Estimating Post-treatment Recurrence After Multidrug-Resistant Tuberculosis Treatment Among Patients With and Without Human Immunodeficiency Virus: The Impact of Assumptions About Death and Missing Follow-up.

BACKGROUND: Quantification of recurrence risk following successful treatment is crucial to evaluating regimens for multidrug- or rifampicin-resistant (MDR/RR) tuberculosis (TB). However, such analyses are complicated when some patients die or become lost during post-treatment follow-up. METHODS: We analyzed data on 1991 patients who successfully completed a longer MDR/RR-TB regimen containing bedaquiline and/or delamanid between 2015 and 2018 in 16 countries. Using 5 approaches for handling post-treatment deaths, we estimated 6-month post-treatment TB recurrence risk overall and by HIV status. We used inverse-probability weighting to account for patients with missing follow-up and investigated the impact of potential bias from excluding these patients without applying inverse-probability weights. RESULTS: The estimated TB recurrence risk was 7.4/1000 (95% credible interval: 3.3-12.8) when deaths were handled as non-recurrences and 7.6/1000 (3.3-13.0) when deaths were censored and inverse-probability weights were applied to account for the excluded deaths. The estimated risks of composite recurrence outcomes were 25.5 (15.3-38.1), 11.7 (6.4-18.2), and 8.6 (4.1-14.4) per 1000 for recurrence or (1) any death, (2) death with unknown or TB-related cause, or (3) TB-related death, respectively. Corresponding relative risks for HIV status varied in direction and magnitude. Exclusion of patients with missing follow-up without inverse-probability weighting had a small impact on estimates. CONCLUSIONS: The estimated 6-month TB recurrence risk was low, and the association with HIV status was inconclusive due to few recurrence events. Estimation of post-treatment recurrence will be enhanced by explicit assumptions about deaths and appropriate adjustment for missing follow-up data.

Holographic Nano-Imaging of Terahertz Dirac Plasmon Polaritons in Topological Insulator Antenna Resonators.

Excitation of Dirac plasmon polaritons (DPPs) in bi-dimensional materials have attracted considerable interest in recent years, both from perspectives of understanding their physics and exploring their transformative potential for nanophotonic devices, including ultra-sensitive plasmonic sensors, ultrafast saturable absorbers, modulators, and switches. Topological insulators (TIs) represent an ideal technological platform in this respect because they can support plasmon polaritons formed by Dirac carriers in the topological surface states. Tracing propagation of DPPs is a very challenging task, particularly at terahertz (THz) frequencies, where the DPP wavelength becomes over one order of magnitude shorter than the free space photon wavelength. Furthermore, severe attenuation hinders the comprehensive analysis of their characteristics. Here, the properties of DPPs in real TI-based devices are revealed. Bi2Se3 rectangular antennas can efficiently confine the propagation of DPPs to a single dimension and, as a result, enhance the DPPs visibility despite the strong intrinsic attenuation. The plasmon dispersion and loss properties from plasmon profiles are experimentally determined, along the antennas, obtained using holographic near-field nano-imaging in a wide range of THz frequencies, from 2.05 to 4.3 THz. The detailed investigation of the unveiled DPP properties can guide the design of novel topological quantum devices exploiting their directional propagation.

The challenge of estimating global termite methane emissions.

Methane is a powerful greenhouse gas, more potent than carbon dioxide, and emitted from a variety of natural sources including wetlands, permafrost, mammalian guts and termites. As increases in global temperatures continue to break records, quantifying the magnitudes of key methane sources has never been more pertinent. Over the last 40 years, the contribution of termites to the global methane budget has been subject to much debate. The most recent estimates of termite emissions range between 9 and 15 Tg CH4 year-1, approximately 4% of emissions from natural sources (excluding wetlands). However, we argue that the current approach for estimating termite contributions to the global methane budget is flawed. Key parameters, namely termite methane emissions from soil, deadwood, living tree stems, epigeal mounds and arboreal nests, are largely ignored in global estimates. This omission occurs because data are lacking and research objectives, crucially, neglect variation in termite ecology. Furthermore, inconsistencies in data collection methods prohibit the pooling of data required to compute global estimates. Here, we summarise the advances made over the last 40 years and illustrate how different aspects of termite ecology can influence the termite contribution to global methane emissions. Additionally, we highlight technological advances that may help researchers investigate termite methane emissions on a larger scale. Finally, we consider dynamic feedback mechanisms of climate warming and land-use change on termite methane emissions. We conclude that ultimately the global contribution of termites to atmospheric methane remains unknown and thus present an alternative framework for estimating their emissions. To significantly improve estimates, we outline outstanding questions to guide future research efforts.

