Analytical validation of HER2DX genomic test for early-stage HER2-positive breast cancer.

BACKGROUND: HER2DX, a multianalyte genomic test, has been clinically validated to predict breast cancer recurrence risk (relapse risk score), the probability of achieving pathological complete response post-neoadjuvant therapy (pCR likelihood score), and individual ERBB2 messenger RNA (mRNA) expression levels in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This study delves into the comprehensive analysis of HER2DX's analytical performance. MATERIALS AND METHODS: Precision and reproducibility of HER2DX risk, pCR, and ERBB2 mRNA scores were assessed within and between laboratories using formalin-fixed paraffin-embedded (FFPE) tumor tissues and purified RNA. Robustness was appraised by analyzing the impact of tumor cell content and protocol variations including different instruments, reagent lots, and different RNA extraction kits. Variability was evaluated across intratumor biopsies and genomic platforms [RNA sequencing (RNAseq) versus nCounter], and according to protocol variations. RESULTS: Precision analysis of 10 FFPE tumor samples yielded a maximal standard error of 0.94 across HER2DX scores (1-99 scale). High reproducibility of HER2DX scores across 29 FFPE tumors and 20 RNAs between laboratories was evident (correlation coefficients >0.98). The probability of identifying score differences >5 units was ≤5.2%. No significant variability emerged based on platform instruments, reagent lots, RNA extraction kits, or TagSet thaw/freeze cycles. Moreover, HER2DX displayed robustness at low tumor cell content (10%). Intratumor variability across 212 biopsies (106 tumors) was <4.0%. Concordance between HER2DX scores from 30 RNAs on RNAseq and nCounter platforms exceeded 90.0% (Cohen's κ coefficients >0.80). CONCLUSIONS: The HER2DX assay is highly reproducible and robust for the quantification of recurrence risk, pCR likelihood, and ERBB2 mRNA expression in early-stage HER2-positive breast cancer.

Equipping for risk: Lessons learnt from the UK shale-gas experience on assessing environmental risks for the future geoenergy use of the deep subsurface.

findings are presented from an investigation to improve understanding of the environmental risks associated with developing an unconventional-hydrocarbons industry in the UK. The EQUIPT4RISK project, funded by UK Research Councils, focused on investigations around Preston New Road (PNR), Fylde, Lancashire, and Kirby Misperton Site A (KMA), North Yorkshire, where operator licences to explore for shale gas by hydraulic fracturing (HF) were issued in 2016, although exploration only took place at PNR. EQUIPT4RISK considered atmospheric (greenhouse gases, air quality), water (groundwater quality) and solid-earth (seismicity) compartments to characterise and model local conditions and environmental responses to HF activities. Risk assessment was based on the source-pathway-receptor approach. Baseline monitoring of air around the two sites characterised the variability with meteorological conditions, and isotopic signatures were able to discriminate biogenic methane (cattle) from thermogenic (natural-gas) sources. Monitoring of a post-HF nitrogen-lift (well-cleaning) operation at PNR detected the release of atmospheric emissions of methane (4.2 ± 1.4 t CH4). Groundwater monitoring around KMA identified high baseline methane concentrations and detected ethane and propane at some locations. Dissolved methane was inferred from stable-isotopic evidence as overwhelmingly of biogenic origin. Groundwater-quality monitoring around PNR found no evidence of HF-induced impacts. Two approaches for modelling induced seismicity and associated seismic risk were developed using observations of seismicity and operational parameters from PNR in 2018 and 2019. Novel methodologies developed for monitoring include use of machine learning to identify fugitive atmospheric methane, Bayesian statistics to assess changes to groundwater quality, a seismicity forecasting model seeded by the HF-fluid injection rate and high-resolution monitoring of soil-gas methane. The project developed a risk-assessment framework, aligned with ISO 31000 risk-management principles, to assess the theoretical combined and cumulative environmental risks from operations over time. This demonstrated the spatial and temporal evolution of risk profiles: seismic and atmospheric impacts from the shale-gas operations are modelled to be localised and short-lived, while risk to groundwater quality is longer-term.

An in situ FTIR study of the plasma- and thermally-driven reaction of isopropyl alcohol at CeO2: evidence for a loose transition state involving Ce3+?

