1,959 research outputs found
Operations auditing, a study of the newest phase of internal auditin
The purpose of this paper is to stipulate internal auditing as an independent appraisal activity within an organization for the review of accounting, financial, and other operations as a basis for service to management
Studies relating to the breast, its tumours and fluids
This thesis comprises 61 papers which describe work undertaken between 1972 and
1985. The research was performed in order to obtain basic information on the
environment and the biochemical processes existing within the female breast. It
was thereby hoped to achieve a better understanding of events which occur during
the development of breast disease, particularly breast cancer.Hormones are involved not only in the natural development of normal breast but
also in the aetiology of many breast abnormalities and, most importantly, in the
continued growth of a proportion of breast cancers. A major aspect of the research
described in this thesis is concerned with the measurement of steroid hormones,
their metabolism and receptors in the breast, its tumours and secretions.
Additionally studies have been performed to assess the significance of other
markers of tumour behaviour and to determine whether agents such as LHRH analogues
have direct effects within the breast.The potential of the breast to modify its own hormonal environment has been
investigated by performing in vitro incubations with steroid precursors. Pathways
leading to both active androgens and oestrogens have been identified. Biosynthesis
of 5 reduced androgens occurs in all types of breast tissue but is particularly
associated with apocrine differentiation. The production of oestrogen or
"aromatization" was detected in a proportion of breast cancers but not in non-malignant
tissue. The significance of tumour aromatase is controversial but it may be
important in oestrogen-dependent cancers growing in post-menopausal women who have
low circulating levels of oestrogen.In order to estimate levels of androgen precursors within the breast, measurements
of DHA sulphate have been made in breast secretions obtained by nipple aspiration
and breast cyst fluids. Remarkably high, but variable, concentrations have been
detected. Further investigations of the composition of such breast fluids have shown
them to have a distinctive composition in terms of ionic content, major types of
immunoglobulins and concentrations of plasma-, platelet-associated and other proteins.
Cyst fluids may be subdivided into two major populations which are lined by different
epithelium and have a differing natural history.Several series of breast cancers have been analysed for either androgen receptors,
progestogen receptors, cyclic AMP binding proteins, prostaglandins or expression of
lectin binding. These have been suggested to be markers of metastatic potential or
hormone-responsiveness. Inter-relationships have been made with oestrogen receptors
and other tumour/patient characteristics but assessment of clinical value awaits
patient follow-up.The possibility that polypeptide hormones have direct actions on the breast was
investigated by culturing breast cancer cells with LHRH and its analogues. Marked
inhibitory effects which appear to be mediated by a specific recognition mechanism have
been demonstrated. These findings are reviewed in terms of their significance to the
management of patients with breast disease.SECTION A STEROID METABOLISM BV THE HUMAN BREAST AND ITS TUMOURS
1. Miller W R, McDonald D, Forrest A P M and Shivas A A (1 973)
Metabolism of androgens by human breast tissue. The Lancet
i; 912-913.
2. Miller W R, McDonald D and Forrest A P M (1 973)
Steroidogenesis in human breast cancer, benign breast disease
and normal breast tissue. Biochemical Society Transactions
l;762-765.
3. Miller W R, McDonald D, MacFadyen I, Roberts M M and Forrest A
P M (1974) Androgen metabolism in gynaecomastic breast
tissue. Clinical Endocrinology 3.; 123-130.
4. Miller W R and Forrest A P M (1974) Oestradiol synthesis by
a human breast carcinoma. The Lancet ii:866-868.
5. Miller W R and Forrest A P M (1 976) Oestradiol synthesis
from C.|q steroids by human breast cancers. Br J Cancer
33.; 116-118.
6. Miller ¥ R, Shivas A A and Forrest A P M (1978) Factors
affecting testosterone metabolism by human breast tissues.
Clinical Oncology l;77-85.