Low detection rate of RT-PCR-confirmed COVID-19 using IgM/IgG rapid antibody tests in a large community sample in Lima, Peru.

BACKGROUND: Rapid IgM/IgG antibody tests were largely used in lieu of RT-PCR tests as part of COVID-19 public health response activities in Lima, Peru. To assess their utility, we explored the relationship between the time since onset of several COVID-19-related symptoms and the sensitivity of a rapid combined IgM/IgG antibody test. METHODS: We collected data from a community sample of individuals (n = 492) who received concurrent RT-PCR and rapid IgM/IgG antibody testing between May 2020 and March 2021. We estimated the sensitivity of the antibody test, against the RT-PCR test, by weeks since symptom onset via segmented regression analysis. RESULTS: The overall sensitivity of the rapid IgM/IgG antibody test was 46.7% (95% CI, 42.4-51.2%). Among 372 (75.6%) participants who reported COVID-19-related symptoms, sensitivity increased from 30.4% (95% CI, 24.7-36.6%) in week 1 after symptom onset to 83.3% (95% CI, 41.6-98.4%) in week 4. The test sensitivity increased by 31.9% (95% CI, 24.8-39.0%) per week until week 2 to 3, then decreased by - 6.0% (95% CI, - 25.7-13.7%) per week thereafter. CONCLUSION: Rapid antibody tests are a poor substitute for RT-PCR testing, regardless of presenting symptoms. This highlights the need for future pandemic planning to include timely and equitable access to gold-standard diagnostics, treatment, and vaccination.

Strong Coupling in Semiconductor Hyperbolic Metamaterials.

Semiconductor-based layered hyperbolic metamaterials (HMMs) house high-wavevector volume plasmon polariton (VPP) modes in the infrared spectral range. VPP modes have successfully been exploited in the weak-coupling regime through the enhanced Purcell effect. In this paper, we experimentally demonstrate strong coupling between the VPP modes in a semiconductor HMM and the intersubband transition of epitaxially embedded quantum wells. We observe clear anticrossings in the dispersion curves for the zeroth-, first-, second-, and third-order VPP modes, resulting in upper and lower polariton branches for each mode. This demonstration sets the stage for the creation of novel infrared optoelectronic structures combining HMMs with embedded epitaxial emitter or detector structures.

How Well Does TSTin3D Predict Risk of Active Tuberculosis in the Canadian Immigrant Population? An External Validation Study.

BACKGROUND: The online Tuberculin Skin Test/Interferon Gamma Release Assay (TST/IGRA) Interpreter V3.0 (TSTin3D), a tool for estimating the risk of active tuberculosis (TB) in individuals with latent TB infection (LTBI), has been in use for more than a decade, but its predictive performance has never been evaluated. METHODS: People with a positive TST or IGRA result from 1985 to 2015 were identified using a health data linkage that involved migrants to British Columbia, Canada. Comorbid conditions at the time of LTBI testing were identified from physician claims, hospitalizations, vital statistics, outpatient prescriptions, and kidney and HIV databases. The risk of developing active TB within 2 and 5 years was estimated using TSTin3D. The discrimination and calibration of these estimates were evaluated. RESULTS: A total of 37 163 individuals met study inclusion criteria; 10.4% were tested by IGRA. Generally, the TSTin3D algorithm assigned higher risks to demographic and clinical groups known to have higher active TB risks. Concordance estimates ranged from 0.66 to 0.68 in 2- and 5-year time frames. Comparing predicted to observed counts suggests that TSTin3D overestimates active TB risks and that overestimation increases over time (with relative bias of 3% and 12% in 2- and 5-year periods, respectively). Calibration plots also suggest that overestimation increases toward the upper end of the risk spectrum. CONCLUSIONS: TSTin3D can discriminate adequately between people who developed and did not develop active TB in this linked database of migrants with predominately positive skin tests. Further work is needed to improve TSTin3D's calibration.

