Incidence and timing of pregnancy loss following timed artificial insemination or timed embryo transfer with a fresh or frozen in vitro-produced embryo.

The aim of this study was to characterize the incidence and timing of pregnancy loss from service event (timed artificial insemination or timed embryo transfer) to parturition. Lactating Holstein-Friesian cows were randomly assigned to receive either artificial insemination (AI, n = 243) or embryo transfer (ET, n = 863) with a fresh or frozen in vitro-produced blastocyst derived from oocytes collected from the ovaries of elite dairy donors (n = 14 Holstein Friesian and n = 8 Jersey) and elite beef donors (n = 21 Angus) using transvaginal ovum pick-up. In addition, oocytes were collected from the ovaries of beef heifers of known pedigree following slaughter at a commercial abattoir (n = 119). Blood samples were collected on d 7 from all cows to determine progesterone concentration and from subsets of cows on d 18 (n = 524) and d 25 (n = 378) to determine mRNA abundance of interferon-stimulated gene-15 and pregnancy-specific protein B concentration, respectively, to provide an early pregnancy diagnosis. Transrectal ultrasonography was conducted to determine pregnancy status on d 32, d 62 and d 125 after synchronized ovulation. Parturition date was recorded for all cows that reached a term delivery. The predicted probability of pregnancy (%) varied at each time point (d7, 18, 25, 32, 62, 125, parturition) depending on treatment (AI: 77.0, 60.2, 52.3, 48.8, 47.0, 44.6, 44.0; fresh ET: 100.0, 69.5, 60.3, 56.1, 48.4, 46.8, 45.5; frozen ET: 100.0, 61.7, 52.2, 41.6, 32.9, 31.8, 30.2). Irrespective of treatment, the largest proportion of pregnancy loss occurred in the period from service event (AI on d 0 or ET on d 7) to d 18, with minimal loss occurring between d 62 and parturition (AI: 1.8%, fresh ET: 1.9%, frozen ET: 3.5%). Treatment differences in the predicted probability of pregnancy per service event were detected between fresh ET vs frozen ET on d 32 and both AI and fresh ET vs frozen ET on d 62, 125 and at parturition. There was greater probability of pregnancy loss between d 32 and 62 following ET (Fresh: 11.3%, Frozen: 18.0%) than AI (4.0%). The percentage of cows that calved following transfer of a fresh embryo (45.5%) was similar to AI (44.0%), but less when a frozen embryo was transferred (30.2%). In conclusion, AI and fresh ET led to a greater probability of a cow becoming pregnant and maintaining the pregnancy to term than frozen ET. Cows that were still pregnant on d 62 had a very strong likelihood of maintaining the pregnancy to full-term parturition, irrespective of treatment. Further work is required to improve the likelihood of pregnancy establishment and reduce embryonic and fetal mortality following transfer of a cryopreserved in vitro-produced embryo.

Associations between newly discovered polymorphisms in the Bos taurus growth hormone receptor gene and performance traits in Holstein-Friesian dairy cattle.

Variations in the growth hormone receptor (GHR) gene sequence are associated with performance traits in cattle. For example, the single nucleotide polymorphism (SNP) F279Y in transmembrane exon 8 has a strong association with milk yield. In this study, 32 previously unreported, putative novel SNPs (31 in the 5' non-coding region) were identified by resequencing ∼19 kb of the GHR gene in genomic DNA from 22 cattle of multiple breeds. A population of 848 Holstein-Friesian AI sires was subsequently genotyped for the 32 putative novel SNPs and seven published SNPs (including F279Y, one in exon 1A promoter and five in exon 10). Associations between each segregating SNP and genetic merit for performance were quantified in the 848 Holstein-Friesians using weighted animal linear mixed models. Six of the published SNPs and seven of the novel SNPs were associated with at least one of the traits--milk yield, fat yield, protein yield, fat percentage, protein percentage, somatic cell score, calving interval, survival and growth and size traits. Even when the allelic substitution effect (P < 0.001) of F279Y was accounted for, the allelic substitution effect of one of the novel SNPs (GHR4.2) in the 5' non-coding region of GHR was associated with a lactation milk yield of 37.46 kg (P < 0.001). GHR4.2 and F279Y were not in linkage disequilibrium (r(2) = 0.00, D' = 0.04) in the 848 Holstein-Friesians, indicating that their association with milk yield was independent.

