Thresholds for disease persistence in models for tick-borne infections including non-viraemic transmission, extended feeding and tick aggregation.

Lyme disease and Tick-Borne Encephalitis (TBE) are two emergent tick-borne diseases transmitted by the widely distributed European tick Ixodes ricinus. The life cycle of the vector and the number of hosts involved requires the development of complex models which consider different routes of pathogen transmission including those occurring between ticks that co-feed on the same host. Hence, we consider here a general model for tick-borne infections.

Isolation and characterization of an IgNAR variable domain specific for the human mitochondrial translocase receptor Tom70.

The new antigen receptor (IgNAR) from sharks is a disulphide bonded dimer of two protein chains, each containing one variable and five constant domains, and functions as an antibody. In order to assess the antigen-binding capabilities of isolated IgNAR variable domains (VNAR), we have constructed an in vitro library incorporating synthetic CDR3 regions of 15-18 residues in length. Screening of this library against the 60 kDa cytosolic domain of the 70 kDa outer membrane translocase receptor from human mitochondria (Tom70) resulted in one dominant antigen-specific clone (VNAR 12F-11) after four rounds of in vitro selection.

Empirical evidence for key hosts in persistence of a tick-borne disease.

An important epidemiological consequence of aggregated host-parasite associations occurs when parasites are vectors of pathogens. Those hosts that attract many vectors will tend to be the focus of transmission. But to what extent, and can we identify characteristics of these key hosts? We investigated these questions with respect to the host-tick relationship of the yellow-necked mouse, Apodemus flavicollis, a critical host in the maintenance of the zoonotic disease, tick-borne encephalitis.

Risk assessment in clinical pharmacy.

Medication error forms a major proportion of the errors in the medical system. Despite many studies of adverse drug events, there are no systematic ways of ensuring safety, or of assessing how safe a pharmaceutical system is. Risk assessment is required in hazardous industries such as nuclear power or oil and gas.

Dextrin characterization by high-performance anion-exchange chromatography--pulsed amperometric detection and size-exclusion chromatography--multi-angle light scattering--refractive index detection.

Starch hydrolysis products, or dextrins, are widely used throughout the food industry for their functional properties. Dextrins are saccharide polymers linked primarily by alpha-(1 --> 4) D-glucose units and are prepared by partial hydrolysis of starch. Hydrolysis can be accomplished by the use of acid, enzymes, or by a combination of both.

Focus group interviews: a guide for palliative care researchers and clinicians.

The focus group interview is an increasingly common qualitative research method used by health professionals. General approaches to conducting focus groups have been published. There has, however, been minimal exploration of issues regarding the use of focus groups with palliative care populations and data analysis procedures have been underreported.

The midwife and postnatal contraceptive advice.

Following childbirth, most hormonal methods are an effective way to prevent an unwanted pregnancy. There are a few medical conditions that may prevent a woman taking the COC; these need consultation with a family planning doctor. On the whole most oestrogen-free methods are suitable, particularly if a woman is breastfeeding.

The experience of research participation for family caregivers of palliative care cancer patients.

There have been concerns raised regarding the ethical merit of involving dying patients and family caregivers as research participants. This study sought feedback from 103 primary family caregivers who had participated in a longitudinal research project. Caregivers were sent a questionnaire regarding the benefits and negative aspects associated with participating in research while also supporting or having supported a relative dying of cancer.

Long-term 6-year experience with finasteride in patients with benign prostatic hyperplasia.

Objectives: To summarize the 6-year clinical trial data with finasteride. Benign prostatic hyperplasia is a chronic and progressive disease and therefore assessment of long-term safety and efficacy is important.

Methods: The North American and International Phase III Finasteride trials enrolled symptomatic men with enlarged prostate glands.

Keystone symposia: antibody-based therapeutics for cancer.

This important conference focused on the latest developments in therapeutic antibodies, particularly for their design, production and formulation for cancer therapy. Engineered antibodies currently represent over 30% of biopharmaceuticals in clinical trials, highlighted by the recent FDA approvals of Zevalin (ibritumomab tiuxetan, IDEC Pharmaceuticals) for cancer radioimmunotherapy and Humira (adalimumab, Abbott Laboratories) for rheumatoid arthritis [1,2]. An impressive array of international speakers was assembled in Banff by the organisers L Weiner (Fox Chase Cancer Center, USA) and P Carter (Amgen and Seattle Genetics).

Recombinant antibodies for cancer diagnosis and therapy.

Recombinant antibodies currently represent over 30% of biopharmaceuticals in clinical trials, highlighted by the recent Food and Drug Administration (FDA) approvals of Zevalin(TM) (ibritumomab-tiuxetan; IDEC Pharmaceuticals, San Dieago, CA, USA) for cancer radioimmunotherapy and Humira(TM) (adalimumab; Abbott Laboratories, IL, USA) for rheumatoid arthritis. Together, these FDA approvals have excited the biotechnology industry, particularly since sales of recombinant antibodies are increasing rapidly to a predicted US dollar 4 billion per annum worldwide in 2003. To date, 10 engineered therapeutic antibodies have gained FDA approval and many others are in Phase III trials.