Acceptability, feasibility, and impact of a pilot tuberculosis literacy and treatment counselling intervention: a mixed methods study.

BACKGROUND: There is a need for innovative strategies to improve TB testing uptake and patient retention along the continuum of TB care early-on in treatment without burdening under-resourced health systems. We used a mixed methods approach to develop and pilot test a tuberculosis literacy and counselling intervention at an urban clinic in KwaZulu Natal, South Africa, to improve TB testing uptake and retention in tuberculosis care. METHODS: We engaged in discussions with clinic staff to plan and develop the intervention, which was delivered by senior social work students who received one-week training. The intervention included: 1) group health talks with all patients attending the primary clinic; and 2) individual counselling sessions, using motivational interviewing techniques, with newly diagnosed tuberculosis patients. We compared social work students' tuberculosis knowledge, attitudes, and practices before and after their training. We assessed the change in number of tuberculosis diagnostic tests performed after implementation via an interrupted time series analysis with a quasi-Poisson regression model. We compared pre- and post-intervention probabilities of treatment initiation and completion using regression analyses, adjusting for potential baseline confounders. We conducted focus groups with the students, as well as brief surveys and one-on-one interviews with patients, to assess acceptability, feasibility, and implementation. RESULTS: During the study period, 1226 individuals received tuberculosis diagnostic testing and 163 patients started tuberculosis treatment, of whom 84 (51.5%) received individual counselling. The number of diagnostic tuberculosis tests performed increased by 1.36 (95%CI 1.23-1.58) times post-intervention, adjusting for background calendar trend. Probabilities of TB treatment initiation and treatment completion increased by 10.1% (95%CI 1.5-21.3%) and 4.4% (95%CI -7.3-16.0%), respectively. Patients found the counselling sessions alleviated anxiety and increased treatment self-efficacy. Social work students felt the clinic staff were collaborative and highly supportive of the intervention, and that it improved patient engagement and adherence. CONCLUSIONS: Engaging clinic staff in the development of an intervention ensures buy-in and collaboration. Education and counselling before and early-on in tuberculosis treatment can increase tuberculosis testing and treatment uptake. Training junior social workers can enable task-shifting in under-resourced settings, while addressing important service gaps in tuberculosis care.

Darker ants dominate the canopy: Testing macroecological hypotheses for patterns in colour along a microclimatic gradient.

Gradients in cuticle lightness of ectotherms have been demonstrated across latitudes and elevations. Three key hypotheses have been used to explain these macroecological patterns: the thermal melanism hypothesis (TMH), the melanism-desiccation hypothesis (MDH) and the photo-protection hypothesis (PPH). Yet the broad abiotic measures, such as temperature, humidity and UV-B radiation, typically used to detect these ecogeographical patterns, are a poor indication of the microenvironment experienced by small, cursorial ectotherms like ants. We tested whether these macroecological hypotheses explaining cuticle lightness held at habitat and microclimatic level by using a vertical gradient within a tropical rainforest. We sampled 222 ant species in lowland, tropical rainforest across four vertical strata: subterranean, ground, understory and canopy. We recorded cuticle lightness, abundance and estimated body size for each species and calculated an assemblage-weighted mean for cuticle lightness and body size for each vertical stratum. Abiotic variables (air temperature, vapour pressure deficit and UV-B radiation) were recorded for each vertical stratum. We found that cuticle lightness of ant assemblages was vertically stratified: ant assemblages in the canopy and understory were twice as dark as assemblages in ground and subterranean strata. Cuticle lightness was not correlated with body size, and there was no support for the TMH. Rather, we attribute this cline in cuticle lightness to a combination of the MDH and the PPH. Our findings indicate that broad macroecological patterns can be detected at much smaller spatial scales and that microclimatic gradients can shape trait variation, specifically the cuticle lightness of ants. These results suggest that any changes to microclimate that occur due to land-use change or climate warming could drive selection of ants based on cuticle colour, altering assemblage structure and potentially ecosystem functioning.

