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Many areas of the Earth's crust deform by distributed extensional faulting and complex fault interactions are often observed. Geodetic data generally indicate a simpler picture of continuum deformation over decades but relating this behaviour to earthquake occurrence over centuries, given numerous potentially active faults, remains a global problem in hazard assessment. We address this challenge for an array of seismogenic faults in the central Italian Apennines, where crustal extension and devastating earthquakes occur in response to regional surface uplift. We constrain fault slip-rates since ~18 ka using variations in cosmogenic 36Cl measured on bedrock scarps, mapped using LiDAR and ground penetrating radar, and compare these rates to those inferred from geodesy. The 36Cl data reveal that individual faults typically accumulate meters of displacement relatively rapidly over several thousand years, separated by similar length time intervals when slip-rates are much lower, and activity shifts between faults across strike. Our rates agree with continuum deformation rates when averaged over long spatial or temporal scales (104 yr; 102 km) but over shorter timescales most of the deformation may be accommodated by <30% of the across-strike fault array. We attribute the shifts in activity to temporal variations in the mechanical work of faulting.

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PURPOSE: Postsurgical endophthalmitis is a sight-threatening problem. We introduce a simple approach by using a single application of thermoresponsive controlled-release microspheres, loaded with moxifloxacin, to prevent bacterial endophthalmitis in a rabbit endophthalmitis prevention model. METHODS: We separated 24 rabbits into 3 treatment groups in which topical drop treatment was placed onto the conjunctival cul-de-sac: (1) a single drop of controlled-release microspheres containing moxifloxacin, (2) a single drop of controlled-release microspheres without moxifloxacin, and (3) multiple topical treatment with moxifloxacin alone every 15 minutes for 1 hour. All rabbits were challenged, 1 hour after microspheres drop placement and immediately after the fifth topical dose of moxifloxacin, with anterior chamber injections of Staphylococcus aureus. Rabbits in the topical moxifloxacin group also were treated after challenge and four additional times over the next 24 hours. After 24 hours, the rabbits were clinically evaluated for endophthalmitis and the animals were euthanized to culture for intraocular S. aureus. The treatment groups were compared statistically for bacterial endophthalmitis. RESULTS: No eyes had endophthalmitis, based on clinical presentation and/or positive culture, in the groups with controlled-release microspheres loaded with moxifloxacin (0/8, 0%) or multiple drops of topical moxifloxacin (0/8, 0%). In contrast, 8 of 8 eyes (100%; P = 0.0001), had endophthalmitis among eyes treated with controlled-release microspheres drops without moxifloxacin. CONCLUSION: A single drop of controlled-release microspheres loaded with moxifloxacin was successful in preventing endophthalmitis. Further clinical studies will be required to confirm the full potential of controlled-release anti-infective loaded microspheres to prevent endophthalmitis. TRANSLATIONAL RELEVANCE: This study presents a simple method of prophylaxis to prevent postsurgical endophthalmitis.

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Given the widespread use and misuse of methamphetamine (METH) and methylphenidate (MPD), especially in relation to women of childbearing age, it is important to consider the long-lasting effects of these drugs on the brain of the developing fetus. Male and female C57Bl/6J mice were prenatally exposed to METH (5mg/kg), MPD (10mg/kg), or saline. Following a 3-month washout, behavioral analysis using the 5-Choice Serial Reaction Time Task (5CSRTT) was performed on adult mice. After reaching training criteria, performance on a pseudo-random intertrial interval test session revealed decrements in 5CSRTT behavior. Prenatally-treated METH and MPD mice demonstrated significant increases in impulsivity, compulsivity, and motivation for reward compared to their saline controls. There were sex by drug interactions indicating a possible sexually dimorphic response to these prenatal drug exposures. Of particular clinical interest, we find that mice prenatally exposed to METH or MPD express characteristics of both inhibitory control decrements and heightened motivation for rewards, which represent core symptoms of addiction and other impulse control disorders.

