Unusual coordination mode for 1,3-diphosphete ligands towards a Cr-Cr quintuple bond complex.

The reaction of LCr5̲CrL (L = N2C25H29, 1) with the phosphaalkynes R-C≡P (R = tBu, Me, Ad) yields the neutral dimerisation compounds [L2Cr2(µ,η1:η1:η2:η2-P2C2R2)] (R = tBu (2), Me (3)) and the tetrahedrane complex [L2Cr2(µ,η2:η2-PCAd)] (4). The 1,3-diphosphete ligands in complexes 2 and 3 are the first to possess this structural feature spanned over a metal-metal multiple bond, while the slightly bigger adamantyl phosphaalkyne remains a monomer in 4 with a side-on coordination mode.

Genetic analyses of metabolic body weight, carcass weight and body conformation traits in Nordic dairy cattle.

Improving feed efficiency in dairy cattle by animal breeding has started in the Nordic countries. One of the two traits included in the applied Saved feed index is called maintenance and it is based on the breeding values for metabolic BW (MBW). However, BW recording based on heart girth measurements is decreasing and recording based on scales is increasing only slowly, which may weaken the maintenance index in future. Therefore, the benefit of including correlated traits, like carcass weight and conformation traits, is of interest. In this study, we estimated genetic variation and genetic correlations for eight traits describing the energy requirement for maintenance in dairy cattle including: first, second and third parity MBW based on heart girth measurements, carcass weight (CARW) and predicted MBW (pMBW) based on predicted slaughter weight, and first parity conformation traits stature (ST), chest width (CW) and body depth (BD). The data consisted of 21329 records from Finnish Ayrshire and 9780 records from Holstein cows. Heritability estimates were 0.44, 0.53, 0.56, 0.52, 0.54, 0.60, 0.17 and 0.26 for MBW1, MBW2, MBW3, CARW, pMBW, ST, CW and BD, respectively. Estimated genetic correlations among MBW traits were strong (>0.95). Genetic correlations between slaughter traits (CARW and pMBW) and MBW traits were higher (from 0.77 to 0.90) than between conformation and MBW traits (from 0.47 to 0.70). Our results suggest that including information on carcass weight and body conformation as correlated traits into the maintenance index is beneficial when direct BW measurements are not available or are difficult or expensive to obtain.

General and selective deoxygenation by hydrogen using a reusable earth-abundant metal catalyst.

Chemoselective deoxygenation by hydrogen is particularly challenging but crucial for an efficient late-stage modification of functionality-laden fine chemicals, natural products, or pharmaceuticals and the economic upgrading of biomass-derived molecules into fuels and chemicals. We report here on a reusable earth-abundant metal catalyst that permits highly chemoselective deoxygenation using inexpensive hydrogen gas. Primary, secondary, and tertiary alcohols as well as alkyl and aryl ketones and aldehydes can be selectively deoxygenated, even when part of complex natural products, pharmaceuticals, or biomass-derived platform molecules. The catalyst tolerates many functional groups including hydrogenation-sensitive examples. It is efficient, easy to handle, and conveniently synthesized from a specific bimetallic coordination compound and commercially available charcoal. Selective, sustainable, and cost-efficient deoxygenation under industrially viable conditions seems feasible.

Risk aversion affects economic values of blue fox breeding scheme.

The profit and production of an average Finnish blue fox farm was simulated using a deterministic bio-economic farm model. Risk was included using Arrow-Prat absolute risk aversion coefficient and profit variance. Risk-rated economic values were calculated for pregnancy rate, litter loss, litter size, pelt size, pelt quality, pelt colour clarity, feed efficiency and eye infection. With high absolute risk aversion, economic values were lower than with low absolute risk aversion. Economic values were highest for litter loss (18.16 and 26.42 EUR), litter size (13.27 and 19.40 EUR), pregnancy (11.99 and 18.39 EUR) and eye infection (12.39 and 13.81 EUR). Sensitivity analysis showed that selection pressure for improved eye health depended strongly on proportion of culled animals among infected animals and much less on the proportion of infected animals. The economic value of feed efficiency was lower than expected (6.06 and 8.03 EUR). However, it was almost the same magnitude as pelt quality (7.30 and 7.30 EUR) and higher than the economic value of pelt size (3.37 and 5.26 EUR). Risk factors should be considered in blue fox breeding scheme because they change the relative importance of traits.

