'Nesting networks': Women's experiences of social network support in high-risk pregnancy.

OBJECTIVE: Social support, an individual's social relationships (both online and offline), may provide protection against adverse mental health outcomes, such as anxiety and depression, which are high in women who have been hospitalised with high-risk pregnancy. This study explored the social support available to women at higher risk of preeclampsia during pregnancy by examining personal social networks. DESIGN: Semi-structured interviews were accompanied by social network mapping using the web-based social networking tool GENIE. SETTING: England. PARTICIPANTS: Twenty-one women were recruited, of whom 18 were interviewed both during pregnancy and postnatally between April 2019 and April 2020. Nineteen women completed maps pre-natally, 17 women completed maps pre-natally and post-natally. Women were taking part in the BUMP study, a randomised clinical trial that included 2441 pregnant individuals at higher risk of preeclampsia and recruited at a mean of 20 weeks' gestation from 15 hospital maternity units in England between November 2018 and October 2019. RESULTS: Women's social networks tightened during pregnancy. The inner network changed most dramatically postnatally with women reporting fewer network members. Interviews revealed networks were primarily 'real-life' rather than online social networks, with members providing emotional, informational, and practical support. Women with a high-risk pregnancy valued the relationships they developed with health professionals during pregnancy, and would like their midwife to have a more central role in their networks by providing informational and, where needed, emotional support. The social network mapping data supported the qualitative accounts of changing networks across high-risk pregnancy. CONCLUSION: Women with a high-risk pregnancy seek to build "nesting networks" to support them through pregnancy into motherhood. Different types of support are sought from trusted sources. Midwives can play a key role. PRACTICE IMPLICATIONS: As well as highlighting other potential needs during pregnancy and the ways in which they can be met, support from midwives has a key role. Through talking to women early in their pregnancy, signposting information and explaining ways to contact health professionals regarding informational or emotional support would fill a gap that currently is met by other aspects of their network.

INTEND II randomized clinical trial of intraoperative duct endoscopy in pathological nipple discharge.

BACKGROUND: The majority of lesions resulting in pathological nipple discharge are benign. Conventional surgery is undirected and targeting the causative lesion by duct endoscopy may enable more accurate surgery with fewer complications. METHODS: Patients requiring microdochectomy and/or major duct excision were randomized to duct endoscopy or no duct endoscopy before surgery. Primary endpoints were successful visualization of the pathological lesion in patients randomized to duct endoscopy, and a comparison of the causative pathology between the two groups. The secondary endpoint was to compare the specimen size between groups. RESULTS: A total of 68 breasts were studied in 66 patients; there were 31 breasts in the duct endoscopy group and 37 in the no-endoscopy group. Median age was 49 (range 19-81) years. Follow-up was 5·4 (i.q.r. 3·3-8·9) years in the duct endoscopy group and 5·7 (3·1-9·0) years in no-endoscopy group. Duct endoscopy had a sensitivity of 80 (95 per cent c.i. 52 to 96) per cent, specificity of 71 (44 to 90) per cent, positive predictive value of 71 (44 to 90) per cent and negative predictive value of 80 (52 to 96) per cent in identifying any lesion. There was no difference in causative pathology between the groups. Median volume of the surgical resection specimen did not differ between groups. CONCLUSION: Diagnostic duct endoscopy is useful for identifying causative lesions of nipple discharge. Duct endoscopy did not influence the pathological yield of benign or malignant diagnoses nor surgical resection volumes. Registered as INTEND II in CancerHelp UK clinical trials database (https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-changes-inside-the-breast-ducts-of-women-who-have-nipple-discharge).

Polygenic risk assessment reveals pleiotropy between sarcoidosis and inflammatory disorders in the context of genetic ancestry.