Anaerobic co-digestion of pig manure and food waste; effects on digestate biosafety, dewaterability, and microbial community dynamics.

This study assessed the effect of varying pig manure (PM)/food waste (FW) mixing ratio and hydraulic retention time (HRT) on methane yields, digestate dewaterability, enteric indicator bacteria and microbial communities during anaerobic co-digestion. Three 10 L digesters were operated at 39 °C, each with a PM/FW feedstock composition of 85%/15%, 63%/37% and 40%/60% (volatile solids basis). While the PM/FW ratio was different among reactors, the organic loading rate applied was equal, and increased stepwise with reducing HRT. The effects of three different HRTs were studied: 41, 29, and 21 days. Increasing the proportion of FW in the feedstock significantly increased methane yields, but had no significant effect on counts of enteric indicator bacteria in the digestate or specific resistance to filtration, suggesting that varying the PM/FW feedstock composition at the mixing ratios studied should not have major consequences for digestate disposal. Decreasing HRT significantly increased volumetric methane yields, increased digestate volatile solids concentrations and increased the proportion of particles >500 µm in the digestate, indicating that decreasing HRT to 21 days reduced methane conversion efficiency High throughput 16S rRNA sequencing data revealed that microbial communities were just slightly affected by changes in digester operating conditions. These results would provide information useful when optimizing the start-up and operation of biogas plants treating these substrates.

Quality-of-life assessment in cancer treatment protocols: research issues in protocol development.

BACKGROUND: Interest in incorporating quality of life as an end point in clinical studies of cancer treatment has intensified in recent years. PURPOSE: We provide practical suggestions that will assist investigators considering including quality-of-life assessment in phase III therapeutic trials. METHODS: We discuss issues important in study planning, including quality-of-life definition, priority studies for quality-of-life assessment, eligibility requirements, and design. CONCLUSIONS: Many of the problems that quality-of-life studies have encountered, from protocol approval to data analysis, could be addressed and alleviated during protocol development. This discussion is intended to assist and stimulate investigators conducting research in this area.

Characterisation of the Whole Blood mRNA Transcriptome in Holstein-Friesian and Jersey Calves in Response to Gradual Weaning.

Weaning of dairy calves is an early life husbandry management practice which involves the changeover from a liquid to a solid feed based diet. The objectives of the study were to use RNA-seq technology to examine the effect of (i) breed and (ii) gradual weaning, on the whole blood mRNA transcriptome of artificially reared Holstein-Friesian and Jersey calves. The calves were gradually weaned over 14 days (day (d) -13 to d 0) and mRNA transcription was examined one day before gradual weaning was initiated (d -14), one day after weaning (d 1), and 8 days after weaning (d 8). On d -14, 550 genes were differentially expressed between Holstein-Friesian and Jersey calves, while there were 490 differentially expressed genes (DEG) identified on d 1, and 411 DEG detected eight days after weaning (P < 0.05; FDR < 0.1). No genes were differentially expressed within breed, in response to gradual weaning (P > 0.05). The pathways, gene ontology terms, and biological functions consistently over-represented among the DEG between Holstein-Friesian and Jersey were associated with the immune response and immune cell signalling, specifically chemotaxis. Decreased transcription of several cytokines, chemokines, immunoglobulin-like genes, phagocytosis-promoting receptors and g-protein coupled receptors suggests decreased monocyte, natural killer cell, and T lymphocyte, chemotaxis and activation in Jersey compared to Holstein-Friesian calves. Knowledge of breed-specific immune responses could facilitate health management practices better tailored towards specific disease sensitivities of Holstein-Friesian and Jersey calves. Gradual weaning did not compromise the welfare of artificially-reared dairy calves, evidenced by the lack of alterations in the expression of any genes in response to gradual weaning.

