Biomarkers of ageing in New Zealand VLBW young adults and controls.

BACKGROUND: There is individual variation in physiological ageing. Former very low birthweight (VLBW; birthweight < 1500 g) young adults may have less satisfactory measurements on some physiological parameters than term controls. We hypothesized that a summation score of physiological biomarkers that change with age would show VLBW adults to have a more advanced physiologic age than controls. METHODS: VLBW adults (229; 71% survivors of a national VLBW cohort) and term-born controls (100) were clinically assessed at 26-30 years. Ten measured physiological biomarkers were selected and measurements converted to z-scores using normative reference data. Between-group comparisons were tested for statistical significance for individual biomarker z-scores and a summation score. RESULTS: Nine of 10 biomarkers showed a mean z-score suggestive of older physiological age in the VLBW group versus controls. The observed mean difference in the summation score was highly significant (p < 0.001), representing a mean shift of 0.47 SD in the distribution of test scores for VLBW relative to controls. CONCLUSIONS: Utilizing a 10-biomarker score, VLBW young adults have a score indicative of poorer physiological functioning than term-born controls. Repeating these measures after an interval could provide insights into the comparative pace of ageing between VLBW and term-born adults. IMPACT: A summation score of 10 physiological biomarkers that are known to change with age shows that former very low birthweight adults have significantly poorer physiological functioning by the end of their third decade than term-born controls. This result adds to existing literature showing very preterm and very low birthweight young adults often have physiological and metabolic test results that are less satisfactory than those from term controls, despite mostly being in the normal range for age; for instance, higher systolic blood pressure. Although the pace of ageing in later years is yet to be established, the implications of this study are that preventative measures and lifestyle choices that impact on physiological ageing might have even greater importance for very preterm and very low birthweight graduates.

Sudden Cardiac Death Due to Deficiency of the Mitochondrial Inorganic Pyrophosphatase PPA2.

We have used whole-exome sequencing in ten individuals from four unrelated pedigrees to identify biallelic missense mutations in the nuclear-encoded mitochondrial inorganic pyrophosphatase (PPA2) that are associated with mitochondrial disease. These individuals show a range of severity, indicating that PPA2 mutations may cause a spectrum of mitochondrial disease phenotypes. Severe symptoms include seizures, lactic acidosis, cardiac arrhythmia, and death within days of birth. In the index family, presentation was milder and manifested as cardiac fibrosis and an exquisite sensitivity to alcohol, leading to sudden arrhythmic cardiac death in the second decade of life. Comparison of normal and mutant PPA2-containing mitochondria from fibroblasts showed that the activity of inorganic pyrophosphatase was significantly reduced in affected individuals. Recombinant PPA2 enzymes modeling hypomorphic missense mutations had decreased activity that correlated with disease severity. These findings confirm the pathogenicity of PPA2 mutations and suggest that PPA2 is a cardiomyopathy-associated protein, which has a greater physiological importance in mitochondrial function than previously recognized.

Laboratory performance of sweat conductivity for the screening of cystic fibrosis.

BACKGROUND: There are several complementary English-language guidelines for the performance of the sweat chloride test. These guidelines also incorporate information for the collection of conductivity samples. However, recommendations for the measurement and reporting of sweat conductivity are less clear than for sweat chloride. The aim of the study was to develop an understanding of the testing and reporting practices of sweat conductivity in Australasian laboratories. METHODS: A survey specifically directed at conductivity testing was sent to the 12 laboratories registered with the Royal College of Pathologists of Australasia Quality Assurance Programs. RESULTS: Nine (75%) laboratories participated in the survey, seven of whom used Wescor Macroduct® for collecting sweat and the Wescor SWEAT·CHEK™ for conductivity testing, and the remaining two used the Wescor Nanoduct®. There was considerable variation in frequency and staffing for this test. Likewise, criteria about which patients it was inappropriate to test, definitions of adequate collection sweat rate, cutoffs and actions recommended on the basis of the result showed variations between laboratories. CONCLUSIONS: Variations in sweat conductivity testing and reporting reflect many of the same issues that were revealed in sweat chloride test audits and have the potential to lead to uncertainty about the result and the proper action in response to the result. We recommend that sweat testing guidelines should include clearer statements about the use of sweat conductivity.

