Estimates of the burden of human rabies deaths and animal bites in India, 2022-23: a community-based cross-sectional survey and probability decision-tree modelling study.

BACKGROUND: Reliable and recent data of human rabies deaths and animal bites are not available in India, where a third of global cases occur. Since there is a global target of eliminating dog-mediated human rabies by 2030, understanding whether the country is on track is essential. We aimed to estimate the animal-bite burden and the number of human rabies deaths in India. METHODS: We conducted a community-based nationwide cross-sectional survey with a multistage cluster-sampling design from March 2, 2022 to Aug 26, 2023, covering 60 districts in 15 Indian states. The head of the household or an adult family member was interviewed to collect information about animal-bite history in family members, receipt of anti-rabies vaccination (ARV), and death following animal bite in the family. Annual animal-bite incidence along with 95% CIs were estimated after applying the sampling weights and adjusting for clustering. We estimated annual human rabies deaths using a decision-tree probability model with parameters from the community survey and laboratory data on rabies positivity among suspected rabid dogs. FINDINGS: Of the 337 808 individuals residing in the 78 807 households surveyed, 2052 gave a history of animal bite, mostly (1576 [76·8%]) due to dogs in the past 1 year. The weighted and adjusted annual incidence of animal bite was 6·6 (95% CI 5·7-7·6) per 1000 population, translating into 9·1 million bites nationally. Annual dog-bite incidence was 5·6 (4·8-6·6) per 1000. Among people who had been bitten by a dog, 323 (20·5%) did not receive ARV, and 1043 (66·2%) received at least three doses. Nearly half (615 [49·1%]) of the 1253 individuals who received one dose did not complete their full course of vaccination. We estimated 5726 (95% uncertainty interval 3967-7350) human rabies deaths occurring annually in India. INTERPRETATION: Although there was a substantial decline in human rabies deaths over the past two decades, to eliminate dog-mediated human rabies by 2030, India needs to fast-track its actions by adopting a focused one-health approach. Integrating human and animal surveillance, ensuring timely administration of full course of post-exposure prophylaxis, and accelerating dog vaccination across the country are crucial steps towards this goal. FUNDING: Indian Council of Medical Research.

Lessons Learned From a Peer-Supported Differentiated Care and Nutritional Supplementation for People With TB in a Southern Indian State.

Two critical components of patient support systems for people with TB are regular counseling and locally managed nutritional support. As part of an ongoing differentiated TB care initiative called Tamil Nadu Kasanoi Erappila Thittam (meaning TB death-free initiative in Tamil, TN-KET) to reduce TB deaths, adults with TB with very severe undernutrition, respiratory insufficiency, or poor performance status are identified at diagnosis (triage-positive) and prioritized for referral, comprehensive clinical assessment, and inpatient care. Between January and June 2023, in 6 districts, a pilot exercise was conducted in which trained TB survivors, known as TB champions, provided baseline counseling and additional counseling (if required) to triage-positive people with TB at diagnosis. Additionally, people with TB with severe undernutrition were prioritized for nutritional supplementation for at least 3 months. Among 652 people with TB who were triage-positive at diagnosis, the program staff shared details of 145 (22%), and all were counseled by TB champions (baseline counseling). Program staff identified 74 (11%) triage-positive people with TB who required additional counseling (i.e., those refusing referral or admission or continued admission), and 71 (96%) were counseled by TB champions. Among these, 54 (76%) were admitted or readmitted and successfully discharged. In addition, among 1,042 people with TB with severe undernutrition, program staff shared details of 390 (38%), of which 60% received nutritional supplementation through the efforts of TB champions. We conclude that TB champions were able to provide quality and timely peer support through direct counseling and by mobilizing local resources for nutritional support. The engagement of TB champions can be further strengthened by establishing robust coordination mechanisms with the TB program. Lessons from this pilot will contribute to the Tamil Nadu State TB Cell's plans to expand the role of TB champions and enhance community participation to end TB in India.

Ni-kshay Poshan Yojana: receipt and utilization among persons with TB notified under the National TB Elimination Program in India, 2022.