This paper reports on the thermally-driven and non-thermal plasma-driven reaction of IsoPropyl Alcohol (IPA) on ceria (CeO2) with the aim to investigate the differences between plasma catalytic interactions and the analogous thermal reactions. Both were studied by in situ infrared spectroscopy: using diffuse reflectance for the thermal reaction and reflectance infrared for the plasma. For the thermal reaction, the activity towards the formation of acetone and acetaldehyde and, at higher temperatures, CO2 was dependent upon the coverage of surface carbonates and bicarbonates, suggesting at least some of these species blocked the relevant active sites. However, for the first time, methane and cold CO was observed and this was interpreted in terms of a roaming mechanism taking place at the surface via a loose transition state. By contrast, the plasma-driven process was not inhibited by adsorbed carbonaceous species producing acetone followed by isophorone and a polymethylacetylene-like polymer. Comparisons are made between the equivalent thermal and plasma reactions of isopropyl alcohol on Macor and tin oxide surfaces. On Macor the plasma produced similar products whereas on tin oxide there was no reaction. This suggests that the selection of catalysts for plasma processing cannot necessarily be determined from the equivalent thermal process.

Evaluating an anaerobic digestion (AD) feedstock derived from a novel non-source segregated municipal solid waste (MSW) product.

In many nations industrial scale AD of non-agricultural waste materials (such as MSW) has not yet reached its full potential, often constrained by the lack of secure, inexpensive, high quality AD feedstocks, and markets for the resulting digestate material. We tested the output material of a high throughput novel industrial process to define its potential as an AD feedstock (based on quality and consistency). This process, designed to circumvent the constraints of source segregation while still generating segregated waste streams, resulted in the production of a temporally homogenous fibrous material with: an average moisture content of 44.2 (±2.33)%; C:N ratio of ∼32.9:1 (±3.46:1), C:P ratio of ∼228:1 and gross calorific value of 17.4 (±0.29)MJ/kg(DM). This material provided a CH4 yield of between 201 and 297m3 CH4/tonne(DM) (271-401m3CH4/tonne(vs)) comparable to commonly used AD feedstocks. Material contaminant levels were temporally consistent (P>0.05), (average values being Cd 0.63 (±0.19), Cu 56.3 (±7.45), Crtot 51.4 (±4.41), Hg<0.3, Ni 28.9 (±5.17), Pb 79.2 (±23.71), Zn 202 (±44.5), total polyaromatic hydrocarbons (PAH) 2.2 (±0.3), and total polychlorinated biphenyls (PCB) (<0.2)mg/kg(DM)). Calculated digestate contaminant levels were below the median contaminant threshold limits for anaerobic digestates of all countries within the European Union i.e. of Cd 3.35, Cu 535, Crtot 535, Hg 8.15, Ni 185, Pb 397.5, Zn 2100mg/kg(DM). We suggest that novel high throughput processes that produce high quality AD feedstocks, may have a place in further diversion of waste from landfill.

An in situ FTIR spectroscopic and thermogravimetric analysis study of the dehydration and dihydroxylation of SnO2: the contribution of the (100), (110) and (111) facets.

Nanoparticulate SnO2 produced by a hydrothermal method was characterised by BET, XRD, TGA-MS and in situ variable temperature diffuse reflectance infra red spectroscopy (DRIFTS) to determine the surface behaviour of water. For the (100) facets, hydrogen bonding does not occur, and water adsorption is less strong than for the (111) and (110) facets where hydrogen bonding does occur. Reversible uptake of oxygen was observed. These findings have implications for other surface-gas reactions in which Ni and Sb co-doped SnO2 (NATO) anodes are used for ozone generation. BET showed the relatively high surface area and nanometer scale of the SnO2 particles, whilst XRD confirmed the nano dimension of the crystallites and showed only the cassiterite phase. TGA analysis indicated four temperature regions over which mass loss was observed. These and the in situ DRIFTS studies revealed the existence of various forms of water associated with specific crystal facets of the SnO2, as well as the existence of isolated O-H groups and adsorbed oxygen species. Electronic absorptions were also observed and the data rationalised in terms of the existence of both free electron absorptions, and absorptions from oxygen vacancy states. The role of adsorbed molecular oxygen in electrochemical ozone generation at Ni and Sb co-doped SnO2 (NATO) anodes was strongly suggested by this work.

Effect of reconstruction methods and x-ray tube current-time product on nodule detection in an anthropomorphic thorax phantom: A crossed-modality JAFROC observer study.

