Unit costs and cost-effectiveness of a device to improve TB treatment adherence in China.

BACKGROUND: Adherence to TB drugs is crucial for improving treatment outcomes. Digital adherence technologies can improve adherence; however, there is a lack of evidence on cost-effectiveness. This study aimed to explore the cost-effectiveness of medication event reminder monitors (MERM) in China compared with the standard of care, using results from a pragmatic, cluster-randomised superiority trial of an electronic MERM in China. METHODS: We collected primary unit cost data from the societal perspective, both at and above the health facility level. We estimated the incremental cost-effectiveness of MERM using a Markov model with a 20-year time horizon; a 3% discount rate was applied to costs and outcomes. We explored uncertainty through a series of sensitivity and scenario analyses. RESULTS: The incremental cost of MERM was $27.22 per patient. Probabilistic sensitivity analysis showed significant uncertainty about the intervention's cost-effectiveness. Changing assumptions around key parameters substantially affected our estimated incremental cost-effectiveness ratio. CONCLUSIONS: Although the incremental cost of the MERM box was low, current evidence does not indicate that the intervention would be cost-effective. However, the intervention's cost-effectiveness could improve if implemented as part of a broader strategy, including enhanced patient management.

CONTEXTE: Il est crucial de respecter les médicaments antituberculeux pour améliorer les résultats du traitement. Les technologies numériques peuvent améliorer l'observance, mais il existe un manque de preuves sur leur rapport coût-efficacité. Cette étude a examiné le rapport coût-efficacité des moniteurs de rappel d'événements médicamenteux (MERM, pour l'anglais, « medication event reminder monitors ¼) en Chine par rapport aux soins standards, en se basant sur les résultats d'un essai pragmatique randomisé en grappes d'un MERM électronique en Chine. MÉTHODES: Les coûts unitaires primaires du point de vue de la société ont été collectés et analysés à la fois au niveau de l'établissement de santé et au-delà. Pour évaluer le rapport coût-efficacité différentiel du MERM, nous avons utilisé un modèle de Markov sur une période de 20 ans, en appliquant un taux d'actualisation de 3% aux coûts et aux résultats. Afin de prendre en compte les incertitudes, nous avons effectué plusieurs analyses de sensibilité et de scénarios. RÉSULTATS: Le coût supplémentaire du MERM s'élevait à 27,22 $ par patient. L'analyse de sensibilité probabiliste a révélé une incertitude importante concernant le rapport coût-efficacité de l'intervention. La variation des hypothèses liées aux paramètres clés a eu un impact significatif sur le rapport coût-efficacité différentiel estimé. CONCLUSIONS: Bien que le coût différentiel de la boîte MERM soit faible, les données actuelles n'indiquent pas que l'intervention serait rentable. Toutefois, le rapport coût-efficacité de l'intervention pourrait être amélioré si elle était mise en œuvre dans le cadre d'une stratégie plus large, comprenant une meilleure prise en charge des patients.

Challenges for room temperature operation of electrically pumped GeSn lasers.

Recent demonstrations of room-temperature lasing in optically pumped GeSn show promise for future CMOS compatible lasers for Si-photonics applications. However, challenges remain for electrically pumped devices. Investigation of the processes that limit device performance is therefore vital in aiding the production of future commercial devices. In this work, a combined experimental and modelling approach is utilised to explore the dominant loss processes in current devices. By manipulating the band structure of functioning devices using high hydrostatic pressure techniques at low temperature, the dominant carrier recombination pathways are identified. This reveals that 93 ± 5% of the threshold current is attributable to defect-related recombination at a temperature, T = 85 K. Furthermore, carrier occupation of L-valley states (carrier leakage) is responsible for 1.1 ± 0.3% of the threshold current, but this sharply increases to 50% with a decrease of just 30 meV in the L- Γ separation energy. This indicates that thermal broadening of a similar order may reproduce these adverse effects, limiting device performance at higher temperatures. Temperature dependent calculations show that carrier occupation of indirect valley L-states strongly affects the transparency carrier density and is therefore very sensitive to the Sn composition, leading to an effective operational temperature range for given Sn compositions and strain values. Recommendations for future device designs are proposed based on band structure and growth optimisations.