Sarcoidosis is a complex disease of unknown etiology characterized by the presence of granulomatous inflammation. Though various immune system pathways have been implicated in disease, the relationship between the genetic determinants of sarcoidosis and other inflammatory disorders has not been characterized. Herein, we examined the degree of genetic pleiotropy common to sarcoidosis and other inflammatory disorders to identify shared pathways and disease systems pertinent to sarcoidosis onset. To achieve this, we quantify the association of common variant polygenic risk scores from nine complex inflammatory disorders with sarcoidosis risk. Enrichment analyses of genes implicated in pleiotropic associations were further used to elucidate candidate pathways. In European-Americans, we identify significant pleiotropy between risk of sarcoidosis and risk of asthma (R2=2.03%; P=8.89 × 10-9), celiac disease (R2=2.03%; P=8.21 × 10-9), primary biliary cirrhosis (R2=2.43%; P=2.01 × 10-10) and rheumatoid arthritis (R2=4.32%; P=2.50 × 10-17). These associations validate in African Americans only after accounting for the proportion of genome-wide European ancestry, where we demonstrate similar effects of polygenic risk for African-Americans with the highest levels of European ancestry. Variants and genes implicated in European-American pleiotropic associations were enriched for pathways involving interleukin-12, interleukin-27 and cell adhesion molecules, corroborating the hypothesized immunopathogenesis of disease.

Adaptive trials for tuberculosis: early reflections on theory and practice.

SETTING: Adaptive designs (ADs) have been proposed for anti-tuberculosis treatment trials. This call for innovation occurs against the backdrop of fundamental changes in the acceptable evidence base in anti-tuberculosis treatment. OBJECTIVE: To contextualise ADs for tuberculosis (TB) and explore early responses from those working in the field. DESIGN: In this qualitative study investigating processes of theoretical and practical change in randomised controlled trials, 24 interviews were conducted with professionals involved in AD trials, half of whom worked in the TB field. RESULTS: Clinical trialists working on AD trials in TB are positive about the efficiency these designs offer, but remain cautious about their suitability. In addition to technical concerns, informants discussed the challenges of implementing AD in developing countries, including limited regulatory capacity to evaluate proposals, investments needed in infrastructure and site capacity, and challenges regarding informed consent. Respondents identified funding, interdisciplinary communication and regulatory and policy responses as additional concerns potentially affecting the success of AD for TB. CONCLUSION: Empirical research is needed into patient experiences of AD, including informed consent. Further consideration of the contexts of innovation in trial design is needed. These are fundamental to the successful translation of theory into practice.

Meta-analysis of executive functioning in ecstasy/polydrug users.

Ecstasy/3,4-methylenedioxymethamphetamine (MDMA) use is proposed to cause damage to serotonergic (5-HT) axons in humans. Therefore, users should show deficits in cognitive processes that rely on serotonin-rich, prefrontal areas of the brain. However, there is inconsistency in findings to support this hypothesis. The aim of the current study was to examine deficits in executive functioning in ecstasy users compared with controls using meta-analysis. We identified k = 39 studies, contributing 89 effect sizes, investigating executive functioning in ecstasy users and polydrug-using controls. We compared function-specific task performance in 1221 current ecstasy users and 1242 drug-using controls, from tasks tapping the executive functions - updating, switching, inhibition and access to long-term memory. The significant main effect demonstrated overall executive dysfunction in ecstasy users [standardized mean difference (SMD) = -0.18, 95% confidence interval (CI) -0.26 to -0.11, Z = 5.05, p < 0.001, I 2 = 82%], with a significant subgroup effect (χ 2 = 22.06, degrees of freedom = 3, p < 0.001, I 2 = 86.4%) demonstrating differential effects across executive functions. Ecstasy users showed significant performance deficits in access (SMD = -0.33, 95% CI -0.46 to -0.19, Z = 4.72, p < 0.001, I 2 = 74%), switching (SMD = -0.19, 95% CI -0.36 to -0.02, Z = 2.16, p < 0.05, I 2 = 85%) and updating (SMD = -0.26, 95% CI -0.37 to -0.15, Z = 4.49, p < 0.001, I 2 = 82%). No differences were observed in inhibitory control. We conclude that this is the most comprehensive analysis of executive function in ecstasy users to date and provides a behavioural correlate of potential serotonergic neurotoxicity.

Aesthetic and oncologic outcomes after one-stage immediate breast reconstruction using a permanent biodimensional expandable implant.