7. Miller W R (1981) Inhibition of aromatization by
aminoglutethimide in breast cancers - clinical relevance. In
"Aminoglutethimide. An alternative endocrine therapy for
breast carcinoma" ed. R W Elsdon-Dew, I M Jackson and G F B
Birdwood. Royal Society of Medicine International Congress
and Symposium Series No. 53. Academic Press Inc (London) Ltd.
8. Miller W R, Hawkins R A and Forrest A P M (1981) Steroid
metabolism and oestrogen receptors in human breast carcinomas.
Europ J Cancer (Clin Oncology) 17:913-917.
9. Mason R C, Burns D A, Miller W R, Hawkins R A and Forrest A P
M (1981) Tumour steroid synthesis and oestrogen receptor
status in breast cancer patients. Breast Cancer Treatment &
Research l;263-266.
10. Miller W R, Hawkins R A and Forrest A P M (1 982)
Significance of aromatase activity in human breast cancer.
Cancer Research 42:3365-3368.
11. Miller W R Aromatase activity and breast cancer. Turkey
National Cancer Prevention Association Booklet.
12. Miller W R and Forrest A P M (1 978) In vitro effects of
oestradiol on testosterone metabolism by human breast cancers.
European J Cancer 14:865-867.
13. Mason R C, Miller W R, Hawkins R A, Brown M S and Forrest A P
M (1983) Effects of drugs associated with
hyperprolactinaemia and plasma steroids and on steroid
receptors and metabolism in human breast cancer. Breast
Cancer Research and Treatment 3;331-338.
14. Miller W R, Telford J, Dixon J M and Shivas A A (1985)
Androgen metabolism and apocrine differentiation in human
breast cancer. Breast Cancer: Research and Treatment 3; 67-
73.
15. Miller W R (1986) Steroid metabolism in breast
cancer. In "Breast cancer: Treatment and Progress" Ed. B A
Stoll. Published Blackwell Scientific Publications,
pp.156-172
16. MillerW R (1986) Steroid metabolism in breast cancer.
Reviews on Endocrine-Related Cancer. 23;23-30.SECTION B. STEROID METABOLISM BY (A) RAT MAMMARY TUMOURS AND (B)
OTHER HUMAN TISSUES
17. Miller W R, Forrest A P M and Hamilton T (1974) Steroid
metabolism by human breast and rat mammary carcinoma.
Steroids 235379-395.
18. Miller W R (1976) Hyperprolactinaemia and steroid metabolism
by rat mammary adenocarcinoma. Cancer Research 36.5336-338.
19. Miller W R, Buchan R and Forrest A P M (1974) Effects of
prolactin upon C₁₉ steroid metabolism by rat mammary
carcinoma. Biochemical Society Transactions 2.5312-314,
20. Buchan P, Fraser A T and Miller W R (1976) The effect of
perphenazine treatment on testosterone metabolism by
established rat mammary carcoinomas. Biochem Soc Transact
A; 1100-1102.
21. Buchan P and Miller W R (1978) Perphenazine and testosterone
metabolism by mammary tumours in oophorectomised rats.
Biochem Soc Transact 6;133-134.
22. Miller W R (1976) Hormone status and testosterone metabolism
of DMBA induced rat mammary carcinomas. Br J Cancer 34:296-
298
23. Miller W R (1976) In vitro effects of oestrogen on 5α
reduction of testosterone in hormone dependent rat mammary
carcinomata. Br J Cancer 33:474-477.
24. Miller W R (1976) in vitro effects of prolactin upon
testosterone metabolism by rat mammary carcinomas. European
J Cancer 18:679-682.
25. Miller W R and Telford J (1 975) The effect of oestrogen on
steroid metabolism by rat mammary carcinomas. Bui Soc Int
Chir 3A;531-533.
26. Miller W R (1980) The effects of serial passage on the
endocrine response and steroid metabolism of a rat
transplantable mammary carcinoma. Br J Cancer J(2.;326-330.
27. Miller W R, Stewart R and Hawkins R A (1979) Hormonal status
and steroid metabolism in two transplantable rat mammary
tumours.
Br J Cancer 29.;200-204.