PURPOSE: To evaluate nodule detection in an anthropomorphic chest phantom in computed tomography (CT) images reconstructed with adaptive iterative dose reduction 3D (AIDR(3D)) and filtered back projection (FBP) over a range of tube current-time product (mAs). METHODS: Two phantoms were used in this study: (i) an anthropomorphic chest phantom was loaded with spherical simulated nodules of 5, 8, 10, and 12 mm in diameter and +100, -630, and -800 Hounsfield units electron density; this would generate CT images for the observer study; (ii) a whole-body dosimetry verification phantom was used to ultimately estimate effective dose and risk according to the model of the BEIR VII committee. Both phantoms were scanned over a mAs range (10, 20, 30, and 40), while all other acquisition parameters remained constant. Images were reconstructed with both AIDR(3D) and FBP. For the observer study, 34 normal cases (no nodules) and 34 abnormal cases (containing 1-3 nodules, mean 1.35 ± 0.54) were chosen. Eleven observers evaluated images from all mAs and reconstruction methods under the free-response paradigm. A crossed-modality jackknife alternative free-response operating characteristic (JAFROC) analysis method was developed for data analysis, averaging data over the two factors influencing nodule detection in this study: mAs and image reconstruction (AIDR(3D) or FBP). A Bonferroni correction was applied and the threshold for declaring significance was set at 0.025 to maintain the overall probability of Type I error at α = 0.05. Contrast-to-noise (CNR) was also measured for all nodules and evaluated by a linear least squares analysis. RESULTS: For random-reader fixed-case crossed-modality JAFROC analysis, there was no significant difference in nodule detection between AIDR(3D) and FBP when data were averaged over mAs [F(1, 10) = 0.08, p = 0.789]. However, when data were averaged over reconstruction methods, a significant difference was seen between multiple pairs of mAs settings [F(3, 30) = 15.96, p < 0.001]. Measurements of effective dose and effective risk showed the expected linear dependence on mAs. Nodule CNR was statistically higher for simulated nodules on images reconstructed with AIDR(3D) (p < 0.001). CONCLUSIONS: No significant difference in nodule detection performance was demonstrated between images reconstructed with FBP and AIDR(3D). mAs was found to influence nodule detection, though further work is required for dose optimization.

An evaluation of the social and private efficiency of adoption: anaerobic digesters and greenhouse gas mitigation.

Climate science has begun to recognize the important role of non-carbon dioxide greenhouse gas emissions, including methane. Given the important contribution of methane, anaerobic digesters (ADs) on dairy farms in the U.S. present an opportunity to reduce greenhouse gas (GHG) emissions. We quantify the social and private costs and benefits of ADs that have been adopted in California and find that, despite high initial costs, large reductions in GHG emissions bring significant social benefits and represent good social investments given a $36 per-ton social cost of carbon. Subsidies that lower the initial private investment cost can help align socially and privately optimal adoption decisions.

South African medical schools: Current state of selection criteria and medical students' demographic profile.

BACKGROUND: Selection of medical students at South African (SA) medical schools must promote equitable and fair access to students from all population groups, while ensuring optimal student throughput and success, and training future healthcare practitioners who will fulfil the needs of the local society. In keeping with international practices, a variety of academic and non-academic measures are used to select applicants for medical training programmes in SA medical schools. OBJECTIVES: To provide an overview of the selection procedures used by all eight medical schools in SA, and the student demographics (race and gender) at these medical schools, and to determine to what extent collective practices are achieving the goals of student diversity and inclusivity. METHODS: A retrospective, quantitative, descriptive study design was used. All eight medical schools in SA provided information regarding selection criteria, selection procedures, and student demographics (race and gender). Descriptive analysis of data was done by calculating frequencies and percentages of the variables measured. RESULTS: Medical schools in SA make use of academic and non-academic criteria in their selection processes. The latter include indices of socioeconomic disadvantage. Most undergraduate medical students in SA are black (38.7%), followed by white (33.0%), coloured (13.4%) and Indian/Asian (13.6%). The majority of students are female (62.2%). The number of black students is still proportionately lower than in the general population, while other groups are overrepresented. CONCLUSION: Selection policies for undergraduate medical programmes aimed at redress should be continued and further refined, along with the provision of support to ensure student success.

Towards a framework for analysis of eye-tracking studies in the three dimensional environment: a study of visual search by experienced readers of endoluminal CT colonography.