Characterisation of haematological profiles and whole blood relative gene expression levels in Holstein-Friesian and Jersey bull calves undergoing gradual weaning.

Haematological profiles indicate the health status of an animal and can be used to identify sub-clinical stress responses. The objectives of the study were to examine (i) the effect of breed and plane of nutrition, on haematological profiles of artificially reared Holstein-Friesian and Jersey bull calves in response to gradual weaning, and (ii) the effect of breed on immune response genes in bovine whole blood using real-time quantitative PCR. Holstein-Friesian and Jersey bull calves were group housed indoors and individually fed using an automatic feeder. They were allocated to a high, medium or low plane of nutrition, based on milk replacer (MR) and concentrate. The nutrition treatments were calculated using National Research Council guidelines in order to achieve a high, medium or low growth rate for each respective breed. During the weaning phase MR was gradually reduced over a 14-day (d) period (d -13 to d 0). Calves were blood sampled on d -14, -6, -3, 0, 1, 3, 8 and 14 relative to weaning (d 0) for subsequent haematological analysis. On d -14, 1 and 8, a subset of eight Holstein-Friesian calves randomly selected from the medium nutrition treatment and eight Jersey calves randomly selected from the high nutrition treatment, were blood sampled for gene expression profiling, targeting biomarkers of weaning stress. These two treatment groups were chosen to examine the effect of breed on expression of the genes of interest, as energy intake and animal performance were similar. There was no effect of breed×plane of nutrition interaction nor effect of plane of nutrition on any variable measured (P>0.05). Gradual weaning produced differential biological responses in the two breeds evidenced by breed×time interactions for lymphocyte, monocyte and red blood cell number, plasma haemoglobin and haptoglobin concentrations (P<0.05). The typical stress response consisting of neutrophilia and lymphopaenia was not observed for any treatment. An immune response to gradual weaning was observed as the relative gene expression level of the pro-apoptotic gene, Fas, increased on d 1 relative to d -14 (P<0.05). Relative gene expression levels were greater in Jersey calves compared with Holstein-Friesian for the pro-inflammatory cytokine CXCL8 (P=0.05) and the glucocorticoid receptor, GRα (P<0.05). The increased levels of these transcripts suggest that Jersey calves may have a more sensitive immune system compared with Holstein-Friesian.

Human rights and interviews.

Regulations from the US Department of Health, Education, and Welfare define consent in the conduct of research involving human beings. As requirements expand, these regulations have assumed considerable importance for psychiatric research, including research interviews. The author's experience with one committee on research involving human beings provided the impetus for the present report. Subjects were drawn from a prospective study of couples in a home dialysis program. Thirty couples were systematically interviewed concerning social, personal, medical, and psychiatric history. After completion of the interview, subjects were asked a series of questions concerning their feelings about being interviewed. Although most subjects found the experience to be pleasant, nearly half believed it might upset other patients. However, none believed any long-term harm could come from the conduct of the interview itself. It is therefore concluded that the potential harm of structured interviews in severely medically ill patients and their spouses is essentially nil.

Reactive psychoses and schizophrenia with good prognosis.

Cross-national studies have indicated that American psychiatrists diagnose schizophrenia more often than others. Clinical, genetic, and follow-up studies suggest that many patients diagnosed as having acute schizophrenia might be more appropriately diagnosed as having affective disorder. Forty probands diagnosed in Aarhus, Denmark, as having reactive psychoses are compared with 28 probands diagnosed in St Louis as having schizophrenia with good prognosis. Clinical differences largely reflect diagnostic criteria, with the patients from the St Louis group frequently having diagnosable affective disorder. A smaller proportion, 39% of the patients from St Louis, could be considered for the diagnosis of reactive psychosis. This is additional evidence supporting the use of the diagnostic category, reactive psychoses. Patients ordinarily given the diagnoses acute schizophrenic episode and/or schizo-affective schizophrenia may be more appropriately diagnosed as having (1) affective disorder and (2) reactive psychoses.

