Sharing the load: How a personally coloured calculator for grapheme-colour synaesthetes can reduce processing costs.

Synaesthesia refers to a diverse group of perceptions. These unusual perceptions are defined by the experience of concurrents; these are conscious experiences that are catalysed by attention to some normally unrelated stimulus, the inducer. In grapheme-colour synaesthesia numbers, letters, and words can all cause colour concurrents, and these are independent of the actual colour with which the graphemes are displayed. For example, when seeing the numeral '3' a person with synaesthesia might experience green as the concurrent irrespective of whether the numeral is printed in blue, black, or red. As a trait, synaesthesia has the potential to cause both positive and negative effects. However, regardless of the end effect, synaesthesia incurs an initial cost when compared with its equivalent example from normal perception; this is the additional processing cost needed to generate the information on the concurrent. We contend that this cost can be reduced by mirroring the concurrent in the environment. We designed the Digital-Colour Calculator (DCC) app, allowing each user to personalise and select the colours with which it displays its digits; it is the first reported example of a device/approach that leverages the concurrent. In this article we report on the reactions to the DCC for a sample of fifty-three synaesthetes and thirty-five non-synaesthetes. The synaesthetes showed a strong preference for the DCC over its normal counterpart. The non-synaesthetes showed no obvious preference. When using the DCC a subsample of the synaesthete group showed consistent improvement in task speed (around 8%) whereas no synaesthete showed a decrement in their speed.

Spatial distribution of PM2.5-bound elements in eighteen cities over China: policy implication and health risk assessment.

In this study, 30 elements in fine particulate matter (PM2.5) were measured in 18 Chinese cities in 2013. Elemental pollution in northern, southwest, and central China were severe, attributing to excessive coal and biomass combustion in these regions. The concentrations of S, Cl, and K in these areas were 8.21 ± 3.90, 4.03 ± 1.96, and 1.59 ± 0.613 µg/m3, respectively, which were 1.6-2.7 times higher than those in other regions of China. In addition, the industrial emissions in northeast and north China were large, leading to the elevated heavy metal concentration of 1.32 ± 1.17 µg/m3, especially Zn, Pb, Cr, Cd, and Br. Soil dust was the highest in northwest China among the five regions with the concentration of crustal elements of 6.37 ± 4.51 µg/m3. Moreover, although the levels of elemental concentration in east and southeast China were relatively acceptable, regulators must pay attention to elevated level of V (0.009 ± 0.006 µg/m3) in these areas. Compared with 2003, several elements have deteriorated in some cities. For example, As increased by 70%, 18%, and 155% in Changchun, Beijing, and Jinchang, respectively. However, ~ 77% measured elements, e.g., Ti, Fe, and Pb markedly reduced in 2013, with reduction rates of 13-81%. These indicate that the government's policies related to particle-bound elements have shown certain positive environmental effects. For the health risks from the heavy metals in 2013, the non-cancer risks of As and Cd must not be neglected. The cancer risks of As and Pb were much higher than the international safety limit (10-4). More prominent health risks were found in southwest, central, and northwest China. Therefore, the government should accelerate the shift to cleaner energy in underdeveloped areas of China to obtain more environmental and health benefits.

Economic and clinical outcomes of the nurse practitioner-led Sydney Adventist Hospital Community Palliative Care Service.

Objective The aim of this study was to assess the clinical, economic and personal impacts of the nurse practitioner-led Sydney Adventist Hospital Community Palliative Care Service (SanCPCS) Methods Parallel economic analysis of usual care was conducted prospectively with patients from the enhanced SanCPCS. A convenient retrospective sample from the initial service was used to determine the impact of the enhanced service on patient care. A time series survey was used with patients and carers from within the expanded service group in order to measure patient outcomes and values as they approached death. Results Patients of the SanCPCS were less likely to die in hospital and had fewer hospital admissions. In addition, the service halved the estimated hospitalisation cost per patient, but the length of hospital stay was not affected by the service. The SanCPCS was more beneficial for women in terms of fewer hospital admissions and lower costs. Patients' choices regarding place of care and death and what was 'important' to them changed over time. For instance, patients tended to prefer being at home as they approached death, and being pain free doubled in importance. Conclusions Nurse practitioner-led community palliative care services have the potential to result in significant economic and personal benefits for patients and their families in need of such care. What is known about the topic? National trends show an emphasis on community services with the aim of promoting and supporting the choice of dying at home, and this coincides with drives to reduce hospital costs and length of stay. Community-based palliative care services may offer substantial economic and clinical benefits. What does this paper add? The SanCPCS was the first nurse practitioner-led community-based palliative care service in Australia. The expansion of this service led to significantly fewer admissions and deaths in hospital, and halved the estimated hospitalisation cost per patient. What are implications for practitioners? Nurse practitioner-led models for care in the out-patient or community setting are a logical direction for palliative services through the engagement of specialised providers uniquely trained to support, nurture, guide and educate patients and their carers.