BACKGROUND: Ni-kshay Poshan Yojana (NPY), a direct benefit transfer scheme under the National Tuberculosis Elimination Program (NTEP) in India, provides a monthly benefit of INR500 for nutritional support of persons with TB (PwTB). OBJECTIVES: To determine the proportion of PwTB receiving atleast one NPY instalment and pattern of utilisation; to ascertain factors associated with NPY non-receipt and association of NPY receipt with TB treatment outcome. METHODS: In our cross-sectional study, we used multi-stage sampling to select PwTB whose treatment outcome was declared between May 2022 and February 2023. A cluster-adjusted, generalized linear model was used to identify factors associated with the non-receipt of NPY and determine association between NPY receipt and TB treatment outcome. RESULTS: Among 3201 PwTB, 2888 (92.7%; 95% CI 89.8%, 94.8%) had received at least one NPY instalment, and 1903 (64.2%; 95% CI 58.9%, 69.2%) self-reported receipt of benefit. The median (IQR) time to receipt of first instalment was 105 (60,174) days. Non-receipt was significantly higher among PwTB from states with low TB score (aPR = 2.34; 95%CI 1.51, 3.62), who do not have bank account (aPR = 2.48; 95%CI 1.93, 3.19) and with unknown/missing diabetic status (aPR = 1.69; 95%CI 1.11, 2.55). Unfavorable treatment outcomes were associated with non-receipt of NPY (aPR 4.93; 95%CI 3.61,6.75) after adjusting for potential confounders. CONCLUSION: Majority of the PwTB received atleast one NPY instalment, but they experience significant delays. Most of the recipients utilised NPY for nutrition. Longitudinal follow-up studies are required to study the impact of NPY on treatment outcomes.

Main findings: Five years since implementation, almost ninety percent of persons with tuberculosis in India had received at least one benefit under Ni-kshay Poshan Yojana, most of whom utilise it for nutrition.Added knowledge: Persons with tuberculosis in India experience a median delay of over three months to receive the first instalment of the benefit.Global health impact for policy and action: Ensuring timely credit of benefits is crucial to enable its utilisation by persons with tuberculosis for better nutrition and favourable treatment outcomes.

Molecular Endotypes of Idiopathic Pulmonary Fibrosis: A Latent Class Analysis of Two Multicenter Observational Cohorts.

Rationale: Idiopathic pulmonary fibrosis (IPF) causes irreversible fibrosis of the lung parenchyma. Although antifibrotic therapy can slow IPF progression, treatment response is variable. There exists a critical need to develop a precision medicine approach to IPF. Objectives: To identify and validate biologically driven molecular endotypes of IPF. Methods: Latent class analysis (LCA) was independently performed in prospectively recruited discovery (n = 875) and validation (n = 347) cohorts. Twenty-five plasma biomarkers associated with fibrogenesis served as class-defining variables. The association between molecular endotype and 4-year transplant-free survival was tested using multivariable Cox regression adjusted for baseline confounders. Endotype-dependent differential treatment response to future antifibrotic exposure was then assessed in a pooled cohort of patients naive to antifibrotic therapy at the time of biomarker measurement (n = 555). Measurements and Main Results: LCA independently identified two latent classes in both cohorts (P < 0.0001). WFDC2 (WAP four-disulfide core domain protein 2) was the most important determinant of class membership across cohorts. Membership in class 2 was characterized by higher biomarker concentrations and a higher risk of death or transplant (discovery, hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.64-2.48; P < 0.001; validation, HR, 1.95; 95% CI, 1.34-2.82; P < 0.001). In pooled analysis, significant heterogeneity in treatment effect was observed between endotypes (P = 0.030 for interaction), with a favorable antifibrotic response in class 2 (HR, 0.64; 95% CI, 0.45-0.93; P = 0.018) but not in class 1 (HR, 1.19; 95% CI, 0.77-1.84; P = 0.422). Conclusions: In this multicohort study, we identified two novel molecular endotypes of IPF with divergent clinical outcomes and responses to antifibrotic therapy. Pending further validation, these endotypes could enable a precision medicine approach for future IPF clinical trials.

Need for operational simplicity and timely disbursal of benefits-a qualitative exploration of the implementation of a direct benefit transfer scheme for persons with tuberculosis in India.