Reactive psychoses. A family study.

Reactive, or psychogenic, psychoses have been given the most attention in the literature by Scandinavian investigators. We defined diagnostic criteria for reactive psychoses emphasizing differences with manic-depressive psychoses and schizophrenia. Forty Danish probands were selected and family history data was obtained by personal interview and record review. In order to compare our results with other investigations, we age corrected family history data. Siblings of reactive probands were found to have significantly more reactive psychoses than siblings of manic-depressives or schizophrenics, and significantly less schizophrenia than siblings of schizophrenics. Although there was some genetic overlap with manic-depressive psychosis, we believe that the findings are sufficiently distinct to warrant the separate diagnostic category of reactive psychoses.

ECT versus chlorpromazine in mania.

The efficacy of ECT in the treatment of depression is well recognized. In mania its efficacy is less well acknowledged. This report compares ECT, chlorpromazine, and no active treatment in mania. Twenty-eight control patients diagnosed as manic were selected from consecutive admissions to the University of Iowa Psychiatric Hospital in the period 1935-1941 when there was no active treatment given. Twenty-eight patients treated with ECT were selected from the period 1945-1949, and 28 chlorpromazine-treated patients were selected from the period 1958-1964. Symptoms sufficient to fulfill a research diagnosis of mania had to be documented in the record for all patients. Results compare symptomatology, duration of hospital admission, discharge condition, discharge category, social recovery, and follow-up. Both ECT and chlorpromazine were superior to no active treatment for outcome measures considered. Ten chlorpromazine-treated patients did not respond satisfactorily to the chlorpromazine treatment but recovered with ECT treatment.

Nursing management of the patient receiving Taxol therapy.

Taxol is an important new antitumor agent with demonstrated efficacy in ovarian and breast cancer. Toxicities identified, including cardiac, hypersensitivity reactions, and neurologic, require careful nursing assessment for management, Additional toxicities may be identified as Taxol is combined with other chemotherapeutic agents. Studies to determine the most effective dose and schedule are ongoing. The current evaluation of this new drug presents an important opportunity for nurses to contribute to its development through both clinical and research endeavors. Such contributions will facilitate the optimal nursing care of patients treated with Taxol.

ECT in the treatment of mania: a controlled study.

In a chart review study of manic patients, the author found that ECT remarkably improved outcome variables of condition at discharge, duration of hospitalization, and social recovery in comparison with an untreated matched control group. More conclusive evidence would depend on a prospective trial with random assignment of manic patients to ECT, lithium carbonate, and major tranquilizers and blind evaluation of outcome.

Psychiatric illness and human renal transplantation.

This study focuses on physiological as well as psychological causes for psychiatric illness in renal transplant recipients. During an 18 month period 20 transplant recipients were evaluated in psychiatric consultation. A variety of psychiatric illnesses were noted with eight having a secondary depression diagnosed according to psychiatric research criteria. Case histories of these patients indicated that corticosteroid and meythyldopa therapy were significant etiologic agents in the development of the depressive syndrome. A step-wise approach to the management of patients with depressed mood or slowed thinking was proposed.

Detection of single-copy genes in DNA from transgenic plants by nonradioactive Southern blot analysis.

Improvements to the sensitivity, speed, and reproducibility of digoxigenin (DIG)-labeled probes and chemiluminescent substrates makes these compounds increasingly popular to detect nucleic acids. High sensitivity and low background are essential in Southern blot analysis, particularly with plant DNA. This article describes a nonradioactive system to detect single-copy genes in transgenic plants. Labeling using the polymerase chain reaction (PCR) was employed to produce highly sensitive and reusable DIG-labeled probes. The background was reduced by immobilizing the DNA onto nylon filters by alkaline transfer and by minimized gel handling; the signal-to-noise ratio was improved by modification of the detection procedure.