Active testing of groups at increased risk of acquiring SARS-CoV-2 in Canada: costs and human resource needs.

BACKGROUND: Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely passive, which impedes epidemic control. We defined active testing strategies for SARS-CoV-2 using reverse transcription polymerase chain reaction (RT-PCR) for groups at increased risk of acquiring SARS-CoV-2 in all Canadian provinces. METHODS: We identified 5 groups who should be prioritized for active RT-PCR testing: contacts of people who are positive for SARS-CoV-2, and 4 at-risk populations - hospital employees, community health care workers and people in long-term care facilities, essential business employees, and schoolchildren and staff. We estimated costs, human resources and laboratory capacity required to test people in each group or to perform surveillance testing in random samples. RESULTS: During July 8-17, 2020, across all provinces in Canada, an average of 41 751 RT-PCR tests were performed daily; we estimated this required 5122 personnel and cost $2.4 million per day ($67.8 million per month). Systematic contact tracing and testing would increase personnel needs 1.2-fold and monthly costs to $78.9 million. Conducted over a month, testing all hospital employees would require 1823 additional personnel, costing $29.0 million; testing all community health care workers and persons in long-term care facilities would require 11 074 additional personnel and cost $124.8 million; and testing all essential employees would cost $321.7 million, requiring 25 965 added personnel. Testing the larger population within schools over 6 weeks would require 46 368 added personnel and cost $816.0 million. Interventions addressing inefficiencies, including saliva-based sampling and pooling samples, could reduce costs by 40% and personnel by 20%. Surveillance testing in population samples other than contacts would cost 5% of the cost of a universal approach to testing at-risk populations. INTERPRETATION: Active testing of groups at increased risk of acquiring SARS-CoV-2 appears feasible and would support the safe reopening of the economy and schools more broadly. This strategy also appears affordable compared with the $169.2 billion committed by the federal government as a response to the pandemic as of June 2020.

Interventions to improve retention-in-care and treatment adherence among patients with drug-resistant tuberculosis: a systematic review.

The global loss to follow-up (LTFU) rate among drug-resistant tuberculosis (DR-TB) patients remains high at 15%. We conducted a systematic review to explore interventions to reduce LTFU during DR-TB treatment.We searched for studies published between January 2000 and December 2017 that provided any form of psychosocial or material support for patients with DR-TB. We estimated point estimates and 95% confidence intervals of the proportion LTFU. We performed subgroup analyses and pooled estimates using an exact binomial likelihood approach.We included 35 DR-TB cohorts from 25 studies, with a pooled proportion LTFU of 17 (12-23)%. Cohorts that received any form of psychosocial or material support had lower LTFU rates than those that received standard care. Psychosocial support throughout treatment, via counselling sessions or home visits, was associated with lower LTFU rates compared to when support was provided through a limited number of visits or not at all.Our review suggests that psychosocial support should be provided throughout DR-TB treatment in order to reduce treatment LTFU. Future studies should explore the potential of providing self-administered therapy complemented with psychosocial support during the continuation phase.

Far-field thermal emission from a semiconductor hyperbolic metamaterial.

This paper investigates the far-field thermal emission of a Si:InAs/AlSb semiconductor hyperbolic metamaterial (HMM). Understanding the thermal emission of HMMs could result in advancements in thermophotovoltaics and thermal emission management. In recent years, there has been controversy about whether the large wavevector volume plasmon polariton (VPP) modes that exist in HMMs could be outcoupled into the far field using a grating and give rise to super-Planckian thermal emission. In this experiment, gold gratings with varying periods were applied to the surface of the HMM to outcouple the VPP modes into free space. The sample was heated to 185°C, and the polarized thermal emission was measured using Fourier transform infrared spectroscopy. The HMM showed minimal angle sensitivity up to 50°. The sample showed multiple peaks in emission which corresponded to the resonant wavelengths of the VPP modes, demonstrating outcoupling from these modes. Although these modes showed increases in the emissivity, super-Planckian emission was not observed. Emission from VPP modes could be leveraged to create materials with designer emissivity profiles.