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ABT-925, a selective dopamine D3 receptor (DRD3) antagonist, was tested in schizophrenia. A DRD3 gene polymorphism results in an S9G amino-acid change that has been associated with lower risk of schizophrenia, higher affinity for dopamine and some antipsychotics, and differential response to some antipsychotics. The effect of S9G genotype on response to ABT-925 was examined. DNA samples (N=117) were collected in a proof-of-concept, double-blind, randomized, placebo-controlled study of ABT-925 (50 or 150 mg QD) in acute exacerbation of schizophrenia. A pre-specified analysis assessed impact of genotype (SS versus SG+GG) on change from baseline to final evaluation for the Positive and Negative Syndrome Scale (PANSS) total score using analysis of covariance with genotype, treatment and genotype-by-treatment interaction as factors, and baseline score as covariate. Significant genotype-by-treatment interaction (P=0.015) was observed for change from baseline to final evaluation for the PANSS total score. Within subgroup analyses showed significant improvement from placebo in the SG+GG group treated with ABT-925 150 mg. More favorable clinical outcomes were observed in patients treated with ABT-925 150 mg who carried the DRD3 G allele than in those who carried the DRD3 SS genotype.

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A comparative analysis of the direct effects of amphetamine and methamphetamine exposure on BV2 microglia cells in the presence and absence of cellular debris was performed. A significant dose-dependent and treatment-dependent effect of amphetamine and methamphetamine on BV2 cells was demonstrated: methamphetamine, but not amphetamine, inhibited phagocytosis, and a differential regulation of cytokines was observed in response to amphetamine and methamphetamine.

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In vivo effectiveness of topical antibiotics may depend on their ability to associate with epithelial cells to provide continued protection, but this contribution is not measured by standard antibiotic susceptibility tests. We report a new in vitro method that measures the ability of test antibiotics azithromycin (AZM), erythromycin (ERY), tetracycline (TET), and bacitracin (BAC) to associate with mammalian cells and to protect these cells from destruction by bacteria. Mammalian cell lines were grown to confluence using antibiotic-free medium and then incubated in medium containing a single antibiotic (0 to 512 µg/ml). After incubation, the cells were challenged with Staphylococcus aureus ocular isolates, without antibiotics added to the culture medium. Epithelial cell layer integrity was assessed by gentian violet staining, and the minimum cell layer protective concentration (MCPC) of an antibiotic sufficient to protect the mammalian cells from S. aureus was determined. Staining was also quantified and analyzed. Bacterial viability was determined by culture turbidity and growth on agar plates. Preincubation of Chang and human corneal limbal epithelial cells with AZM, ERY, and TET at ≥64 µg/ml provided protection against AZM-susceptible S. aureus strains, with increasing protection at higher concentrations. TET toxicity was demonstrated at >64 µg/ml, whereas AZM displayed toxicity to one cell line at 512 µg/ml. BAC failed to show consistent protection at any dose, despite bacterial susceptibility to BAC as determined by traditional antibiotic susceptibility testing. A range of antibiotic effectiveness was displayed in this cell association assay, providing data that may be considered in addition to traditional testing when determining therapeutic dosing regimens.

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Progress in laser wakefield accelerators indicates their suitability as a driver of compact free-electron lasers (FELs). High brightness is defined by the normalized transverse emittance, which should be less than 1π mm mrad for an x-ray FEL. We report high-resolution measurements of the emittance of 125 MeV, monoenergetic beams from a wakefield accelerator. An emittance as low as 1.1±0.1π mm mrad is measured using a pepper-pot mask. This sets an upper limit on the emittance, which is comparable with conventional linear accelerators. A peak transverse brightness of 5×10¹5 A m⁻¹ rad⁻¹ makes it suitable for compact XUV FELs.

