Intermolecular dynamics of NH3-rare gas complexes in the ν2 umbrella region of NH3 investigated by rovibrational laser jet-cooled spectroscopy and ab initio calculations.

High resolution jet-cooled spectroscopy experiments have been realized to investigate the intermolecular dynamics of van der Waals (vdW) heterodimers between NH3 and rare gas (Rg) atoms in the ν2 umbrella mode region of NH3. With respect to a previous study dedicated to NH3-Ar [Asselin et al. Mol. Phys. 116, 3642 (2018)], the sensitivity and spectral resolution of our laser spectrometer coupled to a pulsed supersonic jet have been significantly improved to derive more accurate excited state spectroscopic parameters from rovibrational analyses. In addition, we calculated the ground and ν2 excited vibration-rotation-tunneling (VRT) states of these complexes on the four-dimensional ab initio potential energy surfaces from Loreau et al. [J. Chem. Phys. 141, 224303 (2014), ibid. 143, 184303 (2015).] Transition frequencies and intensities of the allowed ν2 = 1 ← 0 transitions obtained from the calculated energy levels and wave functions agree well with the experimental data and are helpful in their analysis. By means of a pseudodiatomic model with the assumption of weak Coriolis coupling, the rovibrational analysis of both the Πe/f(j = 1,k = 0) ←Σf(j = 0,k = 0) and Σf(j = 1,k = 0) ←Σf(j = 0,k = 0) transitions in ortho NH3-Rg (Rg = Ne, Ar, Kr, Xe) complexes enabled us to determine reliable excited state parameters and derive accurate values of the effective vdW bond length Reff, force constant ks, and vdW stretching frequency νs. Comparison between the experimental structural parameters and those from the ab initio calculated VRT levels shows good agreement for NH3-Ne, NH3-Ar and NH3-Kr, and a similar variation of Reff, ks, and νs with the polarizability of Rg in the ground and ν2 excited states. Anomalously small values of νs and ks derived for NH3-Xe in the Πe/f(j = 1,k = 0) state suggest that the applied model is not valid in this case, due to the presence of another state coupling to the perturbed Πf state. Such a state could not be found, however.

Correlation Between Intraoperative and Pathological Findings for Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: This study aimed to examine the correlation between intraoperative and pathological findings for patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) and to determine their prognostic significance. METHODS: Pathological reports of all colorectal cancer (CRC) patients undergoing CRS/HIPEC between 2009 and 2016 were retrospectively reviewed. Pathological specimens lacking tumor cells were defined as negative pathological specimens (NPS). The intraoperative peritoneal cancer index (PCI) and pathological PCI (excluding NPS) were calculated separately. Receiver operating characteristic (ROC) curves were applied to compare the prognostic value of intraoperative and pathological scoring systems. RESULTS: For 108 CRC patients, 113 CRS/HIPEC procedures were performed. Of 959 pathological specimens examined, 178 (18.6%) were NPS. Overall, 78 procedures (69%) showed NPS. In 52 procedures (46%), the pathological PCI differed from the intraoperative PCI (∆PCI > 0). The ROC areas for intraoperative PCI and pathological PCI were similar in predicting 1-year overall survival (OS), 2-year OS, and 1-year disease-free survival (all p values not significant). However, for the patients with NPS, the number of positive specimens (containing tumor tissue) was superior to intraoperative PCI in predicting 2-year OS (ROC under the curve areas, 0.69 vs. 0.58, respectively; p = 0.012). In addition, a subgroup of 15 patients with a high ∆PCI (≥ 3) had a more favorable median OS than a matched group of 30 patients with similar intraoperative PCI and a ∆PCI of 0 (median survival not reached vs. 21.6 months, respectively; p = 0.05). CONCLUSIONS: In the majority of CRC CRS/HIPEC procedures, NPS may be found. Among patients with NPS, pathological correlation may have a prognostic significance.

Does Medial Patellofemoral Osteoarthritis Influence Outcome Scores and Risk of Revision After Fixed-bearing Unicompartmental Knee Arthroplasty?