Effects of footwear midsole thickness on running biomechanics.

Shoe manufacturers launch running shoes with increased (e.g., maximalists) or decreased (e.g., minimalists) midsole thickness and claim that they may prevent running injury. Previous studies tested footwear models with different midsole thicknesses on the market but the shoe construct was not strictly comparable. Therefore, in the present study, we examined the effect of midsole thickness, from 1-mm to 29-mm, in a standard test shoe prototype on the vertical loading rates, footstrike angle and temporal spatial parameters in distance runners. Fifteen male habitual rearfoot strikers were recruited from local running clubs. They were asked to run on an instrumented treadmill in shoes with different midsole thicknesses. We found significant interactions between midsole thickness with vertical loading rates (p < 0.001), footstrike angle (p = 0.013), contact time (p < 0.001), cadence (p = 0.003), and stride length (p = 0.004). Specifically, shoes with thinner midsole (1- and 5-mm) significantly increased the vertical loading rates and shortened the contact time, when compared with thicker midsole shoes (25- and 29-mm). However, we did not observe any substantial differences in the footstrike angle, cadence and stride length between other shod conditions. The present study provides biomechanical data regarding the relationship between full spectrum midsole thicknesses and running biomechanics in a group of rearfoot strikers.

Treatment and outcomes in children with multidrug-resistant tuberculosis: A systematic review and individual patient data meta-analysis.

BACKGROUND: An estimated 32,000 children develop multidrug-resistant tuberculosis (MDR-TB; Mycobacterium tuberculosis resistant to isoniazid and rifampin) each year. Little is known about the optimal treatment for these children. METHODS AND FINDINGS: To inform the pediatric aspects of the revised World Health Organization (WHO) MDR-TB treatment guidelines, we performed a systematic review and individual patient data (IPD) meta-analysis, describing treatment outcomes in children treated for MDR-TB. To identify eligible reports we searched PubMed, LILACS, Embase, The Cochrane Library, PsychINFO, and BioMedCentral databases through 1 October 2014. To identify unpublished data, we reviewed conference abstracts, contacted experts in the field, and requested data through other routes, including at national and international conferences and through organizations working in pediatric MDR-TB. A cohort was eligible for inclusion if it included a minimum of three children (aged <15 years) who were treated for bacteriologically confirmed or clinically diagnosed MDR-TB, and if treatment outcomes were reported. The search yielded 2,772 reports; after review, 33 studies were eligible for inclusion, with IPD provided for 28 of these. All data were from published or unpublished observational cohorts. We analyzed demographic, clinical, and treatment factors as predictors of treatment outcome. In order to obtain adjusted estimates, we used a random-effects multivariable logistic regression (random intercept and random slope, unless specified otherwise) adjusted for the following covariates: age, sex, HIV infection, malnutrition, severe extrapulmonary disease, or the presence of severe disease on chest radiograph. We analyzed data from 975 children from 18 countries; 731 (75%) had bacteriologically confirmed and 244 (25%) had clinically diagnosed MDR-TB. The median age was 7.1 years. Of 910 (93%) children with documented HIV status, 359 (39%) were infected with HIV. When compared to clinically diagnosed patients, children with confirmed MDR-TB were more likely to be older, to be infected with HIV, to be malnourished, and to have severe tuberculosis (TB) on chest radiograph (p < 0.001 for all characteristics). Overall, 764 of 975 (78%) had a successful treatment outcome at the conclusion of therapy: 548/731 (75%) of confirmed and 216/244 (89%) of clinically diagnosed children (absolute difference 14%, 95% confidence interval [CI] 8%-19%, p < 0.001). Treatment was successful in only 56% of children with bacteriologically confirmed TB who were infected with HIV who did not receive any antiretroviral treatment (ART) during MDR-TB therapy, compared to 82% in children infected with HIV who received ART during MDR-TB therapy (absolute difference 26%, 95% CI 5%-48%, p = 0.006). In children with confirmed MDR-TB, the use of second-line injectable agents and high-dose isoniazid (15-20 mg/kg/day) were associated with treatment success (adjusted odds ratio [aOR] 2.9, 95% CI 1.0-8.3, p = 0.041 and aOR 5.9, 95% CI 1.7-20.5, p = 0.007, respectively). These findings for high-dose isoniazid may have been affected by site effect, as the majority of patients came from Cape Town. Limitations of this study include the difficulty of estimating the treatment effects of individual drugs within multidrug regimens, only observational cohort studies were available for inclusion, and treatment decisions were based on the clinician's perception of illness, with resulting potential for bias. CONCLUSIONS: This study suggests that children respond favorably to MDR-TB treatment. The low success rate in children infected with HIV who did not receive ART during their MDR-TB treatment highlights the need for ART in these children. Our findings of individual drug effects on treatment outcome should be further evaluated.