Efficiency of TB service provision in the public and private health sectors in Ethiopia.

BACKGROUND: The Ethiopian Government has identified efficiency of TB services as a key priority in planning and budgeting. Understanding the magnitude and sources of inefficiencies is key to ensuring value for money and improved service provision, and a requirement from donors to justify resource needs. This study identifies the cost of providing a wide range of TB services in public and private facilities in Ethiopia.METHODS: Financial and economic unit costs were estimated from a health provider´s perspective, and collected retrospectively in 26 health facilities using both top-down (TD) and bottom-up (BU) costing approaches for each TB service output. Capacity inefficiency was assessed by investigating the variation between TD and BU unit costs where the factor was 2.0 or more.RESULTS: Overall, TD unit costs were two times higher than BU unit costs. There was some variation across facility ownership and level of care. Unit costs in urban facilities were on average 3.8 times higher than in rural facilities.CONCLUSION: We identified some substantial inefficiencies in staff, consumable and capital inputs. Addressing these inefficiencies and rearranging the TB service delivery modality would be important in ensuring the achievement of the country´s End TB strategy.

Cost of TB services: approach and summary findings of a multi-country study (Value TB).

BACKGROUND: There are currently large gaps in unit cost data for TB, and substantial variation in the quality and methods of unit cost estimates. Uncertainties remain about sample size, range and comprehensiveness of cost data collection for different purposes. We present the methods and results of a project implemented in Kenya, Ethiopia, India, The Philippines and Georgia to estimate unit costs of TB services, focusing on findings most relevant to these remaining methodological challenges.METHODS: We estimated financial and economic unit costs, in close collaboration with national TB programmes. Gold standard methods included both top-down and bottom-up approaches to resource use measurement. Costs are presented in 2018 USD and local currency unit.RESULTS: Cost drivers of outputs varied by service and across countries, as did levels of capacity inefficiency. There was substantial variation in unit cost estimates for some interventions and high overhead costs were observed. Estimates were subject to sampling uncertainty, and some data gaps remain.CONCLUSION: This paper describes detailed methods for the largest TB costing effort to date, to inform prioritisation and planning for TB services. This study provides a strong baseline and some cost estimates may be extrapolated from this data; however, regular further studies of similar quality are needed to add estimates for remaining gaps, or to add new or changing services and interventions. Further research is needed on the best approach to extrapolation of cost data. Costing studies are best implemented as partnerships with policy makers to generate a community of mutual learning and capacity development.

Cost of TB prevention and treatment in the Philippines in 2017.

BACKGROUND: The Philippines aims to accelerate TB reduction through the provision of universally accessible and affordable services. The objectives of this paper are to estimate the costs of TB services and interventions using a health systems´ perspective, and to explore cost differences in service delivery via primary care facilities or hospitals.METHODS: Data were collected from a multi-stage stratified random sampling of 28 facilities in accordance with Global Health Cost Consortium costing standards and analysis tools. Unit costs (in US$) estimated using top-down (TD) and bottom-up (BU) approaches, are summarised following Value TB reporting standards and by broad facility type.RESULTS: Cost of delivering 32 TB services and eight interventions varied by costing method and delivery platform. Average BU costs ranged from US$0.38 for treatment support visits, US$2.5 for BCG vaccination, US$19.48 for the Xpert® MTB/RIF test to US$3,677 for MDR-TB treatment using the long regimen. Delivering TB care in hospitals was generally more costly than in primary care facilities, except for TB prevention in children and MDR-TB treatment using the long regimen.CONCLUSION: Comprehensive costing data for TB care in the Philippines are now available to aid in the design, planning, and prioritisation of delivery models to End TB.

Costs of TB services in India (No 1).