BACKGROUND: Patellofemoral osteoarthritis (OA) and anterior knee pain sometimes are considered contraindications for unicompartmental knee arthroplasty (UKA). However, several studies have demonstrated excellent patient-reported outcome scores in patients with patellofemoral OA treated with medial mobile-bearing UKA. Because these studies assessed the outcome of mobile-bearing UKA only, we were interested to see whether that finding also applies to fixed-bearing medial UKA. QUESTIONS/PURPOSES: (1) Does patellofemoral OA influence patient-reported outcome scores after medial fixed-bearing UKA? (2) Does untreated medial patellofemoral OA increase the revision rate after medial fixed-bearing UKA? METHODS: Between 2008 and 2015, one surgeon performed 308 medial fixed-bearing UKAs of a single design. Of those, 80 (26%) had patellofemoral OA of at least moderate severity (ICRS III or IV), and 228 (74%) did not. During that period, the surgeon did not use patellofemoral OA as a contraindication to UKA. In all, 13 patients (10%) in the patellofemoral OA group were lost before 2-year minimum followup, and 20 (11%) in the control group (without patellofemoral OA) were lost; all other patients were available, seen in the last 5 years, and included in this retrospective study. Mean (± SD) followup in the patellofemoral OA group was 39 ± 25 months, and it was 41 ± 23 in the control group. There were 100 women and 120 men. Patients had a mean age ± SD of 65 ± 10 years and mean ± SD BMI of 29 ± 4.5 kg/m.The intraoperative status of the patellofemoral joint was assessed using the International Cartilage Repair Society (ICRS) classification. The primary study endpoint was the Forgotten Joint Score (FJS-12); we also compared scores on the Lonner PatelloFemoral Score (LPFS), Oxford Knee Score (OKS) and Short-Form 12 (SF-12). With the numbers available, we had 80% power to detect a difference of 12.3 points on the Forgotten Joint Score. A secondary endpoint was femoral or tibial component revision for any reason verified over the phone for each included patient. RESULTS: With the numbers available, there was no difference in FJS-12 score between the UKA with patellofemoral OA group and the group without patellofemoral OA 71 ± 29 versus 77 ± 26, mean difference - 6; 95% CI, -16 to 4.5; p = 0.270). Likewise, with the numbers available, we saw no differences in LPFS, OKS and SF-12. There was no difference in survivorship from all-cause revision at 4 years between the patellofemoral OA group and the group without patellofemoral OA (98%; 95% CI, 85.8-99.7 versus 99.5%; 95% CI, 96.0-99.2%; p = 0.352). CONCLUSIONS: Patients with medial osteoarthritis in this single-center study generally benefitted from medial fixed-bearing UKA with good-to-excellent outcomes scores at short term, whether or not medial patellofemoral wear is present. LEVEL OF EVIDENCE: Level III, therapeutic study.

Implications of Stoma Formation as Part of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Formation of protective stoma as part of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) may be an effective tool in reducing anastomotic leak incidence. Our aim was to evaluate the incidence and implications of stoma formation during CRS-HIPEC and to examine whether a creation of protective stoma reduces the postoperative morbidity. METHODS: A cohort retrospective analysis of all CRS-HIPEC procedures performed between 2004 and 2016 was conducted. Predicting factors for stoma formation were assessed by comparing all patients who underwent stoma formation to those who did not; both groups were then restricted to cases with ≥2 bowel anastomoses and compared in terms of perioperative outcomes in order to determine whether protective stoma confers a morbidity benefit. RESULTS: One hundred and ninety-nine CRS-HIPEC procedures were performed on 186 patients. Thirty-four patients (17%) underwent stoma formation, 24 of them as protective stoma. Formation of a stoma was correlated with higher peritoneal carcinomatosis index score (13.6 ± 8 vs. 9.5 ± 7.7, p = 0.007), larger number of organs resected (p < 0.001), greater number of anastomoses (p < 0.001), prolonged operative time (8.1 ± 2.7 vs. 6.6 ± 2.2 h, p = 0.002), and prolonged hospital stay (12 vs. 8.5 days, p = 0.001). In procedures requiring ≥2 anastomoses, formation of protective stoma reduced the anastomotic leak rate (6 vs. 37%, p = 0.025), the morbidity rate (6 vs. 41%, p = 0.017), and reoperation rate (0 vs. 28%, p = 0.03). Overall, 15 patients (44%) underwent stoma reversal, 3 of whom had a complication treated non-operatively. CONCLUSIONS: Protective stoma should be considered in extensive CRS-HIPEC procedures requiring two or more bowel anastomoses in order to reduce the postoperative morbidity rate.