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Genetic variation and resemblance among relatives are fundamentals of quantitative genetics. Our purpose was to identify bulls with a bimodal pattern of inheritance in the quest for new discoveries about the inheritance of calf survival. A bimodal pattern of inheritance for calf survival was identified in sons of Holstein bulls. A bimodal pattern of inheritance indicates 2 groups of sons resulting from an allele effect, a grandsire effect, or some other common factor. Different combinations (AA, Aa, aa) of 2 alleles at a locus cause varying phenotypes to be expressed. Bulls that are heterozygous for loci affecting reproductive performance may have a bimodal pattern of inheritance if the difference in effect of the 2 alleles is large. If the bimodal pattern is caused by an allele effect, then molecular markers can be identified for use in marker-assisted selection breeding programs. Data on predicted transmitting ability for perinatal survival for the first parity of 8,678 sons of 599 sires were collected from 1984 through 1997 from the National Association of Animal Breeders calving ease database, which included 7 Midwestern states. Sixteen bulls were identified with a potential bimodal pattern of inheritance because they had 2 distinct groups of sons. The 2 groups of sons were separated by calculating the coefficient of variation for each possible combination of sons; the combination that gave the smallest coefficient of variation difference between the 2 groups was considered the correct distribution of the sons into those groups. Bulls with a bimodal distribution were analyzed to determine the distribution of the grandsons among the maternal grandsires (MGS) of the 2 groups of the bimodal distribution. The bimodal distribution may be a result of heterozygous sires or MGS that are homozygous for low or high survival. If the bimodal distribution is caused by a MGS effect, then marker-assisted selection can still be used by evaluating the MGS instead of the sires.

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The excitation of plasma waves over a length of up to 8 cm is demonstrated using laser guiding of intense laser pulses through hydrogen-filled glass capillary tubes. The plasma waves are diagnosed by spectral analysis of the transmitted laser radiation. The dependence of the spectral redshift-measured as a function of filling pressure, capillary tube length, and incident laser energy-is in excellent agreement with simulation results. The longitudinal accelerating field inferred from the simulations is in the range of 1-10 GV/m.

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The escalated use of artificial insemination in swine has increased the importance of determining fertility of a semen sample before it is used. Multiple laboratory assays have been developed to assess fertilizing potential but they have yielded inconsistent results. This experiment sought to determine the relationship between in vitro competitive zona binding ability and in vivo fertility based on heterospermic inseminations and paternity testing. The zona pellucida binding ability and fertility of sperm from 15 boars was assessed by comparing sperm from one boar with sperm from other individual boars in a pairwise fashion using four ejaculates. The relationship of zona binding ability to the mean number of piglets sired per litter for each boar as well as historic fertility data (litter size and farrowing rate) was assessed. The in vitro competition assay consisted of labeling sperm from each boar of the pair with a different fluorophore and incubating an equal number of sperm from each boar in the same droplet with porcine oocytes. The competitive assay was highly effective in ranking boars by zona binding ability (R2=0.94). Paternity testing using microsatellite markers was used to determine the mean number of piglets sired per litter for each boar during heterospermic inseminations. The pairwise heterospermic insemination assay was effective in ranking boar fertility (R2=0.59). Using historical data from these boars, average litter size and farrowing rate were correlated (r=0.81, p<0.001). However, zona binding ability was not significantly correlated with historic farrowing rate data or historic average litter size. Boar sperm zona binding ability was also not correlated significantly with the mean number of piglets sired per litter following heterospermic insemination. But the number of piglets sired by each boar was related to a combination of zona binding ability, sperm motility, normal morphology, acrosomal integrity, and the presence of distal droplets (R2=0.70). These results suggest that zona binding ability is not an accurate predictor of fertilizing ability when used alone; however, when coupled with other sperm assessments, fertility may be predicted successfully.