Serotonergic activation of locomotor behavior and posture in one-day old rats.

The purpose of this study was to determine what dose of quipazine, a serotonergic agonist, facilitates air-stepping and induces postural control and patterns of locomotion in newborn rats. Subjects in both experiments were 1-day-old rat pups. In Experiment 1, pups were restrained and tested for air-stepping in a 35-min test session. Immediately following a 5-min baseline, pups were treated with quipazine (1.0, 3.0, or 10.0 mg/kg) or saline (vehicle control), administered intraperitoneally in a 50 µL injection. Bilateral alternating stepping occurred most frequently following treatment with 10.0 mg/kg quipazine, however the percentage of alternating steps, interlimb phase, and step period were very similar between the 3.0 and 10.0 mg/kg doses. For interlimb phase, the forelimbs and hindlimbs maintained a near perfect anti-phase pattern of coordination, with step period averaging about 1s. In Experiment 2, pups were treated with 3.0 or 10.0 mg/kg quipazine or saline, and then were placed on a surface (open field, unrestrained). Both doses of quipazine resulted in developmentally advanced postural control and locomotor patterns, including head elevation, postural stances, pivoting, crawling, and a few instances of quadrupedal walking. The 3.0 mg/kg dose of quipazine was the most effective at evoking sustained locomotion. Between the 2 experiments, behavior exhibited by the rat pup varied based on testing environment, emphasizing the role that environment and sensory cues exert over motor behavior. Overall, quipazine administered at a dose of 3.0 mg/kg was highly effective at promoting alternating limb coordination and inducing locomotor activity in both testing environments.

Breeding for better eye health in Finnish blue fox (Vulpes lagopus).

The frequency of eye infections in the Finnish blue fox population has increased during the past decade. Eye infection may incur economic losses to producers due to reduced selection intensity, but ethical aspects need to be considered as well because eye infection can be quite painful and reduce animal well-being. The purpose of this study was to determine the potential for genetic selection against susceptibility to eye infection. The data were collected from 2076 blue foxes at the MTT fur animal research station. Genetic parameters were estimated using single- and multiple-trait animal models. The heritability estimate for eye infection was analysed as a binary trait (EYE) and was moderate (0.24 ± 0.07). EYE had a moderate antagonistic genetic correlation (-0.49 ± 0.20) with grading density (thick underfur). The genetic correlation of EYE with grading size or body condition score was estimated without precision, but all size traits had a low antagonistic phenotypic correlation with EYE. Our results suggest that there is genetic variance in susceptibility to EYE, indicating that eye health can be improved through selection. The current recommendation is that the sick animals should be culled immediately. If more efficient selection is needed, the selection index and multiple-trait animal models can be applied in breeding for better eye health.

Genetic parameters of pelt character, feed efficiency and size traits in Finnish blue fox (Vulpes lagopus).

Pelt character traits (size, quality, colour clarity, darkness) are important economic traits in blue fox breeding. Better feed efficiency (FE) is another economically important and new breeding goal for fur animals. The purpose of this study was to determine the correlations between pelt character traits, FE and size traits and to estimate genetic parameters for pelt character traits. Pelt size (pSIcm ) had a high positive genetic correlation with animal grading size (gSI), final body weight (BWFin), body length and daily gain (DG), and a moderate correlation with body condition score (BCS). Animal body length and BCS (describing fatness) were considered as genetically different traits. Genetic correlations between pelt quality and size traits were estimated without precision and did not differ from zero, but colour clarity (pCL) had a low antagonistic genetic correlation with FE. Pelt size and DG had a favourable genetic correlation with FE but a fairly high unfavourable genetic correlation with dry matter feed intake. The current emphasis on selection for larger animal and pelt size improves FE indirectly, but selection for larger pelt size favours fast-growing and fat individuals and simultaneously increases feed intake. The detected genetic connections between FE, size, feed intake and pCL should be taken into account in the Finnish blue fox breeding programme.

