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T Brown

Publications and source records attributed to T Brown.

At least 37 records · Page 2Linked to original sources
PubMed2004

The Asian Epidemic Model: a process model for exploring HIV policy and programme alternatives in Asia.

Process models offer opportunities to explore the effectiveness of different programme and policy alternatives by varying input behaviours and model parameters to reflect programmatic/policy effects. The Asian Epidemic Model (AEM) has been designed to reflect the primary groups and transmission modes driving HIV transmission in Asia. The user adjusts AEM fitting parameters until HIV prevalence outputs from the model agree with observed epidemiological trends. The AEM resultant projections are closely tied to the epidemiological and behavioural data in the country. In Thailand and Cambodia they have shown good agreement with observed epidemiological trends in surveillance populations and with changes in HIV transmission modes, AIDS cases, male:female ratios over time, and other external validation checks. By varying the input behaviours and STI trends, one can examine the impact of different prevention efforts on the future course of the epidemic. In conclusion, the AEM is a semi-empirical model, which has worked well in Asian settings. It provides a useful tool for policy and programme analysis in Asian countries.

Asia↗
PubMed2004

The UNAIDS Estimation and Projection Package: a software package to estimate and project national HIV epidemics.

This paper describes the Estimation and Projection Package (EPP) for estimating and projecting HIV prevalence levels in countries with generalised epidemics. The paper gives an overall summary of the software and interface. It describes the process of defining and modelling a national epidemic in terms of locally relevant sub-epidemics and the four epidemiological parameters used to fit a curve to produce the prevalence trends in the epidemic. It also provides an example of using the EPP in a country with a generalised epidemic. The paper discusses the strengths and weaknesses of the software and its envisaged future developments.

Adolescent↗
PubMed2004

Uncertainty in estimates of HIV/AIDS: the estimation and application of plausibility bounds.

OBJECTIVES: To establish the accuracy of the country specific estimates of HIV prevalence, incidence, and AIDS mortality published every 2 years by UNAIDS and WHO. METHODS: We review sources of error in the data used to generate national HIV/AIDS and where possible estimate their statistical properties. We use numerical and approximate analytic methods to estimate the combined impact of these errors on HIV/AIDS estimates. Heuristic rules are then derived to produce plausible bounds about these estimates for countries with different types of epidemic and different qualities of surveillance system. RESULTS: Although 95% confidence intervals (CIs) can be estimated for some sources of error, the sizes of other sources of error must be based on expert judgment. We therefore produce plausible bounds about HIV/AIDS estimates rather than statistical CIs. The magnitude of these bounds depends on the stage of the epidemic and the quality and coverage of the sentinel HIV surveillance system. The bounds for adult estimates are narrower than those for children, and those for prevalence are narrower than those for new infections. CONCLUSIONS: This paper presents a first attempt at a rigorous description of the errors associated with estimation of global statistics of an infectious disease. The proposed methods work well in countries with generalised epidemics (>1% adult HIV prevalence) where the quality of surveillance is good. Although methods have also been derived for countries with low level or concentrated epidemics, more data on the biases in the estimation process are required.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Surveillance and modelling of HIV, STI, and risk behaviours in concentrated HIV epidemics.

BACKGROUND: HIV epidemics in most countries are highly concentrated among population subgroups such as female sex workers, injecting drug users, men who have sex with men, mobile populations, and their sexual partners. The perception that they are important only when they cause epidemic expansion to general populations has obscured a critical lack of coverage of preventive interventions in these groups, as well as appropriate methods for monitoring epidemic and behavioural risk trends. The difficulties in accessing such groups have likewise often cast doubt on the representativeness of observed disease and behavioural risk estimates and their validity and reliability, particularly those related to sampling and the measurement of risk behaviours. OBJECTIVES: To review methodological obstacles in conducting surveillance with population subgroups in concentrated HIV epidemics, elaborate on recent advancements that partially overcome these obstacles, and illustrate the importance of modelling integrated HIV, STI, and behavioural surveillance data. METHODS: Review of published HIV, STI, and behavioural surveillance data, research on epidemic dynamics, and case studies from selected countries. CONCLUSIONS: The population subgroups that merit regular and systematic surveillance in concentrated epidemics are best determined through extensive assessment and careful definition. Adherence to recently refined chain referral and time location sampling methods can help to ensure more representative samples. Finally, because of the inherent limitations of cross sectional surveys in understanding associations between complex sexual behaviours and HIV and STI transmission, mathematical models using multiple year data offer opportunities for integrated analysis of behavioural change and HIV/STI trends.