OBJECTIVE: Eye tracking in three dimensions is novel, but established descriptors derived from two-dimensional (2D) studies are not transferable. We aimed to develop metrics suitable for statistical comparison of eye-tracking data obtained from readers of three-dimensional (3D) "virtual" medical imaging, using CT colonography (CTC) as a typical example. METHODS: Ten experienced radiologists were eye tracked while observing eight 3D endoluminal CTC videos. Subsequently, we developed metrics that described their visual search patterns based on concepts derived from 2D gaze studies. Statistical methods were developed to allow analysis of the metrics. RESULTS: Eye tracking was possible for all readers. Visual dwell on the moving region of interest (ROI) was defined as pursuit of the moving object across multiple frames. Using this concept of pursuit, five categories of metrics were defined that allowed characterization of reader gaze behaviour. These were time to first pursuit, identification and assessment time, pursuit duration, ROI size and pursuit frequency. Additional subcategories allowed us to further characterize visual search between readers in the test population. CONCLUSION: We propose metrics for the characterization of visual search of 3D moving medical images. These metrics can be used to compare readers' visual search patterns and provide a reproducible framework for the analysis of gaze tracking in the 3D environment. ADVANCES IN KNOWLEDGE: This article describes a novel set of metrics that can be used to describe gaze behaviour when eye tracking readers during interpretation of 3D medical images. These metrics build on those established for 2D eye tracking and are applicable to increasingly common 3D medical image displays.

Profiling undergraduates' generic learning skills on entry to medical school; an international study.

BACKGROUND: Medical education faces challenges posed by widening access to training, a demand for globally competent healthcare workers and progress towards harmonisation of standards. AIM: To explore potential challenges arising from variation in diversity and educational background of medical school entrants. METHOD: This study investigated the reported experience and confidence, in a range of 31 generic skills underpinning learning, of 2606 medical undergraduates entering 14 medical schools in England and South Africa, using a validated questionnaire. RESULTS: Responses suggest that there is considerable similarity in prior educational experience and confidence skills profiles on entry to South African and English medical schools. South African entrants reported significantly more experience in 'Technical skills', 'Managing their own Learning', and 'Presentation', while English students reported increased experience in 'IT' skills. South African undergraduates reported more confidence in 'Information Handling', while English students were more confident in 'IT' skills. The most noticeable difference, in 'IT' skills, is probably due to documented differences in access to computer facilities at high school level. Differences between individual schools within each country are noticeable. CONCLUSIONS: Educators need to acquire a good understanding of their incoming cohorts, and ensure necessary tailored support for skills development.

Investigating carbonate formation in urban soils as a method for capture and storage of atmospheric carbon.

This paper investigates the potential for engineered urban soils to capture and store atmospheric carbon (C). Calcium (Ca) and magnesium (Mg) bearing waste silicate minerals within the soil environment can capture and store atmospheric C through the process of weathering and secondary carbonate mineral precipitation. Anthropogenic soils, known to contain substantial quantities of Ca and Mg-rich minerals derived from demolition activity (particularly cement and concrete), were systematically sampled at the surface across a 10 ha brownfield site, Science Central, located in the urban centre of Newcastle upon Tyne, U.K. Subsequent analysis yielded average carbonate contents of 21.8±4.7% wt CaCO(3). Isotopic analysis demonstrated δ(18)O values between -9.4‰ and -13.3‰ and δ(13)C values between -7.4‰ and -13.6‰ (relative to Pee Dee Belemnite), suggesting that up to 39.4±8.8% of the carbonate C has been captured from the atmosphere through hydroxylation of dissolved CO(2) in high pH solutions. The remaining carbonate C is derived from lithogenic sources. 37.4 kg of atmospheric CO(2) has already been captured and stored as carbonate per Mg of soil across the site, representing a carbon dioxide (CO(2)) removal rate of 12.5 kg CO(2) Mg(-1) yr(-1). There is the potential for capture and storage of a further 27.3 kg CO(2) Mg(-1) in residual reactive materials, which may be exploited through increased residence time (additional in situ weathering). Overall, the Science Central site has the potential to capture and store a total of 64,800 Mg CO(2) as carbonate minerals. This study illustrates the potential for managing urban soils as tools of C capture and storage, an important ecosystem service, and demonstrates the importance of studying C storage in engineering urban anthropogenic soils.