Effect of linseed cake supplementation on digestibility and faecal and haematological parameters in dogs.

The experiment was conducted with a 6 x 4 cyclic changeover design. Six adult Alaskan huskies were assigned to diets containing 0%, 2%, 4%, 6% and 8% linseed cake. A linear decrease in the apparent digestibilities of organic matter (OM) (p < 0.020), ether extract (EE) (p < 0.003), neutral detergent fibre (p < 0.015), nitrogen-free extract (NFE) (p < 0.001) and crude carbohydrates (p < 0.001) was noted. Digestibilities of dry matter (DM) and crude protein (CP) were unaffected by the treatment. Wet weight of faeces increased (p < 0.001) and DM of faeces decreased (p < 0.001) linearly as the percentage of dietary linseed cake increased. Serum cholesterol concentration tended to decrease (p = 0.094) as the proportion of linseed cake increased. Apparent OM, EE, CP and NFE digestibility coefficients for linseed cake were 52%, 77%, 54% and 37%, respectively, and the digestible energy (DE) value was 13.22 MJ/kg DM. Our results showed that working and racing dogs fed the extruded and kibbled diet can utilize up to 4.2% linseed cake of diet DM as a fibre source without severe reductions in nutrient digestibility or feed consumption. Even higher levels of linseed cake, up to 8.5% of diet DM, can be used for normal or obese dogs, but more faeces will be excreted.

[Me3SiN(PPh3)-ICN]: a new labile donor-acceptor complex.

The reaction behavior of trimethylsilyl phosphanimine, Me3SiNPPh3, toward the pseudohalogen species XCN (X = Cl, Br, and I), especially the intermediate formation of [Me3SiN(PPh3)-XCN] adduct complexes, was investigated in solution. Only the ICN adduct was shown to be metastable in solution, with respect to further reaction into Ph3PNCN and Me3SiX, and can be intercepted. Raman and X-ray data of the ICN adduct revealed a very labile donor-acceptor complex with the iodine atom of the ICN moiety loosely bound to the nitrogen atom of Me3SiNPPh3. There are two distinct rather long N...I bonds with bond lengths of 2.634(1) and 2.739(14) A. The structure and bonding are discussed on the basis of natural bond orbital analysis and valence bond considerations.

Lanthanide-mediated ligand transfer reactions--a route to late transition metal bisamido complexes.

The reaction of [[O(SiMe2Ap)2)2LnLi(thf)n] 1 (Ln = Nd, n= 2) and 2 (Ln = La, n = 3) in hexane with [(dme)NiCl2] (dme = dimethoxyethane) and [(cod)PtCl2] (cod = 1,5-cyclooctadiene) leads to the dimeric Ni complex [[O(SiMe2Ap)2]2Ni2] (3) and the mononuclear platinum compound [O(SiMe2Ap)2Pt] (4). respectively (O(SiMe2ApH)2 = bis(4-methyl-2-pyridylamino)tetramethyldisiloxane). Compounds 3 and 4 have been characterized by X-ray crystal structure analysis. The ligand-transfer reactions probably proceed via heterobimetallic intermediates. A model complex of such an intermediate [[O(SiMe2Ap)2)2NdPdMe] (7) was isolated by reacting 1 with [(cod)PdMeCl]. Applications of complex 3 in ethylene oligomerization were investigated. Highly branched oligomers with a very narrow molecular weight distribution (Mn =230 gmol(-1) (relative to polystyrene standards), Mw/M= 1.14) are produced when Et3Al2Cl3 is employed as a co-catalyst and CH2Cl2 as the solvent (TOF = 122000 h(-1). Treatment of one equivalent of 1 or 2 with two equivalents of [(cod)CuCl] results in the formation of the polycyclic tetranuclear complex [[O(SiMe2Ap)2]2Cu4] (8). An X-ray crystal structure analysis of 8 shows channels formed by a series of fourteen-membered rings in the solid state.