Psychological support for the patient on chemotherapy.

The benefits of chemotherapy are frequently accompanied by side effects that can cause significant toxicity. Specific aspects of treatment contribute to the patient's psychological distress and should be identified by care-givers. Practical support interventions are possible and include both prevention and management techniques. Such strategies should be used in an ongoing manner as part of the professional relationship with the patient and may be enhanced by the inclusion of outside resources.

Building quality of life assessment into cancer treatment studies.

Quality of life is increasingly recognized as an important outcome of cancer treatment. However, quality of life research poses considerable problems in design and implementation. This article provides guidelines for the preparation of phase III therapeutic protocols that include quality of life assessment. The guidelines emphasize the distinct requirements of quality of life research and provide specific recommendations for the questions that need to be addressed in protocol development.

The ethical context of healthcare reform.

The purpose of this article is to provide a summary discussion of healthcare reform, frame it in an ethical context, and present the necessity for oncology nurses to consider the important ethical considerations that accompany any decisions for change. The resulting implications for oncology nursing are presented with recommendations that the issues of healthcare reform be incorporated into oncology nursing research, clinical practice, administration, and education. All components of the profession have a contribution to make as proposals for change move from public debate to the enactment of national initiatives.

Reimbursement of biotherapy: present status, future directions--perspectives of the hospital-based oncology nurse.

Cancer is a set of diseases that affects one in four Americans and which is too often fatal. For many types of cancer, there is no fully satisfactory treatment. Therefore, investigational therapy provided in a formal, peer-reviewed clinical trial can present the best available treatment for patients with life-threatening malignancies. At a time when clinical cancer research is at a particularly promising point and multiple new biologics are on the horizon, the traditional partnership of the federal government, the pharmaceutical industry, private institutions, and insurers is threatened. The issue of increasing concern is the impact of changes in third-party reimbursement policy on cancer clinical investigation. Although its incidence, magnitude, and geographic distribution have not been specifically defined, this issue is generating serious concern and intense national debate. The growing denials of patient-care costs related to clinical trials serve to threaten patient access to potentially efficacious therapy. The implications of this reimbursement issue are tremendous for both clinical investigation and patient care. The refusal to pay for patient-care costs related to investigational therapy may adversely influence clinical trial design and will certainly affect the speed with which new therapies are developed. When insurers refuse to cover these clinical costs, only affluent individuals have access to the most promising treatments. Nursing actions can positively affect the reimbursement debate. Nurses must develop cost-efficient plans of care and the means to evaluate their effectiveness. Educating patients about and assisting them with reimbursement issues maximizes their prospects for receiving appropriate investigational therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

The ethical foundation of informed consent in clinical research.

OBJECTIVES: To provide a foundation for understanding the ethical concept of informed consent with particular emphasis on the characteristics and principles that make it a moral imperative. DATA SOURCES: Government reports, published articles, and book chapters from the ethics literature. CONCLUSIONS: Informed consent is central to the conduct of cancer clinical trials and good patient care. It is a thoughtful, collaborative process whereby an individual gives autonomous authorization and the decision of the individual is respected by the health professionals. IMPLICATIONS FOR NURSING PRACTICE: Understanding the theory and practice of informed consent is an essential aspect of the nurses role. There are many challenges to this process in the oncology setting because of the severity of the diseases and the complexity of the research, and nurses must be prepared to assure that informed decision-making takes place.

Efforts to recruit the economically disadvantaged to national clinical trials.

Clinical trials are vital for the development of state-of-the-art cancer prevention and treatment. A goal for trial recruitment should be to have a representative sample of the total population by gender, race, culture, ethnicity, and socioeconomic status as appropriate. Increased sensitivity to the unique barriers and access to care issues required to achieve a representative sample are necessary. Knowledge and understanding of recruitment problems and strategies to resolve them are developing; however, much more is needed before we can fully address and resolve all of the relevant issues. Nurses have a key role in identification, education, and recruitment of special populations including the SED to clinical trials.