ROCView: prototype software for data collection in jackknife alternative free-response receiver operating characteristic analysis.

ROCView has been developed as an image display and response capture (IDRC) solution to image display and consistent recording of reader responses in relation to the free-response receiver operating characteristic paradigm. A web-based solution to IDRC for observer response studies allows observations to be completed from any location, assuming that display performance and viewing conditions are consistent with the study being completed. The simplistic functionality of the software allows observations to be completed without supervision. ROCView can display images from multiple modalities, in a randomised order if required. Following registration, observers are prompted to begin their image evaluation. All data are recorded via mouse clicks, one to localise (mark) and one to score confidence (rate) using either an ordinal or continuous rating scale. Up to nine "mark-rating" pairs can be made per image. Unmarked images are given a default score of zero. Upon completion of the study, both true-positive and false-positive reports can be downloaded and adapted for analysis. ROCView has the potential to be a useful tool in the assessment of modality performance difference for a range of imaging methods.

Contaminant mobility and carbon sequestration downstream of the Ajka (Hungary) red mud spill: The effects of gypsum dosing.

A number of emergency pollution management measures were enacted after the accidental release of caustic bauxite processing residue that occurred in Ajka, western Hungary in October, 2010. These centred on acid and gypsum dosing to reduce pH and minimise mobility of oxyanion contaminants mobile at high pH. This study assessed the effectiveness of gypsum dosing on contaminant mobility and carbon sequestration through assessment of red mud and gypsum-affected fluvial sediments via elemental analysis and stable isotope analysis. There was a modest uptake of contaminants (notably As, Cr, and Mn) on secondary carbonate-dominated deposits in reaches subjected to gypsum dosing. C and O stable isotope ratios of carbonate precipitates formed as a result of gypsum dosing were used to quantify the importance of the neutralisation process in sequestering atmospheric carbon dioxide. This process was particularly pronounced at sites most affected by gypsum addition, where up to 36% of carbonate-C appears to be derived from atmospheric in-gassing of CO(2). The site is discussed as a large scale analogue for potential remedial approaches and carbon sequestration technologies that could be applied to red mud slurries and other hyperalkaline wastes. The results of this work have substantial implications for the aluminium production industry in which 3-4% of the direct CO(2) emissions may be offset by carbonate precipitation. Furthermore, carbonation by gypsum addition may be important for contaminant remediation, also providing a physical stabilisation strategy for the numerous historic stockpiles of red mud.

Silicate production and availability for mineral carbonation.

Atmospheric carbon dioxide sequestered as carbonates through the accelerated weathering of silicate minerals is proposed as a climate change mitigation technology with the potential to capture billions of tonnes of carbon per year. Although these materials can be mined expressly for carbonation, they are also produced by human activities (cement, iron and steel making, coal combustion, etc.). Despite their potential, there is poor global accounting of silicates produced in this way. This paper presents production estimates (by proxy) of various silicate materials including aggregate and mine waste, cement kiln dust, construction and demolition waste, iron and steel slag, and fuel ash. Approximately 7-17 billion tonnes are produced globally each year with an approximate annual sequestration potential of 190-332 million tonnes C. These estimates provide justification for additional research to accurately quantify the contemporary production of silicate minerals and to determine the location and carbon capture potential of historic material accumulations.

The optimal cut-off for predicting large oesophageal varices using transient elastography is disease specific.

The diagnosis of cirrhosis requires screening for oesophageal varices by upper gastrointestinal endoscopy. In many countries, serological tests and elastography are replacing liver biopsy for diagnosing cirrhosis. The aims of this study were to see whether there was an optimal cut-off of liver stiffness that could predict the presence of large (>F2) oesophageal varices and whether this was disease specific. A total of two hundred and twenty-two patients with all cause cirrhosis (Child class A) were screened, and 211 had successful elastography and are included in the analysis. Of the patients studied, one hundred and thirty-two patients had no or small F1 varices and 79 had large varices. Liver stiffness of 19.8 kPa had a negative predictive value of 91% and a positive predictive value of 55% with an area under the curve (AUC) on receiver operating characteristics (ROC) of 0.73 in differentiating between small and large varices. Seven patients with large varices would have been incorrectly classified. In the 157 patients with hepatitis C as the aetiology of cirrhosis, the negative predictive value was 98% and only one patient was misclassified. Liver stiffness was superior in diagnostic accuracy to platelet count in all patients. A liver stiffness of >19.8 kPa could be utilized as a cut-off for endoscopy and beta blocker utilization, particularly in patients with hepatitis C.