BACKGROUND: There is a dearth of economic analysis required to support increased investment in TB in India. This study estimates the costs of TB services from a health systems´ perspective to facilitate the efficient allocation of resources by India´s National Tuberculosis Elimination Programme.METHODS: Data were collected from a multi-stage, stratified random sample of 20 facilities delivering TB services in two purposively selected states in India as per Global Health Cost Consortium standards and using Value TB Data Collection Tool. Unit costs were estimated using the top-down (TD) and bottom-up (BU) methodology and are reported in 2018 US dollars.RESULTS: Cost of delivering 50 types of TB services and four interventions varied according to costing method. Key services included sputum smear microscopy, Xpert® MTB/RIF and X-ray with an average BU costs of respectively US$2.45, US$17.36 and US$2.85. Average BU cost for bacille Calmette-Guérin vaccination, passive case-finding, TB prevention in children under 5 years using isoniazid and first-line drug treatment in new pulmonary and extrapulmonary TB cases was respectively US$0.76, US$1.62, US$2.41, US$103 and US$98.CONCLUSION: The unit cost of TB services and outputs are now available to support investment decisions, as diagnosis algorithms are reviewed and prevention or treatment for TB are expanded or updated in India.

Cost of TB services in the public and private sectors in Georgia (No 2).

BACKGROUND: Patient-centred care along with optimal financing of inpatient and outpatient services are the main priorities of the Georgia National TB Programme (NTP). This paper presents TB diagnostics and treatment unit cost, their comparison with NTP tariffs and how the study findings informed TB financing policy.METHODS: Top-down (TD) and bottom-up (BU) mean unit costs for TB interventions by episode of care were calculated. TD costs were compared with NTP tariffs, and variations in these and the unit costs cost composition between public and private facilities was assessed.RESULTS: Outpatient interventions costs exceeded NTP tariffs. Unit costs in private facilities were higher compared with public providers. There was very little difference between per-day costs for drug-susceptible treatment and NTP tariffs in case of inpatient services. Treatment day financing exceeded actual costs in the capital (public facility) for drug-resistant TB, and this was lower in the regions.CONCLUSION: Use of reliable unit costs for TB services at policy discussions led to a shift from per-day payment to a diagnosis-related group model in TB inpatient financing in 2020. A next step will be informing policy decisions on outpatient TB care financing to reduce the existing gap between funding and costs.

Cost of TB services in healthcare facilities in Kenya (No 3).

BACKGROUND: The reduction of Kenya´s TB burden requires improving resource allocation both to and within the National TB, Leprosy and Lung Disease Program (NTLD-P). We aimed to estimate the unit costs of TB services for budgeting by NTLD-P, and allocative efficiency analyses for future National Strategic Plan (NSP) costing.METHODS: We estimated costs of all TB interventions in a sample of 20 public and private health facilities from eight counties. We calculated national-level unit costs from a health provider´s perspective using bottom-up (BU) and top-down (TD) approaches for the financial year 2017-2018 using Microsoft Excel and STATA v16.RESULTS: The mean unit cost for passive case-finding (PCF) was respectively US$38 and US$60 using the BU and TD approaches. The unit BU and TD costs of a 6-month first-line treatment (FLT) course, including monitoring tests, was respectively US$135 and US$160, while those for adult drug-resistant TB (DR-TB) treatment was respectively US$3,230.28 and US$3,926.52 for the 9-month short regimen. Intervention costs highlighted variations between BU and TD approaches. Overall, TD costs were higher than BU, as these are able to capture more costs due to inefficiency (breaks/downtime/leave).CONCLUSION: The activity-based TB unit costs form a comprehensive cost database, and the costing process has built-in capacity within the NTLD-P and international TB research networks, which will inform future TB budgeting processes.

Determining the value of TB active case-finding: current evidence and methodological considerations.

Active case-finding (ACF) is an important component of the End TB Strategy. However, ACF is resource-intensive, and the economics of ACF are not well-understood. Data on the costs of ACF are limited, with little consistency in the units and methods used to estimate and report costs. Mathematical models to forecast the long-term effects of ACF require empirical measurements of the yield, timing and costs of case detection. Pragmatic trials offer an opportunity to assess the cost-effectiveness of ACF interventions within a 'real-world´ context. However, such analyses generally require early introduction of economic evaluations to enable prospective data collection on resource requirements. Closing the global case-detection gap will require substantial additional resources, including continued investment in innovative technologies. Research is essential to the optimal implementation, cost-effectiveness, and affordability of ACF in high-burden settings. To assess the value of ACF, we must prioritize the collection of high-quality data regarding costs and effectiveness, and link those data to analytical models that are adapted to local settings.