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The effects of suckling intensity on milk yield and piglet growth were determined when lactation capacity of the sow was enhanced through overexpression of a mammary-specific transgene, bovine alpha-lactalbumin. Lactational response to increased suckling stimulation was determined by fostering litters of the same age (d 1) or 7 d older (d 7) than the day of lactation to sows nontransgenic (control) or transgenic (TG) for bovine alpha-lactalbumin. Twenty first-parity gilts were allocated to 4 treatments dependent on gilt genotype and age of litter fostered (control d 1, control d 7, TG d 1, and TG d 7). Litters were standardized to 10 piglets within 24 h postpartum, and nonbirth piglets were fostered to gilts with an equal litter BW within age groups at 36 h postpartum. Milk yield was determined by the weigh-suckle-weigh method on d 6, 9, 12, 15, and 18 of lactation. Mean daily milk yield was greater (P = 0.031) for TG gilts compared with control gilts and tended to be greater (P = 0.056) for all gilts with d-7 piglets compared with those with d-1 piglets. Daily milk yield of TG d 7 gilts increased rapidly to peak at d 9 and was greater than milk yield of all control gilts at d 9 (P < 0.01), 12 (P < 0.02), and 15 (P < 0.02). Mean daily milk yield of TG d 7 gilts was 2.1 kg greater (P = 0.002) than for control d 7 gilts and 2.0 kg greater (P = 0.004) than for TG d 1 gilts. Daily milk yield of control d 1 gilts was not different from that of TG d 1 gilts (P = 0.49) or control d 7 gilts (P = 0.63). Piglet BW gain between d 3 and 6 was greater (P < 0.01) in the TG d 7 group than for all other groups and was greater (P < 0.05) than the control groups between d 6 and 9. No difference was found when comparing accumulated BW gain of the piglets between the day of age at foster (d 1 vs. 7; P = 0.606) or between the control d 1 and control d 7 groups (P = 0.759). Accumulated BW gain of piglets suckling TG d 7 gilts from d 3 through 9 was greater (P < 0.02) than that of the other groups and continued to be greater (P < 0.05) than that of either of the control groups through d 15. However, by d 15, accumulated BW gain of piglets suckling TG d 1 gilts was no longer different (P = 0.40) from that of the TG d 7 group and was greater (P < 0.05) than that of the control d 1 group. The enhanced lactation potential of these TG gilts synergized with suckling intensity to stimulate increased milk production during early lactation, resulting in increased piglet growth.

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The objective of this study was to compare milk loss and treatment costs for cows with clinical mastitis that were given antibiotics in addition to supportive treatment or supportive treatment alone. Between January 1994 and January 1996, 116,876 daily milk records on 676 lactations were taken at the University of Illinois Dairy Research Farm. Clinical mastitis was diagnosed during 124 lactations with 25,047 daily milk records, and 1417 of the daily milk records were on days when clinical mastitis was present. Cows with clinical mastitis were randomly assigned to one of 2 treatment groups: N (supportive treatment only) or A (antibiotics in addition to supportive treatment). Extent of antibiotic and supportive treatment varied according to twice daily severity scores. Projected and actual daily milk yields were estimated utilizing a random regression test-day model, and the differences were summed over 305 d of lactation to estimate lactational milk yield loss. The actual amount of discarded milk was added to milk yield loss to determine total milk loss per lactation. A cost analysis that included milk loss and treatment costs was then performed. Cows with clinical mastitis that were given only supportive treatment lost 230 +/- 172 kg (mean +/- standard error of mean [SEM]) more milk and incurred 94 +/- 51 dollars (SEM) more cost per lactation than cows given antibiotics and supportive treatment. Cows given only supportive treatment showed a response pattern of 305-d milk yield loss and economic loss per lactation that varied 2 to 3 times as much as cows treated with antibiotics. Based on reduced milk loss, better reliability (less variable response), and lower economic loss, the addition of antibiotics to supportive treatment was more efficacious and cost effective than supportive treatment alone.

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A field study was conducted to evaluate the influence of milking frequency (3 or 6 times/d [3x or 6x, respectively]) during the initial 21 d of lactation on milk and milk component yield and mammary gland health as indicated by somatic cell count. During 2 seasons, spring and fall, multiparous cows were milked 6 times/d until d 21 of lactation and then returned to the 3 times/d frequency for the remainder of lactation (6x; n = 9). Multiparous cows milked 3 times/d from the beginning of lactation served as a control group (3x; n = 17). With the exception of milking frequency, all other aspects of management, including housing, milk harvesting, and feeding, were identical between the groups and were consistent with industry norms. Retrospective analysis of Dairy Herd Improvement Association records was used to evaluate milk yield, milk component yield, and somatic cell scores. As expected, 6x cows produced more milk on the first test day than 3x cows. Compared with 3x cows, higher milk yields persisted for 6x cows from test day 2 through 6, indicating a persistent effect of early lactation milking frequency on milk yield potential for that lactation. Milk component yield followed a similar pattern: 6x cows produced significantly more protein, fat, and total solids than did control cows throughout the study. With regard to udder health, 6x cows had lower somatic cell counts at the first test day relative to 3x cows and had reduced somatic cell scores for the first 3 mo of lactation, which suggests that early lactation milking frequency influences the mammary gland capacity to resist infection in addition to improving milk production efficiency.