INTRODUCTION: Immediate breast reconstruction (IBR) with implants is the commonest method of reconstructive surgery after mastectomy. With careful patient selection, a stable implant pocket can be created at the primary operation to decrease the likelihood of further surgery to adjust the reconstructed side. One-stage IBR is cost effective but failed procedures requiring early revision may be costly as permanent expanders are expensive. METHODS: Data were prospectively collected on all women undergoing a planned one-stage immediate breast reconstruction between 1997 and 2010. All patients had a Style 150 implant (Allergan, Marlow, UK). Descriptive statistics, Kaplan-Meier plots and, where applicable, Cox Proportional Hazards Regression was used to compare outcomes between groups. RESULTS: 249 planned one-stage IBRs were performed in 193 women, median age 45 years (range 20-77) with median follow-up of 101 months (range 27-159 months). 18/193 (9%) patients required implant exchange at 12 months and 66% of patients maintained their original implants at the time of census. Implant assisted latissimus appears to be robust even when radiotherapy was delivered. Disease free survival and breast cancer mortality were as expected for the breast cancer stage treated. CONCLUSION: With careful patient selection, one-stage implant IBR using a definitive anatomical expandable implant provides good long term reconstruction and safe oncologic outcome. Direct to implant decision algorithms may be influenced by future developments in acellular dermal matrix technology, but the ability to create a single-stage stable implant pocket with good surgical technique should not be forgotten.

Retained wound vacuum foam in non-healing wounds: a real possibility.

Negative pressure wound therpay (NPWT) has revolutionised the management of chronic wounds, particularly pressure ulcers (PU). Frequently, PUs are too large to close primarily, so NPWT is used to assist in management on an outpatient basis. If not closely monitored, NPWT closure foam can be accidentally left in patients. Here we describe two cases where NPWT closure foam was left in patients resulting in persistent infections. Additionally, some suggestions of how to help avoid these should be 'never' events are provided.

Increased prevalence and geographic spread of the cardiopulmonary nematode Angiostrongylus vasorum in fox populations in Great Britain.

The nematode Angiostrongylus vasorum is becoming more widely recorded globally, and is of increasing concern as a cause of disease in dogs. Apparent geographic spread is difficult to confirm due to a lack of standardized disease recording systems, increasing awareness among veterinary clinicians, and recent improvements in diagnostic technologies. This study examines the hypothesis that A. vasorum has spread in recent years by repeating the methods of a previous survey of the fox population. The hearts and lungs of 442 foxes from across Great Britain were collected and examined by dissection and flushing of the pulmonary circulation and microscopic inspection of tracheal scrapes. Sampling and parasite extraction methods were identical to an earlier survey in 2005 to ensure comparability. Prevalence of A. vasorum was 18·3% (exact binomial confidence bounds 14·9-22·3), compared with 7·3% previously (5·3-9·9, n = 546), and had increased significantly in most regions, e.g. 7·4% in the Northern UK (previously zero) and 50·8% in the south-east (previously 23·2%). Other nematodes identified were Crenosoma vulpis (prevalence 10·8%, CI 8·1-14·2) and Eucoleus aerophilus (31·6%, CI 27·3-36·2). These data support the proposal that A. vasorum has increased in prevalence and has spread geographically in Great Britain.

fNIRS suggests increased effort during executive access in ecstasy polydrug users.

BACKGROUND: Ecstasy use is associated with cognitive impairment, believed to result from damage to 5-HT axons. Neuroimaging techniques to investigate executive dysfunction in ecstasy users provide a more sensitive measure of cognitive impairment than behavioural indicators. The present study assessed executive access to semantic memory in ecstasy polydrug users and non-users. METHODS: Twenty ecstasy polydrug users and 20 non-user controls completed an oral variant of the Chicago Word Fluency Test (CWFT), whilst the haemodynamic response to the task was measured using functional near-infrared spectroscopy (fNIRS). RESULTS: There were no between-group differences in many background measures including measures of sleep and mood state (anxiety, arousal, hedonic tone). No behavioural differences were observed on the CWFT. However, there were significant differences in oxy-Hb level change at several voxels relating to the left dorsolateral prefrontal cortex (DLPFC) and right medial prefrontal cortex (PFC) during the CWFT, indicating increased cognitive effort in ecstasy users relative to controls. Regression analyses showed that frequency of ecstasy use, total lifetime dose and amount used in the last 30 days was significant predictors of oxy-Hb increase at several voxels after controlling for alcohol and cannabis use indices. CONCLUSION: The results suggest that ecstasy users show increased activation in the PFC as a compensatory mechanism, to achieve equivalent performance to non-users. These findings are in agreement with much of the literature in the area which suggests that ecstasy may be a selective serotonin neurotoxin in humans.

Differences in prefrontal blood oxygenation during an acute multitasking stressor in ecstasy polydrug users.

