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Biomedical subjects

D Chisholm

Publications and source records attributed to D Chisholm.

At least 37 records · Page 2Linked to original sources

Toward real-world sequencing by microdevice electrophoresis.

We report results using a microdevice for DNA sequencing using samples from chromosome 17, obtained from the Whitehead Institute Center for Genome Research (WICGR) production line. The device had an effective separation distance of 11.5 cm and a lithographically defined injection width of 150 microm. The four-color raw data were processed, base-called by the sequencing software Trout, and compared to the corresponding ABI 377 sequence from WICGR. With a criteria of 99% accuracy, we achieved average continuous reads of 505 bases in 27 min with 3% linear polyacrylamide (LPA) at 150 V/cm, and 460 bases in 22 min with 4% LPA at 200 V/cm at a temperature of 45 degrees C. In the best case, up to 565 bases could be base-called with the same accuracy in <25 min. In some instances, Trout allowed for accurate base-calling down to a resolution R as low as R = 0.35. This may be due in part to the high signal-to-noise ratio of the microdevice. Unlike many results reported on capillary machines, no additional sample cleanup other than ethanol precipitation was required. In addition, DNA fragment biasing (i.e., discrimination against larger fragments) was reduced significantly through the unique sample injection mechanism of the microfabricated device. This led to increased signal strength for long fragments, which is of great importance for the high performance of the microdevice.

Base Sequence↗

Does a hostel's managing agency determine the access to psychiatric services of its residents?

This study examines the effect of managing agency (local authority, private or voluntary) on the use of other health and social care services by residents in mental health hostels and group homes with different levels of staffing in England and Wales. The sample comprised 1323 residents in 275 facilities in eight districts. The measures of service use were number of days in hospital and number of other service contacts. There were highly significant differences between facilities with similar levels of staffing managed by different agencies. Residents in the voluntary sector used fewer community services overall; residents in low-staffed local authority facilities used more services than those in similar facilities managed by other agencies. These differences were not easily explained by differences in the social or clinical characteristics of residents. This suggests that there may be organisational factors, e.g. hostel staff, knowledge of services, which influence access to and use of community services.

Adult↗

Public, private and voluntary residential mental health care: is there a cost difference?

OBJECTIVES: To determine how public (NHS or local government), private (for-profit) and voluntary (non-profit) providers of residential mental health care compare. Do they support different clienteles? And do their services cost different amounts? METHODS: Based on a cross-sectional survey of residential care facilities and their residents in eight English and Welsh localities, the characteristics and costs of care in the different sectors (NHS, local government, private, voluntary) were compared. Variations in cost were examined in relation to residents' characteristics using multiple regression analyses, which also allowed standardisation of results before making inter-sectoral comparisons. RESULTS: Private and voluntary providers of residential care support different clienteles from the public sector. The patterns of inter-sectoral cost differences vary between London and non-London localities. In London, voluntary sector facilities may be more cost-efficient than the other sectors, but local government/private sector comparisons show no consistent difference. Outside London, the results suggest clear cost advantages for the private and voluntary sectors over the local government sector. CONCLUSIONS: Private and voluntary providers may have some economic advantages over their public counterparts. However, outcomes for residents were not studied, leaving unanswered the question of comparative cost-effectiveness.

Community Mental Health Services↗

London-east Anglia randomised controlled trial of cognitive-behavioural therapy for psychosis. III: Follow-up and economic evaluation at 18 months.

BACKGROUND: A randomised controlled trial of cognitive-behavioural therapy (CBT) for people with medication-resistant psychosis showed improvements in overall symptomatology after nine months of treatment; good outcome was strongly predicted by a measure of cognitive flexibility concerning delusions. The present paper presents a follow-up evaluation 18 months after baseline. METHOD: Forty-seven (78% of original n = 60) participants were available for follow-up at 18 months, and were reassessed on all the original outcome measures (see Part I). An economic evaluation was also completed. RESULTS: Those in the CBT treatment group showed a significant and continuing improvement in Brief Psychiatric Rating Scale scores, whereas the control group did not change from baseline. Delusional distress and the frequency of hallucinations were also significantly reduced in the CBT group. The costs of CBT appear to have been offset by reductions in service utilisation and associated costs during follow-up. CONCLUSIONS: Improvement in overall symptoms was maintained in the CBT group 18 months after baseline and nine months after intensive therapy was completed. CBT may be a specific and cost-effective intervention in medication-resistant psychosis.

Adult↗

The metabolically obese, normal-weight individual revisited.

