopy (ICP-OES) was used to measure ion release into solution. Enamel blocks were analysed by Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR), and HAp by X-ray diffraction (XRD) and neutron diffraction (ND). RESULTS: ICP-OES analysis of the acidic solutions showed a decrease in [Ca(2+)] and [PO4(3-)] release with increasing [Zn(2+)]. FTIR revealed a α-hopeite (α-Zn3(PO4)2.4H2O)-like phase on the enamel surfaces at >107ppm [Zn(2+)]. XRD and ND analysis confirmed a zinc-phosphate phase present alongside the HAp. CONCLUSIONS: This study confirms that zinc reduces enamel demineralization. Under the conditions studied, zinc acts predominantly on enamel surfaces at PO4(3-) sites in the HAp lattice to possibly form an α-hopeite-like phase. CLINICAL SIGNIFICANCE: These results have a significant implication on the understanding of the fundamental chemistry of zinc in toothpastes and demonstrate its therapeutic potential in preventing tooth mineral loss.

Comparison study of portable bladder scanner versus cone-beam CT scan for measuring bladder volumes in post-prostatectomy patients undergoing radiotherapy.

INTRODUCTION: In post-prostatectomy radiotherapy to the prostatic bed, consistent bladder volume is essential to maintain the position of treatment target volume. We assessed the differences between bladder volume readings from a portable bladder scanner (BS-V) and those obtained from planning CT (CT-V) or cone-beam CT (CBCT-V). Interfraction bladder volume variation was also determined. METHODS: BS-V was recorded before and after planning CT or CBCT. The percentage differences between the readings using the two imaging modalities, standard deviations and 95% confidence intervals were determined. Data were analysed for the whole patient cohort and separately for the older BladderScan™ BVI3000 and newer BVI9400 model. Interfraction bladder volume variation was determined from the percentage difference between the CT-V and CBCT-V. Treatment duration, incorporating the time needed for BS and CBCT, was recorded. RESULTS: Fourteen patients were enrolled, producing 133 data sets for analysis. BS-V was taken using the BVI9400 in four patients (43 data sets). The mean BS-V was 253.2 mL, and the mean CT-V or CBCT-V was 199 cm(3). The mean percentage difference between the two modalities was 19.7% (SD 42.2; 95%CI 12.4 to 26.9). The BVI9400 model produced more consistent readings, with a mean percentage difference of -6.2% (SD 27.8; 95% CI -14.7 to -2.4%). The mean percentage difference between CT-V and CBCT-V was 31.3% (range -48% to 199.4%). Treatment duration from time of first BS reading to CBCT was, on average, 12 min (range 6-27). CONCLUSIONS: The BS produces bladder volume readings of an average 19.7% difference from CT-V or CBCT-V and can potentially be used to screen for large interfraction bladder volume variations in radiotherapy to prostatic bed. The observed interfraction bladder volume variation suggests the need to improve bladder volume consistency. Incorporating the BS into practice is feasible.