Colonoscopy after the first episode of acute diverticulitis: challenging management paradigms.

BACKGROUND: Colonoscopy is commonly recommended after the first episode of acute diverticulitis to exclude colorectal neoplasia. Recent data have challenged this paradigm due to insufficient diagnostic yield. The aim of this study was to assess whether colonoscopy after the first episode of acute diverticulitis is needed to exclude colorectal neoplasia. METHODS: We performed a retrospective cohort analysis of medical records of patients admitted for the first episode of acute diverticulitis between January 2008 and December 2012. Ambulatory colonoscopy was routinely recommended at discharge. Clinical follow-up and telephone surveys were used for data collection. RESULTS: Four hundred and twenty-five patients with a mean age of 62.6 years (range 21-98 years) were admitted during the 5-year period. Three hundred and ten (72.9 %) patients underwent colonoscopy at median time of 3.2 months after discharge. Five patients (1.6 %) of the 310 available for evaluation had malignant findings in colonoscopy. Of those, one patient had rectal carcinoma away from the inflamed site and one had colonic lymphoma. None of the 95 patients <50 years of age was found to have adenocarcinoma of the colon. CONCLUSIONS: Cancer is rarely detected in colonoscopy following the first episode of acute diverticulitis. These results question this indication for colonoscopy, especially in patients under 50.

Body mass index and common mental disorders: exploring the shape of the association and its moderation by age, gender and education.

BACKGROUND: Obesity is known to be associated with increased prevalence of common mental disorders (for example, depression and anxiety), and there is evidence of age and gender differences in this relationship. However, categorisation of body mass index (BMI) and age has limited our ability to understand the nature of these differences. This study used continuous values of BMI and age to explore the shape of the association between common mental disorders and BMI and whether it varied with age, gender and education. METHOD: The analysis used cross-sectional data on 7043 adults from the English 2007 Adult Psychiatric Morbidity Survey. Common mental disorders were assessed using the revised Clinical Interview Schedule (CIS-R). Cubic splines allowed BMI and age to have non-linear effects in the logistic regression analysis. RESULTS: BMI was strongly associated with the presence of common mental disorders, and there was clear evidence that this association varied with gender and age. In young women the probability of having a disorder increased as BMI increased, whereas in young men the relationship was U-shaped-probabilities were higher for both underweight and obese men. These associations diminished in older age groups, particularly when potential confounders such as physical health were taken into account. There was no evidence that the relationship varied with education. CONCLUSIONS: Age and gender differences must be taken into account when investigating the link between BMI or obesity and common mental disorders. Furthermore, results of studies that categorise BMI may be highly sensitive to the width of the 'normal weight' reference category.

Effect of rumen-undegradable protein supplementation and fresh forage composition on nitrogen utilization of dairy ewes.