Cross-Sectional Studies↗
PubMed2004

Breast cancer detection rates, and standardised detection ratios for prevalence screening in the New Zealand breast cancer screening programme.

OBJECTIVES: To calculate breast cancer detection to expected incidence ratios and standardised detection ratios (SDRs) for the New Zealand breast cancer screening programme. METHOD: Breast cancer registrations for 1976-1999 were obtained from the New Zealand Cancer Registry. Using these registrations, the incidence in the absence of screening was projected for 1999 and 2000. These projections, and the invasive breast cancers detected in the New Zealand programme during 1999 and 2000, were used to calculate the detection to expected incidence ratios and SDRs. RESULTS: In 1999, the breast cancer detection rate was 5.6 per 1000 women screened. The expected incidence among these women in the absence of screening was 2.3 per 1000, a detection to expected incidence ratio of 2.4. The SDR was 0.84 (0.76-0.94). In 2000, the breast cancer detection rate was 6.0 per 1000 women screened. The expected incidence among these women in the absence of screening was 2.4 per 1000, a detection to expected incidence ratio of 2.5. The SDR was 0.90 (0.81 - 0.99). CONCLUSIONS: In the first two years of the national programme, detection to expected incidence ratios were less than 3.0, and the SDR results were below 1.0. It may be unrealistic to expect new screening programmes to achieve SDRs of 1.0 immediately. At a similar stage, the UK National Health Service Breast Cancer Screening Programme (NHSBSP) also reported SDRs of less than 1.0 and therefore lower than expected cancer detection rates compared with the Swedish Two-County trial. An encouraging finding was that SDRs in five of the six screening regions improved in the second year of the New Zealand screening programme.

Breast Neoplasms↗
PubMed2003

Sequence-selective metalation of double-helical oligodeoxyribonucleotides with PtII, MnII, and ZnII ions.

Reactions of [PtCl(dien)](+) (dien=diethylenetriamine), Mn(2+) and Zn(2+) ions with three different double-helical oligodeoxyribonucleotides, which contain the central sequence GGXY (XY=AT, TA or CC) have been monitored by NMR spectroscopy. 2 D [(1)H, (15)N] HSQC/HMQC NMR spectroscopy using (15)N-labeled Pt(dien) shows that the rate of formation of 3'-G-N 7 and 5'-G-N 7 platinated adducts is highly sequence dependent. The relative rates of platination of 5'-G versus 3'-G are largest for the sequence -GGCC-, for which only a small fraction of the 3'-G adduct is formed; for -GGTA-, the rate of 5'-G platination is about eight times that of 3'-G, and for -GGAT- the ratio is 1.2. These values are in qualitative agreement with those obtained for G-N 7/Mn(2+) selectivity as determined by paramagnetic line broadening of the adjacent G-H 8, and also G-N 7/Zn(2+) selectivity as determined by G-H 8 chemical shift changes. Fluctuation in the nucleophilicity of G-N 7 may be explained by variation of the pi-stacking interaction between base residues along the double helix. The reaction mixtures containing platinated 3'-G and 5'-G fractions were separated by HPLC. Since the duplexes are self-complementary, the platinated single strands were readily annealed to duplexes with twofold symmetry and analyzed by 2 D [(1)H, (1)H] NOESY NMR spectroscopy. Unexpectedly, the 5'-G-H 8 resonance signals of both 5'-G and 3'-G platinated duplexes showed large downfield shifts in the range delta=0.3-0.6 ppm, while the 3'-G-H 8 resonance signals in both cases exhibited no, or only slight, upfield shifts. Resonance signals for several other protons in the central region undergo large chemical shift variations induced by platination, indicating that monofunctional binding to DNA leads to appreciable conformational changes.

Base Sequence↗
PubMed2003

Forensic web watch--forensic podiatry.

A search for forensic podiatry sites on the Internet revealed thousands of 'hits', of which very few were of any educational merit. Following extensive sifting of these addresses, it was found that only a few of the associations for human identification included any information on forensic podiatry methods. The search was also made difficult by many websites failing to make the distinction between studies of footwear prints and forensic podiatry: the study of barefoot impressions. At present, the volume and quality of information on the World Wide Web does not reflect the potential importance of podiatry in forensic investigations. The need for improvement in the quality and available information this field is therefore recommended.

Journal Article↗
PubMed2003

An Irish three-generation family of Cornelia de Lange syndrome displaying autosomal dominant inheritance.

The existence of familial de Lange syndrome has been documented in sibs and in parent-child families, but the inheritance pattern continues to be the cause of much debate. We describe a classically affected neonate with de Lange syndrome, an affected mother and probably affected maternal grandmother. These cases show evidence for a dominantly inherited syndrome with a de Lange phenotype.