BACKGROUND: Ni-kshay Poshan Yojana (NPY) is a direct benefit transfer scheme of the Government of India introduced in 2018 to support the additional nutritional requirements of persons with TB (PwTB). Our recent nationwide evaluation of implementation and utilization of NPY using programmatic data of PwTB from nine randomly selected Indian states, reported a 70% coverage and high median delay in benefit credit. We undertook a qualitative study between January and July 2023, to understand the detailed implementation process of NPY and explore the enablers and barriers to effective implementation and utilization of the NPY scheme. METHODS: We followed a grounded theory approach to inductively develop theoretical explanations for social phenomena through data generated from multiple sources. We conducted 36 in-depth interviews of national, district and field-level staff of the National Tuberculosis Elimination Programme (NTEP) and NPY beneficiaries from 30 districts across nine states of India, selected using theoretical sampling. An analytical framework developed through inductive coding of a set of six interviews, guided the coding of the subsequent interviews. Categories and themes emerged through constant comparison and the data collection continued until theoretical saturation. RESULTS: Stakeholders perceived NPY as a beneficial initiative. Strong political commitment from the state administration, mainstreaming of NTEP work with the district public healthcare delivery system, availability of good geographic and internet connectivity and state-specific grievance redressal mechanisms and innovations were identified as enablers of implementation. However, the complex, multi-level benefit approval process, difficulties in accessing banking services, perceived inadequacy of benefits and overworked human resources in the NTEP were identified as barriers to implementation and utilization. CONCLUSION: The optimal utilization of NPY is enabled by strong political commitment and challenged by its lengthy implementation process and delayed disbursal of benefits. We recommend greater operational simplicity in NPY implementation, integrating NTEP activities with the public health system to reduce the burden on the program staff, and revising the benefit amount more equitably.

Gold-Catalyzed Arylative Cope Rearrangement.

Cope rearrangements have garnered significant attention owing to their ability to undergo structural reorganization in stereoselective manner. While substantial advances have been achieved over decades, these rearrangements remained applicable exclusively to parent 1,5-hexadienes. Herein, we disclose the gold-catalyzed arylative Cope rearrangement of 1,6-heptadienes via a cyclization-induced [3,3]-rearrangement employing ligand-enabled gold redox catalysis. Detailed mechanistic investigations including several control experiments, cross-over experiment, HRMS analysis, 31P NMR and DFT studies have been performed to underpin the mechanism.

Post-campaign coverage evaluation of a measles and rubella supplementary immunization activity in five districts in India, 2019-2020.

BACKGROUND: In alignment with the Measles and Rubella (MR) Strategic Elimination plan, India conducted a mass measles and rubella vaccination campaign across the country between 2017 and 2020 to provide a dose of MR containing vaccine to all children aged 9 months to 15 years. We estimated campaign vaccination coverage in five districts in India and assessed campaign awareness and factors associated with vaccination during the campaign to better understand reasons for not receiving the dose. METHODS AND FINDINGS: Community-based cross-sectional serosurveys were conducted in five districts of India among children aged 9 months to 15 years after the vaccination campaign. Campaign coverage was estimated based on home-based immunization record or caregiver recall. Campaign coverage was stratified by child- and household-level risk factors and descriptive analyses were performed to assess reasons for not receiving the campaign dose. Three thousand three hundred and fifty-seven children aged 9 months to 15 years at the time of the campaign were enrolled. Campaign coverage among children aged 9 months to 5 years documented or by recall ranged from 74.2% in Kanpur Nagar District to 90.4% in Dibrugarh District, Assam. Similar coverage was observed for older children. Caregiver awareness of the campaign varied from 88.3% in Hoshiarpur District, Punjab to 97.6% in Dibrugarh District, Assam, although 8% of children whose caregivers were aware of the campaign were not vaccinated during the campaign. Failure to receive the campaign dose was associated with urban settings, low maternal education, and lack of school attendance although the associations varied by district. CONCLUSION: Awareness of the MR vaccination campaign was high; however, campaign coverage varied by district and did not reach the elimination target of 95% coverage in any of the districts studied. Areas with lower coverage among younger children must be prioritized by strengthening the routine immunization programme and implementing strategies to identify and reach under-vaccinated children.

Direct benefit transfer for nutritional support of patients with TB in India-analysis of national TB program data of 3.7 million patients, 2018-2022.