Previous trials with dairy ewes fed stored feeds indicate a positive effect of rumen-undegradable protein (RUP) supplementation on milk yield. However, dairy sheep production in the United States is primarily based on grazing mixed grass-legume pastures, which contain a high proportion of rumen-degradable protein. Two trials were conducted to evaluate the effects of high-RUP protein supplementation and fresh forage composition on milk yield and N utilization of lactating dairy ewes fed in confinement or on pasture. In a cut-and-carry trial, 16 multiparous dairy ewes in mid-lactation were randomly assigned to 8 pens of 2 ewes each. Pens were randomly assigned 1 of 2 protein supplementation treatments, receiving either 0.0 or 0.3 kg of a high-RUP protein supplement (Soy Pass, LignoTech USA Inc., Rothschild, WI) per day. Within supplementation treatment, pens were randomly assigned to 1 of 4 forage treatments, which were applied in a 4×4 Latin square design for 10-d periods. Forage treatments included the following percentages of orchardgrass:alfalfa dry matter: 25:75, 50:50, 75:25, and 100:0. No interactions were observed between supplement and forage treatments. Supplementation with a high-RUP source tended to increase milk yield by 9%. Milk yield, milk protein yield, milk urea N, and urinary urea N excretion increased linearly with increased percentage of alfalfa. Milk N efficiency was greatest on the 100% orchardgrass diet. In a grazing trial, 12 multiparous dairy ewes in mid lactation were randomly assigned to 3 groups of 4 ewes each. Within group, 2 ewes were randomly assigned to receive either 0.0 or 0.3 kg of a high-RUP protein supplement (SoyPlus, West Central Cooperative, Ralston, IA) per day. Grazing treatments were arranged in a 3×3 Latin square design and applied to groups for 10-d periods. Ewes grazed paddocks that contained the following percentages of surface area of pure stands of orchardgrass:alfalfa: 50:50, 75:25, and 100:0. No interactions were found between supplement and forage treatments. Milk yield, milk protein yield, and milk urea N increased linearly with increased percentage of alfalfa in the paddock. In conclusion, supplementing with high-RUP protein tended to increase milk yield and increasing the proportion of alfalfa in the diet increased dry matter intake, milk yield, and protein yield of lactating dairy ewes fed or grazing fresh forage.

Effect of protein degradability on milk production of dairy ewes.

The objective of this experiment was to determine the effect of protein degradability of dairy sheep diets on milk yield and protein utilization across 2 levels of milk production. Three diets were formulated to provide similar energy concentrations and varying concentrations of rumen-degradable protein (RDP) and rumen-undegradable protein (RUP): 12% RDP and 4% RUP (12-4) included basal levels of RDP and RUP, 12% RDP and 6% RUP (12-6) included additional RUP, and 14% RDP and 4% RUP (14-4) included additional RDP. Diets were composed of alfalfa-timothy cubes, whole and ground corn, whole oats, dehulled soybean meal, and expeller soybean meal (SoyPlus, West Central, Ralston, IA). Estimates of RDP and RUP were based on the Small Ruminant Nutrition System model (2008) and feed and orts were analyzed for Cornell N fractions. Eighteen multiparous dairy ewes in midlactation were divided by milk yield (low and high) into 2 blocks of 9 ewes each and were randomly assigned within block (low and high) to 3 pens of 3 ewes each. Dietary treatments were arranged in a 3 x 3 Latin square within each block and applied to pens for 14-d periods. We hypothesized that pens consuming high-RUP diets (12-6) would produce more milk and milk protein than the basal diet (12-4) and pens consuming high-RDP diets (14-4) would not produce more milk than the basal diet (12-4). Ewes in the high-milk-yield square consumed more dry matter and produced more milk, milk fat, and milk protein than ewes in the low-milk-yield square. There was no effect of dietary treatment on dry matter intake. Across both levels of milk production, the 12-6 diet increased milk yield by 14%, increased milk fat yield by 14%, and increased milk protein yield by 13% compared with the 14-4 and 12-4 diets. Gross N efficiency (milk protein N/intake protein N) was 11 and 15% greater in the 12-6 and 12-4 diets, respectively, compared with the 14-4 diet. Milk urea N concentration was greater in the 12-6 diet and tended to be greater in the 14-4 diet compared with the 12-4 diet, indicating that the excretion of urea N in this study was more closely related to dietary crude protein concentration than to protein degradability.

Effect of prepartum photoperiod on milk production and prolactin concentration of dairy ewes.

