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IntroductionTruenat MTB-RIF assay (Truenat), a nucleic acid amplification test (NAAT), is a real-time polymerase chain reaction (RT-PCR) chip-based assay that can detect Mycobacterium tuberculosis (Mtb) and rifampicin (RIF) drug resistance using portable, battery-operated devices. The National TB Elimination Program (NTEP) in India introduced this novel tool at the district and subdistrict level in 2020. This study aimed to assess the level and causes of inconclusive results (invalid results, errors, and indeterminate results) in MTB and RIF testing at NTEP sites and the root causes of these in the programmatic setting.MethodsTruenat testing data from 1,690 functional Truenat sites under the NTEP from April to June 2021 were analyzed to assess the rates of errors, invalid MTB results, and indeterminate RIF results. Following this analysis, 12 Truenat sites were selected based on site performance in Truenat testing, diversity of climatic conditions, and geographical terrain. These sites were visited to assess the root causes of their high and low rates of inconclusive results using a structured checklist.ResultsA total of 327,649 Truenat tests performed for MTB and RIF testing were analyzed. The rate of invalid MTB results was 5.2% [95% confidence interval (CI): 5.11–5.26; n = 16,998] and the rate of errors was 2.5% (95% CI: 2.46–2.57; n = 8,240) in Truenat MTB chip testing. For Mtb-positive samples tested using the Truenat RIF chip for detection of RIF resistance (n = 40,926), the rate of indeterminate results was 15.3% (95% CI: 14.97–15.67; n = 6,267) and the rate of errors was 1.6% (95% CI: 1.53–1.78; n = 675). There was a 40.1% retesting gap for Mtb testing and a 78.2% gap for inconclusive RR results. Among the inconclusive results retested, 27.9% (95% CI: 27.23–28.66; n = 4,222) were Mtb-positive, and 9.2% (95% CI: 7.84–10.76; n = 139) were detected as RR.ConclusionThe main causes affecting Truenat testing performance include suboptimal adherence to standard operating procedures (SOPs), inadequate training, improper storage of testing kits, inadequate sputum quality, lack of quality control, and delays in the rectification of machine issues. Root cause analysis identified that strengthening of training, external quality control, and supervision could improve the rate of inconclusive results. Ensuring hands-on training of technicians for Truenat testing and retesting of samples with inconclusive results are major recommendations while planning for Truenat scale-up. The recommendations from the study were consolidated into technical guidance documents and videos and disseminated to laboratory staff working at the tiered network of TB laboratories under the NTEP in order to improve Truenat MTB-RIF testing performance.

The complete diagnostic evaluation of tuberculosis based on its drug-resistance profile is critical for appropriate treatment decisions. The TB diagnostic landscape in India has been transformed with the scaling-up of WHO-recommended diagnostics, but challenges remain with specimen transportation, completing diagnostic assessment, turnaround time (TAT), and maintaining laboratories. Private laboratories have demonstrated efficiencies for specimen collection, transportation, and the timely testing and issue of results. A one-stop TB diagnostic model was designed to assess the feasibility of providing end-to-end diagnostic services in the Hisar district of Haryana state, India. A NTEP-certified private laboratory was engaged to provide the services, complementing the existing public sector diagnostic services. A total of 10,164 specimens were collected between May 2022 and January 2023 and these were followed for the complete diagnostic assessment of Drug-Susceptible TB (DS-TB) and Drug-Resistant TB (DR-TB) and the time taken for issuing results. A total of 2152 (21%) patients were detected with TB, 1996 (93%) Rifampicin-Sensitive and 134 (6%) with Rifampicin-Resistant TB. Nearly 99% of the patients completed the evaluation of DS-TB and DR-TB within the recommended TAT. The One-Stop TB/DR-TB Diagnostic Solution model has demonstrated that diagnostic efficiencies could be enhanced through the strategic purchase of private laboratory services.

A novel quercetin-phospholipid-complex (QPLC)-loaded matrix film for improved transdermal delivery of quercetin was developed. QPLC formulation, prepared using a solvent-evaporation method was optimized using a central-composite design. The optimized QPLC formulation was characterized by particle size and zeta potential analysis, thermal analysis, Fourier transform infrared spectroscopy (FTIR), and proton nuclear magnetic resonance spectroscopy (1H-NMR). QPLC formulation was functionally evaluated for solubility and in vitro dissolution of quercetin. Matrix films of pure quercetin (Q-MF) or QPLC (QPLC-MF) were prepared using a solvent casting method. The prepared Q-MF and QPLC-MF were characterized for weight uniformity, folding endurance, moisture content, and moisture uptake. The films were also functionally characterized for in vitro diffusion of quercetin through a dialysis membrane and ex vivo permeability of quercetin across rat skin. Finally, the anti-inflammatory activity of the films was evaluated on carrageenan-induced paw edema in Wistar albino rats. The experimental design identified the optimal formulation and process variables for the preparation of QPLC. The validation of the obtained model using these values confirmed the suitability and robustness of the model. The physical-chemical characterization of the prepared QPLC supported the formation of a stable complex. The solubility analysis of QPLC showed a 22-fold increase in quercetin aqueous solubility, compared to pure quercetin. The dissolution results exhibited a significantly higher rate and extent of quercetin dissolution from QPLC compared to that of pure quercetin. The permeability of quercetin from Q-MF and QPLC-MF across rat skin mirrored those obtained from the dissolution studies. Topical application of QPLC-MF exhibited a significant (p