BACKGROUND: Patients with TB have additional nutritional requirements and thus additional costs to the household. Ni-kshay Poshan Yojana(NPY) is a Direct Benefit Transfer (DBT) scheme under the National Tuberculosis Elimination Programme(NTEP) in India which offers INR 500 monthly to all notified patients with TB for nutritional support during the period of anti-TB treatment. Five years after its implementation, we conducted the first nationwide evaluation of NPY. METHODS: In our retrospective cohort study using programmatic data of patients notified with TB in nine randomly selected Indian states between 2018 and 2022, we estimated the proportion of patients who received at least one NPY instalment and the median time to receive the first instalment. We determined the factors associated (i) with non-receipt of NPY using a generalised linear model with Poisson family and log link and (ii) with time taken to receive first NPY benefit in 2022 using quantile regression at 50th percentile. RESULTS: Overall, 3,712,551 patients were notified between 2018 and 2022. During this period, the proportion who received at least one NPY instalment had increased from 56.9% to 76.1%. Non-receipt was significantly higher among patients notified by private sector (aRR 2.10;2.08,2.12), reactive for HIV (aRR 1.69;1.64,1.74) and with missing/undetermined diabetic status (aRR 2.02;1.98,2.05). The median(IQR) time to receive the first instalment had reduced from 200(109,331) days in 2018 to 91(51,149) days in 2022. Patients from private sector(106.9;106.3,107.4days), those with HIV-reactive (103.7;101.8,105.7days), DRTB(104.6;102.6,106.7days) and missing/undetermined diabetic status (115.3;114,116.6days) experienced longer delays. CONCLUSIONS: The coverage of NPY among patients with TB had increased and the time to receipt of benefit had halved in the past five years. Three-fourths of the patients received at least one NPY instalment, more than half of whom had waited over three months to receive the first instalment. NTEP has to focus on timely transfer of benefits to enable patients to meet their additional nutritional demands, experience treatment success and avoid catastrophic expenditure.

Genetic assessment of captive breeding program of Indian Pangolin: implications for conservation and management.

BACKGROUND: Captive breeding programs play a vital role in conservation of threatened species, necessitating an understanding of genetic diversity among captive individuals to ensure long-term genetic viability, appropriate mate selection, and successful reintroduction to native habitats. METHODS AND RESULTS: We did not observe any recent genetic bottleneck, and population showed moderate genetic diversity. The estimated effective population size, representing individuals capable of contributing genetically to future generations, was estimated as 18.6 individuals (11.4-35.1 at 95% CI). Based on the genetic make-up and allelic diversity, we found seventeen pangolins (11 females and 6 males) were genetically unrelated and relatively more potent than others. CONCLUSION: In this study, we evaluated the captive breeding program of the Indian pangolin population at the Pangolin Conservation Breeding Centre in Nandankanan Zoological Park, Bhubaneswar, Odisha. We highlight the significance of genetic monitoring within the captive population of Indian pangolin for preserving genetic diversity and ensuring the long-term survival of the species. We established the genetic profiles of all 29 pangolins and identified 17 pangolins to be prioritized for enhanced breeding and future zoo exchange programs. We appreciate the zoo authorities for promoting genetic assessment of pangolin for better and more effective monitoring of the captive breeding of the endangered Indian pangolin.

Biomimetic Helical Hydrogen Bonded Organic Framework Membranes for Efficient Uranium Recovery from Seawater.

Inspired by the uranyl-imidazole interactions via nitrogen's (N's) of histidine residues in single helical protein assemblies with open framework geometry that allows through migration/coordination of metal ions. Here, preliminary components of a stable hydrogen-bonded organic framework (HOF) are designed to mimic the stable single helical open framework with imidazole residues available for Uranium (U) binding. The imidazolate-HOF (CSMCRIHOF2-S) is synthesized with solvent-directed H-bonding in 1D array and tuned hydrophobic CH-π interactions leading to single helix pattern having enhanced hydrolytic stability. De-solvation led CSMCRIHOF2-P with porous helical 1D channels are transformed in a freestanding thin film that showcased improved mass transfer and adsorption of uranyl carbonate. CSMCRIHOF2-P thin film can effectively extract ≈14.8 mg g-1 in 4 weeks period from natural seawater, with > 1.7 U/V (Uranium to Vanadium ratio) selectivity. This strategy can be extended for rational designing of hydrolytically stable, U selective HOFs to realize the massive potential of the blue economy toward sustainable energy.

Development and validation of a CT-based deep learning algorithm to augment non-invasive diagnosis of idiopathic pulmonary fibrosis.