Noncovalent scFv multimers of tumor-targeting anti-Lewis(y) hu3S193 humanized antibody.

Single-chain variable fragments (scFvs) of anti-Lewis(y) hu3S193 humanized antibody were constructed by joining the V(H) and V(L) domains with either +2 residues, +1 residue, or by directly linking the domains. In addition two constructs were synthesized in which one or two C-terminal residues of the V(H) domain were removed (-1 residue, -2 residue) and then joined directly to the V(L) domain. An scFv construct in the reverse orientation with the V(L) joined directly to the V(H) domain was also synthesized.

Single-chain Fv multimers of the anti-neuraminidase antibody NC10: the residue at position 15 in the V(L) domain of the scFv-0 (V(L)-V(H)) molecule is primarily responsible for formation of a tetramer-trimer equilibrium.

Single-chain variable fragment of the murine monoclonal antibody NC10 specific to influenza virus N9 neuraminidase, joined directly in the V(L) to V(H) orientation (scFv-0), forms an equilibrium mixture of tetramer and trimer with the tetramer as the preferred multimeric species. In contrast, the V(H)-V(L) isomer was previously shown to exist exclusively as a trimer. Computer-generated trimeric and tetrameric scFv models, based on the refined crystal structure for NC10 Fv domain, were constructed and used to evaluate factors influencing the transition between V(L)-V(H) trimer and tetramer.

Interstitial laser coagulation versus transurethral prostate resection for treating benign prostatic obstruction: a randomized trial with 2-year follow-up.

Objectives: To investigate whether interstitial laser coagulation (ILC) is as effective and as safe as transurethral resection of the prostate (TURP). The treatment of choice for bladder outflow obstruction secondary to benign prostatic hyperplasia is TURP. However, ILC is a less invasive outpatient procedure that may be as effective and safe as TURP.

The effect of aggressiveness on the population dynamics of a territorial bird.

A central issue in ecology lies in identifying the importance of resources, natural enemies and behaviour in the regulation of animal populations. Much of the debate on this subject has focused on animals that show cyclic fluctuations in abundance. However, there is still disagreement about the role of extrinsic (food, parasites or predators) and intrinsic (behaviour) factors in causing cycles.

The crystal structure of an anti-CEA scFv diabody assembled from T84.66 scFvs in V(L)-to-V(H) orientation: implications for diabody flexibility.

Diabodies (scFv dimers) are small, bivalent antibody mimetics of approximately 55kDa in size that possess rapid in vivo targeting pharmacokinetics compared to the intact parent antibody, and may prove highly suitable for imaging and therapeutic applications. Here, we describe T84.66Di, the first diabody crystal structure in which the scFvs comprise V domains linked in the V(L)-to-V(H) orientation.

Alzheimer's disease and total plasma aminothiols.

Background: Plasma homocysteine is elevated in Alzheimer's disease, but little is known regarding levels of related aminothiols in the disease. We therefore determined total plasma homocysteine, cysteine, and glutathione levels in patients and control subjects and investigated their relationship with cognitive scores.

Methods: We performed a prospective, case-controlled survey based in two UK Psychogeriatric Assessment Centres.

Epidemiological consequences of a pathogen having both virulent and avirulent modes of transmission: the case of rabbit haemorrhagic disease virus.

A number of pathogens cause chronic infection in survivors of acute disease and this is believed to be a common means of persistence, including for highly virulent agents. We present a model in which transmission from chronically infected hosts causes chronic infection in naive individuals, without causing acute disease--indeed 'protecting' against it. Thus the pathogen obtains the benefit of virulence (high transmission rate), but mitigates against the cost (high host mortality).

Stochasticity accelerates nematode egg development.

Day-degrees models of nematode development assume that temperature stochasticity has no effect on the development rate of infective stages as long as the mean temperature is held constant. This assumption was tested in this study. Unembryonated Heterakis gallinarum eggs were subjected to nocturnal and diurnal daily temperature cycles at 12 and 17 C.

Intervention development for enhanced lay palliative caregiver support - the use of focus groups.

Caring for a family member or friend dying of cancer can be extremely stressful. Past research identified that lay caregivers frequently report unmet needs related to guidance and support to assist them to provide care. This study sought to extend prior needs-based research towards the development of a new nursing intervention focused on the guidance and support provided to persons caring for a relative or friend dying of cancer.

Supporting foster parents: caring voices.

This article reports the responses of foster parents to a mailed questionnaire on the supports needed to maintain their caring role. An overarching finding was the need for respect and recognition, manifested in many ways, which appeared to be in short supply. In addition, the presence of several ambiguities in the relationships between agency, children in care, and the foster parents was revealed, requiring acknowledgment and discussion between the parties.