Synthesis and structural characterization of novel silenes stabilized by intramolecular coordination of a dialkylamino group.

Two intramolecularly donor-stabilized silenes, 1-(8-dimethylamino-1-naphthyl)-1,2,2-tris(trimethylsilyl)silene (6a) and 1-(2-dimethylaminomethylphenyl)-1,2,2-tris(trimethylsilyl)silene (6b), were synthesized according to a novel one-step process by the reaction of (dichloromethyl)tris(trimethylsilyl)silane (1) with a twofold molar excess of 8-dimethylamino-1-naphthyllithium or 2-(dimethylaminomethyl)phenyllithium, respectively. Compounds 6a and 6b are thermally stable compounds. X-ray structural analyses of both silenes revealed strong donor-acceptor interactions between the dialkylamino groups and the electrophilic silene silicon atoms (Si-N distances: 6a: 1.751(3) A; 6b: 1.749(3) A) that lead to pyramidalization at the silicon centers. In contrast, the configuration at the silene carbon atoms was found to be planar. The Si=C distances (6a: 1.751(3) A; 6b: 1.749(3) A) fit with literature data of comparable compounds. Addition of water or methanol to the Si=C bonds of 6a,b afforded the silanols 7a,b and the methoxysilanes 8a,b, respectively. The compound 1-(8-dimethylaminomethyl-1-naphthyl)-1,2,2-tris(trimethylsilyl)silene (6c), generated following the same procedure by the reaction of 1 with 8-(dimethylaminomethyl)-1-naphthyllithium (molar ratio 1:2) proved to be unstable at room temperature and underwent rapid insertion of the Si=C group into a methylene C-H bond of the dimethylaminomethylnaphthyl ligand to afford the 1-silaacenaphthene 9.

Highlights in the Renaissance of Amidometal Chemistry.

Turning a disadvantage to an advantage: The rather disappointing reactivity of the metal - nitrogen bond in comparison to the metal - carbon bond resulted in the neglect of amidometal chemistry after its heyday at the end of the 1960s and beginning of the 1970s. Today it is precisely this disadvantage which is being applied through the use of amido ligands to produce inert complex fragments with well-defined reaction centers. In this way the chemistry of the early transition metals has been markedly enriched, and interesting alternatives to the classically regarded cyclopentadienyl ligands are now available.

Extrafamilial sexual abuse: treatment for child victims and their families.

OBJECTIVES: To decrease the emotional distress of child victims of extrafamilial sexual abuse (ESA) and their families. To provide crisis intervention, individual and group treatment in response to an expressed need in the community. To pilot the use of group treatment for child victims of ESA under age 10. METHOD: This discussion describes intervention with a sample of 246 child victims, ages 2-14 years, and 323 parents who participated in the program from 1984 to 1991. This pilot project operated at a university medical facility and was located off campus in an outpatient child abuse center. Priority was given to child victims under age 7. Child victims and their families were evaluated after investigative interviews by law enforcement agencies were completed. A treatment plan was developed based on clinical assessment. Families participated in crisis counseling, individual treatment for the child victim and/or parent, Children's Treatment Groups, Parent Support Groups, or were referred to other resources. Clinical assessment of treatment progress included weekly case review by child and parent therapists, video analysis and observation of Children's Treatment Group sessions, consultation with parents and collateral contacts. RESULTS: A family approach and services for parents in addition to intervention for child victims were determined to be key components in facilitating recovery. Clinical observations and client feedback showed positive outcomes for child victims and parents with crisis counseling, Children's Treatment groups, and Parent Support Groups. The extent of intervention ranged from one session to 24 months with an average participation of 6-9 months. Follow up surveys were returned by parents for 48 child victims and results are reported. Themes, parallels in responses, and recovery factors for child victims and parents are discussed. CONCLUSIONS: The need for intervention and a community-based program was demonstrated by (1) the significant disruption in functioning that occurred for child victims of ESA and their families, (2) the risk for long term sequelae, (3) the high incidence of extrafamilial sexual abuse, and 4) the consistent, large number of requests for services. Family-centered crisis services, Children's Treatment Groups, and Parent Support Groups can be effectively based at child advocacy centers, out patient care clinics, or other community agencies. The results of formal outcome measures and longitudinal studies is needed to determine how child victims and parents benefit from specific treatment modalities and to better guide the use of limited resources.