Cost of tuberculosis treatment in low- and middle-income countries: systematic review and meta-regression.

BACKGROUND: Despite a scarcity of tuberculosis (TB) cost data, a substantial body of evidence has been accumulating for drug-susceptible TB (DS-TB) treatment. In this study, we review unit costs for DS-TB treatment from a provider´s perspective. We also examine factors driving cost variations and extrapolate unit costs across low- and middle-income countries (LMICs).METHODS: We searched published and grey literature for any empirically collected TB cost estimates. We selected a subgroup of estimates looking at DS-TB treatment. We extracted information on activities and inputs included. We standardised costs into an average per person-month, fitted a multi-level regression model and cross-validated country-level predictions. We then extrapolated estimates for facility-based, directly observed DS-TB treatment across countries.RESULTS: We included 95 cost estimates from 28 studies across 17 countries. Costs predictions were sensitive to characteristics such as delivery mode, whether hospitalisation was included, and inputs accounted for, as well as gross domestic product per capita. Extrapolation results are presented with uncertainty intervals (UIs) for LMICs. Predicted median costs per 6 months of treatment were US$315.30 (95% CI US$222.60-US$417.20) for low-income, US$527.10 (95% CI US$395.70-US$743.70) for lower middle-income and US$896.40 (95% CI US$654.00-US$1214.40) for upper middle-income countries.CONCLUSIONS: Our study provides country-level DS-TB treatment cost estimates suitable for priority setting. These estimates, while not standing as a substitute for local high-quality primary data, can inform global, regional and national exercises.

Childhood adversity and clinical and psychosocial outcomes in psychosis.

AIMS: Associations between childhood abuse and various psychotic illnesses in adulthood are commonly reported. We aim to examine associations between several reported childhood adverse events (sexual abuse, physical abuse, emotional abuse, neglect and interpersonal loss) among adults with diagnosed psychotic disorders and clinical and psychosocial outcomes. METHODS: Within a large epidemiological study, the 2010 Australian National Survey of Psychosis (Survey of High Impact Psychosis, SHIP), we used logistic regression to model childhood adverse events (any and specific types) on 18 clinical and psychosocial outcomes. RESULTS: Eighty percent of SHIP participants (1466/1825) reported experiencing adverse events in childhood (sexual abuse, other types of abuse and interpersonal loss). Participants reporting any form of childhood adversity had higher odds for 12/18 outcomes we examined. Significant associations were observed with all psychosocial outcomes (social dysfunction, victimisation, offending and homelessness within the previous 12 months, and definite psychosocial stressor within 12 months of illness onset), with the strongest association for homelessness (odds ratio (OR) = 2.82). Common across all adverse event types was an association with lifetime depression, anxiety and a definite psychosocial stressor within 12 months of illness onset. When adverse event types were non-hierarchically coded, sexual abuse was associated with 11/18 outcomes, other types of abuse 13/18 and, interpersonal loss occurring in the absence of other forms of abuse was associated with fewer of the clinical and psychosocial outcomes, 4/18. When adverse events types were coded hierarchically (to isolate the effect of interpersonal loss in the absence of abuse), interpersonal loss was associated with lower odds of self-reproach (OR = 0.70), negative syndrome (OR = 0.75) and victimisation (OR = 0.82). CONCLUSIONS: Adverse childhood experiences among people with psychosis are common, as are subsequent psychosocial stressors. Mental health professionals should routinely enquire about all types of adversities in this group and provide effective service responses. Childhood abuse, including sexual abuse, may contribute to subsequent adversity, poor psychosocial functioning and complex needs among people with psychosis. Longitudinal research to better understand these relationships is needed, as are studies which evaluate the effectiveness of preventative interventions in high-risk groups.

Safety and clinical effect of i.v. infusion of cyclopropyl-methoxycarbonyl etomidate (ABP-700), a soft analogue of etomidate, in healthy subjects.

