Mechanisms of protein modification during model anti-viral heat-treatment bioprocessing of beta-lactoglobulin variant A in the presence of sucrose.

To ensure the safety of plasma and recombinant therapeutic proteins, heat treatment is routinely applied to these biopharmaceuticals as a means of virus inactivation. However, to maintain protein integrity during heat treatment it is necessary to use high concentrations of thermostabilizing excipients, such as sucrose, in order to prevent protein damage. In this study we describe the covalent modifications inferred to a model protein, beta-lactoglobulin A, that occur during typical and extended anti-viral heat treatments.

Cost analysis of the treatment of schizophrenia in the UK. A simulation model comparing olanzapine, risperidone and haloperidol.

Objective: To compare the costs of 2 atypical drug therapies (olanzapine and risperidone) with one another and with a conventional antipsychotic (haloperidol) in the treatment of schizophrenia.

Design And Setting: The analysis is based on a simulation model with parameter values taken mainly from clinical trial data in patients with schizophrenia, and was conducted within a UK context.

Results: The 3 therapies are approximately cost neutral over a 5-year period (olanzapine 35,701 Pounds, risperidone 36,590 Pounds and haloperidol 36,653 Pounds).

Using health production functions to evaluate treatment effectiveness: an application to a community mental health service.

The randomized controlled trial (RCT) is the recommended means of evaluating health care effectiveness and cost-effectiveness. Whilst representing a 'gold-standard' in health services research, RCT evidence on the clinical and economic desirability of services and treatments is often absent. Where RCT evidence is lacking, or where it is infeasible to implement randomized controlled comparisons, longitudinal observational and naturalistic data sources when analysed appropriately can yield useful insights regarding the clinical effectiveness and economic efficiency of treatments.

Activation of the interleukin 2 receptor: a possible role for tyrosine phosphatases.

Engagement of interleukin-2 (IL-2) mediates the heterodimeridation of the common beta chain (beta(c)) and common gamma chain (gamma(c)) of the IL-2 receptor (IL-2R). This is sufficient and necessary for receptor activation and signal transduction. It is generally held that the IL-2R is activated by the trans-activity of the protein tyrosine kinases (PTKs) Jak1 and Jak3 associated with beta(c) and gamma(c) respectively.

Assessment approaches for older people receiving social care: content and coverage.

Background: Assessment was identified as one of the 'cornerstones' of community care. This study presents findings from the first nationally representative analysis of assessment documents used by social services agencies in the UK.

Method: In this paper analysis is made of 50 assessment documents used for the 'comprehensive' assessment of older people.

Patient education literature and help seeking behaviour: perspectives from an evaluation in the United Kingdom.

Decisions by patients upon when to use health care services are a major influence on the consumption of health care resources. Patient education--often based upon written information on how to identify symptoms of common illnesses, when to seek help and how to self-treat--is an increasingly popular strategy to rationalise demand. A large body of literature, in evaluating the impact of such written information, has though overlooked the possession or acquisition of comparable publications by respondents in the course of the studies.

The quality of general dental care: public and users' perceptions.

Background: Systematic evidence about how the public and users perceive and experience the quality of general dental care is in short supply, particularly in light of the recent changes in the general dental service. The study reported here attempted to fill this gap.

Objectives: To identify the criteria the public and users adopt in evaluating the quality of general dental care, and to identify the extent and nature of perceived concerns with general dental care.

Pro-norm and anti-norm deviance within and between groups.

Participants evaluated other individuals who deviated in either an anti- or pro-normative direction relative to normative members. In Study 1, in-group gender-normative members were rated more positively than deviant members. The pro-norm deviant was viewed as more attractive than the anti-norm deviant.

Alcohol withdrawal and hypokalaemia: a case report.

A case is presented where a 25-year-old man developed a serious hypokalaemia (K(+) 2.2 mmol/l) during alcohol withdrawal, despite intravenous saline treatment and normal feeding. As hypokalaemia can be symptom-free, we want to draw attention to the combination of vomiting, malnutrition and alcohol withdrawal, as these can cause lethal complications.

Attention and joint attention in preschool children with autism.

Three experiments examined the role of attention in explaining dyadic (child-adult) and triadic (child-adult-object) joint attention difficulties in autism. Experiments 1 and 2 investigated children's ability to orient to an adult's attention bid and to follow the direction of a human or nonhuman cue. Experiment 3 tested ability to disengage and shift attention to objects.

Ascertainment of families for a linkage study of alcoholism.

