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S Cawley

Publications and source records attributed to S Cawley.

At least 19 recordsLinked to original sources
PubMed2006

LdCompare: rapid computation of single- and multiple-marker r2 and genetic coverage.

UNLABELLED: The scale of genetic-variation datasets has increased enormously and the linkage equilibrium (LD) structure of these polymorphisms, particularly in whole-genome association studies, is of great interest. The significant computational complexity of calculating single- and multiple-marker correlations at a genome-wide scale remains challenging. We have developed a program that efficiently characterizes whole-genome LD structure on large number of SNPs in terms of single- and multiple-marker correlations. AVAILABILITY: LdCompare is licensed under the GNU General Public License (GPL). Source code, documentation, testing datasets and precompiled executables are available for download at: http://www.affymetrix.com/support/developer/tools/devnettools.affx

Algorithms↗
PubMed2006

The health-related utility and health-related quality of life of hospital-treated subjects with type 1 or type 2 diabetes with particular reference to differing severity of peripheral neuropathy.

AIMS/HYPOTHESIS: We characterised symptom severity of diabetic peripheral neuropathy (DPN) in people with diabetes, and correlated this with health-related utility and health-related quality of life. MATERIALS AND METHODS: The study was undertaken in Cardiff and the Vale of Glamorgan, Wales. A postal survey was mailed to a random sample of subjects identified as having diabetes. Data were collected on the symptoms of neuropathy using the Neuropathic Total Symptom Score (self-administered) (NTSS-6-6A) and on quality of life using the Quality of Life in Diabetes Neuropathy Instrument (QoL-DN), EueroQoL five dimensions (EQ5D) and Short Form 36 (SF36). Other information, such as demographics and self-reported drug use, was also collected. The anonymised data were linked to routine inpatient and outpatient healthcare data. RESULTS: Responses were received from 1,298 patients. For patients with a clinically confirmed diagnosis of DPN, the mean NTSS-6-SA score was 6.16 vs 3.19 in patients without DPN (p<0.001). Four categories of severity were defined, ranging from none to severe. All quality of life measures showed a deterioration between these groups: the EQ5D(index) fell from an average of 0.81 in those without symptoms to 0.25 in those with severe symptoms, the SF36 general health profile fell from 59.9 to 25.5 (p<0.001) and the QoL-DN increased from 25.8 to 48.1 (p<0.001). Multivariate models also demonstrated that this relationship remained after controlling for other factors. CONCLUSIONS/INTERPRETATION: This study demonstrated that severity of DPN symptoms was predictive of poor health-related utility and decreased quality of life. Furthermore, it provides detailed utility data for economic evaluation of treatment of typical diabetes-related morbidity states. Reducing DPN morbidity should be a priority.

Adult↗
PubMed2002

The significance of suicide notes in the elderly.

Suicide notes are traditionally considered as markers of the severity of the suicide attempt and are said to provide valuable insight into the thinking of suicide victims before the fatal act. Few studies have described the characteristics of elderly suicide note-writers and their final thoughts. This study is a retrospective view of suicide notes obtained from coroners' records of all elderly suicides in Cheshire over a period of 10 years, 1989-1998. Out of 125 suicides, 54 (43%) had suicide notes, which were reported in the coroner's records. Of these there were 31 (57%) male and 23 (43%) female subjects. Elderly suicide note-leavers were more likely to be unknown to psychiatric services (p < 0.01) and to have used a non-violent method of suicide (p < 0.01). Sex, marital status, social isolation, mental or physical morbidity did not appear to be linked with leaving a suicide note. More cases that took an overdose, used plastic bags, electrocuted themselves, or used car exhaust also left suicide notes. Those who died by more violent means such as hanging, drowning, jumping from height, immolation or wounding appeared less likely to have left a suicide note. No statistically significant difference in the content of the suicide notes was observed in relation to sex or age. Many elderly are isolated and may have no one to write a note to, while others have lost the ability to express themselves. Therefore, it is not possible to say that the different incidence of note leaving observed for suicide was due to differing levels of suicidal intent. Although only a proportion of elderly suicide victims leave suicide notes, the absence of a suicide note must not be considered an indicator of a less serious attempt.