Time trends and risk factors for rhinoconjunctivitis in New Zealand children: an International Study of Asthma and Allergies in Childhood (ISAAC) survey.

AIM: To investigate prevalence, time trends and factors associated with rhinitis and rhinoconjunctivitis not related to acute infections in New Zealand. METHODS: The International Study of Asthma and Allergies in Childhood (ISAAC) surveyed children aged 6-7 and 13-14 years for symptoms of these conditions. Five New Zealand centres were surveyed on two occasions (Phase One and Phase Three) 8-10 years apart. In Phase Three, questions were included on environmental factors, which might be associated with rhinoconjunctivitis. We report findings related to symptoms of rhinoconjunctivitis among 24 190 New Zealand children. RESULTS: Symptoms of rhinoconjunctivitis in the past year were reported in 11.4% of 6- to 7-year-old children and 18% of 13- to 14-year-old adolescents in Phase Three compared with 9.5 and 19.1%, respectively, in Phase One. Severe symptoms of rhinoconjunctivitis were reported in 0.5% of children and 0.8% of adolescents. Current symptoms were more common in males at 6-7 years and in females of 13-14 years, and Maori and Pacific Island ethnic groups had higher prevalence compared with those of European descent, especially in the older age group. For immigrant children, there was a very strong positive relationship between symptoms and length of time resident in New Zealand, supporting the probable importance of environmental factors. A positive association was found between symptoms and use of paracetamol in infancy or in the last year, and weaker associations were noted for antibiotic use, exercise, and regular pasta ingestion. CONCLUSIONS: Further study of environmental factors is recommended.

Cross-sectional survey of risk factors for asthma in 6-7-year-old children in New Zealand: International Study of Asthma and Allergy in Childhood Phase Three.

AIM: To identify risk factors for asthma in primary school-aged children in New Zealand. METHODS: A cross-sectional survey of 10,873 6-7-year-old children in Auckland, Bay of Plenty, Nelson and Christchurch (a response rate of 85.2%). A questionnaire was completed by the parent or care giver. RESULTS: 22.2% of children wheezed in the last 12 months (current wheeze). Maori children were at greater risk of current wheeze compared with European children (adjusted odds ratio (adjOR) = 1.37; 95% confidence interval = 1.18-1.59). Antibiotics and paracetamol used in the first year of life were associated with an increased risk of current wheeze (adjOR = 1.78 (1.56-2.04) and adjOR = 1.31 (1.06-1.61), respectively). Watching television for 5 or more hours per day was associated with an increased risk of current wheeze (adjOR = 1.44 (1.13-1.83)). Milk and egg consumption in the last 12 months was associated with a reduced risk of current wheeze. CONCLUSIONS: This study has identified risk factors for asthma in children aged 6-7 years, although causal pathways cannot be established. These associations have important public health implications if causal.

Compound Heterozygous Inheritance of Mutations in Coenzyme Q8A Results in Autosomal Recessive Cerebellar Ataxia and Coenzyme Q10 Deficiency in a Female Sib-Pair.

Autosomal recessive ataxias are characterised by a fundamental loss in coordination of gait with associated atrophy of the cerebellum. There is significant clinical and genetic heterogeneity amongst inherited ataxias; however, an early molecular diagnosis is essential with low-risk treatments available for some of these conditions. We describe two female siblings who presented early in life with unsteady gait and cerebellar atrophy. Whole exome sequencing revealed compound heterozygous inheritance of two pathogenic mutations (p.Leu277Pro, c.1506+1G>A) in the coenzyme Q8A gene (COQ8A), a gene central to biosynthesis of coenzyme Q (CoQ). The paternally derived p.Leu277Pro mutation is predicted to disrupt a conserved motif in the substrate-binding pocket of the protein, resulting in inhibition of CoQ10 production. The maternal c.1506+1G>A mutation destroys a canonical splice donor site in exon 12 affecting transcript processing and subsequent protein translation. Mutations in this gene can result in primary coenzyme Q10 deficiency type 4, which is characterized by childhood onset of cerebellar ataxia and exercise intolerance, both of which were observed in this sib-pair. Muscle biopsies revealed unequivocally low levels of CoQ10, and the siblings were subsequently established on a therapeutic dose of CoQ10 with distinct clinical evidence of improvement after 1 year of treatment. This case emphasises the importance of an early and accurate molecular diagnosis for suspected inherited ataxias, particularly given the availability of approved treatments for some subtypes.