Intravenous itasetron: establishing the effective dose range for the prophylactic control of acute emesis in cancer patients undergoing high-dose cisplatin chemotherapy.

Nausea and vomiting induced by chemotherapy are a major cause of distress to patients and reduce compliance with potentially beneficial treatment. Itasetron hydrochloride is a new 5-hydroxytryptamine3 (5-HT3) antagonist with potent antiemetic properties. It is more potent than ondansetron in animal models and in early clinical studies it demonstrates a long half-life and does not undergo hepatic biotransformation before elimination. The aim of this open, uncontrolled study was to establish the effective dose range of itasetron hydrochloride given intravenously (i.v.) to patients due to receive high-dose cisplatin chemotherapy (50-120 mg/m2) for the first time. Thirty-nine patients were enrolled in the trial and received a single i.v. infusion of itasetron hydrochloride at a dose of 17-280 microg/kg body weight before commencing the cisplatin infusion (median dose 90-110 mg/m2). Antiemetic protection was demonstrated by doses in the range of 35-280 microg/kg. The 17 microg/kg dose was not effective. Treatment failure (>5 emetic episodes/24 hours) was reported in only six (16%) of the 38 evaluable patients over all treatment groups. Adverse events were generally mild or moderate and of a similar type and incidence to those of current 5-HT3 antagonists. Physicians' and patients' assessments of efficacy and tolerability of itasetron hydrochloride were similar, the majority rating the treatment as 'good' or 'very good'. In conclusion, itasetron hydrochloride is effective in the dose range 35-280 microg/kg in preventing cisplatin-induced emesis. Taken together with results from a larger dose-finding study, a dose corresponding to 35 microg/kg (equivalent to 2.5 mg itasetron, calculated as free base) has been pursued in Phase III studies with the i.v. formulation.

Immunotherapy of metastatic malignant melanoma by a vaccine consisting of autologous interleukin 2-transfected cancer cells: outcome of a phase I study.

We performed a phase I trial to evaluate the safety and tolerability of repeated skin injections of IL-2-transfected autologous melanoma cells into patients with advanced disease. Cell suspensions, propagated from excised metastases, were IL-2 gene transfected by adenovirus-enhanced transferrinfection and X-irradiated prior to injection. Vaccine production was successful in 54% of the patients. Fifteen patients (37%) received two to eight skin vaccinations of either 3 x 10(6) (intradermal) or 1 x 10(7) (half intradermal, half subcutaneous) transfected melanoma cells per vaccination (secreting 140-17,060 biological response modifier program units of IL-2/10(6) cells/24 hr). Analyses of safety and efficacy were carried out in 15 and 14 patients, respectively. Overall, the vaccine was well tolerated. All patients displayed modest local reactions (erythema, induration, and pruritus) and some experienced flu-like symptoms. Apart from newly appearing (4 of 14) and increasing (5 of 14) anti-adenovirus and newly detectable anti-nuclear antibody titers (1 of 15), recipients developed de novo or exhibited increased melanoma cell-specific delayed-type hypersensitivity (DTH) reactions (8 of 15) and vitiligo (3 of 15) and showed signs of tumor regression (3 of 15). This supports the idea of a vaccine-induced or -amplified anti-cancer immune response. None of the patients exhibited complete or partial regressions, but five of them experienced periods of disease stabilization. Three of these individuals received more than the four planned vaccinations and their mean survival time was 15.7 +/- 3.5 months as compared to 7.8 +/- 4.6 months for the entire patient cohort. These data indicate that IL-2-producing, autologous cancer cells can be safely administered to stage IV melanoma patients and could conceivably be of benefit to patients with less advanced disease.