Nearly 20 years ago, it was suggested that individuals exist who are not obese on the basis of height and weight, but who, like people with overt obesity, are hyperinsulinemic, insulin-resistant, and predisposed to type 2 diabetes, hypertriglyceridemia, and premature coronary heart disease. Since then it has become increasingly clear that such metabolically obese, normal-weight (MONW) individuals are very common in the general population and that they probably represent one end of the spectrum of people with the insulin resistance syndrome. Available evidence also suggests that MONW individuals could account for the higher prevalence of type 2 diabetes, cardiovascular disease, and other disorders in people with a BMI in the 20-27 kg/m2 range who have gained modest amounts of weight (2-10 kg of adipose mass) in adult life. Specific factors that appear to predispose MONW, as well as more obese individuals, to insulin resistance include central fat distribution, inactivity, and a low VO2max. Because these factors are potentially reversible and because insulin resistance may contribute to the pathogenesis of many diseases, it is our premise that a compelling argument can be made for identifying MONW individuals and treating them with diet, exercise, and possibly pharmacological agents before these diseases become overt, or at least early after their onset. One reason for doing so is that disorders such as type 2 diabetes may be accompanied by irreversible consequences, e.g., ischemic heart disease and nephropathy, at the time of diagnosis or shortly thereafter. Another is that MONW individuals in general should be younger and more amenable and responsive to diet and exercise therapy than are obese patients with established disease. That long-term diet and exercise can work is suggested by two large studies in which, over 5-6 years, the incidence of diabetes was diminished in nonobese and minimally obese patients with impaired glucose tolerance. Based on these considerations and the emerging worldwide epidemic of type 2 diabetes, we believe that studies to assess whether therapies aimed at young MONW individuals can prevent the development of type 2 diabetes and other diseases, including perhaps obesity itself, are urgently needed.

Adult↗

QALYs and mental health care.

Quality-adjusted life year measures (QALYs) have been fervently debated by researchers and decision makers concerned with resource allocation in the health care sector. They have been heralded as important aids to planning and priority setting, but also criticised on technical and ethical grounds. This paper examines these arguments with special reference to mental health care, the intention being to highlight the strengths and shortcomings of QALYs in this context. Issues pertinent to the application of QALYs in health care evaluation more generally are also reviewed. Whilst the rationale and underlying principles of the utility measurement approach are sound, the generic QALY as it is currently constructed represents an insensitive measure of the outcomes of mental health care. In the event of an increasingly QALY-driven priority-setting environment, however, abandonment of QALYs runs the risk of inappropriately marginalising people with mental illnesses in the resource allocation process. This opens up the possibility of developing a mental-health specific measure of utility that, in combination with cost data, would provide useful and appropriate summary information across treatments and programmes of mental health care.

Cost-Benefit Analysis↗

The cost consequences of changing the hospital-community balance: the mental health residential care study.

BACKGROUND: Altering the balance of provision between hospital and community care is a key and often contentious component of mental health care policy in many countries. Implementation of this policy in the UK has been slowed by the apparent shortage of suitable community accommodation for people with long-term needs for care and support. Among the consequences could be the silting up of hospital beds by people who could be supported more appropriately elsewhere, in turn denying in-patient treatment to people with acute psychiatric problems and unnecessarily pushing up health service expenditure. METHODS: Using data collected in a survey of hospital and residential accommodation services and their residents in eight areas of England and Wales, the cost components of today's balance of care were explored. Comprehensive costs were calculated and their associations with resident characteristics examined using multiple regression analyses. RESULTS: On a like-with-like basis, the costs of hospital in-patient treatment for inappropriately placed patients greatly exceeded the costs of community-based care. CONCLUSION: Further reduction of hospital beds, however, is not the panacea for an appropriate balance of mental health care, given the unknown but potentially considerable extent of unmet demand, as well as the impact of previous in-patient bed reductions apparent in the services surveyed. Rather, service providers and purchasers should focus on developing community-based care (including increased provision of 24-hour nursed beds) by ensuring that resources released through earlier closure programmes have been redeployed for their intended use and by accessing additional pump-priming or bridging resources.

Chronic Disease↗

The mental health residential care study: predicting costs from resident characteristics.

BACKGROUND: Little information is available on the costs of residential care for people with mental health problems, and there are very few research data on how or why the costs of provision vary. METHOD: As part of a broader study based on data collected from across the residential care sectors in eight districts and using multiple regression analysis, research has examined whether and which resident characteristics are associated with higher or lower costs. RESULTS: Resident characteristics account for approximately 21% of the observed variation in inter-resident costs. Separate analyses were conducted for people in the London and non-London districts. The resident characteristics that were found to be significant predictors of cost include: age, gender, ethnic group, history of psychiatric admissions, diagnosis, emotional lability, daily living skills, social interaction and network, aggression, suicidal tendencies, drug abuse and legal status. Examination of the residual ('unexplained') costs found significant differences between facility types, sectors (private and voluntary being less costly than public, other things being equal) and districts. CONCLUSIONS: The associations uncovered by these analyses can inform commissioners' planning and purchasing activities, at both the macro and micro levels, by revealing those resident needs and circumstances that are associated with higher costs.

Adolescent↗

The mental health residential care study: classification of facilities and description of residents.