Assessment of Soil to Mitigate Antibiotics in the Environment Due to Release of Wastewater Treatment Plant Effluent.

With low levels of human antibiotics in the environment due to release of wastewater treatment plant (WWTP) effluent, concern is rising about impacts on human health and antibiotic resistance development. Furthermore, WWTP effluent may be released into waterways used as drinking water sources. The aim of this study was to analyze three antibiotics important to human health (sulfamethoxazole, ofloxacin, and trimethoprim) in soil and groundwater at a long-term wastewater reuse system that spray irrigates effluent. Soil samples were collected (i) at a site that had not received irrigation for 7 mo (approximate background concentrations), and then at the same site after (ii) one irrigation event and (iii) 10 wk of irrigation. Water samples were collected three times per year to capture seasonal variability. Sulfamethoxazole was typically at the highest concentrations in effluent (22 ± 3.7 µg L) with ofloxacin and trimethoprim at 2.2 ± 0.6 and 1.0 ± 0.02 µg L, respectively. In the soil, ofloxacin had the highest background concentrations (650 ± 204 ng kg), whereas concentrations of sulfamethoxazole were highest after continuous effluent irrigation (730 ± 360 ng kg). Trimethoprim was only quantified in soil after 10 wk of effluent irrigation (190 ± 71 ng kg). Groundwater concentrations were typically <25 ng L with high concentrations of 660 ± 20 and 67 ± 7.0 ng L for sulfamethoxazole and ofloxacin, respectively. Given that antibiotics interacted with the soil profile and groundwater concentrations were frequently about 1000-fold lower than effluent, soil may be an adequate tertiary treatment for WWTP effluent leading to improved water quality and protection of human health.

Prognostic value of interferon-γ release assays and tuberculin skin test in predicting the development of active tuberculosis (UK PREDICT TB): a prospective cohort study.