Genetic parameters for the milk coagulation properties and prevalence of noncoagulating milk in Finnish dairy cows.

The genetic parameters were estimated for milk coagulation properties and milk production traits, and the prevalence of noncoagulating milk in the Finnish dairy cattle population was investigated. Data were included for 789 Finnish Ayrshire cows and 86 Finnish Friesian cows from 51 herds. The animal model used for estimation included fixed effects for parity, stage of lactation, breed, and herd. Further, effects of milk protein genotypes on phenotypic and genetic variation in the studied traits were examined. Heritability estimates for the milk coagulation properties were moderately high. The kappa-casein B allele was associated with the best phenotypic and genetic values for curd firmness, and the A and E alleles were associated with the poorest. About 24% of the additive genetic variation in the curd firmness was due to milk protein polymorphism. About 8% of the Finnish Ayrshire cows in the present study produced noncoagulating milk. Because of the occurrence of the noncoagulating milk and a possibly unfavorable genetic trend in the milk coagulation properties, it would be important to improve these traits in the Finnish Ayrshire breed. Milk coagulation properties could be improved directly by selecting for these traits or indirectly by favoring the kappa-casein B allele or by selecting against genetic markers associated with poorly coagulating or noncoagulating milk.

Comparison of oral itasetron with oral ondansetron: results of a double-blind, active-controlled phase II study in chemotherapy-naive patients receiving moderately emetogenic chemotherapy.

Itasetron hydrochloride is a new 5-hydroxytryptamine3 (5-HT3) antagonist. Experimental investigations show that orally it is rapidly absorbed (about 90 min), is highly bioavailable (greater than 90%), has a long half-life (about 12 h) and is more potent (about 10 times) in animal models than ondansetron, currently standard therapy for the prophylactic control of chemotherapy induced nausea and vomiting. This paper describes the results of a study designed to assess the efficacy and tolerability of five (0.5, 1, 2, 4 and 8 mg) twice-daily doses of itasetron hydrochloride, in comparison with 8 mg b.i.d. ondansetron. Assessments were made in patients (n = 104) with histologically confirmed cancer (excluding head and neck tumors) and about to receive their first course of moderately emetogenic chemotherapy. Itasetron hydrochloride demonstrated comparable efficacy to ondansetron; no statistically significant between-group differences were observed in the primary (complete response rate) or secondary (nausea and delayed emesis) efficacy criteria. Adverse events were similar in type and incidence across all treatment groups, and were those expected for this therapeutic class. The tolerability of itasetron hydrochloride was assessed as 'very good' or 'rather good' by 81% of patients and 89% of physicians. In conclusion, itasetron hydrochloride is effective and well tolerated in patients receiving moderately emetogenic chemotherapy. Oral doses of 1 mg b.i.d. or above will be used in further clinical studies.

A therapeutic preschool for abused children: the KEEPSAFE Project. Kempe Early Education Project Serving Abused Families.

Twenty-four children attended a therapeutic preschool for physically and sexually abused children, the Kempe Early Education Project Serving Abused Families (KEEPSAFE), over a 3-year period from 1985-1988. The program provided early education and therapy for abused children so that they could improve developmentally, socially, and emotionally, with the aim that the children would be suitable to enter the public education system. The therapeutic preschool was combined with a home visitation program for the child's parents or primary caretaker, focusing on improving the quality of interaction between the adult and child. The majority of children made developmental gains at a faster rate than would normally be expected as measured by the McCarthy Scales of Children's Abilities and the Peabody Picture Vocabulary Test. Although all 24 children were thought at onset of intervention to be unable to participate in a public school setting, after 12 months in the program over 79% were staffed into the public school system eight (33.3%) into a regular classroom. Three others (12.5%) needed residential care, and two were too young to enter public school. Even though a therapeutic preschool is expensive in terms of the high staff to child ratio needed, it is likely to be beneficial in improving the developmental skills of abused children.