Adult↗
PubMed2003

A clinical approach to the management of a patient with suspected renovascular disease who presents with leg ischemia.

Atherosclerotic renal artery stenosis (ARAS) may cause hypertension, progressive renal failure, and recurrent pulmonary edema. It typically occurs in high risk patients with coexistent vascular disease elsewhere. Most patients with ARAS are likely to die from coronary heart disease or stroke before end-stage renal failure occurs. Recent controlled trials have shown that most patients undergoing angioplasty to treat renovascular hypertension still need antihypertensive agents 6 or 12 months after the procedure. Nevertheless, the number of antihypertensive agents required to control blood pressure adequately is lower following angioplasty than for medication alone. Trials assessing the value of revascularization for preserving renal function or preventing clinical events are only in the early recruitment phase. Revascularization should be undertaken in patients with ARAS and resistant hypertension or heart failure, and probably in those with rapidly deteriorating renal function or with an increase in plasma creatinine levels during angiotensin-converting enzyme inhibition. With or without revascularization, medical therapy using antihypertensive, hypolipidemic and antiplatelet agents is necessary in almost all cases.

Humans↗
PubMed2002

Delivery of glucose-6-phosphatase in a canine model for glycogen storage disease, type Ia, with adeno-associated virus (AAV) vectors.

Therapy in glycogen storage disease type Ia (GSD Ia), an inherited disorder of carbohydrate metabolism, relies on nutritional support that postpones but fails to prevent long-term complications of GSD Ia. In the canine model for GSD Ia, we evaluated the potential of intravenously delivered adeno-associated virus (AAV) vectors for gene therapy. In three affected canines, liver glycogen was reduced following hepatic expression of canine glucose-6-phosphatase (G6Pase). Two months after AAV vector administration, one affected dog had normalization of fasting glucose, cholesterol, triglycerides, and lactic acid. Concatamerized AAV vector DNA was confirmed by Southern blot analysis of liver DNA isolated from treated dogs, as head-to-tail, head-to-head, and tail-to-tail concatamers. Six weeks after vector administration, the level of vector DNA signal in each dog varied from one to five copies per cell, consistent with variation in the efficiency of transduction within the liver. AAV vector administration in the canine model for GSD Ia resulted in sustained G6Pase expression and improvement in liver histology and in biochemical parameters.

Animals↗
PubMed2002

Behavioural knowledge, causal beliefs and self-efficacy as predictors of special educators' emotional reactions to challenging behaviours.

Theoretical models and emerging empirical data suggest that the emotional reactions of staff to challenging behaviours may affect their responses to challenging behaviours and their psychological well-being. However, there have been few studies focusing on factors related to staff emotional reactions. Seventy staff working in educational environments with children with intellectual disability and/or autism completed a self-report questionnaire that measured demographic factors, behavioural causal beliefs, behavioural knowledge, perceived self-efficacy, and emotional reactions to challenging behaviours. Regression analyses revealed that behavioural causal beliefs were a positive predictor, and self-efficacy and behavioural knowledge were negative predictors of negative emotional reactions to challenging behaviours. Staff with formal qualifications also reported more negative emotional reactions. No other demographic factors emerged as significant predictors. The results suggest that behavioural causal beliefs, low self-efficacy and low behavioural knowledge may make staff vulnerable to experiencing negative emotional reactions to challenging behaviours. Researchers and clinicians need to address these issues in staff who work with people with challenging behaviours.

Adolescent↗
PubMed2002

Cochlear implants in children with craniofacial syndromes: assessment and outcomes.

The aim of this retrospective study was to review the outcomes for children with craniofacial syndromes who had received a cochlear implant. The group comprised four children (three girls, one boy) aged between 3.3 and 10.1 years (mean 6.3 years) at time of implantation with the Cochlear CI-22M device. Two children had the CHARGE association. one had Goldenhar's syndrome and one had brachio-oculo-facial syndrome. All had full electrode insertion at time of surgery. At follow-up, three of the children demonstrated benefit in detection, recognition and identification of environmental sounds, and they continued to gain receptive spoken language skills, although none had intelligible speech. The group required careful mapping and higher levels of electrical stimulation of the implant compared to normal child implantees. Stimulation of the facial nerve was a problem with one child. The pre-implantation assessment of these children requires extensive interdisciplinary discussion and careful radiological investigation. Cases should be carefully selected. Parents should receive realistic counselling about outcomes and the time commitment necessary, as habilitation of these children can take twice as long as that of children without additional special needs. Post-implantation, these children continue to require well-coordinated medical and interdisciplinary management.