BACKGROUND: Cyclopropyl-methoxycarbonyl metomidate, or ABP-700, is a second generation analogue of etomidate, developed to retain etomidate's beneficial haemodynamic and respiratory profile but diminishing its suppression of the adrenocortical axis. The objective of this study was to characterise the safety and efficacy of 30-min continuous infusions of ABP-700, and to assess its effect on haemodynamics and the adrenocortical response in healthy human volunteers. METHODS: Five cohorts involving 40 subjects received increasing infusion doses of ABP-700, propofol 60 µg kg-1 min-1 or placebo. Safety was evaluated through adverse event (AE) monitoring, safety laboratory tests, and arterial blood gasses. Haemodynamic and respiratory stability were assessed by continuous monitoring. Adrenocortical function was analysed by adrenocorticotropic hormone (ACTH) stimulation tests. Clinical effect was measured using the modified observer's assessment of alertness/sedation (MOAA/S) and continuous bispectral index monitoring. RESULTS: No serious AEs were reported. Haemodynamic and respiratory effects included mild dose-dependent tachycardia, slightly elevated blood pressure, and no centrally mediated apnoea. Upon stimulation with ACTH, no adrenocortical depression was observed in any subject. Involuntary muscle movements (IMM) were reported, which were more extensive with higher dosing regimens. Higher dosages of ABP-700 were associated with deeper sedation and increased likelihood of sedation. Time to onset of clinical effect was variable throughout the cohorts and recovery was swift. CONCLUSIONS: Infusions of ABP-700 showed a dose-dependent hypnotic effect, and did not cause severe hypotension, severe respiratory depression, or adrenocortical suppression. The presentation and nature of IMM is a matter of concern. CLINICAL TRIAL REGISTRATION: NTR4735.

Unfolding the band structure of GaAsBi.

Typical supercell approaches used to investigate the electronic properties of GaAs(1-x)Bi(x) produce highly accurate, but folded, band structures. Using a highly optimized algorithm, we unfold the band structure to an approximate [Formula: see text] relation associated with an effective Brillouin zone. The dispersion relations we generate correlate strongly with experimental results, confirming that a regime of band gap energy greater than the spin-orbit-splitting energy is reached at around 10% bismuth fraction. We also demonstrate the effectiveness of the unfolding algorithm throughout the Brillouin zone (BZ), which is key to enabling transition rate calculations, such as Auger recombination rates. Finally, we show the effect of disorder on the effective masses and identify approximate values for the effective mass of the conduction band and valence bands for bismuth concentrations from 0-12%.

Cost and cost-effectiveness of tuberculosis treatment shortening: a model-based analysis.

BACKGROUND: Despite improvements in treatment success rates for tuberculosis (TB), current six-month regimen duration remains a challenge for many National TB Programmes, health systems, and patients. There is increasing investment in the development of shortened regimens with a number of candidates in phase 3 trials. METHODS: We developed an individual-based decision analytic model to assess the cost-effectiveness of a hypothetical four-month regimen for first-line treatment of TB, assuming non-inferiority to current regimens of six-month duration. The model was populated using extensive, empirically-collected data to estimate the economic impact on both health systems and patients of regimen shortening for first-line TB treatment in South Africa, Brazil, Bangladesh, and Tanzania. We explicitly considered 'real world' constraints such as sub-optimal guideline adherence. RESULTS: From a societal perspective, a shortened regimen, priced at USD1 per day, could be a cost-saving option in South Africa, Brazil, and Tanzania, but would not be cost-effective in Bangladesh when compared to one gross domestic product (GDP) per capita. Incorporating 'real world' constraints reduces cost-effectiveness. Patient-incurred costs could be reduced in all settings. From a health service perspective, increased drug costs need to be balanced against decreased delivery costs. The new regimen would remain a cost-effective option, when compared to each countries' GDP per capita, even if new drugs cost up to USD7.5 and USD53.8 per day in South Africa and Brazil; this threshold was above USD1 in Tanzania and under USD1 in Bangladesh. CONCLUSION: Reducing the duration of first-line TB treatment has the potential for substantial economic gains from a patient perspective. The potential economic gains for health services may also be important, but will be context-specific and dependent on the appropriate pricing of any new regimen.