BACKGROUND: The NHS is no longer a virtual monopoly provider of mental health residential care. This makes it difficult to assess the volume, range and adequacy of local provision. METHOD: Local data collectors used standard instruments to collect detailed information about 368 facilities (with 1951 residents) providing mental health residential care in eight districts. Because local definitions were inconsistent, facilities were reclassified on the basis of facility size and extent of day and night cover. The eight categories of accommodation are compared on levels of staffing, staff qualifications and the characteristics of their residents. RESULTS: There was a nearly threefold variation between districts in the total number of residential places available per unit of population, and even greater variation in the number of places with 24-hour waking cover. Most residents have long-term, severe mental illness and severe impairment. Long-stay wards accommodate people who pose greater risk of violence than do the two types of non-hospital facility with 24-hour waking cover (P < 0.001). The former also employ a much greater proportion of staff with formal care qualifications and, in particular, nursing qualifications than the latter (49% v. 15%, P < 0.001). CONCLUSIONS: It is suggested that one consequence of the diversification in provision of mental health residential accommodation has been a relative reduction in the proportion of provision available to the most severely disabled. This might apply particularly to those who pose a risk of acting violently.

Aged↗

Two outbreaks of Salmonella enteritidis phage type 4 infection associated with the consumption of fresh shell-egg products.

In 1988 there were two outbreaks of infection with Salmonella enteritidis phage type 4 in adjacent local authorities. The first affected 18 of 75 helpers and guests who attended a private function. Investigations revealed that home-made vanilla ice-cream containing uncooked eggs was the vehicle of infection and the causative organism was identified at the premises of the egg producer. The second affected 84 of 422 delegates attending a conference dinner, and 12 of 50 hotel staff at risk. A dessert made with lightly-cooked egg yolk and raw egg white was associated with infection, and the epidemic strain was cultured from the shell of an egg and an environmental sample from the producer's farm. It is of interest that one outbreak involved free-range and one battery-produced eggs, and that in one the vehicle was prepared at home and in the other in commercial premises. In neither incident was any deficiency in standards of egg production or catering practice discovered.

Animals↗

Recovery of a soybean urease genomic clone by sequential library screening with two synthetic oligodeoxynucleotides.

We report the first isolation of a low-copy-number gene from a complex higher plant (soybean) genome by direct screening with synthetic oligodeoxynucleotide (oligo) probes. A synthetic, mixed, 21-nucleotide (nt) oligo (21-1) based on a seven amino acid (aa) sequence from soybean seed urease, was used to screen genomic libraries of soybean (Glycine max [L.] Merr.) in the lambda Charon 4 vector. Twenty homologous clones were recovered from a screen of 500,000 plaques. These were counterscreened with embryo-specific cDNA (15-2 cDNA) made by priming with a second, mixed 15-nt oligo (15-2), based on a Jack bean (Canavalia ensiformis) urease peptide [Takishima et al., J. Natl. Def. Med. Coll. 5 (1980) 19-23]. Five out of 20 clones were homologous to 15-2 cDNA and proved to be identical. Nucleotide sequence analysis of representative clone E15 confirmed that it contained urease sequences. Subclones of E15 homologous to the oligo probes contain a deduced amino acid sequence which matches 108 of 130 aa residues of an amino acid run in a recently published [Mamiya et al., Proc. Jap. Acad. 61B (1985) 359-398] complete protein sequence for Jack-bean seed urease. Using clone E15 as a probe of soybean embryonic mRNA revealed a homologous 3.8-kb species that is the size of the urease messenger. This species is absent from mRNA of embryos of a soybean seed urease-null mutant. However, both urease-positive and urease-null genomes contain the 11-kb DNA fragment bearing urease sequences.

Amino Acid Sequence↗

Isolation of multiple genomic sequences coding for chicken myosin heavy chain protein.

A genomic bank has been constructed using DNA isolated from a dystrophic strain of chickens. The library was screened for myosin heavy chain (MHC) sequences using a cDNA probe and 11 positive recombinants isolated. Identity of the clones was confirmed by positive RNA selection via hybridization of the clones with muscle RNA and subsequent translation of the hybridizable RNA in vitro. Restriction maps indicate that the clones can be divided into 7 distinct groups; some of these groups do, however, share similar or homologous sequences. Hydridization of the clones to RNA derived from leg, breast, heart, and brain reveals that all of the clones code for the muscle-specific MHC isoforms. These experiments also show that there are at least 3 size classes of MHC mRNA sequences, whose relative amounts appear to be modulated in a tissue- and developmental stage-specific manner.

Animals↗

Insulin and glucagon responses of transplanted intrasplenic pancreatic islets.

Two transplant procedures have been investigated in which one third of the pancreas was autotransplanted into the splenic pulp of dogs. The two procedures consist of simple mechanical dissociation of the pancreas or mechanical dissociation followed by collagenase digestion. The ability of the endocrine segment of the transplant to survive and function was assessed by stimulation with arginine and measurement of insulin and glucagon response. The results demonstrate that both transplant procedures result in functioning beta and alpha cells that rapidly secrete both insulin and glucagon in response to arginine stimulation. However, greater insulin responses were obtained when mechanically dissociated but nonenzyme digested pancreatic tissue was used for transplantation. The spleen appears to be an excellent transplant site for the reception of endocrine pancreatic tissue and allowed both beta and alpha cells to survive following transplantation.

Animals↗