Acquired and congenital fast albumin bands; insights from electrospray TOF analysis of whole plasma into drug binding and albumin recycling.

OBJECTIVES: To define the underlying cause of unusual fast albumin bands detected on plasma protein electrophoresis of two patients. METHOD: Plasma was examined by electrospray time-of-flight mass spectrometry (TOF MS) to assess the possibility of congenital or acquired structural modifications. RESULTS: In one patient whole protein MS indicated a drop of 486Da in the mass of 5.1% of the albumin molecules. This and the presence of an additional minor product (65,806Da) lacking a C-terminal phenylalanine (-147Da) indicated that this was albumin Rugby Park; an electrophoretically fast albumin variant caused by a splice site mutation (GT>CT) in intron 13 of the albumin gene. The second patient had an acquired alteration with a drift of albumin mobility to the anode. This severely ill patient was on intra venous antibiotics and electrospray TOF MS showed a stuttered repetition of the 66,439/66,558Da albumin isoforms at multiples of 455-459Da corresponding to the covalent attachment of 1, 2, 3 and 4 molecules of flucloxacillin. This modification of +455Da was also detected in a control on a 1g/day oral dose of flucloxacillin. CONCLUSION: Both aberrations were associated with diminished albumin concentrations. The C-terminal truncation of Rugby Park (albumin, 29g/l) likely interferes with receptor binding and albumin scavenging, while the 20g/l albumin in the second patient was mostly due to renal disease. In both cases electrospray TOF MS proved a rapid (5min) sensitive (0.2µl plasma) and highly informative way of analysing whole plasma or serum.

Asthma prevalence in European, Maori, and Pacific children in New Zealand: ISAAC study.

The International Study of Asthma and Allergies in Childhood (ISAAC) demonstrated that the highest prevalence of asthma in the world is in English-speaking countries, including New Zealand. In this paper, we compare asthma symptom prevalence in the three major ethnic groups (Maori, Pacific, and European) in the six participating centers in New Zealand. Hospital admission rates for asthma are higher among Maori and Pacific children compared to European children. The working hypothesis was that there were important differences in prevalence of asthma symptoms or diagnosis between ethnic groups which might explain these observed differences in asthma morbidity. In each center in 1992-1993, we sampled approximately 3000 children at each of the age brackets 6-7 years and 13-14 years. There were 37592 participants. Maori children had higher rates of diagnosed asthma and reported asthma symptoms than Pacific children in both age groups (diagnosed asthma in 6-7-year-olds: Maori, 31.7%; Pacific, 21.2%; 95% confidence interval on difference (CID), 7.2, 13.8; P < 0.001; 13-14-year-olds: Maori, 24.7%; Pacific, 19.2%; CID 2.5, 8.5; P < 0.001; recent wheeze in 6-7-year-olds: Maori, 27.6%; Pacific, 22.0%; CID, 2.6, 8.6; P < 0.001; 13-14-year-olds: Maori, 30.8%; Pacific, 21.1%; CID, 4.8, 14.5; P < 0.001;). European children had rates intermediate between those of Maori and Pacific children (6-7-year-olds) or similar to those of Maori children (13-14-year-olds), but had the lowest prevalence of night waking with wheeze in both age groups (e.g., 6-7-year-olds: European, 2.6%; Maori, 5.8%; Pacific, 5.7%; European-Maori CID: -4.2, -2.2, P < 0.001; European-Pacific CID: -4.7, -1.7, P < 0.001; Maori-Pacific CID: -1.7, 1.8, P = 1.0). The pattern of differences closely resembled that in a 1985 Auckland study, despite a 1.5-1.7-fold overall increase in prevalence. In conclusion, there are important differences in asthma prevalence among Maori, Pacific, and European children. These differences are small compared to worldwide variation, but their pattern is stable over time. The higher rate of severe asthma symptoms that Maori and Pacific children report may be one reason for the increased asthma morbidity in these groups. Further studies are needed to determine the reasons for these apparent differences in asthma severity.

Electrolytes in sick neonates - which sodium is the right answer?