Long photoperiods during established lactation increase milk production in dairy cattle and dairy sheep, but recent research in cattle and dairy goats suggests an additional influence of prepartum day length on milk yield in the subsequent lactation. The proposed mechanism of function is the level and role of circulating prolactin in mammary development. The objectives of this study were to evaluate the effect of prepartum photoperiod on milk production, milk composition, and prolactin concentration of 22 multiparous dairy ewes exposed to short day prepartum photoperiod (SDPP; 8 h of light:16 h of dark) or long day prepartum photoperiod (LDPP; 16 h of light:8 h of dark) for at least 6 wk prepartum. During the first 8 wk of lactation, SDPP ewes tended to produce more milk than LDPP ewes (2.43 vs. 2.29 kg/d, respectively), and the milk of SDPP ewes had a greater fat percentage than that of LDPP ewes (6.04 vs. 5.51%, respectively). Due to daily milk yield and greater fat content, SDPP ewes produced more 6.5% fat-corrected milk (+0.30 +/- 0.08 kg/d) and 6.5% fat- and 5.8% protein-corrected milk (+0.28 +/- 0.08 kg/d) than LDPP ewes. For the lactation period of 180 d, SDPP ewes produced more test day milk than LDPP ewes (1.76 vs. 1.60 +/- 0.05 kg/d, respectively), but there were no differences in milk fat or protein percentages. Ewes in both treatments experienced a prolactin surge at lambing, but SDPP ewes had lower circulating prolactin concentration than LDPP ewes from 4 to 0.5 wk before lambing (14.7 vs. 51.3 +/- 4.2 mg/dL, respectively). These data suggest that decreased prepartum photoperiod may be important for increasing milk production in dairy ewes and may provide a management strategy for dairy sheep producers to increase milk yield.

Effects of supplementation and stage of lactation on performance of grazing dairy ewes.

The majority of dairy sheep in the world are fed pasture and supplemental grain during lactation; however, no trials have reported the effects of supplementation of dairy ewes grazing improved pastures in North America. In trial 1, 56 three-year-old grazing dairy ewes in early [21 +/- 10 d in milk (DIM)] or late (136 +/- 9 DIM) lactation were fed 0 or 0.82 kg of dry matter/d per ewe of supplement (16.5% crude protein mixture of corn and a soybean meal-based high-protein pellet) in a 2 x 2 factorial arrangement of treatments. There were no significant interactions between stage of lactation and supplementation treatments. Average test-day milk production was higher in early-lactation ewes than in late-lactation ewes (1.74 vs. 1.21 kg/d, respectively). Although test-day milk protein percentage was higher in late-lactation ewes than in early-lactation ewes (5.02 vs. 4.86%, respectively), there was no difference in milk fat percentage between stages of lactation. Supplemented ewes had higher milk production (1.59 vs. 1.36 kg/d, respectively), lower milk fat percentage (5.75 vs. 6.00%, respectively), and lower milk protein percentage (4.84 vs. 5.04%, respectively) than unsupplemented ewes. Milk urea N levels were similar between the 2 stages of lactation and between the 2 supplementation treatments and were above recommended levels for dairy sheep, indicating an excess intake or inefficient utilization of protein for both supplementation treatments. In trial 2, 96 two-, three-, and four-year-old grazing dairy ewes in midlactation (112 +/- 21 DIM) were randomly assigned to 4 treatments of 0, 0.41, 0.82, or 1.24 kg of dry matter/d per ewe of whole corn. Average test-day milk production increased linearly and milk fat percentage decreased quadratically with increasing amounts of corn supplementation. Milk protein yield increased linearly, and milk urea N levels decreased quadratically with increasing amounts of corn supplementation, suggesting an improvement in the utilization of pasture protein with increasing dietary energy intake.

Factors affecting ewe performance in a crossbred dairy sheep research flock in the United States.