BACKGROUND: Tackling tuberculosis requires testing and treatment of latent tuberculosis in high-risk groups. The aim of this study was to estimate the predictive values of the tuberculin skin test (TST) and two interferon-γ release assays (IGRAs) for the development of active tuberculosis in high-risk groups-ie, people in recent contact with active tuberculosis cases and from high-burden countries. METHOD: In this prospective cohort study, we recruited participants from 54 centres (eg, clinics, community settings) in London, Birmingham, and Leicester in the UK. Participants were eligible if they were aged 16 years or older and at high risk for latent tuberculosis infection (ie, recent contact with someone with active tuberculosis [contacts] or a migrant who had arrived in the UK in the past 5 years from-or who frequently travelled to-a country with a high burden of tuberculosis [migrants]). Exclusion criteria included prevalent cases of tuberculosis, and participants who were treated for latent tuberculosis after a positive test result in this study. Each participant received three tests (QuantiFERON-TB Gold-In Tube, T-SPOT.TB, and a Mantoux TST). A positive TST result was reported using three thresholds: 5 mm (TST-5), 10 mm (TST-10), and greater than 5 mm in BCG-naive or 15 mm in BCG-vaccinated (TST-15) participants. Participants were followed up from recruitment to development of tuberculosis or censoring. Incident tuberculosis cases were identified by national tuberculosis databases, telephone interview, and review of medical notes. Our primary objective was to estimate the prognostic value of IGRAs compared with TST, assessed by the ratio of incidence rate ratios and predictive values for tuberculosis development. The study was registered with ClinicalTrials.gov, NCT01162265, and is now complete. FINDINGS: Between May 4, 2010, and June 1, 2015, 10 045 people were recruited, of whom 9610 were eligible for inclusion. Of this cohort, 4861 (50·6%) were contacts and 4749 (49·4%) were migrants. Participants were followed up for a median of 2·9 years (range 21 days to 5·9 years). 97 (1·0%) of 9610 participants developed active tuberculosis (77 [1·2%] of 6380 with results for all three tests). In all tests, annual incidence of tuberculosis was very low in those who tested negatively (ranging from 1·2 per 1000 person-years, 95% CI 0·6-2·0 for TST-5 to 1·9 per 1000 person-years, 95% CI 1·3-2·7, for QuantiFERON-TB Gold In-Tube). Annual incidence in participants who tested positively were highest for T-SPOT.TB (13·2 per 1000 person-years, 95% CI 9·9-17·4), TST-15 (11·1 per 1000 person-years, 8·3-14·6), and QuantiFERON-TB Gold In-Tube (10·1 per 1000 person-years, 7·4-13·4). Positive results for these tests were significantly better predictors of progression than TST-10 and TST-5 (eg, ratio of test positivity rates in those progressing to tuberculosis compared with those not progressing T-SPOT.TB vs TST-5: 1·99, 95% CI 1·68-2·34; p<0·0001). However, TST-5 identified a higher proportion of participants who progressed to active tuberculosis (64 [83%] of 77 tested) than all other tests and TST thresholds (≤75%). INTERPRETATION: IGRA-based or BCG-stratified TST strategies appear most suited to screening for potential disease progression among high-risk groups. Further work will be needed to assess country-specific cost-effectiveness of each screening test, and in the absence of highly specific diagnostic tests, cheap non-toxic treatments need to be developed that could be given to larger groups of people at potential risk. FUNDING: National Institute for Health Research Health Technology Assessment Programme 08-68-01.

The duration of protection of school-aged BCG vaccination in England: a population-based case-control study.

Background: Evidence of protection from childhood Bacillus Calmette-Guerin (BCG) against tuberculosis (TB) in adulthood, when most transmission occurs, is important for TB control and resource allocation. Methods: We conducted a population-based case-control study of protection by BCG given to children aged 12-13 years against tuberculosis occurring 10-29 years later. We recruited UK-born White subjects with tuberculosis and randomly sampled White community controls. Hazard ratios and 95% confidence intervals (CIs) were estimated using case-cohort Cox regression, adjusting for potential confounding factors, including socio-economic status, smoking, drug use, prison and homelessness. Vaccine effectiveness (VE = 1 - hazard ratio) was assessed at successive intervals more than 10 years following vaccination. Results: We obtained 677 cases and 1170 controls after a 65% response rate in both groups. Confounding by deprivation, education and lifestyle factors was slight 10-20 years after vaccination, and more evident after 20 years. VE 10-15 years after vaccination was 51% (95% CI 21, 69%) and 57% (CI 33, 72%) at 15-20 years. Subsequently, BCG protection appeared to wane; 20-25 years VE = 25% (CI -14%, 51%) and 25-29 years VE = 1% (CI -84%, 47%). Based on multiple imputation of missing data (in 17% subjects), VE estimated in the same intervals after vaccination were similar [56% (CI 33, 72%), 57% (CI 36, 71%), 25% (-10, 48%), 21% (-39, 55%)]. Conclusions: School-aged BCG vaccination offered moderate protection against tuberculosis for at least 20 years, which is longer than previously thought. This has implications for assessing the cost-effectiveness of BCG vaccination and when evaluating new TB vaccines.

Characterization and health risk assessment of PM2.5-bound organics inside and outside of Chinese smoking lounges.