Dépistage actif chez les groupes courant un risque accru de contracter le SRAS-CoV-2 au Canada : coûts et ressources humaines nécessaires.

CONTEXTE: Le dépistage du coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2) est en grande partie passif, ce qui nuit au contrôle de l'épidémie. Nous avons élaboré des stratégies de dépistage actif du SRAS-CoV-2 au moyen d'une amplification en chaîne par polymérase couplée à une transcription inverse (RT-PCR) chez les groupes courant un risque accru de contracter le virus dans les provinces canadiennes. MÉTHODES: Nous avons identifié 5 groupes qui devraient être prioritaires pour le dépistage actif au moyen d'une RTPCR, soit les gens ayant été en contact avec une personne infectée par le SRAS-CoV-2 et ceux qui appartiennent à 4 populations à risque : employés d'hôpitaux, travailleurs en soins de santé communautaires ainsi qu'employés et résidents d'établissements de soins de longue durée, employés d'entreprises essentielles, et élèves et personnel scolaire. Nous avons estimé les coûts, les ressources humaines et la capacité de laboratoire nécessaires au dépistage des membres de ces groupes ou au dépistage sur des échantillons aléatoires aux fins de surveillance. RÉSULTATS: Du 8 au 17 juillet 2020, 41 751 dépistages par RT-PCR étaient réalisés chaque jour en moyenne dans les provinces canadiennes; nous avons estimé que ces tests mobilisaient 5122 employés et coûtaient 2,4 millions de dollars par jour (67,8 millions de dollars par mois). La recherche et le dépistage systématiques des contacts requerraient 1,2 fois plus de personnel et porteraient les coûts mensuels à 78,9 millions de dollars. S'il était réalisé en 1 mois, le dépistage de tous les employés des hôpitaux nécessiterait 1823 travailleurs supplémentaires et coûterait 29,0 millions de dollars. Pour la même période de temps, le dépistage de tous les travailleurs en soins de santé communautaires et de tous les employés et résidents des établissements de soins de longue durée nécessiterait 11 074 employés supplémentaires et coûterait 124,8 millions de dollars, et celui de tous les travailleurs essentiels nécessiterait 25 965 employés supplémentaires et coûterait 321,7 millions de dollars. Enfin, le dépistage sur 6 semaines de la population scolaire nécessiterait 46 368 employés supplémentaires et coûterait 816,0 millions de dollars. Les interventions visant à pallier les inefficacités, comme le dépistage à partir d'échantillons de salive et le regroupement des échantillons, pourraient réduire les coûts de 40 % et les besoins en personnel, de 20 %. Le dépistage de surveillance sur des échantillons de la population autre que les contacts coûterait 5 % des coûts associés à l'adoption d'une approche universelle de dépistage auprès des populations à risque. INTERPRÉTATION: Le dépistage actif des groupes courant un risque accru de contracter le SRAS-CoV-2 semble faisable et favoriserait la réouverture sûre et à grande échelle de l'économie et des écoles. Cette stratégie semble également abordable lorsque comparée aux 169,2 milliards de dollars versés par le gouvernement fédéral dans la lutte contre la pandémie en date de juin 2020.