28. Miller W R, Shivas A A and Forrest A P M (1974) Steroid
metabolism by human normal thyroid, nodular goitre and thyroid
cancer. Br J Cancer 2Q.; 284-287.
29. Miller W R, Shivas A A and Forrest A P M (1976) Steroid
interconversions by metastatic deposits of a human
bronchogenic carcinoma. Clinical Oncology 2; 127-130.SEQTIQN C - URINARY STEROIDS IN PATIENTS WITH BREAST DISEASE
30. Miller W R, Hamilton T, Champion H R, Wallace I W J, Forrest A
P M, Prescott R J, Cameron E H D and Griffiths K (1975)
Urinary aetiocholanolone in patients with early breast cancer
from South East Scotland and South Wales. Br J Cancer
828:619-627.
31. Prescott R J, Miller W R and Hamilton T (1978) Urinary
aetiocholanolone and prognosis in early carcinoma of the
breast. J Surgical Oncology 10:847-851.SECTION D - COMPOSITION OF BREAST FLUIDS
32. Miller W R, Humeniuk V and Kelly R W (1980)
Dehydroepiandrosterone sulphate in breast secretions. J
Steroid Biochem 18:145-1 51.
33. Miller W R, Humeniuk V and Forrest A P M (1981) Factors
affecting dehydroepiandrosterone sulphate levels in human
breast secretions. Breast Cancer Research & Treatment 1;267-
272.
34. Yap P L, Miller W R, Humeniuk V, Pryde E A D, Mirtle C L and
McClelland D B L (1981) Milk protein concentrations in the
mammary sections of non-lactating women. J Reprod Immunol
2; 49-58.
35. Miller W R, Roberts M M, Creel R J, Yap P L, Kelly R W and
Forrest A P M (1982) Androgen conjugates in human breast
cyst fluids. J.Nat. Can. Inst. 1055-1058.
36. Miller W R and Forrest A P M (1 983) Androgen conjugates in
human breast secretions and cyst fluids. In "Endocrinology
of Cystic Breast Disease" Ed. A Angeli et al. Published by
Raven Press, New York pp. 77-84.
37. Miller W R, Dixon J M, Scott W N and Forrest A P M (1983)
Classification of human breast cysts according to electrolyte
and androgen conjugate composition. Clin Oncology 9;227-232.
38. Dixon J M, Miller W R, Scott W N and Forrest A P M (1983)
The morphological basis of human breast cyst populations. Br
J Surg 70:604-606.
39. Dixon J M and Miller W R (1984) Human Breast cystic disease.
Breast News 1;6—9.
40. Dixon J M, Scott W N and Miller W R (1985) Natural history of
cystic disease: the importance of cyst type. Br J Surg
22.5190-1 92.
41. Dixon J M, Lumsden A B and Miller W R (1 985) The
relationship of cyst type to risk factors for breast cancer
and the subsequent development of breast cancer in patients
with breast cystic disease. Europ J Cancer 21:1Q47-1050.
42. Dixon J M and Miller VI R (1984) The pH of human breast cyst
fluids. Clinical Oncology 10:221-224.
43. Yap P C, Miller W R, Roberts M M, Creel R J, Freedman B, Pryde
E A D and McClelland D B L (1984) Protein concentrations in
fluid from gross cystic disease of the breast. Clinical
Oncology 1 0:35-43.
44. Miller W R and Dixon J M (1986) Hormonal correlates of
apocrine secretion in the breast. Annals of the New York
Academy of Science 464:275-287.
45. Miller W R and Dawes J (1985) Platelet-associated proteins
in human breast cyst fluids. Clin Chim Acta 192:37-42.
46. Dixon J M, Scott W N and Miller W R (1 985) An analysis of
the content and morphology of human breast microcysts. Europ
J of Surg Oncol H; 151-154.SECTION E = MARKERS OF TUMOUR BEHAVIOUR
47. Hawkins R A, Hill A, Freedman B, Killen E, Buchan P, Miller W
R and Forrest A P M (1977) Oestrogen receptor activity and
endocrine status in DMBA induced rat mammary tumours.