BACKGROUND: Cognitive deficits are well documented in ecstasy (3,4-methylenedioxymethamphetamine; MDMA) users, with such deficits being taken as evidence of dysregulation of the serotonin (5-hydroxytryptamine; 5-HT) system. More recently neuroimaging has been used to corroborate these deficits. The present study aimed to assess multitasking performance in ecstasy polydrug users, polydrug users and drug-naive individuals. It was predicted that ecstasy polydrug users would perform worse than non-users on the behavioural measure and this would be supported by differences in cortical blood oxygenation. METHOD: In the study, 20 ecstasy-polydrug users, 17 polydrug users and 19 drug-naive individuals took part. On day 1, drug use history was taken and questionnaire measures were completed. On day 2, participants completed a 20-min multitasking stressor while brain blood oxygenation was measured using functional near infrared spectroscopy (fNIRS). RESULTS: There were no significant differences between the three groups on the subscales of the multitasking stressor. In addition, there were no significant differences on self-report measures of perceived workload (NASA Task Load Index). In terms of mood, ecstasy users were significantly less calm and less relaxed compared with drug-naive controls. There were also significant differences at three voxels on the fNIRS, indicating decreased blood oxygenation in ecstasy users compared with drug-naive controls at voxel 2 (left dorsolateral prefrontal cortex), voxel 14 and voxel 16 (right dorsolateral prefrontal cortex), and compared with polydrug controls at V14. CONCLUSIONS: The results of the present study provide support for changes in brain activation during performance of demanding tasks in ecstasy polydrug users, which could be related to cerebral vasoconstriction.

Plasmapheresis eliminates the negative impact of AAV antibodies on microdystrophin gene expression following vascular delivery.

Duchenne muscular dystrophy is a monogenic disease potentially treatable by gene replacement. Use of recombinant adeno-associated virus (AAV) will ultimately require a vascular approach to broadly transduce muscle cells. We tested the impact of preexisting AAV antibodies on microdystrophin expression following vascular delivery to nonhuman primates. Rhesus macaques were treated by isolated limb perfusion using a fluoroscopically guided catheter. In addition to serostatus stratification, the animals were placed into one of the three immune suppression groups: no immune suppression, prednisone, and triple immune suppression (prednisone, tacrolimus, and mycophenolate mofetil). The animals were analyzed for transgene expression at 3 or 6 months. Microdystrophin expression was visualized in AAV, rhesus serotype 74 sero-negative animals (mean: 48.0 ± 20.8%) that was attenuated in sero-positive animals (19.6 ± 18.7%). Immunosuppression did not affect transgene expression. Importantly, removal of AAV binding antibodies by plasmapheresis in AAV sero-positive animals resulted in high-level transduction (60.8 ± 18.0%), which is comparable with that of AAV sero-negative animals (53.7 ± 7.6%), whereas non-pheresed sero-positive animals demonstrated significantly lower transduction levels (10.1 ± 6.0%). These data support the hypothesis that removal of AAV binding antibodies by plasmapheresis permits successful and sustained gene transfer in the presence of preexisting immunity (natural infection) to AAV.

Electrophysiological indices of response inhibition in human polydrug users.

Previous research in ecstasy users suggests impairment of various executive functions. In general, the executive function of response inhibition appears unaffected by ecstasy use. Nonetheless, it remains a possibility that cognitive tasks alone are not sensitive enough to pick up subtle changes in function. The current study sought to investigate behavioural measures of response inhibition and their electrophysiological correlates in drug users. Twenty ecstasy polydrug users, 20 non-ecstasy polydrug users and 20 drug naïve controls were recruited. Participants completed questionnaires about their background drug use, sleep quality, fluid intelligence and mood state. Each individual also completed a Go/NoGo response inhibition task whilst electroencephalography (EEG) measures were recorded. Analysis of variance (ANOVA) revealed that there were no between-group differences on the behavioural measure of response inhibition. Multivariate analysis of variance (MANOVA) revealed no main effect of group across midline electrodes for the P3, N2 and P2 components. Univariate ANOVA revealed significant between-group differences in the P2 component with the ecstasy user group having a significantly higher mean amplitude than drug naïve controls at two midline frontal electrodes: at Fz and significantly higher mean amplitude than both control groups at FCz. The present study provides evidence of atypical early processing in ecstasy users that is suggestive of compensatory mechanisms ameliorating any behavioural differences.

ERP evidence suggests executive dysfunction in ecstasy polydrug users.