Comparing cost-effectiveness of standardised tuberculosis treatments given varying drug resistance.

There is a growing need to identify appropriate standardised treatment strategies that will adequately treat various forms of drug-resistant tuberculosis (TB) and prevent multidrug-resistant (MDR)-TB. A Markov model estimated treatment-related acquired MDR-TB, mortality, disability-adjusted life years and costs in settings with different prevalence of isoniazid monoresistant TB and MDR-TB. We compared four treatment strategies: 1) the standard World Health Organization recommended treatment strategy; 2) adding ethambutol throughout the 6-month treatment of new cases; 3) using a strengthened standardised retreatment regimen; and 4) using standardised MDR treatment for failures of initial treatment. Treatment-related outcomes were derived from the published literature, and costs from direct surveys. A strengthened retreatment regimen, which could achieve lower failure, relapse and acquired MDR rates in isoniazid monoresistant cases, was predicted to be the most cost-effective strategy in all modelled settings. Empirical MDR treatment of failures of initial treatment was the most costly strategy but resulted in the fewest deaths. Adding ethambutol throughout initial treatment would be most effective in preventing acquired MDR, but would lead to excess cases of blindness. A high priority should be given to improving the standardised retreatment regimen, as this is predicted to produce greater benefits than other recently recommended strategies.

All-semiconductor plasmonic nanoantennas for infrared sensing.

Infrared absorption spectroscopy of vibro-rotational molecular resonances provides a powerful method for investigation of a wide range of molecules and molecular compounds. However, the wavelength of light required to excite these resonances is often orders of magnitude larger than the absorption cross sections of the molecules under investigation. This mismatch makes infrared detection and identification of nanoscale volumes of material challenging. Here we demonstrate a new type of infrared plasmonic antenna for long-wavelength nanoscale enhanced sensing. The plasmonic materials utilized are epitaxially grown semiconductor engineered metals, which results in high-quality, low-loss infrared plasmonic metals with tunable optical properties. Nanoantennas are fabricated using nanosphere lithography, allowing for cost-effective and large-area fabrication of nanoscale structures. Antenna arrays are optically characterized as a function of both the antenna geometry and the optical properties of the plasmonic semiconductor metals. Thin, weakly absorbing polymer layers are deposited upon the antenna arrays, and we are able to observe very weak molecular absorption signatures when these signatures are in spectral proximity to the antenna resonance. Experimental results are supported with finite element modeling with strong agreement.

Quasi-Van der Waals Epitaxial Growth of γ'-GaSe Nanometer-Thick Films on GaAs(111)B Substrates.

GaSe is an important member of the post-transition-metal chalcogenide family and is an emerging two-dimensional (2D) semiconductor material. Because it is a van der Waals material, it can be fabricated into atomic-scale ultrathin films, making it suitable for the preparation of compact, heterostructure devices. In addition, GaSe possesses unusual optical and electronic properties, such as a shift from an indirect-bandgap single-layer film to a direct-bandgap bulk material, rare intrinsic p-type conduction, and nonlinear optical behaviors. These properties make GaSe an appealing candidate for the fabrication of field-effect transistors, photodetectors, and photovoltaics. However, the wafer-scale production of pure GaSe single-crystal thin films remains challenging. This study develops an approach for the direct growth of nanometer-thick GaSe films on GaAs substrates by using molecular beam epitaxy. It yields smooth thin GaSe films with a rare γ'-polymorph. We analyze the formation mechanism of γ'-GaSe using density-functional theory and speculate that it is stabilized by Ga vacancies since the formation enthalpy of γ'-GaSe tends to become lower than that of other polymorphs when the Ga vacancy concentration increases. Finally, we investigate the growth conditions of GaSe, providing valuable insights for exploring 2D/three-dimensional (3D) quasi-van der Waals epitaxial growth.