RATIONALE: Non-invasive diagnosis of idiopathic pulmonary fibrosis (IPF) involves identification of usual interstitial pneumonia (UIP) pattern by computed tomography (CT) and exclusion of other known etiologies of interstitial lung disease (ILD). However, uncertainty in identification of radiologic UIP pattern leads to the continued need for invasive surgical biopsy. We thus developed and validated a machine learning algorithm using CT scans alone to augment non-invasive diagnosis of IPF. METHODS: The primary algorithm was a deep learning convolutional neural network (CNN) with model inputs of CT images only. The algorithm was trained to predict IPF among cases of ILD, with reference standard of multidisciplinary discussion (MDD) consensus diagnosis. The algorithm was trained using a multi-center dataset of more than 2000 cases of ILD. A US-based multi-site cohort (n = 295) was used for algorithm tuning, and external validation was performed with a separate dataset (n = 295) from European and South American sources. RESULTS: In the tuning set, the model achieved an area under the receiver operating characteristic curve (AUC) of 0.87 (CI: 0.83-0.92) in differentiating IPF from other ILDs. Sensitivity and specificity were 0.67 (0.57-0.76) and 0.90 (0.83-0.95), respectively. By contrast, pre-recorded assessment prior to MDD diagnosis had sensitivity of 0.31 (0.23-0.42) and specificity of 0.92 (0.87-0.95). In the external test set, c-statistic was also 0.87 (0.83-0.91). Model performance was consistent across a variety of CT scanner manufacturers and slice thickness. CONCLUSION: The presented deep learning algorithm demonstrated consistent performance in identifying IPF among cases of ILD using CT images alone and suggests generalization across CT manufacturers.

Protocol for establishing a model for integrated influenza surveillance in Tamil Nadu, India.

The potential for influenza viruses to cause public health emergencies is great. The World Health Organisation (WHO) in 2005 concluded that the world was unprepared to respond to an influenza pandemic. Available surveillance guidelines for pandemic influenza lack the specificity that would enable many countries to establish operational surveillance plans. A well-designed epidemiological and virological surveillance is required to strengthen a country's capacity for seasonal, novel, and pandemic influenza detection and prevention. Here, we describe the protocol to establish a novel mechanism for influenza and SARS-CoV-2 surveillance in the four identified districts of Tamil Nadu, India. This project will be carried out as an implementation research. Each district will identify one medical college and two primary health centres (PHCs) as sentinel sites for collecting severe acute respiratory infections (SARI) and influenza like illness (ILI) related information, respectively. For virological testing, 15 ILI and 10 SARI cases will be sampled and tested for influenza A, influenza B, and SARS-CoV-2 every week. Situation analysis using the WHO situation analysis tool will be done to identify the gaps and needs in the existing surveillance systems. Training for staff involved in disease surveillance will be given periodically. To enhance the reporting of ILI/SARI for sentinel surveillance, trained project staff will collect information from all ILI/SARI patients attending the sentinel sites using pre-tested tools. Using time, place, and person analysis, alerts for abnormal increases in cases will be generated and communicated to health authorities to initiate response activities. Advanced epidemiological analysis will be used to model influenza trends over time. Integrating virological and epidemiological surveillance data with advanced analysis and timely communication can enhance local preparedness for public health emergencies. Good quality surveillance data will facilitate an understanding outbreak severity and disease seasonality. Real-time data will help provide early warning signals for prevention and control of influenza and COVID-19 outbreaks. The implementation strategies found to be effective in this project can be scaled up to other parts of the country for replication and integration.

Palladium-Catalyzed Regiodivergent C-H Olefination of Imidazo[1,2a]pyridine Carboxamide and Unactivated Alkenes.

Despite remarkable successes in linear and branched vinyl (hetero) arene synthesis, regiodivergent C-H olefination with a single catalytic system has remained underdeveloped. Overcoming this limitation, a Pd/MPAA-catalyzed regiodivergent C-H olefination of imidazo[1,2a] pyridine carboxamides with unactivated terminal alkenes to generate branched and linear olefinated products depending upon the electronic nature of alkenes is reported herein. Moreover, this protocol can be applied for C-H deuteriation of the corresponding heteroarenes with D2 O as deuterium source. Preliminary experimental studies combined with computational investigations (DFT studies) suggest that regiodivergent olefination can be controlled by olefin insertion and ß-hydride elimination steps.

Quality of active case-finding for tuberculosis in India: a national level secondary data analysis.