BACKGROUND: Deficits in executive functions such as access to semantic/long-term memory have been shown in ecstasy users in previous research. Equally, there have been many reports of equivocal findings in this area. The current study sought to further investigate behavioural and electro-physiological measures of this executive function in ecstasy users. METHOD: Twenty ecstasy-polydrug users, 20 non-ecstasy-polydrug users and 20 drug-naïve controls were recruited. Participants completed background questionnaires about their drug use, sleep quality, fluid intelligence and mood state. Each individual also completed a semantic retrieval task whilst 64 channel Electroencephalography (EEG) measures were recorded. RESULTS: Analysis of Variance (ANOVA) revealed no between-group differences in behavioural performance on the task. Mixed ANOVA on event-related potential (ERP) components P2, N2 and P3 revealed significant between-group differences in the N2 component. Subsequent exploratory univariate ANOVAs on the N2 component revealed marginally significant between-group differences, generally showing greater negativity at occipito-parietal electrodes in ecstasy users compared to drug-naïve controls. Despite absence of behavioural differences, differences in N2 magnitude are evidence of abnormal executive functioning in ecstasy-polydrug users.

Association of ANXA11 genetic variation with sarcoidosis in African Americans and European Americans.

A recent genome-wide association study in a German population and two subsequent studies in European populations found that a non-synonymous single-nucleotide polymorphism (SNP), rs1049550, within the annexin A11 (ANXA11) gene was associated with susceptibility to sarcoidosis. We sought to identify additional ANXA11 variants independently associated with sarcoidosis, determine whether any sarcoidosis-associated ANXA11 variants were associated with chest radiographic phenotypes, and explore human leukocyte antigen (HLA) SNP-SNP interactions with ANXA11. A total of 209 SNPs spanning 100 kb including the 5' promoter, coding, and 3' untranslated regions of ANXA11 were genotyped for 1689 sarcoidosis cases and 1252 controls. After adjustment for rs1049550, two additional novel ANXA11 sarcoidosis associations were identified only in African Americans--rs61860052 (odds ratio (OR)=0.62; 95% confidence interval (CI)=0.40-0.97) and rs4377299 (OR=1.31; 95% CI=1.06-1.63). These associations were more pronounced in radiologically-classified Scadding stage IV sarcoidosis cases. We also identified a significant SNP-SNP interaction between rs1049550 and a sarcoidosis risk SNP (rs9268839) near the HLA-DRA locus. This further genetic dissection of ANXA11 may provide additional insight into the immune dysregulation characteristic of sarcoidosis pathophysiology.

A functional haplotype of UBE2L3 confers risk for systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease with diverse clinical manifestations characterized by the development of pathogenic autoantibodies manifesting in inflammation of target organs such as the kidneys, skin and joints. Genome-wide association studies have identified genetic variants in the UBE2L3 region that are associated with SLE in subjects of European and Asian ancestry. UBE2L3 encodes an ubiquitin-conjugating enzyme, UBCH7, involved in cell proliferation and immune function. In this study, we sought to further characterize the genetic association in the region of UBE2L3 and use molecular methods to determine the functional effect of the risk haplotype. We identified significant associations between variants in the region of UBE2L3 and SLE in individuals of European and Asian ancestry that exceeded a Bonferroni-corrected threshold (P<1 × 10(-4)). A single risk haplotype was observed in all associated populations. Individuals harboring the risk haplotype display a significant increase in both UBE2L3 mRNA expression (P=0.0004) and UBCH7 protein expression (P=0.0068). The results suggest that variants carried on the SLE-associated UBE2L3 risk haplotype influence autoimmunity by modulating UBCH7 expression.

Cannabis-related deficits in real-world memory.

BACKGROUND: Research shows that cannabis users exhibit deficits in prospective memory (PM) and executive function, which persist beyond acute intoxication. However, many studies rely on self-reports of memory failures or use laboratory-based measures that may not mimic functional deficits in the real world. The present study aimed to assess real-world memory functioning. METHOD: Twenty cannabis-only users and 20 non-illicit drug users were recruited. Participants completed a substance use inventory and a mood scale, followed by a non-immersive virtual reality task assessing PM and executive functioning. The task involved the participant playing the role of an office worker for the day and performing routine office duties. A number of subscales were used to assess facets of executive function (planning, adaptive thinking, creative thinking, selection, prioritisation) and PM (time-based, event-based and action-based PM). RESULTS: Multivariate analysis of variance revealed cannabis users performed worse overall on the task, with poor performance on the planning, time-based PM and event-based PM subscales. In addition, indices of cannabis (length, dose, frequency, total use) were correlated with performance on these three subscales. CONCLUSIONS: The present study expands on previously established research, providing support for the cannabis-related deficits in PM and executive functioning, and the role of different aspects of cannabis use in these deficits.

