Personal Computing in the 1990s

Personal computers have changed the way that business is conducted in today\u27s office. Every position in a company is affected by the use of personal computers from secretaries to top level management. Tasks and job duties are performed more easily thereby increasing productivity. Personal computers in the 1990s will be networked via LANs to other personal computers, minicomputers and mainframes to enhance people\u27s abilities and allow them to perform their jobs better. With the increased use of LANs, many LAN productivity applications wUl be utilized that will also increase productivity. E-Mail and groupware software will allow people to interact with each other without leaving their offices. These systems will reduce the amount of needless paperwork and time spent in meetings. The 1990s will also see an increase in the use of portable computers because of the small size and increased expansion capabilities, making it easy for users to tap into the network. These portables will allow employees to work at home and transmit any data to the office. Also, these portables will increase the productivity of many field applications. With the new advancements in personal computing, managers in the 1990s will need to understand these PC-based systems and how they impact individuals in the workplace

Antiretroviral therapy in a community clinic - early lessons from a pilot project

Objectives. To report on operational and clinical problems encountered during the first 6 months of a community-based antiretroviral therapy (ART) programme. Methods. ART was implemented in a primary care setting utilising an easily replicable service-delivery model based on a medical officer and nurse. Therapeutic counsellors, themselves HIV-infected, provided counselling and adherence support. Drug and monitoring costs were charitably funded and provincial health authorities supplied the medical infrastructure. The HIV Research Unit, University of Cape Town, supplied training and additional clinical support. Local HIV primary care clinics provided patient referrals. Standardised ART regimens were used with strict entry criteria (AIDS or CD4 count < 200 cells/µl). Results. Demand for the service was high. Referred patients had advanced disease (AIDS 57%, median CD4 count 96/µl) and high pre-treatment mortality (83/100 person-years). Mycobacterial disease was a major contributor to this mortality (40%). Scheduled clinic visit hours were six times higher during recruitment than maintenance. Attributable costs were: drugs 61%, staff 27%, viral load and CD4 cell counts 10% and safety monitoring 2%. Viral load after 16 weeks of therapy was < 400 copies/ml in the first 16 patients. Conclusions. ART can be successfully implemented within a primary care setting. Drug purchases and staff salaries drive programme costing. The service model is capable of managing 250 - 300 patients on chronic ART, but staffing needs to be increased during recruitment. Attention must be given to the diagnosis of tuberculosis during screening and early ART. Incorporating therapeutic counsellors into the programme increased community involvement and utilised a valuable and previously untapped resource

The role of transforming growth factor-beta (TGF-beta) during ovarian follicular development in sheep

BACKGROUND: Recently, several members of the transforming growth factor-beta (TGF-beta) superfamily have been shown to be essential for regulating the growth and differentiation of ovarian follicles and thus fertility. METHODS: Ovaries of neonatal and adult sheep were examined for expression of the TGF-betas 1–3 and their receptors (RI and RII) by in situ hybridization using ovine cDNAs. The effects of TGF-beta 1 and 2 on proliferation and differentiation of ovine granulosa cells in vitro were also studied. RESULTS: The expression patterns of TGF-beta 1 and 2 were similar in that both mRNAs were first observed in thecal cells of type 3 (small pre-antral) follicles. Expression of both mRNAs continued to be observed in the theca of larger follicles and was also present in cells within the stroma and associated with the vascular system of the ovary. There was no evidence for expression in granulosa cells or oocytes. Expression of TGF-beta 3 mRNA was limited to cells associated with the vascular system within the ovary. TGFbetaRI mRNA was observed in oocytes from the type 1 (primordial) to type 5 (antral) stages of follicular growth and granulosa and thecal cells expressed this mRNA at the type 3 (small pre-antral) and subsequent stages of development. The TGFbetaRI signal was also observed in the ovarian stroma and vascular cells. In ovarian follicles, mRNA encoding TGFbetaRII was restricted to thecal cells of type 3 (small pre-antral) and larger follicles. In addition, expression was also observed in some cells of the surface epithelium and in some stromal cells. In granulosa cells cultured for 6 days, both TGF-beta 1 and 2 decreased, in a dose dependent manner, both the amount of DNA and concentration of progesterone. CONCLUSION: In summary, mRNA encoding both TGF-beta 1 and 2 were synthesized by ovarian theca, stroma and cells of the vascular system whereas TGF-beta 3 mRNA was synthesized by vascular cells. Luteinizing granulosa cells also responded to both TGF-beta 1 and beta 2 in vitro. These findings in sheep are consistent with TGF-beta potentially being an important autocrine regulator of thecal cell function and possibly a paracrine regulator of ovarian cell function at various development stages