BACKGROUND: India has been implementing active case-finding (ACF) for TB among marginalised and vulnerable (high-risk) populations since 2017. The effectiveness of ACF cycle(s) is dependent on the use of appropriate screening and diagnostic tools and meeting quality indicators. OBJECTIVES: To determine the number of ACF cycles implemented in 2021 at national, state (n = 36) and district (n = 768) level and quality indicators for the first ACF cycle. METHODS: In this descriptive study, aggregate TB program data for each ACF activity that was extracted was further aggregated against each ACF cycle at the district level in 2021. One ACF cycle was the period identified to cover all the high-risk populations in the district. Three TB ACF quality indicators were calculated: percentage population screened (≥10%), percentage tested among screened (≥4.8%) and percentage diagnosed among tested (≥5%). We also calculated the number needed to screen (NNS) for diagnosing one person with TB (≤1538). RESULTS: Of 768 TB districts, ACF data for 111 were not available. Of the remaining 657 districts, 642 (98%) implemented one, and 15 implemented two to three ACF cycles. None of the districts or states met all three TB ACF quality indicators' cut-offs. At the national level, for the first ACF cycle, 9.3% of the population were screened, 1% of the screened were tested and 3.7% of the tested were diagnosed. The NNS was 2824: acceptable (≤1538) in institutional facilities and poor for population-based groups. Data were not consistently available to calculate the percentage of i) high-risk population covered, ii) presumptive TB among screened and iii) tested among presumptive. CONCLUSION: In 2021, India implemented one ACF cycle with sub-optimal ACF quality indicators. Reducing the losses between screening and testing, improving data quality and sensitising stakeholders regarding the importance of meeting all ACF quality indicators are recommended.

Transgenic sugarcane with higher levels of BRK1 showed improved drought tolerance.

KEY MESSAGE: Transgenic sugarcane overexpressing BRK1 showed improved tolerance to drought stress through modulation of actin polymerization and formation of interlocking marginal lobes in epidermal leaf cells, a typical feature associated with BRK1 expression under drought stress. BRICK1 (BRK1) genes promote leaf epidermal cell morphogenesis and division in plants that involves local actin polymerization. Although the changes in actin filament organization during drought have been reported, the role of BRK in stress tolerance remains unknown. In our previous work, the drought-tolerant Erianthus arundinaceus exhibited high levels of the BRK gene expression under drought stress. Therefore, in the present study, the drought-responsive gene, BRK1 from Saccharum spontaneum, was transformed into sugarcane to test if it conferred drought tolerance in the commercial sugarcane cultivar Co 86032. The transgenic lines were subjected to drought stress, and analyzed using physiological parameters for drought stress. The drought-induced BRK1-overexpressing lines of sugarcane exhibited significantly higher transgene expression compared with the wild-type control and also showed improved physiological parameters. In addition, the formation of interlocking marginal lobes in the epidermal leaf cells, a typical feature associated with BRK1 expression, was observed in all transgenic BRK1 lines during drought stress. This is the first report to suggest that BRK1 plays a role in sugarcane acclimation to drought stress and may prove to be a potential candidate in genetic engineering of plants for enhanced biomass production under drought stress conditions.

Shedding Novel Photophysical Insights Toward Discriminative Detection of Three Toxic Heavy Metal Ions and a hazard class 1 nitro-explosive By Using a Simple AIEE Active Luminogen.

In this work, we introduced a simple aggregation-induced emission enhancement (AIEE) sensor (PHCS) which can selectively detect and discriminate three environmentally and biologically imperative heavy metal ions (Cu2+, Co2+ and Hg2+) and a hazard class 1 categorized nitro-explosive picric acid (PA) in differential media. By virtue of its weak fluorescence attributes in pure organic medium owing to the synergistic operation of multiple photophysical quenching mechanisms, the molecular probe showcased highly selective 'TURN ON' fluorogenic response towards hazardous Hg2+ with a limit of detection (LOD) as low as 97 nM. Comprehensive investigation of binding mechanism throws light on the cumulative effect of probe-metal complexation induced chelation enhanced fluorescence (CHEF) effect and subsequent AIEE activation within the formed probe-metal adducts. Noteworthily, the probe (PHCS) can be readily used in real water samples for the quantitative determination of Hg2+ in a wide concentration range. In addition, the probe displayed modest colorimetric recognition performances to selectively detect and discriminate two essential heavy metal ions (Cu2+ and Co2+) with a LOD of 96 nM and 65 nM for Cu2+ and Co2+ respectively, in semi-aqueous medium. Intriguingly, based on high photoluminescence efficiency, the AIEE active nano-aggregated PHCS displayed a remarkable propensity to be used as a selective and ultra-sensitive 'TURN-OFF' fluorogenic chemosensor towards PA with LOD of 34.4 ppb in aqueous medium. Finally, we specifically shed light on the interaction of PHCS hydrosol towards PA using some unprecedented techniques, which helped uncover new photophysical insights of probe-explosive molecule interaction. We shed light on novel photophysical insights toward unique multifunctional sensory aptitude of a simple aggregation-induced emission enhancement active organic functional molecule in differential media, enabling ultra-sensitive discriminative detection of toxic heavy metal ions and explosive molecule simultaneously.