The Role of Optical Phonon Confinement in the Infrared Dielectric Response of III-V Superlattices.

Polar dielectrics are key materials of interest for infrared (IR) nanophotonic applications due to their ability to host phonon-polaritons that allow for low-loss, subdiffractional control of light. The properties of phonon-polaritons are limited by the characteristics of optical phonons, which are nominally fixed for most "bulk" materials. Superlattices composed of alternating atomically thin materials offer control over crystal anisotropy through changes in composition, optical phonon confinement, and the emergence of new modes. In particular, the modified optical phonons in superlattices offer the potential for so-called crystalline hybrids whose IR properties cannot be described as a simple mixture of the bulk constituents. To date, however, studies have primarily focused on identifying the presence of new or modified optical phonon modes rather than assessing their impact on the IR response. This study focuses on assessing the impact of confined optical phonon modes on the hybrid IR dielectric function in superlattices of GaSb and AlSb. Using a combination of first principles theory, Raman, FTIR, and spectroscopic ellipsometry, the hybrid dielectric function is found to track the confinement of optical phonons, leading to optical phonon spectral shifts of up to 20 cm-1 . These results provide an alternative pathway toward designer IR optical materials.

Effectiveness of a bedaquiline, linezolid, clofazimine "core" for multidrug-resistant tuberculosis.

Rationale: Treatment outcomes may be compromised among patients with multidrug- or rifampicin-resistant tuberculosis with additional fluoroquinolone resistance. Evidence is needed to inform optimal treatment for these patients. Objectives: We compared the effectiveness of longer individualized regimens comprised of bedaquiline for 5 to 8 months, linezolid, and clofazimine to those reinforced with at least 1 third-tier drug and/or longer duration of bedaquiline. Methods: We emulated a target trial to compare the effectiveness of initiating and remaining on the core regimen to one of five regimens reinforced with (1) bedaquiline for ≥9 months, (2) bedaquiline for ≥9 months and delamanid, (3) imipenem, (4) a second-line injectable, or (5) delamanid and imipenem. We included patients in whom a fluoroquinolone was unlikely to be effective based on drug susceptibility testing and/or prior exposure. Our analysis consisted of cloning, censoring, and inverse-probability weighting to estimate the probability of successful treatment. Measurements and Main Results: Adjusted probabilities of successful treatment were high across regimens, ranging from 0.75 (95%CI:0.61, 0.89) to 0.84 (95%CI:0.76, 0.91). We found no substantial evidence that any of the reinforced regimens improved effectiveness of the core regimen, with ratios of treatment success ranging from 1.01 for regimens reinforced with bedaquiline ≥9 months (95%CI:0.79, 1.28) and bedaquiline ≥9 months plus delamanid (95%CI:0.81, 1.31) to 1.11 for regimens reinforced by a second-line injectable (95%CI:0.92, 1.39) and delamanid and imipenem (95%CI:0.90, 1.41). Conclusions: High treatment success underscores the effectiveness of regimens comprised of bedaquiline, linezolid, and clofazimine, highlighting the need for expanded access to these drugs.

Polariton design and modulation via van der Waals/doped semiconductor heterostructures.

Hyperbolic phonon polaritons (HPhPs) can be supported in materials where the real parts of their permittivities along different directions are opposite in sign. HPhPs offer confinements of long-wavelength light to deeply subdiffractional scales, while the evanescent field allows for interactions with substrates, enabling the tuning of HPhPs by altering the underlying materials. Yet, conventionally used noble metal and dielectric substrates restrict the tunability of this approach. To overcome this challenge, here we show that doped semiconductor substrates, e.g., InAs and CdO, enable a significant tuning effect and dynamic modulations. We elucidated HPhP tuning with the InAs plasma frequency in the near-field, with a maximum difference of 8.3 times. Moreover, the system can be dynamically modulated by photo-injecting carriers into the InAs substrate, leading to a wavevector change of ~20%. Overall, the demonstrated hBN/doped semiconductor platform offers significant improvements towards manipulating HPhPs, and potential for engineered and modulated polaritonic systems.