An exploration of the perceptions of caring held by students entering nursing programmes in the United Kingdom: A longitudinal qualitative study phase 1

In a climate of intense international scrutiny of healthcare and nursing in particular, there is an urgent need to identify, foster and support a caring disposition in student nurses worldwide. Yet relatively little is known about how core nursing values are shaped during education programmes and this warrants further investigation. This longitudinal study commencing in February 2013 examines the impact of an innovative nursing curriculum based on a humanising framework (Todres et al. 2009) and seeks to establish to what extent professional and core values are shaped over the duration of a three year nursing programme. This paper reports on Phase One which explores student nurses' personal values and beliefs around caring and nursing at the start of their programme. Undergraduate pre-registration nursing students from two discrete programmes (Advanced Diploma and BSc (Honours) Nursing with professional registration) were recruited to this study. Utilising individual semi-structured interviews, data collection commenced with February 2013 cohort (n = 12) and was repeated with February 2014 (n = 24) cohort. Findings from Phase One show that neophyte student nurses are enthusiastic about wanting to care and aspire to making a difference to patients and their families. This research promises to offer contributions to the debate around what caring means and in particular how it is understood by student nurses. Findings will benefit educators and students which will ultimately impact positively on those in receipt of healthcare

The negotiation and co-construction of meaning and understanding within a postgraduate online learning community

There is an increasing development of courses and course components taught through teaching and learning dialogues online yet there is little secure knowledge regarding the educational quality and outcomes of these dialogues. Drawing on contemporary socio-cultural research, this paper adapts a well-established analytical framework (see Mercer, 1995) that has been developed to understand face to face educational dialogues to the new context of asynchronous electronic conferencing. The work reported is derived from an in-depth case study of a tutorial group of 11 students enrolled on a course within the Open University's MA in Open and Distance Learning. The course was taught on-line to an international cohort of students from wide-ranging academic backgrounds. The analyses of electronic conference archives presented here focus on understanding the students’ on-line collaborative work and the ways in which they constructed meaning, negotiated shared understanding and supported each other in the process of learning at a distance. The implications of the findings for educational practice are considered

Social and professional influences on antimicrobial prescribing for doctors-in-training: a realist review.

Background: Antimicrobial resistance has led to widespread implementation of interventions for appropriate prescribing. However, such interventions are often adopted without an adequate understanding of the challenges facing doctors-in-training as key prescribers. Methods: The review followed a realist, theory-driven approach to synthesizing qualitative, quantitative and mixed-methods literature. Consistent with realist review quality standards, articles retrieved from electronic databases were systematically screened and analysed to elicit explanations of antimicrobial prescribing behaviours. These explanations were consolidated into a programme theory drawing on social science and learning theory, and shaped though input from patients and practitioners. Results: By synthesizing data from 131 articles, the review highlights the complex social and professional dynamics underlying antimicrobial prescribing decisions of doctors-in-training. The analysis shows how doctors-in-training often operate within challenging contexts (hierarchical relationships, powerful prescribing norms, unclear roles and responsibilities, implicit expectations about knowledge levels, uncertainty about application of knowledge in practice) where they prioritize particular responses (fear of criticism and individual responsibility, managing one's reputation and position in the team, appearing competent). These complex dynamics explain how and why doctors-in-training decide to: (i) follow senior clinicians' prescribing habits; (ii) take (or not) into account prescribing aids, advice from other health professionals or patient expectations; and (iii) ask questions or challenge decisions. This increased understanding allows for targeted tailoring, design and implementation of antimicrobial prescribing interventions. Conclusions: This review contributes to a better understanding of how antimicrobial prescribing interventions for doctors-in-training can be embedded more successfully in the hierarchical and inter-professional dynamics of different healthcare settings