Temperature stable mid-infrared GaInAsSb/GaSb Vertical Cavity Surface Emitting Lasers (VCSELs).

GaInAsSb/GaSb based quantum well vertical cavity surface emitting lasers (VCSELs) operating in mid-infrared spectral range between 2 and 3 micrometres are of great importance for low cost gas monitoring applications. This paper discusses the efficiency and temperature sensitivity of the VCSELs emitting at 2.6 µm and the processes that must be controlled to provide temperature stable operation. We show that non-radiative Auger recombination dominates the threshold current and limits the device performance at room temperature. Critically, we demonstrate that the combined influence of non-radiative recombination and gain peak-cavity mode de-tuning determines the overall temperature sensitivity of the VCSELs. The results show that improved temperature stable operation around room temperature can only be achieved with a larger gain peak-cavity mode de-tuning, offsetting the significant effect of increasing non-radiative recombination with increasing temperature, a physical effect which must be accounted for in mid-infrared VCSEL design.

Potential Intercontinental Movement of Influenza A(H7N9) Virus into North America by Wild Birds: Application of a Rapid Assessment Framework.

A critical question surrounding emergence of novel strains of avian influenza viruses (AIV) is the ability for wild migratory birds to translocate a complete (unreassorted whole genome) AIV intercontinentally. Virus translocation via migratory birds is suspected in outbreaks of highly pathogenic strain A(H5N1) in Asia, Africa and Europe. As a result, the potential intercontinental translocation of newly emerging AIV such as A(H7N9) from Eurasia to North America via migratory movements of birds remains a concern. An estimated 2.91 million aquatic birds move annually between Eurasia and North America with an estimated AIV prevalence as high as 32.2%. Here, we present a rapid assessment to address the likelihood of whole (unreassorted)-genome translocation of Eurasian strain AIV into North America. The scope of this assessment was limited specifically to assess the weight of evidence to support the movement of an unreassorted AIV intercontinentally by migratory aquatic birds. We developed a rapid assessment framework to assess the potential for intercontinental movement of avian influenzas by aquatic birds. This framework was iteratively reviewed by a multidisciplinary panel of scientific experts until a consensus was established. Our assessment framework identified four factors that may contribute to the potential for introduction of any AIV intercontinentally into North America by wild aquatic birds. These factors, in aggregate, provide a framework for evaluating the likelihood of new forms of AIV from Eurasia to be introduced by aquatic birds into North America. Based on our assessment, we determined that the potential for introduction of A(H7N9) into North America through aquatic migratory birds is possible, but the likelihood ranges from extremely low to low.

Physicochemical and toxicological profiling of ash from the 2010 and 2011 eruptions of Eyjafjallajökull and Grímsvötn volcanoes, Iceland using a rapid respiratory hazard assessment protocol.

The six week eruption of Eyjafjallajökull volcano in 2010 produced heavy ash fall in a sparsely populated area of southern and south eastern Iceland and disrupted European commercial flights for at least 6 days. We adopted a protocol for the rapid analysis of volcanic ash particles, for the purpose of informing respiratory health risk assessments. Ash collected from deposits underwent a multi-laboratory physicochemical and toxicological investigation of their mineralogical parameters associated with bio-reactivity, and selected in vitro toxicology assays related to pulmonary inflammatory responses. Ash from the eruption of Grímsvötn, Iceland, in 2011 was also studied. The results were benchmarked against ash from Soufrière Hills volcano, Montserrat, which has been extensively studied since the onset of eruptive activity in 1995. For Eyjafjallajökull, the grain size distributions were variable: 2-13 vol% of the bulk samples were <4 µm, with the most explosive phases of the eruption generating abundant respirable particulate matter. In contrast, the Grímsvötn ash was almost uniformly coarse (<3.5 vol%<4 µm material). Surface area ranged from 0.3 to 7.7 m2 g(-1) for Eyjafjallajökull but was very low for Grímsvötn (<0.6 m2 g(-1)). There were few fibre-like particles (which were unrelated to asbestos) and the crystalline silica content was negligible in both eruptions, whereas Soufrière Hills ash was cristobalite-rich with a known potential to cause silicosis. All samples displayed a low ability to deplete lung antioxidant defences, showed little haemolysis and low acute cytotoxicity in human alveolar type-1 like epithelial cells (TT1). However, cell-free tests showed substantial hydroxyl radical generation in the presence of hydrogen peroxide for Grímsvötn samples, as expected for basaltic, Fe-rich ash. Cellular mediators MCP-1, IL-6, and IL-8 showed chronic pro-inflammatory responses in Eyjafjallajökull, Grímsvötn and Soufrière Hills samples, despite substantial differences in the sample mineralogy and eruptive styles. The value of the pro-inflammatory profiles in differentiating the potential respiratory health hazard of volcanic ashes remains uncertain in a protocol designed to inform public health risk assessment, and further research on their role in volcanic crises is warranted.