PM2.5 samples were collected at six indoor public places that contained dedicated smoking lounges. Samples were taken in the smoking lounges, at two indoor locations outside of the lounges, and in outdoor air near the venues. Organic carbon (OC), elemental carbon (EC), and non-polar organic compounds including polycyclic aromatic hydrocarbons (PAHs), n-alkanes (n-C16 to n-C40), iso/anteiso-alkanes (C29 to C33), hopanes and phthalate esters (PAEs) were quantified. Average PM2.5 levels of 170.2 ± 85.9 µg/m3 in the lounges exceeded limits of 25 µg/m3 set by World Health Organization (WHO); these levels were 5.4 and 3.9 times higher than those indoors and outdoors, respectively. High ratios of OC to PM2.5, OC to EC, and PAHs diagnostic ratios in the lounges indicated contributions from environmental tobacco smoke (ETS). The maximum carbon number (Cmax) and carbon preference indices (CPI) for n-alkanes showed ETS transport from the enclosed lounges to nearby indoor non-smoking areas. Iso/anteiso-alkanes in the lounges were 876.5 ng/m3, ∼80 times higher than outdoor levels. 17α(H)-21ß(H),30-norhopane and 17α(H)-21ß(H),(22R)-homohopane were much higher in the lounges than outdoor air, but they cannot be directly attributed to ETS. Estimated carcinogenic risks of PAHs in the lounges exceeded the acceptable level of 10- 6.

Observational study to estimate the changes in the effectiveness of bacillus Calmette-Guérin (BCG) vaccination with time since vaccination for preventing tuberculosis in the UK.

BACKGROUND: Until recently, evidence that protection from the bacillus Calmette-Guérin (BCG) vaccination lasted beyond 10 years was limited. In the past few years, studies in Brazil and the USA (in Native Americans) have suggested that protection from BCG vaccination against tuberculosis (TB) in childhood can last for several decades. The UK's universal school-age BCG vaccination programme was stopped in 2005 and the programme of selective vaccination of high-risk (usually ethnic minority) infants was enhanced. OBJECTIVES: To assess the duration of protection of infant and school-age BCG vaccination against TB in the UK. METHODS: Two case-control studies of the duration of protection of BCG vaccination were conducted, the first on minority ethnic groups who were eligible for infant BCG vaccination 0-19 years earlier and the second on white subjects eligible for school-age BCG vaccination 10-29 years earlier. TB cases were selected from notifications to the UK national Enhanced Tuberculosis Surveillance system from 2003 to 2012. Population-based control subjects, frequency matched for age, were recruited. BCG vaccination status was established from BCG records, scar reading and BCG history. Information on potential confounders was collected using computer-assisted interviews. Vaccine effectiveness was estimated as a function of time since vaccination, using a case-cohort analysis based on Cox regression. RESULTS: In the infant BCG study, vaccination status was determined using vaccination records as recall was poor and concordance between records and scar reading was limited. A protective effect was seen up to 10 years following infant vaccination [< 5 years since vaccination: vaccine effectiveness (VE) 66%, 95% confidence interval (CI) 17% to 86%; 5-10 years since vaccination: VE 75%, 95% CI 43% to 89%], but there was weak evidence of an effect 10-15 years after vaccination (VE 36%, 95% CI negative to 77%; p = 0.396). The analyses of the protective effect of infant BCG vaccination were adjusted for confounders, including birth cohort and ethnicity. For school-aged BCG vaccination, VE was 51% (95% CI 21% to 69%) 10-15 years after vaccination and 57% (95% CI 33% to 72%) 15-20 years after vaccination, beyond which time protection appeared to wane. Ascertainment of vaccination status was based on self-reported history and scar reading. LIMITATIONS: The difficulty in examining vaccination sites in older women in the high-risk minority ethnic study population and the sparsity of vaccine record data in the later time periods precluded robust assessment of protection from infant BCG vaccination > 10 years after vaccination. CONCLUSIONS: Infant BCG vaccination in a population at high risk for TB was shown to provide protection for at least 10 years, whereas in the white population school-age vaccination was shown to provide protection for at least 20 years. This evidence may inform TB vaccination programmes (e.g. the timing of administration of improved TB vaccines, if they become available) and cost-effectiveness studies. Methods to deal with missing record data in the infant study could be explored, including the use of scar reading. FUNDING: The National Institute for Health Research Health Technology Assessment programme. During the conduct of the study, Jonathan Sterne, Ibrahim Abubakar and Laura C Rodrigues received other funding from NIHR; Ibrahim Abubakar and Laura C Rodrigues have also received funding from the Medical Research Council. Punam Mangtani received funding from the Biotechnology and Biological Sciences Research Council.

Systematic evaluation of medium-throughput mRNA abundance platforms.