Evaluation of adherence to highly active antiretroviral therapy in adults in Jamaica / Evaluación de la adhesión a la terapia antiretroviral altamente activa en adultos en Jamaica

BACKGROUND AND PURPOSE: Highly active antiretroviral therapy (HAART) has improved morbidity and mortality and quality of life, revitalized communities and transformed the perception of HIV/AIDS from being a "death sentence" to a chronic illness. Strict and sustained adherence to medication is essential long-term viral suppression. In April 2005, an Adherence Support Programme was introduced to Jamaica's HIV Programme, whereby Persons Living with HIV/ AIDS (PLWHA) who had achieved high levels of adherence were trained to provide support to other PLWHA in order to increase their adherence to HAART regimens. METHODS: A cross-sectional survey of 116 individuals with advanced HIV and on HAART was performed in June and July 2006. RESULTS: Many participants were unemployed, poor persons with limited education. Based on self-report of seven-day adherence, 54.8% of persons were 95-100% adherent, 37.5% were 80-94% adherent and 7.7% were < 80% adherent. Having interacted with an adherence counsellor was not associated with adherence levels. Factors associated with nonadherence were: being away from home (38%), sleeping through dose-time (37%), forgetfulness (37%) and running out of pills (31%). Having no food (26.9%), not wanting to be seen taking medication (20%) and intolerable side effects (18.8%) were also reasons given. Only 44% of persons used aids to remind them of dose times. CONCLUSION: Adherence in this study group is low and may have worsened since 2005. More emphasis must be placed on preparing adults to start HAART. The use of pillboxes and other reminders such as alarm clocks and cell phones must be reinforced.

ANTECEDENTES Y PROPÓSITO: La terapia antiretroviral altamente activa (TARAA) ha producido un marcado mejoramiento en relación con la morbilidad y la mortalidad así como la calidad de la vida. Asimismo, ha revitalizado las comunidades y transformado la percepción del VIH/SIDA, de una "sentencia de muerte" a una enfermedad crónica. La adhesión estricta y sostenida a la medicación es esencial para una supresión viral a largo plazo. En abril de 2005, se introdujo un Programa de Apoyo a la Adhesión como parte del Programa de VIH de Jamaica, mediante el cual personas que viven con VIH/SIDA (PVCVS) y que han alcanzado altos niveles de adhesión, fueron entrenadas con el fin de ayudar a otras PVCVS a aumentar su adhesión a los regimenes de TARAA. MÉTODOS: En junio y julio de 2006 se llevó a cabo un estudio transversal de 116 individuos con VIH avanzado y bajo TARAA. RESULTADOS: Muchos participantes eran personas desempleadas y pobres, con un nivel de educación limitado. Según un auto-reporte de adhesión por 7 días, 54.8% de las personas mostraron una adhesión de 95-100%, 37.5% presentaban una adhesión de 80-94% y 7.7% tenían una adhesión de < 80%. El haber interactuado con un consejero de adhesión no guardaba relación con los niveles de adhesión. Los factores asociados con la adhesión fueron el estar fuera de casa (38%), pasar durmiendo la hora de la dosis (37%), olvido (37%), y el quedarse sin tabletas (31%). No tener alimentos (26.9%), no querer ser visto tomando medicamentos (20%) y efectos colaterales intolerables (18.8%) fueron también razones dadas. Sólo el 44% de las personas usaban ayudas para recordarles las horas de las dosis. CONCLUSIÓN: La adhesión en este grupo de estudio es baja y puede haber empeorado desde el 2005. Hay que hacer más énfasis en preparar a los adultos para que comiencen con TARAA. El uso de cajas de tabletas y otros medios recordatorios tales como despertadores y celulares tiene que ser reforzado.

Transfusion support for a patient with McLeod phenotype without chronic granulomatous disease and with antibodies to Kx and Km.