Aged↗
PubMed2001

History of deliberate self harm may predict methods of fatal self harm in the elderly.

In this study we examined the association between methods of Deliberate Self Harm (DSH) by the elderly and their subsequent methods of Fatal Self Harm (FSH). Data was collected from the files of inquests into suicide by the elderly in Birmingham and Cheshire Coroner's Courts. All the subjects were above the age of 60, had history of deliberate self harm before the final act of fatal self harm and attracted either suicide or open verdict returned by the Coroners over a period of four years 1995-1998. We compared the methods of Deliberate Self Harm (DSH) to the methods of Fatal Self Harm (FSH) used by all the included elderly. 18 per cent of elderly victims of FSH had a previous history of DSH and in 35 per cent of the sample, the last known attempt of DSH occurred more than one year prior to the FSH. The majority of the methods that had been used in elderly DSH were used again in their final act of FSH. Nearly two thirds of all the elderly who died of an overdose had attempted suicide earlier by an overdose and one in five of those who died by hanging or drowning used the same method in an unsuccessful attempt of FSH within 12 months. A detailed history of DSH can improve the quality of risk assessment of self harm in the elderly. As more than one in three elderly victims of FSH attempted DSH more than a year prior to the final act, it is important when assessing an elderly DSH attempt that we obtain any previous case notes and question informants about the distant as well as the recent past.

Aged↗
PubMed2001

Elderly suicide and attempted suicide: one syndrome.

In this study we explore whether elderly suicide victims who had a previous history of attempted suicide differ from those with no similar history. A group of the elderly, who ended their lives with fatal self-harm (FSH) and had a history of deliberate self-harm (DSH) was compared to a matching group of the elderly who also ended their lives with FSH, but who were not known to have had any history of DSH. The comparison was in respect of epidemiological, social, psychological characteristics, service input and methods of suicide. The elderly, with a history of DSH, were more likely to have been known to the mental health services than the elderly who did not have such a history (P<.05). The two groups used similar methods in their final FSH act. The elderly victims of FSH with or without a previous history of DSH share the same characteristics. The two groups appear to be part of one syndrome. Deliberate self-harm in the elderly should be taken seriously as an unsuccessful suicide rather than a manipulative act or a cry for help and attention.

Aged↗
PubMed2000

The genome sequence of Drosophila melanogaster.

The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

Animals↗
PubMed1997

The effects of hippocampal and area parahippocampalis lesions in pigeons: II. Concurrent discrimination and spatial memory.

Two experiments were conducted to examine the effects of bilateral hippocampus (Hp) and area parahippocampalis (APH) lesions in pigeons on the acquisition of a visual and spatial task. In Experiment 1, pigeons were trained on three successive six-pair concurrent discrimination tasks, each using a novel set of stimuli. There was no difference between control unoperated pigeons and Hp-APH pigeons in terms of the number of sessions required to learn either the first, second, or third concurrent discrimination task. In Experiment 2, the same pigeons were trained on an open-field spatial task similar in many ways to the radial-arm maze task used with rats. In contrast to the absence of impairments on the visual concurrent discrimination task, pigeons with Hp-APH lesions were severely impaired on the acquisition of the spatial task. These findings support the view that the Hp-APH in pigeons is important for the processing of spatial, rather than visual information.

Animals↗
PubMed1997

Unexpected death of psychiatric patients: suicide, misadventure, accident or unsolved mystery?

We examined the association between the psychiatric history of patients who were the subjects of a coroner's inquest and the recorded verdict, in a seven-year retrospective review. A suicide verdict was less frequently returned on patients who had inpatient psychiatric treatment compared to other unexpected deaths. History and diagnosis of an alcohol-related condition, method of death and intimation of intent were the main factors that appeared to be associated with the coroner's verdict. Age, sex, duration of illness, time and number of admissions, previous suicide attempts and treatment received did not appear to be significantly associated with the recorded verdict.

Accidents↗
PubMed1990

Cyclosporin A modulation of the acute inflammatory response: an explanation for the effect of CsA on host defences in infection.