Traditionally, researchers working in the field of genetics and alcoholism have used treatment centres and clinics to try and recruit suitable subjects for research purposes. The current study considered a diverse range of possible sources to recruit suitable families for a linkage study of alcoholism. These sources included the press, personal contacts and circular letters to alcohol treatment centres and members of the Substance Misuse Section of the Royal College of Psychiatrists.

Differential regulation of nucleoside and nucleobase transporters in Crithidia fasciculata and Trypanosoma brucei brucei.

The regulation of the activity of purine transporters in two protozoan species, Crithidia fasciculata and Trypanosoma brucei brucei, was investigated in relation to purine availability and growth cycle. In C. fasciculata, two high-affinity purine nucleoside transporters were identified.

Changes in skills for people with intellectual disability: a follow-up of the Camberwell Cohort.

The skills of a total population of children with severe intellectual disability and/or autism from Camberwell, South London, UK, and the initial follow-up data, taken when the subjects were adolescents and young adults (Shah 1986), are described in the present study. Changes in skills over time are presented within the categories of communication, self-care, and educational and cognitive skills, as assessed by the Handicaps, Behaviours and Skills schedule. The results indicated that skills had improved in many areas between times 1 and 2, but that this improvement was more noticeable for the children who had been youngest at time 1.

A survey of the current clinical practice of psychiatrists and accident and emergency specialists in the United Kingdom concerning vitamin supplementation for chronic alcohol misusers.

Although it is well known that B-vitamin deficiencies directly affecting the brain are common in alcohol misuse, no concise guidelines on the use of vitamin supplements in alcohol misusers currently exist in the UK. The purpose of this study was to assess current practice and opinion among UK physicians. Questionnaires were completed by a total of 427 physicians comprising Accident and Emergency (A&E) specialists and psychiatrists, with a response rate of 25%.

Effect of multiple serine/alanine mutations in the transmembrane spanning region V of the D2 dopamine receptor on ligand binding.

Three conserved serine residues (Ser193, Ser194, and Ser197) in transmembrane spanning region (TM) V of the D2 dopamine receptor have been mutated to alanine, individually and in combination, to explore their role in ligand binding and G protein coupling. The multiple Ser -->Ala mutations had no effect on the binding of most antagonists tested, including [3H]spiperone, suggesting that the multiple mutations did not affect the overall conformation of the receptor protein. Double or triple mutants containing an Ala197 mutation showed a decrease in affinity for domperidone, whereas Ala193 mutants showed an increased affinity for a substituted benzamide, remoxipride.

Assessing the ability of people with a learning disability to give informed consent to treatment.

Background: People with a learning disability are increasingly being encouraged to take a more active role in decisions about their psychological and medical treatment, raising complex questions concerning their ability to consent. This study investigates the capacity of people with a learning disability to consent in the context of three treatment vignettes, and the influence of verbal and memory ability on this capacity.

Methods: Measures of verbal ability, memory ability and ability to consent to treatment (ACQ) were administered to 40 people with a learning disability.

Protein modification during antiviral heat bioprocessing.

Heat treatment is routinely used in the preparation of therapeutic protein biopharmaceuticals as a means of viral inactivation. However, in undertaking virucidal heat treatments, a balance must be found between the bioprocessing conditions, virus kill, and the maintenance of protein integrity. In this study, we utilize a simple model protein, hen egg-white lysozyme, to investigate the relationship between antiviral bioprocess conditions (protein formulation and temperature) and the extent and type of protein modification.

Adenosine transporters in bloodstream forms of Trypanosoma brucei brucei: substrate recognition motifs and affinity for trypanocidal drugs.

Adenosine influx by Trypanosoma brucei brucei P1 and P2 transporters was kinetically characterized. The P1 transporter displayed a higher affinity and capacity for adenosine (K(m) = 0.38 +/- 0.

Interpreting the Inventory of Interpersonal Problems: subscales based on an interpersonal theory model.

There remains considerable debate about a theoretically interpretable subscale structure for the Inventory of Interpersonal Problems (IIP). In this paper items are extracted from the IIP to form a 40-item shortened version (the IIP-40) comprising eight subscales, each of five items, which conform to the eight octant positions within Birtchnell's interpersonal octagon: a version of interpersonal theory. The inter-item reliability of the subscale structure is found to be acceptable when tested against a sample of 150 pre-assessment for psychotherapy IIP completions within the Centre for the Study of Psychotherapy (CSP), University of Kent.