The Spooner Agricultural Research Station operated the only dairy sheep research flock in North America through 2016. The original nondairy ewe flock was "bred up" to a crossbred dairy flock through the use of rams and semen of the East Friesian (EF) and Lacaune (LA) dairy breeds. The objective of this study was to determine the environmental and nonadditive genetic effects that influence performance of dairy ewes. The traits analyzed were 180 d adjusted milk (180d MY), fat (180d FY), and protein (180d PY) yields, percentage fat (%F) and protein (%P) in milk, lactation average somatic cell score (LSCS), and number of lambs born per ewe lambing (NLB). The univariate repeatability models included the fixed effects of year of lambing, age, weaning system (except for the trait of NLB), individual breed composition, and individual retained heterosis along with the random additive genetic, permanent environmental, and residual effects. Estimates of heritability were moderate for 180d MY (0.32 ± 0.04), 180d FY (0.26 ± 0.04), and 180d PY (0.29 ± 0.04), high for %F (0.54 ± 0.04) and %P (0.61 ± 0.04), and low for LSCS (0.12 ± 0.03) and NLB (0.08 ± 0.02). Ewes that reared their lambs had lower ( < 0.01) 180d MY, 180d FY, 180d PY, %F, and %P and higher ( < 0.001) LSCS than ewes that had their lambs removed shortly after parturition. Relative to nondairy breeding, EF and LA breeding had positive ( < 0.001) effects on 180d MY, 180d FY, and 180d PY, but a negative ( < 0.03) effect on %P. Purebred EF ewes were predicted to have lower ( < 0.001) %F than purebred LA or nondairy ewes. Purebred LA ewes were predicted to have a higher ( < 0.001) LSCS than purebred EF or nondairy ewes. Purebred EF ewes were expected to be more ( < 0.001) prolific than purebred LA or nondairy ewes. Individual retained heterosis had a favorable ( < 0.01) effect on 180d MY, 180d FY, 180d PY, and NLB. Knowledge of the factors affecting dairy ewe performance are important for dairy sheep producers to make more informed husbandry and breeding decisions.

Estimates of genetic parameters, genetic trends, and inbreeding in a crossbred dairy sheep research flock in the United States.

For the past 2 decades, the Spooner Agriculture Research Station (ARS) of the University of Wisconsin-Madison operated the only dairy sheep research flock in North America. The objectives of the present study were to 1) obtain estimates of genetic parameters for lactation and reproductive traits in dairy ewes, 2) estimate the amount of genetic change in these traits over time, and 3) quantify the level of inbreeding in this flock over the last 20 yr. Multiple-trait repeatability models (MTRM) were used to analyze ewe traits through their first 6 parities. The first MTRM jointly analyzed milk (180-d-adjusted milk yield [180d MY]), fat (180-d-adjusted fat yield [180d FY]), and protein (180-d-adjusted protein yield [180d PY]) yields adjusted to 180 d of lactation; number of lambs born per ewe lambing (NLB); and lactation average test-day somatic cell score (LSCS). A second MTRM analyzed 180d MY, NLB, LSCS, and percentage milk fat (%F) and percentage milk protein (%P). The 3 yield traits were moderately heritable (0.26 to 0.32) and strongly genetically correlated (0.91 to 0.96). Percentage milk fat and %P were highly heritable (0.53 and 0.61, respectively) and moderately genetically correlated (0.61). Milk yield adjusted to 180 d was negatively genetically correlated with %F and %P (-0.31 and -0.34, respectively). Ewe prolificacy was not significantly ( > 0.67) genetically correlated with yield traits, %P, or LSCS but lowly negatively correlated with %F (-0.26). Lactation somatic cell score was unfavorably genetically correlated with yield traits (0.28 to 0.39) but not significantly ( > 0.09) correlated with %F, %P, and NLB. Within-trait multiple-trait models through the first 4 parities revealed that 180d MY, 180d FY, 180d PY, %F, and %P were strongly genetically correlated across parity (0.67 to 1.00). However, the genetic correlations across parity for NLB and LSCS were somewhat lower (0.51 to 0.96). Regressing predicted breeding values for 180d MY, without and with the addition of breed effects, on ewe year of birth revealed a positive genetic gain of 2.30 and 6.24 kg/yr, respectively, over the past 20 yr in this flock. Inbreeding coefficients of ewes with an extended pedigree ranged from 0.0 to 0.29, with an average of 0.07. To optimize genetic gains and avoid excessive inbreeding, the development of a national genetic improvement program should be a top priority for the growing dairy sheep industry.

Modelling complex survey data with population level information: an empirical likelihood approach.

Survey data are often collected with unequal probabilities from a stratified population. In many modelling situations, the parameter of interest is a subset of a set of parameters, with the others treated as nuisance parameters. We show that in this situation the empirical likelihood ratio statistic follows a chi-squared distribution asymptotically, under stratified single and multi-stage unequal probability sampling, with negligible sampling fractions. Simulation studies show that the empirical likelihood confidence interval may achieve better coverages and has more balanced tail error rates than standard approaches involving variance estimation, linearization or resampling.