Previous studies have shown that the administration of cyclosporin A (CsA) to animals with experimentally induced pyelonephritis resulted in considerable exacerbation of infection. T-lymphocytes are not involved in the host response to pyelonephritis but neutrophils are known to be a key component in the pathogenesis of this infection, so the effect of CsA on this inflammatory component was investigated. CsA administration did not affect the metabolic activity of neutrophils in vitro nor their ability to phagocytose and kill microorganisms. However, the ability of neutrophils to mobilize to a sterile inflammatory focus in vivo was significantly impaired. Further experiments, using models of pyelonephritis and subcutaneous infection, demonstrated that the CsA-induced suppression of neutrophil mobilization was directly related to the observed increase in bacterial numbers and exacerbation of tissue damage. Additionally, the actual effect of CsA on host defences and the outcome of infection was found to be dependent on the level of the initial infectious challenge. The results of this study provide an explanation for the current pattern of infectious disease in patients treated with CsA, in whom infection with extracellular pathogens is still common. It is also clear that the effect of CsA on inflammatory mechanisms may explain the efficacy of the agent in inflammatory diseases such as rheumatoid arthritis. This suggests a wider therapeutic role for CsA than is currently recognized.

Acute-Phase Reaction↗
PubMed1988

Peripheral blood leukocyte count as an index of defense status in the leukopenic host.

These experimental studies have investigated the reliability of the peripheral blood leukocyte count to predict whether the leukopenic host can contain or eliminate infection. Additionally, we have investigated the possibility that determination of leukocyte recruitment, supplementary to peripheral blood leukocyte counts, might allow individuals with neutropenia at risk from serious infection to be distinguished with greater certainty. Varying doses of radiation, cyclophosphamide, and methylprednisolone were used to induce distinct levels of leukopenia in rats. Leukocyte recruitment was measured by quantifying the response of neutropenic animals to evocative, subcutaneous stimuli, and the results of this assay were then compared with circulating leukocyte counts in the same individuals. Six models of experimentally induced infection were used to compare circulating and recruitable leukocytes as indicators of the susceptibility of the leukopenic host to infection. Response curves relating leukocyte numbers to host resistance were similar when circulating or recruitable leukocytes were used as an index of defense capability. These findings support the use of peripheral blood leukocyte numbers as an index of resistance to infection in individuals with leukopenia and suggest that functional analyses such as leukocyte recruitment are unlikely to provide additional information.

Animals↗
PubMed1987

Cellular basis of host defence in pyelonephritis. III. Deletion of individual components.

Hosts were depleted of individual cellular components to determine the effects of these manipulations on cellular defence mechanisms in acute and chronic pyelonephritis. T-lymphocytes were found to have little or no involvement in host protection but cyclosporin A administration had a dramatic effect on the gross pathology and bacteriological status of experimentally induced pyelonephritis. This change represented a major depression of host defence status. Cyclosporin A also activated resolved lesions in chronic pyelonephritis, associated with an increase in bacterial numbers. Administration of antineutrophil serum also led to a 1000-fold increase in bacterial numbers in the acute phase but had little effect on the host-parasite balance in chronic pyelonephritis. Macrophage blockade, on the other hand, did not affect the course of either acute or chronic infection. These studies have provided additional information on the immunobiology of experimental pyelonephritis and have focussed attention on the role of neutrophils, and an unidentified mechanism, affected by cyclosporin A, in host defence to renal infection.

Animals↗
PubMed1986

Sustained release of a corticosteroid using polymeric implants.

An effective sustained release method of drug administration, using methylprednisolone incorporated into acrylic bone cement, has been developed. The effect of this form of treatment on peripheral blood leukocytes, lymphoid tissue weight and the inflammatory response has been evaluated. This mode of methylprednisolone administration was compared with conventional systemic therapy and was found to produce rapid and prolonged pharmacological effects at very low plasma levels of drug. A dose response relationship was established and we determined that, for a given quantity of drug, the level and duration of suppression was greater using sustained release therapy. The inflammatory response was also depressed using this mode of administration. These results, coupled with the commercial availability and existing clinical approval of SIMPLEX P bone cement, suggest that further development may lead to useful clinical protocols.