The current work describes the formulation and evaluation of a phospholipid complex of kaempferol to enhance the latter’s aqueous solubility, in vitro dissolution rate, in vivo antioxidant and hepatoprotective activities, and oral bioavailability. The kaempferol-phospholipid complex was synthesized using a freeze-drying method with the formulation being optimized using a full factorial design (32) approach. Our results include the validation of the mathematical model in order to ascertain the role of specific formulation and process variables that contribute favorably to the formulation’s development. The final product was characterized and confirmed by Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), Proton Nuclear Magnetic Resonance Spectroscopy (1H-NMR), and Powder X-ray Diffraction (PXRD) analysis. The aqueous solubility and the in vitro dissolution rate were enhanced compared to that of pure kaempferol. The in vivo antioxidant properties of the kaempferol-phospholipid complex were evaluated by measuring its impact on carbon tetrachloride (CCl4)-intoxicated rats. The optimized phospholipid complex improved the liver function test parameters to a significant level by restoration of all elevated liver marker enzymes in CCl4-intoxicated rats. The complex also enhanced the in vivo antioxidant potential by increasing levels of GSH (reduced glutathione), SOD (superoxide dismutase), catalase and decreasing lipid peroxidation, compared to that of pure kaempferol. The final optimized phospholipid complex also demonstrated a significant improvement in oral bioavailability demonstrated by improvements to key pharmacokinetic parameters, compared to that of pure kaempferol.

The current work describes the formulation and evaluation of a phospholipid complex of kaempferol to enhance the latter’s aqueous solubility, in vitro dissolution rate, in vivo antioxidant and hepatoprotective activities, and oral bioavailability. The kaempferol-phospholipid complex was synthesized using a freeze-drying method with the formulation being optimized using a full factorial design (32) approach. Our results include the validation of the mathematical model in order to ascertain the role of specific formulation and process variables that contribute favorably to the formulation’s development. The final product was characterized and confirmed by Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), Proton Nuclear Magnetic Resonance Spectroscopy (1H-NMR), and Powder X-ray Diffraction (PXRD) analysis. The aqueous solubility and the in vitro dissolution rate were enhanced compared to that of pure kaempferol. The in vivo antioxidant properties of the kaempferol-phospholipid complex were evaluated by measuring its impact on carbon tetrachloride (CCl4)-intoxicated rats. The optimized phospholipid complex improved the liver function test parameters to a significant level by restoration of all elevated liver marker enzymes in CCl4-intoxicated rats. The complex also enhanced the in vivo antioxidant potential by increasing levels of GSH (reduced glutathione), SOD (superoxide dismutase), catalase and decreasing lipid peroxidation, compared to that of pure kaempferol. The final optimized phospholipid complex also demonstrated a significant improvement in oral bioavailability demonstrated by improvements to key pharmacokinetic parameters, compared to that of pure kaempferol.

Thwaites Glacier (TG) plays an important role in future sea-level rise (SLR) contribution from the West Antarctic Ice Sheet. Recent observations show that TG is losing mass, and its grounding zone is retreating. Previous modeling has produced a wide range of results concerning whether, when, and how rapidly further retreat will occur under continued warming. These differences arise at least in part from ill-constrained processes, including friction from the bed, and future atmosphere and ocean forcing affecting ice-shelf and grounding-zone buttressing. Here, we apply the Ice Sheet and Sea-level System Model (ISSM) with a range of specifications of basal sliding behavior in response to varying ocean forcing. We find that basin-wide bed character strongly affects TG's response to sub-shelf melt by modulating how changes in driving stress are balanced by the bed as the glacier responds to external forcing. Resulting differences in dynamic thinning patterns alter modeled grounding-line retreat across Thwaites' catchment, affecting both modeled rates and magnitudes of SLR contribution from this critical sector of the ice sheet. Bed character introduces large uncertainties in projections of TG under equal external forcing, pointing to this as a crucial constraint needed in predictive models of West Antarctica.