BACKGROUND AND OBJECTIVES: Kell antigens are encoded by the KEL gene on the long arm of chromosome 7. Kx antigen is encoded by the XK gene on the short arm of the X chromosome. Kell and Kx proteins in the red cell membrane are covalently linked by a disulphide bond. The McLeod phenotype is characterized by weakened expression of antigens in the Kell blood group system, absence of Km and Kx antigens, and acanthocytosis. It has an X-linked mode of inheritance with transmission through carrier females. Some males with the McLeod syndrome also have chronic granulomatous disease (CGD). It is generally believed that patients with non-CGD McLeod may develop anti-Km but not anti-Kx, but that those with CGD McLeod can develop both anti-Km and anti-Kx. MATERIALS AND METHODS: We present serological data, DNA genotyping and gene sequencing, monocyte monolayer assay and neutrophil oxidative burst test from a patient with the McLeod phenotype without clinical evidence of CGD. RESULTS: We report here the second example of a patient with non-CGD McLeod who developed anti-Kx in addition to anti-Km. Sequencing of our patient's XK gene confirmed the presence of a mutation resulting in a premature stop codon and lack of Kx protein in the red cell membrane, which is consistent with the diagnosis of McLeod syndrome. Neutrophil oxidative burst test was normal, indicating that our patient did not have CGD. The challenge of providing 10 compatible blood units for multiple surgeries was met. CONCLUSION: The second case of a rare entity, a patient with non-CGD McLeod who developed anti-Kx and anti-Km, was managed successfully with a combination of autologous donations and procurement of compatible units from national and international sources.

Evaluation of adherence to highly active antiretroviral therapy in adults in Jamaica.

BACKGROUND AND PURPOSE: Highly active antiretroviral therapy (HAART) has improved morbidity and mortality and quality of life, revitalized communities and transformed the perception of HIV/AIDS from being a "death sentence" to a chronic illness. Strict and sustained adherence to medication is essential long-term viral suppression. In April 2005, an Adherence Support Programme was introduced to Jamaica's HIV Programme, whereby Persons Living with HIV/AIDS (PLWHA) who had achieved high levels of adherence were trained to provide support to other PLWHA in order to increase their adherence to HAART regimens. METHODS: A cross-sectional survey of 116 individuals with advanced HIV and on HAART was performed in June and July 2006. RESULTS: Many participants were unemployed, poor persons with limited education. Based on self-report of seven-day adherence, 54.8% of persons were 95-100% adherent, 37.5% were 80-94% adherent and 7.7% were < 80% adherent. Having interacted with an adherence counsellor was not associated with adherence levels. Factors associated with nonadherence were: being away from home (38%), sleeping through dose-time (37%), forgetfulness (37%) and running out of pills (31%). Having no food (26.9%), not wanting to be seen taking medication (200%) and intolerable side effects (18.8%) were also reasons given. Only 44% of persons used aids to remind them of dose times. CONCLUSION: Adherence in this study group is low and may have worsened since 2005. More emphasis must be placed on preparing adults to start HAART The use of pillboxes and other reminders such as alarm clocks and cell phones must be reinforced.

A randomized, double-blind, placebo-controlled trial of lenalidomide in the treatment of moderately severe active Crohn's disease.

BACKGROUND: Therapy targeted at tumour necrosis factor-alpha has an established role in Crohn's disease. Lenalidomide, an analogue of thalidomide, is an oral immunomodulatory agent with powerful antitumour necrosis factor-alpha properties. It is licensed for myeloma and myelodysplastic syndrome. Based upon reports of thalidomide efficacy, lenalidomide was evaluated in Crohn's disease. AIM: To evaluate the efficacy and safety of lenalidomide in subjects with moderately severe active Crohn's disease. METHODS: In a multicentre, double-blind, placebo-controlled parallel group study 89 subjects were randomized to lenalidomide 25 mg daily, 5 mg daily or placebo. Subjects were treated for 12 weeks. The primary end point was a 70-point reduction in Crohn's Disease Activity Index. RESULTS: The overall clinical response rate was not significantly different between the three groups: lenalidomide 25 mg 26%, lenalidomide 5 mg 48% and placebo 39%. Lenalidomide was generally well tolerated with only one serious adverse event, a deep vein thrombosis, being attributed to treatment. CONCLUSION: Lenalidomide, an oral agent with antitumour necrosis factor-alpha properties, was not effective in active Crohn's disease in contrast to reports of benefit from thalidomide. The reasons for this lack of efficacy are speculative, other physiological activities may offset its action on inflammatory cytokines, or its antitumour necrosis factor-alpha action without apoptosis may be insufficient for activity in Crohn's disease.