Adrenal Cortex Hormones↗
PubMed1986

Cellular basis of host defence in pyelonephritis. I. Chronic infection.

Infection persists for long periods in chronic pyelonephritis, but the cellular basis of the host-parasite relationship is poorly understood. We have obtained quantitative data on the relationship between the pathogen (E. coli) and cellular defence mechanisms. Depletion of cellular components was carried out using whole body irradiation, methylprednisolone, cyclophosphamide or carrageenan and silica particles. A system of administering cyclophosphamide and methylprednisolone through the use of a slow release carrier, as well as graded doses of irradiation, was then developed to allow the controlled reduction of cellular competence. Quantitative studies in a host with chronic pyelonephritis and normal cellular defence reserves showed that severe depletion of granulocytic cells is necessary before host defence mechanisms are adversely affected. This finding conflicts with the observation that microorganisms survive and persist in the kidney for extended periods. Additionally, noncellular factors may also limit bacterial growth.

Animals↗
PubMed1986

Cellular basis of host defence in pyelonephritis. II. Acute infection.

We have investigated the cellular basis of host defence mechanisms in experimental pyelonephritis. Cellular components of the host defence system were depleted using cyclophosphamide, methylprednisolone or radiation. Depletion of cellular competence did not affect the course of infection during the first 16 h after challenge with Escherichia coli, but after 96 h up to a 1000-fold increase in bacterial numbers in the kidneys of cytodepleted animals was demonstrable. When quantitative aspects of the relationship between cellular competence and host defence were studied, it was found that severe depletion of cellular components was necessary before host defence mechanisms were adversely affected. Thus while cellular mechanisms are quantitatively adequate and contribute to host defence in pyelonephritis they have little impact on the immediate post-infection phase. Non-cellular factors however, do limit bacterial proliferation in the acute phase and may be important determinants in the biology of pyelonephritis.

Acute Disease↗
PubMed1985

Extended immunosuppression with cyclophosphamide using controlled-release polymeric implants.

An effective method of prolonged immunosuppressive therapy using cyclophosphamide incorporated into acrylic bone cement has been developed. We have studied the effect of this form of administration of cyclophosphamide on circulating immune cells and the inflammatory response. When the slow release mode of cyclophosphamide administration was compared with conventional systemic therapy, it was found to produce a more rapid and prolonged immunosuppression. A dose-response relationship was established and the biological effects of varying the composition and surface area of the implant were determined. The inflammatory response, assessed by measuring the mobilisation of cells into subcutaneously implanted sponges, was also depressed using this mode of administration. These results, coupled with the commercial availability and existing clinical approval of Simplex P bone cement, suggest that the procedure could lead to useful clinical protocols.

Animals↗
PubMed1985

Immunopotentiation in infectious disease, I. Effect of bestatin on the immune response.

Few immunomodulators are available for the control of infectious disease. One reason has been the lack of a suitable protocol for evaluating such agents. We have presented a series of assays of immune function that will allow a standardized approach to this problem. The value of this protocol has been established using long-term low dose, and short-term high dose, administration of bestatin, a small molecular weight microbial product. The experiments were done using both normal and immunocompromised animals. Bestatin had no effect on circulating leukocytes or the reticuloendothelial system. Leukocyte mobilization and T cell responsiveness in immunocompromised animals were enhanced following bestatin treatment. The antibody response to SRBC doubled in normal animals while the same treatment schedule resulted in a marked reduction in the response to Escherichia coli lipopolysaccharide. These results have established the value of the protocol and identified some new immunomodulating properties of bestatin which may be useful in the control of infectious disease.

Adjuvants, Immunologic↗
PubMedDate not supplied

Brief psychiatric admissions: a review.

Concern about mentally ill patients admitted to psychiatric hospitals for short periods is long standing. Often, admission takes place at night when clinical expertise is in short supply. In this study, the researchers found that these patients were admitted to expensive hospital beds not for health needs but often for social reasons. The authors suggest that community-based, short stay psychiatric units are more suitable for the care of these patients.

Adolescent↗