Glacial hydraulic tremor (GHT) can be monitored to observe changes in location and distribution of water flow beneath glacial ice, allowing the spatiotemporal evolution of subglacial hydrology to be studied continuously and remotely. We use frequency-dependent polarization analysis (FDPA) to classify types of GHT and assess its spatio-temporal extent beneath Rhonegletscher, Switzerland, in a continuous seismic record through 2018 and 2019 at three ice-proximal bedrock-based seismometers. We determine the frequency bands composing the GHT and calculate back azimuth angles pointing to a previously known subglacial channel. We also inspect the relationship between GHT seismic power and water discharge from the glacier to compare daily and seasonal shifts with the observed GHT. We observed the seasonal shift from a distributed system to a channelized system, and our dataset allowed comparison of channel locations within and across seasons, with implications for sediment evacuation and bed erosion. The successful use of this method to assess GHT previously on Taku glacier (the methods of which this project follows) and now Rhonegletscher shows that existing ice-proximal passive seismic installations can be used to easily and continuously monitor subglacial hydraulic activity.

Glacier-bed characteristics that are poorly known and modeled are important in projected sea-level rise from ice-sheet changes under strong warming, especially in the Thwaites Glacier drainage of West Antarctica. Ocean warming may induce ice-shelf thinning or loss, or thinning of ice in estuarine zones, reducing backstress on grounded ice. Models indicate that, in response, more-nearly-plastic beds favor faster ice loss by causing larger flow acceleration, but more-nearly-viscous beds favor localized near-coastal thinning that could speed grounding-zone retreat into interior basins where marine-ice-sheet instability or cliff instability could develop and cause very rapid ice loss. Interpretation of available data indicates that the bed is spatially mosaicked, with both viscous and plastic regions. Flow against bedrock topography removes plastic lubricating tills, exposing bedrock that is eroded on up-glacier sides of obstacles to form moats with exposed bedrock tails extending downglacier adjacent to lee-side soft-till bedforms. Flow against topography also generates high-ice-pressure zones that prevent inflow of lubricating water over distances that scale with the obstacle size. Extending existing observations to sufficiently large regions, and developing models assimilating such data at the appropriate scale, present large, important research challenges that must be met to reliably project future forced sea-level rise.

To increase inclusivity, diversity, equity and accessibility in Antarctic science, we must build more positive and inclusive Antarctic field work environments. The International Thwaites Glacier Collaboration (ITGC) has engaged in efforts to contribute to that goal through a variety of activities since 2018, including creating an open-access ‘Field and Ship Best Practices’ guide, engaging in pre-field season team dynamics meetings, and surveying post-field season reflections and experiences. We report specific actions taken by ITGC and their outcomes. We found that strong and supported early career researchers brought new and important perspectives regarding strategies for transforming culture. We discovered that engaged and involved senior leadership was also critical for expanding participation and securing funding to support efforts. Pre-field discussions involving all field team members were particularly helpful for setting expectations, improving sense of belonging, describing field work best practices, and co-creating a positive work culture.

Marine-terminating glaciers lose mass through melting and iceberg calving, and we find that meltwater drainage systems influence calving timing at Helheim Glacier, a tidewater glacier in East Greenland. Meltwater feeds a buoyant subglacial discharge plume at the terminus of Helheim Glacier, which rises along the glacial front and surfaces through the mélange. Here, we use high-resolution satellite and time-lapse imagery to observe the surface expression of this meltwater plume and how plume timing and location compare with that of calving and supraglacial meltwater pooling from 2011 to 2019. The plume consistently appeared at the central terminus even as the glacier advanced and retreated, fed by a well-established channelized drainage system with connections to supraglacial water. All full-thickness calving episodes, both tabular and non-tabular, were separated from the surfacing plume by either time or by space. We hypothesize that variability in subglacial hydrology and basal coupling drive this inverse relationship between subglacial discharge plumes and full-thickness calving. Surfacing plumes likely indicate a low-pressure subglacial drainage system and grounded terminus, while full-thickness calving occurrence reflects a terminus at or close to flotation. Our records of plume appearance and full-thickness calving therefore represent proxies for the grounding state of Helheim Glacier through time.

Seismic studies of glaciers yield insights into spatio-temporal processes within and beneath glaciers on scales relevant to flow and deformation of the ice. These methods enable direct monitoring of the bed in ways that complement other geophysical techniques, such as geodetic or ground penetrating radar observations. In this work, we report on the analysis of passive seismic data collected from the interior of the North East Greenland Ice Stream, the Greenland ice sheet's largest outlet glacier. We record thousands of basal earthquakes, many of which repeat with nearly identical waveforms. We also record many long-duration glacial tremor episodes that migrate across the seismic network with slow velocities (e.g. ~4–12 m s−1). Analysis of the basal earthquakes indicates a transition between times of individual event activity and times of tremor activity. We suggest that both processes are produced by shear slip at localized asperities along the bed. The transition between discrete and quasi-continuous slipping modes may be driven by pore-water pressure transients or heterogeneous strain accumulation in the ice due to strength contrasts of the underlying till.