Profiling of mRNA abundances with high-throughput platforms such as microarrays and RNA-seq has become an important tool in both basic and biomedical research. However, these platforms remain prone to systematic errors and have challenges in clinical and industrial applications. As a result, it is standard practice to validate a subset of key results using alternate technologies. Similarly, clinical and industrial applications typically involve transitions from a high-throughput discovery platform to medium-throughput validation ones. These medium-throughput validation platforms have high technical reproducibility and reduced sample input needs, and low sensitivity to sample quality (e.g., for processing FFPE specimens). Unfortunately, while medium-throughput platforms have proliferated, there are no comprehensive comparisons of them. Here we fill that gap by comparing two key medium-throughput platforms--NanoString's nCounter Analysis System and ABI's OpenArray System--to gold-standard quantitative real-time RT-PCR. We quantified 38 genes and positive and negative controls in 165 samples. Signal:noise ratios, correlations, dynamic range, and detection accuracy were compared across platforms. All three measurement technologies showed good concordance, but with divergent price/time/sensitivity trade-offs. This study provides the first detailed comparison of medium-throughput RNA quantification platforms and provides a template and a standard data set for the evaluation of additional technologies.

Controversies and unresolved issues in tuberculosis prevention and control: a low-burden-country perspective.

Despite declining incidence in most high-income countries, tuberculosis shows no signs of disappearing in the near future. Although surveillance data from most Western European countries show relatively stable declines in the rate of tuberculosis over the past several decades, some have reported either an increasing rate or a decelerating pace of reduction in recent years. The burden of disease now disproportionately affects high-risk groups such as migrants, homeless persons, and prisoners. In view of the concentration of cases in urban areas and high-risk deprived groups, interventions that may not be efficient when applied to the general population may be highly cost effective when targeted at high-risk groups. In this article, we examine some controversial elements of tuberculosis prevention and control in low-burden countries and recommend issues for further research. In particular, we assess current evidence on the duration of protection by BCG vaccine, the screening of migrants and hard-to-reach groups, and the use of preventive therapy for contacts of cases of infectious multidrug-resistant tuberculosis. This analysis is presented from the perspective of low-tuberculosis-burden, high-income countries attempting to eliminate tuberculosis.

Screening of immigrants in the UK for imported latent tuberculosis: a multicentre cohort study and cost-effectiveness analysis.

BACKGROUND: Continuing rises in tuberculosis notifications in the UK are attributable to cases in foreign-born immigrants. National guidance for immigrant screening is hampered by a lack of data about the prevalence of, and risk factors for, latent tuberculosis infection in immigrants. We aimed to determine the prevalence of latent infection in immigrants to the UK to define which groups should be screened and to quantify cost-effectiveness. METHODS: In our multicentre cohort study and cost-effectiveness analysis we analysed demographic and test results from three centres in the UK (from 2008 to 2010) that used interferon-γ release-assay (IGRA) to screen immigrants aged 35 years or younger for latent tuberculosis infection. We assessed factors associated with latent infection by use of logistic regression and calculated the yields and cost-effectiveness of screening at different levels of tuberculosis incidence in immigrants' countries of origin with a decision analysis model. FINDINGS: Results for IGRA-based screening were positive in 245 of 1229 immigrants (20%), negative in 982 (80%), and indeterminate in two (0·2%). Positive results were independently associated with increases in tuberculosis incidence in immigrants' countries of origin (p=0·0006), male sex (p = 0·046), and age (p < 0·0001). National policy thus far would fail to detect 71% of individuals with latent infection. The two most cost-effective strategies were to screen individuals from countries with a tuberculosis incidence of more than 250 cases per 100,000 (incremental cost-effectiveness ratio [ICER] was £17,956 [£1=US$1·60] per prevented case of tuberculosis) and at more than 150 cases per 100,000 (including immigrants from the Indian subcontinent), which identified 92% of infected immigrants and prevented an additional 29 cases at an ICER of £20,819 per additional case averted. INTERPRETATION: Screening for latent infection can be implemented cost-effectively at a level of incidence that identifies most immigrants with latent tuberculosis, thereby preventing substantial numbers of future cases of active tuberculosis. FUNDING: Medical Research Council and Wellcome Trust.

Panel 2.2: surveillance, early warning alert, and response: communicable and vector-borne diseases.