Survival in crossbred lambs: Breed and heterosis effects.

The objective of this study was to estimate genetic and nongenetic effects affecting survival in crossbred lambs during 3 time periods: through 1 d of age ( = 7,933), 2 to 30 d of age ( = 5,370), and 2 to 60 d of age ( = 5,216) in a population being upgraded to the dairy breeds of East Friesian and Lacaune in which lambs were artificially reared on milk replacer. Survival was analyzed for lambs born in 14 yr from 1998 to 2011 using pedigree information from 14,339 animals born in 23 yr from 1989 to 2011. Date of death, sex, age of the dam, birth type, month and year of birth, and breed composition were recorded, and the proportion of retained heterosis was calculated for each animal. Lambs were crossbreds of 2 or more breeds with 14 breeds represented in the population. Due to low mean genetic contribution of the 12 nondairy breeds, they were placed into 2 groups: meat breeds (Hampshire, Suffolk, and Texel) and maternal breeds (Romanov, Finnsheep, Dorset, Targhee, Rambouillet, Polypay, Katahdin, Arcott Rideau, and Commercial). The proportion of individual retained heterosis was positively associated ( < 0.05) with lamb survival from 2 to 30 and from 2 to 60 d of age. The predicted increase in survival of F lambs compared to purebred lambs was +8.8 and +14.6%, respectively. Predicted survival of meat breed lambs and maternal breed lambs was greater ( ≤ 0.01) than Lacaune lambs during all 3 periods. Predicted survival of East Friesian lambs was consistently lower ( ≤ 0.01) than meat breed and maternal breed lambs during all periods. The predicted survival of East Friesian lambs was numerically greater but not significantly different from Lacaune lambs. There was a lower ( < 0.01) survival of females compared to males through 1 d of age (-5.6%), but females had higher ( < 0.01) survival than males in the other 2 periods (2 to 30 d = +3.3% and 2 to 60 d = +6.0%). Through 1 d of age, lambs of triplet and greater birth types had lower ( < 0.01) survival than single lambs (-6.2%), and lambs from 1-yr-old dams had lower ( < 0.01) survival than lambs from 2-yr-old dams (+4.5%). Estimates of heritability of lamb survival were 0.14 (SE = 0.03), 0.03 (SE = 0.04), and 0.06 (SE = 0.03) for the 3 time periods, respectively. An increase in the proportion of individual retained heterosis was the most important genetic factor associated with increased lamb survival in this study.

Absolute bioavailability of amiodarone in normal subjects.

The relative and absolute bioavailability of different oral forms of amiodarone was examined in 12 subjects. The doses were 5 mg/kg iv, two 200-mg commercial tablets by mouth, two 200-mg tablets (new formulation) by mouth, and 400 mg in a drinkable solution. Plasma levels of amiodarone and its N-desethylated metabolite were determined by HPLC. Statistical analysis indicated bioequivalence of the oral forms for all the kinetic parameters examined. After oral dosing, amiodarone was slowly absorbed and the maximum plasma level (0.55 +/- 0.20 mg/l) was reached in 4.5 hr. The absolute bioavailability of oral amiodarone was calculated by comparison of AUCs after oral dosing with those after intravenous injection. A mean oral bioavailability of 65% +/- 22% was indicated. Since the tablets were bioequivalent to the drinkable solution, incomplete absorption seems not be a result of the dissolution characteristics of the commercial formulation but rather of a first-pass effect.

Routine and quantitative EEG analysis in Gilles de la Tourette's syndrome.

Gilles de la Tourette's syndrome (GdlT) is a neurobehavioral disorder, with a reportedly high frequency of EEG abnormalities. We performed EEGs on 48 consecutive patients with GdlT, and frequency analysis in 26 patients (17 males), and compared the results with those from age- and sex-matched normal controls. Routine 18-channel EEG revealed minimal diffuse nonspecific slowing in only 3 of 48 patients (6%) and in 2 of 26 controls (7.7%). The frequency analysis of the EEG of the 26 GdlT patients and their normal controls showed similar brain activity. We conclude that no significant differences exist between the EEG activity in GdlT patients as compared with that in sex- and age-matched controls in routine as well as in quantitative EEG.