European J Cancer 13.5223-228.
48. Hawkins R A, Hill A, Freedman B, Killen E and Miller W R
(1978) Oestrogen receptor activity in transplantable ovary
independent mammary tumours of the rat. Europ J Cancer
14;83-90.
49. Hawkins R A, Tesdale A, Freedman B, Telford J and Miller W R
(1981) Progestogen and oestrogen receptor activity in ovary
dependent and ovary independent tumours of the rat. Europ J
Cancer 5.558 5-587-
50. Mason R C, Steele R J C, Hawkins R A, Miller W R and Forrest A
P M (1982) Cellularity and the quantification of oestrogen
receptors. Breast Cancer Treatment and Research 2.5239-242.
51. Miller W R, Telford J and Hawkins R A (1 983) Binding of 3h
methyltrienolone (R1881) by human breast cancers. Europ J
Cancer (Clin Oncology) 12.5 1473-1478.
52. Miller W R, Telford J, Dixon J M and Hawkins R A (1 985)
Androgen receptor activity in human breast cancer and its
relationship with oestrogen and progestogen activity. Europ
J Cancer 21;539-542.
53. Watson DMA, Kelly R W, Hawkins R A and Miller W R (1984)
Prostaglandins in human mammary cancer. Br J Cancer 4Q45Q-
464.
54. Miller W R, Senbanjo R 0, Telford J and Watson DMA (1 985)
Cyclic AMP binding proteins in human breast cancer. Br J
Cancer 52.5531-535.
55. Miller W R, Sturgeon C M and Walker R A (1 983) Carcino
embryonic antigen (CEA) in explants of human breast cancer:
comparison of immuno histochemical detection and release
during short-term culture. Br J Cancer 47:429-432.
56. Zangerle P F, Collette J, Hendricks J C, Miller W R and
Franchimont P (1982) Milk proteins and breast cancer. In
"Markers for Diagnosis and Monitoring of Human Cancer" Ed. M I
Colnaghi, G I Buragge, Ghione M. Academic Press, London and
New York. pp 35-49.
57. Walker R A, Hawkins R A and Miller W R (1985) Lectin binding
and steroid receptors in human breast carcinomas. J Pathol 147; 103-106.SECTION F - DIRECT EFFECTS OF POLYPEPTIDES .ON BREAST CANCER CELLS
58. Miller W R, Scott W N, Morris R, Fraser H M and Sharpe R M
(1 985) Growth of human breast cancer cells inhibited by a
luteinizing hormone-releasing hormone agonist. Nature
311;231-233.
59. Miller W R, Scott W N, Morris R, Fraser H M and Sharpe R M
(1986) Direct effects of LHRH and agonists on human breast
cancer cells. "Neuroendocrine Molecular Biology". Ed. G
Fink, A J Harmar, K W McKerns. Plenum Press: New York and
London. Pp.475-488.SECTION G - REVIEWS
60. Forrest A P M and Miller W R (1985) Hormones and female
breast cancer: clinical relevance. In "Accomplishments in
Cancer Research" General Motors Publication Ed J G Fortner
and J E Rhoads.Pub. J B Lippincott Co. Philadelphia pp 134-
151 .