Mycobacterium bovis (bovine tuberculosis) infection in North American wildlife: current status and opportunities for mitigation of risks of further infection in wildlife populations.

Mycobacterium bovis (M. bovis), the causative agent of bovine tuberculosis, has been identified in nine geographically distinct wildlife populations in North America and Hawaii and is endemic in at least three populations, including members of the Bovidae, Cervidae, and Suidae families. The emergence of M. bovis in North American wildlife poses a serious and growing risk for livestock and human health and for the recreational hunting industry. Experience in many countries, including the USA and Canada, has shown that while M. bovis can be controlled when restricted to livestock species, it is almost impossible to eradicate once it has spread into ecosystems with free-ranging maintenance hosts. Therefore, preventing transmission of M. bovis to wildlife may be the most effective way to mitigate economic and health costs of this bacterial pathogen. Here we review the status of M. bovis infection in wildlife of North America and identify risks for its establishment in uninfected North American wildlife populations where eradication or control would be difficult and costly. We identified four common risk factors associated with establishment of M. bovis in uninfected wildlife populations in North America, (1) commingling of infected cattle with susceptible wildlife, (2) supplemental feeding of wildlife, (3) inadequate surveillance of at-risk wildlife, and (4) unrecognized emergence of alternate wildlife species as successful maintenance hosts. We then propose the use of integrated and adaptive disease management to mitigate these risk factors to prevent establishment of M. bovis in susceptible North American wildlife species.

Modulation of the absorption coefficient at 1.3 µm in Ge/SiGe multiple quantum well heterostructures on silicon.

We report modulation of the absorption coefficient at 1.3 µm in Ge/SiGe multiple quantum well heterostructures on silicon via the quantum-confined Stark effect. Strain engineering was exploited to increase the direct optical bandgap in the Ge quantum wells. We grew 9 nm-thick Ge quantum wells on a relaxed Si0.22Ge0.78 buffer and a contrast in the absorption coefficient of a factor of greater than 3.2 was achieved in the spectral range 1290-1315 nm.

Hematopoietic stem cell transplant for systemic lupus erythematosus: Interferon regulatory factor 7 activation correlates with the IFN signature and recurrent disease.

The expression and activation of regulatory factors (IRF) and rinterferon (IFN) response genes were evaluated in a patient treated with autologous hematopoietic stem cell transplant (HSCT) for refractory systemic lupus erythematosus (SLE). In SLE patients, genetic variants of IRF5 and IRF7 have been associated with increased serum IFNα levels, suggesting a pathogenic role in the type I IFN response. Clinical and molecular analyses of an SLE patient treated with high-dose immunosuppressive therapy and autologous stem cell transplant was performed. Western blot analysis showed that induction of IRF7 protein expression correlated with recurrent lupus disease activity. In addition, phosphorylation of IRF3 and activation of 4 E-BP1, a translational repressor of IRF7, preceded the disease flare. In SLE post-transplant, recurrent disease activity and induction of IRF7 protein expression correlated with activation of the IFN signature. This unique trend in regulation of IRF warrants further mechanistic investigation and confirmation with increased numbers of SLE patients.