Integration of TB and ART services fails to improve TB treatment outcomes: Comparison of ART/TB primary healthcare services in Cape Town, South Africa

BACKGROUND: The combined tuberculosis (TB) and HIV epidemics in South Africa (SA) have created enormous operational challenges for a health service that has traditionally run vertical programmes for TB treatment and antiretroviral therapy (ART) in separate facilities. This is particularly problematic for TB/HIV co-infected patients who need to access both services. OBJECTIVE: To determine whether integrated TB facilities had better TB treatment outcomes than single-service facilities in Cape Town, SA. METHODS: TB treatment outcomes were determined for newly registered, adult TB patients (aged > or = 18 years) at 13 integrated ART/TB primary healthcare (PHC) facilities and four single-service PHC facilities from 1 January 2009 to 30 June 2010. A chi2 test adjusted for a cluster sample design was used to compare outcomes by type of facility. RESULTS: Of 13,542 newly registered patients, 10,030 received TB treatment in integrated facilities and 3,512 in single-service facilities. There was no difference in baseline characteristics between the two groups with HIV status determined for 9,351 (93.2%) and 3,227 (91.9%) patients, of whom 6 649 (66.3%) and 2,213 (63%) were HIV-positive in integrated facilities and single-service facilities, respectively. The median CD4+ count of HIV-positive patients was 152 cells/microl (interquartile range (IQR) 71-277) for integrated facilities and 148 cells/microl (IQR 67-260) for single-service facilities. There was no statistical difference in the TB treatment outcome profile between integrated and single-service facilities for all TB patients (p = 0.56) or for the sub-set of HIV-positive TB patients (p = 0.58) CONCLUSION: This study did not demonstrate improved TB treatment outcomes in integrated PHC facilities and showed that the provision of ART in the same facility as TB services was not associated with lower TB death and default rates

Frequent alterations in p16/CDKN2A identified by immunohistochemistry and FISH in chordoma

The expression of p16/CDKN2A, the second most commonly inactivated tumour suppressor gene in cancer, is lost in the majority of chordomas. However, the mechanism(s) leading to its inactivation and contribution to disease progression have only been partially addressed using small patient cohorts. We studied 384 chordoma samples from 320 patients by immunohistochemistry and found that p16 protein was lost in 53% of chordomas and was heterogeneously expressed in these tumours. To determine if CDKN2A copy number loss could explain the absence of p16 protein expression we performed fluorescence in situ hybridisation (FISH) for CDKN2A on consecutive tissue sections. CDKN2A copy number status was altered in 168 of 274 (61%) of samples and copy number loss was the most frequent alteration acquired during clinical disease progression. CDKN2A homozygous deletion was always associated with p16 protein loss but only accounted for 33% of the p16‐negative cases. The remaining immunonegative cases were associated with disomy (27%), monosomy (12%), heterozygous loss (20%) and copy number gain (7%) of CDKN2A, supporting the hypothesis that loss of protein expression might be achieved via epigenetic or post‐transcriptional regulatory mechanisms. We identified that mRNA levels were comparable in tumours with and without p16 protein expression, but other events including DNA promoter hypermethylation, copy number neutral loss of heterozygosity and expression of candidate microRNAs previously implicated in the regulation of CDKN2A expression were not identified to explain the protein loss. The data argue that p16 loss in chordoma is commonly caused by a post‐transcriptional regulatory mechanism that is yet to be defined

Development of a custom on-line ultrasonic vapour analyzer/flowmeter for the ATLAS inner detector, with application to gaseous tracking and Cherenkov detectors

Precision sound velocity measurements can simultaneously determine binary gas composition and flow. We have developed an analyzer with custom electronics, currently in use in the ATLAS inner detector, with numerous potential applications. The instrument has demonstrated ~0.3% mixture precision for C3F8/C2F6 mixtures and < 10-4 resolution for N2/C3F8 mixtures. Moderate and high flow versions of the instrument have demonstrated flow resolutions of +/- 2% F.S. for flows up to 250 l.min-1, and +/- 1.9% F.S. for linear flow velocities up to 15 ms-1; the latter flow approaching that expected in the vapour return of the thermosiphon fluorocarbon coolant recirculator being built for the ATLAS silicon tracker.Comment: Paper submitted to TWEPP2012; Topical Workshop on Electronics for Particle Physics, Oxford, UK, September 17-21, 2012. KEYWORDS: Sonar; Saturated fluorocarbons; Flowmetry; Sound velocity, Gas mixture analysis. 8 pages, 7 figure