61. Miller W R and Anderson, T A Oestrogens, progestogens and
the breast. In "The Menopause". Eds M I Whitehead and J
Studd. Pub.Blackwell Scientific Press (in press)
Scottish Water: The Drift To Privatisation and How Democratisation Could Improve Efficiency and Lower Costs
First paragraph: Scottish Water is a public corporation1 responsible for delivering water and sewerage services in Scotland. It was created in 2002 under the Water Industry Act (Scotland), which amalgamated the three water boards2 who were previously responsible for delivering water services in the North, East and West of Scotland
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Higher measured than modeled ozone production at increased NOx levels in the Colorado Front Range
Abstract. Chemical models must correctly calculate the ozone formation rate, P(O3), to accurately predict ozone levels and to test mitigation strategies. However, air quality models can have large uncertainties in P(O3) calculations, which can create uncertainties in ozone forecasts, especially during the summertime when P(O3) is high. One way to test mechanisms is to compare modeled P(O3) to direct measurements. During summer 2014, the Measurement of Ozone Production Sensor (MOPS) directly measured net P(O3) in Golden, CO, approximately 25 km west of Denver along the Colorado Front Range. Net P(O3) was compared to rates calculated by a photochemical box model that was constrained by measurements of other chemical species and that used a lumped chemical mechanism and a more explicit one. Median observed P(O3) was up to a factor of 2 higher than that modeled during early morning hours when nitric oxide (NO) levels were high and was similar to modeled P(O3) for the rest of the day. While all interferences and offsets in this new method are not fully understood, simulations of these possible uncertainties cannot explain the observed P(O3) behavior. Modeled and measured P(O3) and peroxy radical (HO2 and RO2) discrepancies observed here are similar to those presented in prior studies. While a missing atmospheric organic peroxy radical source from volatile organic compounds co-emitted with NO could be one plausible solution to the P(O3) discrepancy, such a source has not been identified and does not fully explain the peroxy radical model–data mismatch. If the MOPS accurately depicts atmospheric P(O3), then these results would imply that P(O3) in Golden, CO, would be NOx-sensitive for more of the day than what is calculated by models, extending the NOx-sensitive P(O3) regime from the afternoon further into the morning. These results could affect ozone reduction strategies for the region surrounding Golden and possibly other areas that do not comply with national ozone regulations. Thus, it is important to continue the development of this direct ozone measurement technique to understand P(O3), especially under high-NOx regimes
Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I
Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. Affected children commonly suffer acute brain injury in the context of a catabolic state associated with nonspecific illness. The mechanisms underlying injury and age-dependent susceptibility have been unknown, and lack of a diagnostic marker heralding brain injury has impeded intervention efforts. Using a mouse model of GA-I, we show that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance (1H NMR) spectroscopy as a diagnostic marker. Blocking brain lysine uptake reduced glutaric acid levels and brain injury. These findings provide what we believe are new monitoring and treatment strategies that may translate for use in human GA-I
Polymicrobial oral biofilm models: simplifying the complex
Over the past century, numerous studies have used oral biofilm models to investigate growth kinetics, biofilm formation, structure and composition, antimicrobial susceptibility and host–pathogen interactions. In vivo animal models provide useful models of some oral diseases; however, these are expensive and carry vast ethical implications. Oral biofilms grown or maintained in vitro offer a useful platform for certain studies and have the advantages of being inexpensive to establish and easy to reproduce and manipulate. In addition, a wide range of variables can be monitored and adjusted to mimic the dynamic environmental changes at different sites in the oral cavity, such as pH, temperature, salivary and gingival crevicular fluid flow rates, or microbial composition. This review provides a detailed insight for early-career oral science researchers into how the biofilm models used in oral research have progressed and improved over the years, their advantages and disadvantages, and how such systems have contributed to our current understanding of oral disease pathogenesis and aetiology
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Manticore and CS mode : parallelizable encryption with joint cipher-state authentication.
We describe a new mode of encryption with inexpensive authentication, which uses information from the internal state of the cipher to provide the authentication. Our algorithms have a number of benefits: (1) the encryption has properties similar to CBC mode, yet the encipherment and authentication can be parallelized and/or pipelined, (2) the authentication overhead is minimal, and (3) the authentication process remains resistant against some IV reuse. We offer a Manticore class of authenticated encryption algorithms based on cryptographic hash functions, which support variable block sizes up to twice the hash output length and variable key lengths. A proof of security is presented for the MTC4 and Pepper algorithms. We then generalize the construction to create the Cipher-State (CS) mode of encryption that uses the internal state of any round-based block cipher as an authenticator. We provide hardware and software performance estimates for all of our constructions and give a concrete example of the CS mode of encryption that uses AES as the encryption primitive and adds a small speed overhead (10-15%) compared to AES alone
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