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Several laboratory assays have been designed to assess the fertility potential of a semen sample before insemination, but none have been consistent and accurate predictors of fertility. To determine whether zona-binding ability may be a useful fertility predictor, we validated and used an in vitro competitive assay to measure the ability of porcine sperm to bind to the zona pellucida. The zona-binding ability of sperm from 11 boars that exhibited a broad range in average litter size and farrowing rate was determined. Sperm from each boar were compared directly with sperm from eight other boars in a systematic, pairwise fashion. Sperm from two semen samples were labeled with fluorophores at concentrations that did not affect motility or zona-binding ability. An equal number of labeled sperm from each boar was coincubated with homologous oocytes. Least squares means from analysis of variance were used to rank boars based on zona-binding ability. The competitive assay was effective in establishing a ranking of the boars (R2 = 0.62). Furthermore, there was a correlation between zona-binding ability and fertility when estimated by average litter size (r = 0.64, P < 0.05) but not when estimated by farrowing rate (r = -0.28). The explanation for this difference was that litter size and farrowing rate were poorly correlated (r = 0.14). In conclusion, a competitive zona-binding assay distinguished boars that sired either small or large litters. Competitive zona-binding ability may be useful for identifying boars with reduced fertility that produce smaller litters following insemination.

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An optimum-sized dog guide weighs 18 to 32 kg and measures 53 to 64 cm in height at the withers when mature body size is attained. Effects of selection index with and without restrictions, independent trait selection, directional selection, stabilizing selection, and negative assortative mating were modeled using data from German shepherd dogs and Labrador retrievers raised by the Seeing Eye, Inc., Morristown, NJ from 1979 to 1997. The selection goals were to decrease mature weight and mature height in German shepherd dogs and to decrease mature weight and increase mature height in Labrador retrievers. Mature weights were recorded for 1,333 German shepherd dog offspring and their 69 dams and 17 sires, and 1,081 Labrador retriever offspring and their 51 dams and 13 sires. Mature heights also were recorded for offspring and parents, including 871 German shepherd dogs from 70 dams and 15 sires, and 793 Labrador retrievers from 40 dams and 13 sires. Selecting on mature weight alone produced the highest aggregate genetic-economic gain for German shepherd dogs compared with the selection indices with and without restrictions, generating a 2.10-kg decrease in mature weight and a correlated 0.36-cm decrease in mature height. In Labrador retrievers, selecting for mature height alone produced the highest aggregate genetic-economic gain but caused an increase in mature weight. Weighting the two traits equally but in the opposite direction without restrictions was the only index that produced the desired effect of decreasing mature weight and increasing mature height in Labrador retrievers. Response to selection for one generation of directional selection for a single trait included a 0.50-kg decrease in mature weight for German shepherd dogs, a 0.59-kg decrease in mature weight for Labrador retrievers, a 0.18-cm decrease in mature height for German shepherd dogs, and a 0.91-cm increase in mature height for Labrador retrievers. Increasing the percentage of dogs attaining optimum size may decrease the cost of production for the Seeing Eye, Inc., because fewer dogs would need to be raised and trained to provide assistance to the same number of blind individuals.

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The objective of this paper was to estimate the repeatability of objective measurements on the rear legs of dairy cows to see whether higher repeatability estimates could be obtained compared to the corresponding subjective linear score. Between September and November 1998, seven measurements of distance among dewclaw, hip, hock, pinbone, and thurl were taken on 73 cows from the University of Illinois dairy farm. Measurements were combined to define triangles and therefore angles reflecting rear leg structure. Three novice evaluators participated in the experiment, and, on a given day, two sets of measurements were taken by two evaluators. Cows were measured twice at a 1- to 4-wk interval. Size, evaluator, and order of measurement were included in the model as fixed effects. Cow, interactions of cow x evaluator and cow x order of measurement were random effects included in the model. The model explained over 80% of the variation for each variable. Repeatability estimates of the length measurements ranged from 0.61 to 0.89. Repeatability estimates of angles were much lower ranging from 0.00 to 0.24. The variation in natural standing position of the cow hampered the accuracy of the objective measurements. Low estimates of repeatability for angles describing rear leg suggested that objective measurements by novice evaluators were not sufficiently reliable to potentially replace the subjective linear score for rear leg curvature determined by experts. Usefulness of further investigation to find objective measurements that would give a better description of rear legs conformation compared to the corresponding current type trait was questionable.