INTRODUCTION: Hypoproteinaemia leads to spuriously high-sodium values when measured by indirect ion-selective electrodes (ISE) as used in main laboratory analysers compared with direct ISE employed in point-of-care analysers (POCT). The authors, therefore, investigated the occurrence of hypoalbuminaemia and its effect on measured sodium from POCT and the main laboratory analyser of neonatal intensive-care samples. METHOD: Sodium, in paired retrospective samples, measured by the main laboratory and neonatal unit blood-gas (POCT) analysers were compared. RESULTS: Hypoalbuminaemia (<30 g/l) was present in 1400/2420 paired results. Sodium was higher when measured by laboratory analyser, the difference increased with decreasing albumin; sodium (laboratory - POCT)=7.6 (±1.1)-0.22 (±0.04)×albumin. A difference >3 mmol/l was present in 31% and consequently underestimated (9.4%) hyponatraemia and overestimated (3.8%) hypernatraemia. CONCLUSION: Hypoalbuminaemia is common in sick neonates and monitoring electrolytes using POCT and laboratory analysers frequently yield significantly different results with consequent misclassification. In these patients, measurement of electrolytes by direct ISE (blood-gas analyser) may be more accurate.

Time trends, ethnicity and risk factors for eczema in New Zealand children: ISAAC Phase Three.

BACKGROUND: Eczema is a common chronic disease which has significant morbidity and costs for children and their families. Phase One (1993) of the International Study of Asthma and Allergies in Childhood (ISAAC) found a high prevalence of symptoms of eczema in New Zealand. OBJECTIVE: In Phase Three (2001-3) we aimed to answer these three questions: Is the prevalence of eczema changing over time?; Are there ethnic differences in prevalence?; and What are the risk factors for eczema? METHODS: Five New Zealand centres participated in ISAAC Phases One and Three using the same methodology. Questionnaires about ethnicity, symptoms of eczema and environmental factors were completed by parents of 6-7 year olds (children) and self-completed by 13-14 year olds (adolescents). Prevalence and change per year were calculated by centre, ethnicity and gender. Prevalence differences between centres and associations with environmental factors were examined using logistic regression. RESULTS: There was little change in prevalence over time for the children, and a decrease in prevalence for the adolescents. Prevalence was higher among Maori and even higher among Pacific participants than among European children. Positive associations with current eczema symptoms were found for both age groups for truck traffic in the street of residence, and current paracetamol consumption, and for children only, antibiotics or paracetamol in the 1st year of life. Inverse associations were found with residence in New Zealand less than 5 years, consumption of milk, seafood, and eggs, and presence of a dog in the home. CONCLUSION: Eczema remains a significant problem, particularly for young Maori and Pacific New Zealanders in whom less recognition of eczema and poorer access to effective, sustained eczema management may be contributing factors. Reverse causation may explain all the environmental findings apart from truck traffic which is increasing in New Zealand.

BCS1L gene mutation presenting with GRACILE-like syndrome and complex III deficiency.

The clinical presentation of a neonate with GRACILE-like syndrome, complex III deficiency and BCS1L mutations is discussed. This case is compared and contrasted with the original Finnish reports of GRACILE syndrome and other cases with a similar phenotype. This case confirms the pathogenicity of the BCS1L gene mutation c.166C>T, and provides support for the pathogenicity of a sequence variation, c.-588T>A, previously reported.

Trimethylaminuria: causes and diagnosis of a socially distressing condition.

Trimethylaminuria is a disorder in which the volatile, fish-smelling compound, trimethylamine (TMA) accumulates and is excreted in the urine, but is also found in the sweat and breath of these patients. Because many patients have associated body odours or halitosis, trimethylaminuria sufferers can meet serious difficulties in a social context, leading to other problems such as isolation and depression. TMA is formed by bacteria in the mammalian gut from reduction of compounds such as trimethylamine-N-oxide (TMAO) and choline. Primary trimethylaminuria sufferers have an inherited enzyme deficiency where TMA is not efficiently converted to the non-odorous TMAO in the liver. Secondary causes of trimethylaminuria have been described, sometimes accompanied by genetic variations. Diagnosis of trimethylaminuria requires the measurement of TMA and TMAO in urine, which should be collected after a high substrate meal in milder or intermittent cases, most simply, a marine-fish meal. The symptoms of trimethylaminuria can be improved by changes in the diet to avoid precursors, in particular TMAO which is found in high concentrations in marine fish. Treatment with antibiotics to control bacteria in the gut, or activated charcoal to sequester TMA, may also be beneficial.