Gold-Catalyzed 1,2-Dicarbofunctionalization of Alkynes with Organohalides.

Herein, we report the first gold-catalyzed 1,2-dicarbofunctionalization of alkynes using organohalides as non-prefunctionalized coupling partners. The mechanism of the reaction involves an oxidative addition/π-activation mechanism in contrast to the migratory insertion/cis-trans isomerization pathway that is predominantly observed with other transition metals yielding products with anti-selectivity. Mechanistic insights include several control experiments, NMR studies, HR-MSMS analyses, and DFT calculations that strongly support the proposed mechanism.

Estimating the attributable fraction of mortality from acute respiratory distress syndrome to inform enrichment in future randomised clinical trials.

BACKGROUND: Efficiency of randomised clinical trials of acute respiratory distress syndrome (ARDS) depends on the fraction of deaths attributable to ARDS (AFARDS) to which interventions are targeted. Estimates of AFARDS in subpopulations of ARDS could improve design of ARDS trials. METHODS: We performed a matched case-control study using the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE cohort. Primary outcome was intensive care unit mortality. We used nearest neighbour propensity score matching without replacement to match ARDS to non-ARDS populations. We derived two separate AFARDS estimates by matching patients with ARDS to patients with non-acute hypoxaemic respiratory failure (non-AHRF) and to patients with AHRF with unilateral infiltrates only (AHRF-UL). We also estimated AFARDS in subgroups based on severity of hypoxaemia, number of lung quadrants involved and hyperinflammatory versus hypoinflammatory phenotypes. Additionally, we derived AFAHRF estimates by matching patients with AHRF to non-AHRF controls, and AFAHRF-UL estimates by matching patients with AHRF-UL to non-AHRF controls. RESULTS: Estimated AFARDS was 20.9% (95% CI 10.5% to 31.4%) when compared with AHRF-UL controls and 38.0% (95% CI 34.4% to 41.6%) compared with non-AHRF controls. Within subgroups, estimates for AFARDS compared with AHRF-UL controls were highest in patients with severe hypoxaemia (41.1% (95% CI 25.2% to 57.1%)), in those with four quadrant involvement on chest radiography (28.9% (95% CI 13.4% to 44.3%)) and in the hyperinflammatory subphenotype (26.8% (95% CI 6.9% to 46.7%)). Estimated AFAHRF was 33.8% (95% CI 30.5% to 37.1%) compared with non-AHRF controls. Estimated AFAHRF-UL was 21.3% (95% CI 312.8% to 29.7%) compared with non-AHRF controls. CONCLUSIONS: Overall AFARDS mean values were between 20.9% and 38.0%, with higher AFARDS seen with severe hypoxaemia, four quadrant involvement on chest radiography and hyperinflammatory ARDS.

Coherent Dynamic Nuclear Polarization using Chirped Pulses.

This paper presents a study of coherent dynamic nuclear polarization (DNP) using frequency swept pulses at 94 GHz which optimize the polarization transfer efficiency. Accordingly, an enhancement ε ∼ 496 was observed using 10 mM trityl-OX063 as the polarizing agent in a standard 6:3:1 d8-glycerol/D2O/H2O glassing matrix at 70 K. At present, this is the largest DNP enhancement reported at this microwave frequency and temperature. Furthermore, the frequency swept pulses enhance the nuclear magnetic resonance (NMR) signal and reduce the recycle delay, accelerating the NMR signal acquisition.