We describe elongate, wet, subglacial bedforms in the shear margins of the NE Greenland Ice Stream and place some constraints on their formation. Lateral shear margin moraines have been observed across the previously glaciated landscape, but little is known about the ice-flow conditions necessary to form these bedforms. Here we describe in situ sediment bedforms under the NE Greenland Ice Stream shear margins that are observed in active-source seismic and ground-penetrating radar surveys. We find bedforms in the shear margins that are ~500 m wide, ~50 m tall, and elongated nearly parallel to ice-flow, including what we believe to be the first subglacial observation of a shear margin moraine. Acoustic impedance analysis of the bedforms shows that they are composed of unconsolidated, deformable, water-saturated till. We use these geophysical observations to place constraints on the possible formation mechanism of these subglacial features.

Recent seismic measurements from upper Thwaites Glacier indicate that the bed-type variability is closely related to the along-flow basal topography. In high-relief subglacial highlands, stoss sides of topographic highs have a relatively higher acoustic impedance (‘hard’ bed) with lower acoustic impedance (‘soft’ till) on lee sides. This pattern is similar to observations of many deglaciated terrains. Subglacial hydraulic-potential gradient and its divergence show a tendency for water to diverge over the stoss sides and converge into the lee sides. Convergence favors a thicker or more widespread water system, which can more efficiently decouple ice from the underlying till. Under such circumstances, till deformation does occur but, fluxes are relatively small. Till carried from the lee sides onto stoss sides of downstream bumps should couple to the ice more efficiently, increasing the ability for transport by till deformation. In turn, this suggests that steady-state till transport can be achieved if the stoss-side till layer is thin or discontinuous. In addition, the large basal shear stress generated in the highlands seems too high for a bed lubricated by a continuous although thin deforming till, suggesting till discontinuity, which would allow debris-laden ice to erode bedrock on stoss sides, supplying additional till for transport.

The geoPebble system is a network of wirelessly interconnected seismic and GPS sensor nodes with geophysical sensing capabilities for the study of ice sheets in Antarctica and Greenland, as well as mountain glaciers. We describe our design methodology, which has enabled us to develop these state-of-the art units using commercial-off-the-shelf hardware combined with custom-designed hardware and software. Each geoPebble node is a self-contained, wirelessly connected sensor for collecting seismic activity and position information. Each node is built around a three-component seismic recorder, which includes an amplifier, filter, and 24-bit analog-to-digital converter that can sample incoming seismic signals up to 10 kHz. The timing for each node is available from GPS measurements and a local precision oscillator that is conditioned by the GPS timing pulses. In addition, we record the carrier-phase measurement of the L1 GPS signal in order to determine location at sub-decimeter accuracy (relative to other geoPebble nodes within a radius of a few kilometers). Each geoPebble includes 32 GB of solid-state storage, wireless communications capability to a central supervisory unit, and auxiliary measurements capability (including tilt from accelerometers, absolute orientation from magnetometers, and temperature). The geoPebble system has been successfully validated in the field in Antarctica and Greenland.

We describe methods for measuring crystal orientation fabric with sonic waves in an ice core borehole, with special attention paid to vertical-girdle fabrics that are prevalent at the WAIS Divide. The speed of vertically propagating compressional waves in ice is influenced by vertical clustering of the ice crystal c-axes. Shear-wave speeds – particularly the speed separation between fast and slow shear polarizations – are sensitive to azimuthal anisotropy. Sonic data from the WAIS Divide complement thin-section measurements of fabric. Thin sections show a steady transition to strong girdle fabrics in the upper 2000 m of ice, followed by a transition to vertical-pole fabrics below 2500 m depth. Compressional-wave sonic data are inconclusive in the upper ice, due to noise, as well as the method's inherent insensitivity to girdle fabrics. Compared with available thin sections, sonic data provide better resolution of the transition to pole fabrics below 2500 m, notably including an abrupt increase in vertical clustering near 3000 m. Our compressional-wave measurements resolve fabric changes occurring over depth ranges of a few meters that cannot be inferred from available thin sections, but are sensitive only to zenithal anisotropy. Future logging tools should be designed to measure shear waves in addition to compressional waves, especially for logging in regions where ice flow patterns favor the development of girdle fabrics.