Role of MYH9 and APOL1 in African and non-African populations with lupus nephritis.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and organ damage. Lupus nephritis (LN) is one of the most severe manifestations of SLE. Multiple studies reported associations between renal diseases and variants in the non-muscle myosin heavy chain 9 (MYH9) and the neighboring apolipoprotein L 1 (APOL1) genes. We evaluated 167 variants spanning MYH9 for association with LN in a multiethnic sample. The two previously identified risk variants in APOL1 were also tested for association with LN in European-Americans (EAs) (N = 579) and African-Americans (AAs) (N = 407). Multiple peaks of association exceeding a Bonferroni corrected P-value of P < 2.03 × 10(-3) were observed between LN and MYH9 in EAs (N = 4620), with the most pronounced association at rs2157257 (P = 4.7 × 10(-4), odds ratio (OR) = 1.205). A modest effect with MYH9 was also detected in Gullah (rs8136069, P = 0.0019, OR = 2.304). No association between LN and MYH9 was found in AAs, Asians, Amerindians or Hispanics. This study provides the first investigation of MYH9 in LN in non-Africans and of APOL1 in LN in any population, and presents novel insight into the potential role of MYH9 in LN in EAs.

The role of executive functions in human prospective interval timing.

Human timing is thought to be based on the output of an internal clock. Whilst the functioning of this clock is well documented, it is unclear which other cognitive resources may moderate timing. Brown (2006) and Rattat (2010) suggest that the central executive of working memory may be recruited during timing. However it seems likely that the fractionated executive component processes identified by Miyake et al. (2000) and Fisk and Sharp (2004) may differentially contribute to timing performance; further exploration of this was the aim of the present study. An interference paradigm was employed in which participants completed an interval production task, and tasks which have been shown to tap the four key executive component processes (shifting, inhibition, updating and access) under single and dual-task conditions. Comparison of single and dual-task performance indicated that timing always became more variable when concurrently performing a second task. Bidirectional interference only occurred between the interval production task and the memory updating task, implying that both tasks are competing for the same executive resource of updating. There was no evidence in the current study to suggest that switching, inhibition or access was involved in timing, however they may be recruited under more difficult task conditions.

Microhotplate Temperature Sensor Calibration and BIST.

In this paper we describe a novel long-term microhotplate temperature sensor calibration technique suitable for Built-In Self Test (BIST). The microhotplate thermal resistance (thermal efficiency) and the thermal voltage from an integrated platinum-rhodium thermocouple were calibrated against a freshly calibrated four-wire polysilicon microhotplate-heater temperature sensor (heater) that is not stable over long periods of time when exposed to higher temperatures. To stress the microhotplate, its temperature was raised to around 400 °C and held there for days. The heater was then recalibrated as a temperature sensor, and microhotplate temperature measurements were made based on the fresh calibration of the heater, the first calibration of the heater, the microhotplate thermal resistance, and the thermocouple voltage. This procedure was repeated 10 times over a period of 80 days. The results show that the heater calibration drifted substantially during the period of the test while the microhotplate thermal resistance and the thermocouple-voltage remained stable to within about plus or minus 1 °C over the same period. Therefore, the combination of a microhotplate heater-temperature sensor and either the microhotplate thermal resistance or an integrated thin film platinum-rhodium thermocouple can be used to provide a stable, calibrated, microhotplate-temperature sensor, and the combination of the three sensor is suitable for implementing BIST functionality. Alternatively, if a stable microhotplate-heater temperature sensor is available, such as a properly annealed platinum heater-temperature sensor, then the thermal resistance of the microhotplate and the electrical resistance of the platinum heater will be sufficient to implement BIST. It is also shown that aluminum- and polysilicon-based temperature sensors, which are not stable enough for measuring high microhotplate temperatures (>220 °C) without impractically frequent recalibration, can be used to measure the silicon substrate temperature if never exposed to temperatures above about 220 °C.