High sensitivity troponin outperforms contemporary assays in predicting major adverse cardiac events up to two years in patients with chest pain.

BACKGROUND: Previous studies have shown a risk of subsequent major adverse cardiovascular events (MACEs) in patients with suspected acute coronary syndromes (ACSs) and elevated cardiac troponin. The aim of this study was to compare prognostic utility of high-sensitivity troponin with contemporary troponin assays in such patients. METHODS: In total, 332 patients with suspected ACS were investigated between November 2006 and April 2007; all were followed for two years. Blood samples were analysed to compare Roche Elecsys high-sensitivity troponin T (hsTnT), Abbott Architect troponin I 3rd generation (TnI 3) and Roche Elecsys troponin T (TnT), for the prediction of MACE (composite of cardiovascular death, non-fatal myocardial infarction and revascularization). RESULTS: Sixty-eight patients (20.5%) experienced MACE between discharge and two years. Receiver operating characteristic (ROC) curve derived area under the ROC curve (95% confidence intervals) for baseline hsTnT were 0.70 (0.63-0.76), TnI 3 0.66 (0.59-0.73) and TnT 0.61 (0.53-0.69). hsTnT (P = 0.001) was superior to TnT and TnI 3 trended (P = 0.094) to superiority but were equivalent to each other. hsTnT best stratified patients with cumulative event rates for two-year MACE of 35.6% for levels ≥99th percentile, 17.9% for levels between the limit of detection (LOD) and 99th percentile and 5.4% for levels

Comparison of high sensitivity and contemporary troponin assays for the early detection of acute myocardial infarction in the emergency department.

BACKGROUND: Current guidelines define acute myocardial infarction (AMI) by the rise and/or fall of cardiac troponin with ≥1 value above the 99th percentile. Past troponin assays have been unreliable at the lower end of the range. Highly sensitive assays have therefore been developed to increase the clinical sensitivity for detection of myocardial injury. METHODS: Three hundred and thirty-two patients with chest pain suggestive of AMI were prospectively recruited between November 2006 and April 2007. Serial blood samples were analysed to compare Roche Elecsys high sensitivity troponin T (hsTnT), Abbott Architect troponin I 3rd generation (TnI 3) and Roche Elecsys troponin T (TnT) for the diagnosis of AMI. RESULTS: One hundred and ten (33.1%) patients were diagnosed with AMI. Test performance for the diagnosis of AMI, as quantified by receiver operating characteristic area under the curve (95% confidence intervals) for baseline/follow-up troponins were as follows: hsTnT 0.90 (0.87-0.94)/0.94 (0.91-0.97), TnI 3 0.88 (0.84-0.92)/0.93 (0.90-0.96) and TnT 0.80 (0.74-0.85)/0.89 (0.85-0.94). hsTnT was superior to TnT (P < 0.001/0.013 at baseline/follow-up) but equivalent to TnI 3. For patients with a final diagnosis of AMI, baseline troponins were raised in more patients for hsTnT (83.6%) than TnI 3 (74.5%) and TnT (62.7%). A delta troponin of ≥20% increased the specificity of hsTnT from 80.6% to 93.7% but reduced sensitivity from 90.9% to 71.8%. CONCLUSION: hsTnT was superior to TnT but equivalent to TnI 3 for the diagnosis of AMI. Serial troponin measurement increased test performance. hsTnT was the most likely to be raised at baseline in those with AMI. A delta troponin increases specificity but reduces sensitivity.

Appreciating and developing compassionate care in an acute hospital setting caring for older people.