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Two studies were carried out in different wean-to-finish barns to determine the effects of double stocking on pig growth performance. In Study 1, pigs (n = 1,560) were used in a randomized complete block design with a 2 x 2 factorial arrangement of treatments: initial stocking treatment (Single [52 pigs/pen] vs Double [104 pigs/pen] stocked for 10 wk after weaning) and weighing frequency (High [12 times during the study] vs Low [3 times]) on pig performance from weaning (5.9+/-0.01 kg BW; 17 d of age) to harvest (114+/-0.67 kg BW). Floor and feeder space per pig were 0.650 m2 and 4 cm and 0.325 m2 and 2 cm for the single- and double-stocked treatments, respectively. In Study 2, pigs (n = 1,458) were used in a randomized complete block design to evaluate two initial stocking treatments (Single [27 pigs] vs Double [54 pigs] stocked for 10 wk after weaning) on pig performance from weaning (4.8+/-0.01 kg BW; 15 d of age) to harvest (24 wk after weaning). Floor and feeder space per pig were 0.640 m2 and 3.4 cm and 0.320 m2 and 1.7 cm for single- and double-stocked pens, respectively. In both studies, double-stocked pigs were split at the end of wk 10 into two equal-sized groups of similar mean BW and CV of BW, and one group was moved to a different pen in the same building. In Study 1, performance was not affected (P > 0.10) by frequency of weighing. For the first 10 wk after weaning, the Double compared to the Single treatment had lower ADG (7.7 and 7.9%, for Studies 1 and 2, respectively; P < 0.001) and lighter pigs at wk 10 (6.8 and 7.3%, respectively; P < 0.001). During the first 10 wk in Study 1, Double compared to the Single pigs had lower ADFI (7%; P < 0.001) but similar gain:feed (P > 0.10). From wk 11 to harvest, pigs on Double and Single treatments had similar (P > 0.10) ADG in both studies and, in Study 1, ADFI was unaffected by initial stocking treatment, but double-stocked pigs had greater gain:feed (4%, P < 0.01). Double-stocked pigs required an additional 2 d to reach a fixed harvest BW (P < 0.05) in Study 1 and were lighter (4%; P < 0.05) at 24 wk after weaning in Study 2. Carcass measures were similar (P > 0.10) for double- and single-stocked pigs. Double-stocked pigs that were moved at the end of 10 wk had growth performance similar (P > 0.10) to those that remained in the original pen. In summary, double stocking reduced growth rate to 10 wk after weaning but subsequently had no effect on growth rate and improved feed efficiency.

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Meiosis I in Saccharomyces cerevisiae is dependent upon the motor protein Kar3. Absence of Kar3p in meiosis results in an arrest in prophase I. Cik1p and Vik1p are kinesin-associated proteins known to modulate the function of Kar3p in the microtubule-dependent processes of karyogamy and mitosis. Experiments were performed to determine whether Cik1p and Vik1p are also important for the function of Kar3p during meiosis. The meiotic phenotypes of a cik1 mutant were found to be similar to those of kar3 mutants. Cells without Cik1p exhibit a meiotic defect in homologous recombination and synaptonemal complex formation. Most cik1 mutant cells, like kar3 mutants, arrest in meiotic prophase; however, in cik1 mutants this arrest is less severe. These data are consistent with the model that Cik1p is necessary for some, but not all, of the roles of Kar3p in meiosis I. vik1 mutants sporulate at wild-type levels, but have reduced spore viability. This loss in viability is partially attributable to vegetative chromosome loss in vik1 diploids. Cellular localization experiments reveal that Kar3p, Cik1p, and Vik1p are present throughout meiosis and are consistent with Cik1p and Vik1p having different meiotic roles.

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