UCT943, a next generation Plasmodium falciparum PI4K inhibitor preclinical candidate for the treatment of malaria

The 2-aminopyridine MMV048 was the first drug candidate inhibiting; Plasmodium; phosphatidylinositol 4-kinase (PI4K), a novel drug target for malaria, to enter clinical development. In an effort to identify the next generation of PI4K inhibitors, the series was optimized to improve properties such as solubility and antiplasmodial potency across the parasite life cycle, leading to the 2-aminopyrazine UCT943. The compound displayed higher asexual blood stage, transmission-blocking, and liver stage activities than MMV048 and was more potent against resistant; Plasmodium falciparum; and; Plasmodium vivax; clinical isolates. Excellent; in vitro; antiplasmodial activity translated into high efficacy in; Plasmodium berghei; and humanized; P. falciparum; NOD-; scid IL-2R; γ; null; mouse models. The high passive permeability and high aqueous solubility of UCT943, combined with low to moderate; in vivo; intrinsic clearance, resulted in sustained exposure and high bioavailability in preclinical species. In addition, the predicted human dose for a curative single administration using monkey and dog pharmacokinetics was low, ranging from 50 to 80 mg. As a next-generation; Plasmodium; PI4K inhibitor, UCT943, based on the combined preclinical data, has the potential to form part of a single-exposure radical cure and prophylaxis (SERCaP) to treat, prevent, and block the transmission of malaria

Ropes course universality

Ropes courses throughout the U. S. (N=102) were surveyed to determine if they accommodated people with disabilities from the standpoint of attitude, program, and structure (universality). A questionnaire consisting primarily of Likert-type questions was used to establish baseline data on the current universality of surveyed ropes courses. Questions on the five separate components in Sugerman's Model of Universality were used to determine total universality. These components included: resource information, personal attitudes, provision of information, structural accessibility, and program implementation. Results indicated that most respondents had very positive attitudes towards including people with disabilities on the ropes courses. Respondents tended to perceive their courses as structurally accessible to people with physical limitations with the exception of people who used wheelchairs. Results indicated that staff training and available resources were not being utilized by many courses to enhance universality. Information on how to include people with physical disabilities on ropes courses (in the form of resources, training, workshops, and inservices) needs to be developed and readily available to facilitators and directors

Quantitative ultrastructural differences in the cytoplasm of prepubertal lamb and adult ewe oocytes