This is a summary of the presentations and discussion of Surveillance, Early Warning Alert and Response at the Conference, Health Aspects of the Tsunami Disaster in Asia, convened by the World Health Organization (WHO) in Phuket, Thailand, 04-06 May 2005. The topics discussed included issues related to the surveillance, early warning alert, and response to communicable and vector-borne diseases as pertaining to the responses to the damage created by the Tsunami. It is presented in the following major sections: (1) key questions; (2) needs assessment; (3) coordination; (4) gap filling; and (5) capacity building. The key questions section is presented in six sub-sections: (1) communicable diseases; (2) early warning; (3) laboratory capacity and referral networking; (4) coordination of disease surveillance, early warning, and response; (5) health infrastructure rebuilding; and (6) using existing national surveillance plans to enhance disease surveillance and early warning systems.

Source profiles for industrial, mobile, and area sources in the Big Bend Regional Aerosol Visibility and Observational study.

Representative PM2.5 and PM10 source emissions were sampled in Texas during the Big Bend Regional Aerosol Visibility and Observa (BRAVO) study. Chemical source profiles for elements, ions, and carbon fractions of 145 samples are reported for paved and unpaved road dust, soil dust, motor vehicle exhaust, vegetative burning, four coal-fired power stations, an oil refinery catalytic cracker, two cement kilns, and residential meat cooking. Several samples were taken from each emitter and source type, and these were averaged by source type, and in source subgroups based on commonality of chemical composition. The standard deviation represents the variability of the chemical mass fractions. BRAVO profiles differed in some respects from profiles measured elsewhere. High calcium abundances in geological dust, high selenium abundances in coal-fired power stations, and high antimony abundances in oil refinery catalytic cracker emissions were found. Abundances of eight thermally evolved carbon fractions [Atmos. Environ. 28 (15) (1994) 2493] differ among combustion sources, and a Monte Carlo simulation demonstrates that these differences are sufficient to differentiate among several carbon-emitters.

Left ventricular assist devices as permanent heart failure therapy: the price of progress.

BACKGROUND DATA: The REMATCH trial evaluated the efficacy and safety of long-term left ventricular assist device (LVAD) support in stage D chronic end-stage heart failure patients. Compared with optimal medical management, LVAD implantation significantly improved the survival and quality of life of these terminally ill patients. To date, however, there have been no analyses of the cost related to the LVAD survival benefit. This paper addresses the cost of hospital resource use, and its predictors, for long-term LVAD patients. METHODS: Detailed cost data were available for 52 of 68 REMATCH patients randomized to LVAD therapy. We combined the clinical dataset with Medicare data, standard billing forms (UB-92), and line item bills provided directly by clinical centers. Charges were converted to costs by using the Ratio-of-Cost-to-Charges for each major resource category. RESULTS: The mean cost for the initial implant-related hospitalization was $210,187 +/- 193,295. When implantation hospitalization costs are compared between hospital survivors and nonsurvivors, the mean costs increase from $159,271 +/- 106,423 to $315,015 +/- 278,713. Sepsis, pump housing infection, and perioperative bleeding are the major drivers of implantation cost, established by regression modeling. In the patients who survived the procedure (n = 35), bypass time, perioperative bleeding, and late bleeding were the drivers of cost. The average annual readmission cost per patient for the overall cohort was $105,326. CONCLUSIONS: The cost of long-term LVAD implantation is commensurate with other life-saving organ transplantation procedures like liver transplantation. As an evolving technology, there are a number of opportunities for improvement that will likely reduce costs in the future.

An ultra-HTS process for the identification of small molecule modulators of orphan G-protein-coupled receptors.

G-protein-coupled receptors (GPCRs) are the most successful target proteins for drug discovery research to date. More than 150 orphan GPCRs of potential therapeutic interest have been identified for which no activating ligands or biological functions are known. One of the greatest challenges in the pharmaceutical industry is to link these orphan GPCRs with human diseases. Highly automated parallel approaches that integrate ultra-high throughput and focused screening can be used to identify small molecule modulators of orphan GPCRs. These small molecules can then be employed as pharmacological tools to explore the function of orphan receptors in models of human disease. In this review, we describe methods that utilize powerful ultra-high-throughput screening technologies to identify surrogate ligands of orphan GPCRs.