BACKGROUND: There is increasing emphasis in policy, research and practice on the importance of caring in health care. Indeed there is much debate about how to enhance the caring cultures within which health care is provided. This paper argues that a proper systematic analysis of caring practice that works well in care environments may help us to move towards a realistic model for the future which supports staff, patients and families to give and receive compassionate care. AIM: The aim of the project was to explore, develop and articulate strategies that enhanced compassionate relationship centred care in an acute hospital setting, caring for older people. METHODS: Appreciative action research informed the development and evaluation of the project. A range of data generation activities were used to examine what worked well. Following detailed analysis key processes emerged as being central to delivery of compassionate care. Specific action projects were implemented and evaluated to enhance these processes necessary for compassionate caring. FINDINGS: Data from the project helped to articulate the special and often hidden acts that make up compassionate care. In relation to the process of 'knowing who I am and what matters to me' data provided evidence of the value of this process and the potential impact to care. In addition data about the process of doing appreciative action research helped to realise its application and relevance in the health care setting. CONCLUSIONS: Findings from this work suggest that there are a number of significant processes that help people to deliver compassionate care. These need to be articulated, shared more widely across practice, policy and education so that we can build on this excellent practice. IMPLICATIONS FOR PRACTICE: Appreciative action research adopted in this project is an important methodology to supporting practitioners to identify what it is they do well and develop practice to try to make the best caring practice happen most of the time. Academics, policy makers and practitioners should consider the approach of appreciative action research as key to supporting developments in care.

Spectrum of MECP2 mutations in New Zealand Rett syndrome patients.

BACKGROUND: Classical Rett syndrome is a severe neurodevelopmental X-linked dominant disorder affecting 1/15,000 girls worldwide. MECP2 has been identified as the predominant gene associated with Rett syndrome. Approximately 65-85% of patients with classical Rett syndrome have identifiable MECP2 mutations. In comparison, up to 57% of patients with atypical Rett have mutations in the MECP2 gene. OBJECTIVES: To investigate the spectrum and frequency of MECP2 mutations in New Zealand Rett syndrome patients and evaluate whether available clinical criteria were sufficient to direct molecular testing for Rett syndrome. PATIENTS: and Methods MECP2 coding regions were analysed by direct automated DNA sequencing and multiplex ligation dependent probe assay (MLPA) in samples from 74 patients referred for investigation of possible Rett syndrome. Necessary clinical criteria were examined in detail in 18 patients, with 7/18 having identifiable MECP2 mutations. RESULTS: Fifteen patients (20%) carried MECP2 mutations, four of which were novel (one insertion mutation, one complex rearrangement and two deletions). Eleven previously described disease-causing sequence changes and several known polymorphisms were also detected. Ninety per cent of the observed point mutations were cytosine to thymidine (C to T) transitions at a CpG dinucleotide. Only three patients with MECP2 mutations displayed all major clinical criteria associated with Rett syndrome, four were atypical cases. Of the patients not having an identified MECP2 mutation, 8 out of 11 had clinical criteria consistent with variant Rett syndrome and one of these had a balanced translocation involving chromosomes 2p25 and 6p11-12. CONCLUSIONS: This is the first genetic study of Rett syndrome in New Zealand patients describing the MECP2 mutational spectrum. The relatively low observed frequency of MECP2 mutations reflects a wide spectrum of mental disability disorders. In some cases there were insufficient clinical criteria to justify referral for Rett gene testing.

Healthcare-associated Infections: epidemiology, prevention, and therapy.

Reducing nosocomial infection rates is a major component of healthcare improvement. This article reviews the epidemiology, prevention, and therapy for some of the most common healthcare-associated infections, including central line-associated bloodstream infections and catheter-associated urinary tract infections, and 3 common organisms: methicillin-resistant Staphylococcus aureus, multidrug- resistant gram-negative bacteria, and Clostridium difficile.

Sweat testing for cystic fibrosis: standards of performance in Australasia.

BACKGROUND: Accurate measurement of sweat chloride concentration is essential for the diagnosis of cystic fibrosis (CF). We surveyed all laboratories enrolled in the Royal College of Pathologists of Australasia Quality Assurance Program (QAP) for Sweat Electrolytes to determine how closely they comply with the Australian Guidelines for the performance of the sweat test for the diagnosis of CF. METHODS: A detailed questionnaire covering most aspects of sweat collection and analysis was sent to all participating laboratories in 2007. RESULTS: Twenty out of 38 laboratories completed the questionnaire. While adherence to accepted guidelines was noted in many areas, the following main variations were recorded: some laboratories were not doing enough sweat tests to maintain expertise; some were not collecting sweat for the recommended collection time; sweat conductivity was the only test available in some laboratories; there was a lack of agreement between the sweat chloride concentration used to indicate CF or define an equivocal result. CONCLUSIONS: There is room for improvement in the performance of the sweat test in some laboratories in Australasia. The Sweat Testing Working Party of the Australasian Association of Clinical Biochemists is the appropriate body to address the problems involved in sweat testing and to bring about change.