The ability to breed from juvenile sheep and cattle can increase their lifetime productivity and the rate of genetic gain, and thus increase the profitability of the agricultural industry. Unfortunately, oocytes from prepubertal animals have limited potential to undergo normal embryogenesis and produce viable offspring, and little is known about the underlying causes of this reduced competence. The correct quantity, activity and cytoplasmic distribution of organelles are essential for oocyte maturation, fertilisation and subsequent embryo development. However, very few studies have attempted to quantify differences in the cytoplasm of prepubertal and adult oocytes to understand the underlying causes of the reduced quality. Therefore, the aims of this project were firstly; to determine if there were differences in the volumes, morphology or distribution of organelles between oocytes from prepubertal (lamb) and adult ewes both before and after in vitro maturation; and secondly, to determine if treatment of lamb oocytes in vitro with factors that may alter the volume or distribution of these organelles can improve embryo development. Embryos were produced from oocytes from slaughterhouse derived ovaries using standard sheep in vitro embryo production methods to determine blastocyst rate. Oocytes were fixed and processed for electron microscopy and stereology techniques were used to measure the distribution, density and volumes of vesicles, mitochondria and lipid droplets in 12 oocytes per age and time point. The volume of vesicles before maturation was greater in adult ewe compared to lamb oocytes (P = 0.018), and decreased during maturation in both age groups. The volume of mitochondria in adult ewe oocytes increased during maturation (P = 0.005). This was due to an increase in mitochondrial number and was greater than the mitochondrial volume (P = 0.026) and number (P = 0.003) of the mature lamb oocytes, which did not change. There were also differences in the morphology of the mitochondria and the distribution of mitochondria and lipid droplets between adult and lamb oocytes. Studies have attributed improved oocyte competence to an increased number of mitochondria and altered cytoplasmic mitochondrial distribution. However, estimates of mitochondrial number have mainly been based on mitochondrial DNA (mtDNA) copy number performed by qPCR methods while the actual number of copies of mtDNA per mitochondria is not known. Therefore, the current study compared the mtDNA copy number, measured by qPCR, with mitochondrial number estimated by stereology in oocytes from the same cohorts of adult ewes and lambs. Unlike the mitochondrial number estimated by stereology, the mean number of copies of mtDNA did not differ between the two ages either before or after in vitro maturation, but decreased in the lamb oocytes during maturation. These results indicate that mtDNA copy number does not represent actual mitochondrial organelle number. L-carnitine has been shown to increase blastocyst rate and alter mitochondrial distribution when cultured with oocytes during in vitro maturation. It has also been shown to alter expression of mitochondrial biogenesis genes in other cell types. In the current study lamb oocytes were treated with acetyl-L-carnitine during in vitro maturation and this doubled the blastocyst rate compared to untreated oocytes (P = 0.028). Stereology results showed vesicle volume and size, and lipid droplet distribution appeared to be altered. There was no effect of L-carnitine on mitochondrial volume, number or distribution, or mtDNA copy number. In conclusion the results of this research suggest a lower volume of storage vesicles prior to maturation and altered mitochondrial replication, distribution and morphology may underlie the reduced developmental competence of prepubertal lamb oocytes. Treatment with L-carnitine during in vitro maturation can also be used to improve in vitro embryo production methods for oocytes from juvenile lambs

A Quantitative Ultrastructural Study of Oocytes During the Early Stages of Ovarian Follicular Development in Booroola and Wild-Type Sheep

In the sheep ovary, primordial follicles are formed as an oocyte surrounded by either a single layer of flattened granulosa cells (type 1) or a mixture of flattened and cuboidal granulosa cells (type 1a). Booroola sheep have a mutation in the growth factor receptor, activin-like kinase receptor 6 (ALK6) which is expressed in oocytes of follicles at the type 1 stage of development. In Booroola ewes homozygous for the ALK6 mutation (BB), oocytes undergo precocious maturation that appears to be initiated during the preantral growth phase. The aim of this study was to quantify the ultrastructural features of oocytes of ovarian follicles at the types 1/1a, 2 and 3 stages of development, from BB and wild-type (++) ewes. Ovaries from 6 ++ and 5 BB 4 week old ewe lambs were processed for both light microscopy (LM) and electron microscopy (EM). LM and stereological methods were used to estimate the mean volume of the oocytes of each follicular type and genotype. EM images and point counting or linear intercept counting were used to estimate the volume of smooth endoplasmic reticulum (SER), Golgi, mitochondria, vesicles, lipid, ribosomes, zona pellucida (ZP) and cortical granules (CG), and the surface area of the outer and inner mictochondrial membranes, microvilli and cell junctions. Oocytes of type 1/1a follicles of BB animals had a greater diameter than that in ++ animals (BB: 29.76 ± 0.58 μm vs ++: 27.05 ± 0.30 μm; P < 0.01) but there were no significant genotype differences in the oocyte diameters of type 2 or 3 follicles. As the follicles of ++ animals developed from the type 1 through to the type 3 stage, the volume and 3 surface areas of all sub-cellular structures measured within oocytes increased (P < 0.05). In oocytes of type 1/1a follicles of BB animals, the SER, mitochondria and ZP volumes were greater than in ++ animals (P < 0.05) as were the surface areas of the outer mitochondrial membranes, oocyte membrane, and zonula adherens type junctions (P < 0.05). At the type 2 stage of development the lipid volume was greater in oocytes of ++ animals, and at the type 3 stage of development the ribosomal volume was greater in oocytes of BB animals. These results suggest that the ALK6 mutation in BB animals has influenced the ultrastructural properties of oocytes in the type 1/1a follicle. This early genotype difference in follicular characteristics may influence the rate of follicular development during the early developmental stages