Auditory Threshold↗
PubMed2002

Findings of the Naftidrofuryl in Quality of Life (NIQOL) European study program.

BACKGROUND: We report in this paper the findings of a pooled analysis of 3 previously published studies undertaken in Germany, France and Belgium to assess the effects of naftidrofuryl on the quality of life of patients with intermittent claudication. METHODS: A total of 754 patients were randomised in the 3 studies, 709 of whom (358 naftidrofuryl, 351 placebo) were available for the primary intention-to-treat analysis. The primary outcome variable was the change in the disease-related limitation of the quality of life as measured by the CLAU-S questionnaire. This instrument which has been validated in an international study, comprises 47 questions covering 5 dimensions: "daily living", "pain", "social life", "disease specific anxiety" and "mood". RESULTS: A multivariate analysis of covariance adjusted for baseline values, study effect and first order study treatment interaction, demonstrated the global superiority of naftidrofuryl over placebo (p<0.001). A separate covariance analysis for the 5 dimensions showed highly significant differences for "daily living", "pain", "social life" and "mood" (all p<0.01). CONCLUSIONS: In conclusion, this pooled analysis has shown that naftidrofuryl can significantly improve the quality of life of patients with intermittent claudication. These findings, taken together with evidence from previous studies that it improves treadmill walking distances, suggest that naftidrofuryl can play a useful role in the treatment of this condition.

Adult↗
PubMed2001

Elective groin irradiation is not indicated for patients with adenocarcinoma of the rectum extending to the anal canal.

PURPOSE: To evaluate the inguinal nodal failure rate in patients with locally advanced rectal cancer with anal canal involvement (ACI) treated with pelvic chemoradiation without elective inguinal irradiation. METHODS AND MATERIALS: From 1990 and 1998, 536 patients received preoperative or postoperative chemoradiation for rectal cancer with curative intent; 186 patients had ACI (<4 cm from the anal verge on rigid proctoscopy). Two patients had positive inguinal nodes at presentation. Chemoradiation was delivered preoperatively (45 Gy in 25 fraction) or postoperatively (53 Gy in 29 fractions) with concurrent continuous infusion of 5-fluorouracil (300 mg/m2/d). The inguinal region was specifically irradiated in only 2 patients who had documented inguinal nodal disease. RESULTS: The median follow-up was 50 months. Only 6 of 184 ACI patients who had clinically negative inguinal nodes at presentation developed inguinal nodal recurrence (5-year actuarial rate 4%); 4 of the 6 cases were isolated. Two patients underwent successful salvage. Only 1 died of uncontrolled groin disease. Local control was achieved in both patients with inguinal nodal disease at presentation, but both died of metastatic disease. Only 3 patients with tumors >4 cm from the verge developed inguinal recurrence (5-year actuarial rate <1%). CONCLUSIONS: Inguinal nodal failure in rectal cancer patients with ACI treated with neoadjuvant or adjuvant chemoradiation is not high enough to justify routine elective groin irradiation.

Adenocarcinoma↗
PubMed2001

Duplex Scorpion primers in SNP analysis and FRET applications.

Scorpions are fluorogenic PCR primers with a probe element attached at the 5'-end via a PCR stopper. They are used in real-time amplicon-specific detection of PCR products in homogeneous solution. Two different formats are possible, the 'stem-loop' format and the 'duplex' format. In both cases the probing mechanism is intramolecular. We have shown that duplex Scorpions are efficient probes in real-time PCR. They give a greater fluorescent signal than stem-loop Scorpions due to the vastly increased separation between fluorophore and quencher in the active form. We have demonstrated their use in allelic discrimination at the W1282X locus of the ABCC7 gene and shown that they can be used in assays where fluorescence resonance energy transfer is required.

DNA Primers↗
PubMed2001

Affinity of mismatch-binding protein MutS for heteroduplexes containing different mismatches.

We have used bandshift analysis to measure the interaction between the Escherichia coli mismatch-binding protein MutS and synthetic DNA fragments containing all possible DNA mismatches as well as an unpaired T (DeltaT). The order of affinity is found to be DeltaT>GT>GG>AA approximately TT approximately TC>CA>GA>CC>GC. We find that the affinity for GT mismatches is affected by the flanking sequence and decreases in the order G(n)C(n)>(GC)(n)>A(n)T(n)>(AT)(n). Studies with base analogues show good binding to phiT (where phi represents 1',2'-dideoxyribose), but much weaker binding to Gphi.

Adenosine Triphosphatases↗