Short communication: Methicillin-resistant Staphylococcus aureus detection in US bulk tank milk

Staphylococcus aureus is a major cause of mastitis in dairy cattle. This study estimated the herd prevalence of methicillin-resistant Staph. aureus (MRSA) among US dairy herds by testing bulk tank milk (BTM) samples using genotypic and phenotypic methods. A nationally representative sample of 542 operations had BTM cultured for Staph. aureus, and 218 BTM samples were positive upon initial culture. After 4 wk to 4 mo of frozen storage, 87% of 218 samples (n = 190) were still culture positive for Staph. aureus on blood agar, but none were positive for MRSA on the selective indicator medium CHROMagar MRSA. A duplex PCR was used to detect the Staph. aureus-specific nuc gene and the methicillin resistance gene, mecA, in mixed staphylococcal isolates from the 190 BTM samples that were positive for Staph. aureus after storage. Seven samples tested positive for nuc and mecA, and 2 samples tested positive for mecA only. MecA-positive Staphylococcus spp., but not MRSA, were subsequently isolated from 5 samples, whereas neither mecA-positive Staphylococcus spp. nor MRSA was isolated from the remaining 4 samples. Presence of methicillin-resistant, coagulase-negative Staphylococcus spp. may complicate the detection of MRSA by means of PCR on BTM. Bulk tank milk in the United States is not a common source of MRSA

Diagnostic yield of commercial immunodots to diagnose paraneoplastic neurologic syndromes

OBJECTIVE: To investigate the diagnostic yield of commercial immunodots to detect onconeural antibodies associated with paraneoplastic neurologic syndromes (PNSs), we analyzed the proportion of confirmed positive results using alternative techniques. METHODS: Sera (n = 5,300) of patients with suspected PNS were tested by PNS+2 blot (Ravo Diagnostika; January 2016-May 2017) or EUROLINE PNS 12 Ag (Euroimmun; July 2017-November 2018). Positive samples were further explored by in-house indirect immunofluorescence and a third in-house technique (Western blot or cell-based assay) using recombinant protein. Those found negative by these 2 techniques were considered as nonconfirmed. We analyzed the relationship between band intensity and final confirmation. Clinical data were collected for all confirmed results and nonconfirmed EUROLINE immunodots. RESULTS: PNS+2 blot was positive in 128/1,658 (7.7%) sera and confirmed in 47/128 (36.7%). EUROLINE was positive in 186/3,626 (5.1%) and confirmed in 56/186 (30.1%). Confirmation was highly variable among the antibodies tested, from 7.2% (PNS+2 blot) and 5.8% (EUROLINE) for anti-Yo to 88.2% (PNS+2 blot) and 65.0% (EUROLINE) for anti-Hu. None of the 27 weak positive sera by EUROLINE was confirmed. Band intensity in confirmed cases was variable among the antibodies from strong positive for all anti-Yo (n = 3) and anti-Hu (n = 11) to positive (n = 19) or strong positive (n = 9) for anti-SOX1. Among patients with a nonconfirmed EUROLINE result and available clinical information, all had an alternative diagnosis, and only 6.7% had cancer. CONCLUSIONS: Immunodots may be useful for PNS screening, but a threshold should be established for each antibody, and clinical information and confirmation by other techniques are essential. CLASSIFICATION OF EVIDENCE: The study provides Class IV evidence that immunodot assays for onconeural antibodies accurately identify patients with paraneoplastic neurologic syndromes

Fog paradigm for local energy management systems

Cloud Computing infrastructures have been extensively deployed to support energy computation within built environments. This has ranged from predicting potential energy demand for a building (or a group of buildings), undertaking heat profile/energy distribution simulations, to understanding the impact of climate and weather on building operation. Cloud computing usage in these scenarios have benefited from resource elasticity, where the number and types of resources can change based on the complexity of the simulation being considered. While there are numerous advantages of using a cloud based energy management system, there are also significant limitations. For instance, many such systems assume that the data has been pre-staged at a cloud platform prior to simulation, and do not take account of data transfer times from the building to the simulation platform. The need for supporting computation at edge resources, which can be hosted within the building itself or shared within a building complex, has become important over recent year. Additionally, network connectivity between the sensing infrastructure within a built environment and a data centre where analysis is to be carried out can be intermittent or may fail. There is therefore also a need to better understand how computation/analysis can be carried out closer to the data capture site to complement analysis that would be undertaken at the data centre. We describe how the Fog computing paradigm can be used to support some of these requirements, extending the capability of a data centre to support energy simulation within built environments