Ethylene glycol and amino acid derivatives of 5-aminolevulinic acid as new photosensitizing precursors of protoporphyrin IX in cells.

Protoporphyrin IX (PpIX) is used as a photosensitizing agent in photodynamic detection and therapy (PDT) of cancer and is synthesized intracellularly from aminolevulinic acid (ALA) precursors. To evaluate means to specifically target ALA derivatives to defined cells, we have synthesized and characterized ethylene glycol esters and amino acid pseudodipeptide derivatives of ALA as potential specific substrates for cellular esterases and aminopeptidases, respectively. The PpIX formation induced by these products was investigated using cultures of human and rat cell lines of carcinoma and endothelial origins. The cytotoxicity of these compounds in the absence of light was also controlled. The results have shown that ethylenglycol esters can induce high levels of PpIX and are useful at concentrations below their cytotoxicity threshold. From the ALA-amino acid derivatives which were evaluated, the highest PpIX production was obtained using ALA derivatives of neutral amino acids, as compared to acidic or basic amino acids.

The antiaggregating activity of clopidogrel is due to a metabolic activation by the hepatic cytochrome P450-1A.

Clopidogrel and ticlopidine are two well known selective anti-ADP agents which are inactive in vitro and must be administered in vivo to fully exhibit their antiaggregating and antithrombotic effects. Since previous studies have clearly demonstrated that the activation steps take place in the liver, we examined the effect of specific induction or inhibition of cytochrome P450 subfamilies on the antiaggregating activity of clopidogrel. SKF 525-A, a global cytochrome P450 inhibitor, dramatically decreased the antiaggregating effect of clopidogrel, therefore indicating that cytochrome P450 enzymes are involved in the hepatic activation of clopidogrel. The efficacy of clopidogrel was increased in animals pretreated with 3-methylcholanthrene and beta-naphthoflavone, indicating that the cytochrome P450-1A subfamily pathway was mainly involved in the activating metabolism of clopidogrel. The use of specific antibodies directed against the various cytochrome P450 subfamilies ascertained this observation.

Importance of the paracellular pathway for the transport of a new bisphosphonate using the human CACO-2 monolayers model.

The transport of a new bisphosphonate, Tiludronate, was investigated on the human adenocarcinoma cell line, CACO-2. Experiments were performed 7-16 days after cells achieved confluence, conditions under which they form well-differentiated monolayers joined by tight junctions. Tiludronate transport rate across CACO-2 monolayers was independent of the temperature (4 degrees versus 37 degrees), of the polarity of the cell membrane (apical-to-basolateral versus basolateral-to-apical), and of the presence of metabolic poisons (sodium azide). Its transport was enhanced by either the presence of EGTA in the incubation buffer, i.e. when extracellular Ca2+ concentration was reduced, or by the pretreatment of monolayers with EGTA, i.e. when the intercellular spaces and the tight junctions were widened. Based on these different observations, we could suggest that Tiludronate mainly used the paracellular pathway to cross the intestinal epithelium. An increase in the Tiludronate permeability coefficient was also observed following treatment of cells with high Tiludronate concentrations, as a consequence of the direct effect of this compound on the extracellular Ca2+ ions. Hence, for high drug concentrations, i.e. 20 mM, we observed a decrease in free extracellular Ca2+ concentration, an increase in the transepithelial electrical resistance and an increase in the transport of [14C]polyethyleneglycol ([14C]PEG400), a probe for the paracellular pathway. The results indicate that Tiludronate is transported across CACO-2 monolayers by the paracellular route. Moreover, it can affect its own transport by its concentration-dependent effect on tight junction widening.

Nonoperative management of bilateral shattered kidneys from blunt trauma.

Bilateral shattered kidneys secondary to blunt abdominal trauma has not, to our knowledge, been reported. In the case reported herein, severe pulmonary, myocardial, and orthopedic injuries necessitated nonoperative management of this peculiar injury. The patient recovered without sequelae related to the renal injury.