Lamination of >21% Efficient Perovskite Solar Cells with Independent Process Control of Transport Layers and Interfaces.

Transport layer and interface optimization is critical for improving the performance and stability of perovskite solar cells (PSCs) but is restricted by the conventional fabrication approach of sequential layer deposition. While the bottom transport layer is processed with minimum constraints, the narrow thermal and chemical stability window of the halide perovskite (HP) layer severely restricts the choice of top transport layer and its processing conditions. To overcome these limitations, we demonstrate lamination of HPs─where two transport layer-perovskite half-stacks are independently processed and diffusion-bonded at the HP-HP interface─as an alternative fabrication strategy that enables self-encapsulated solar cells. Power conversion efficiencies (PCE) of >21% are realized using cells that incorporate a novel transport layer combination along with dual-interface passivation via self-assembled monolayers, both of which are uniquely enabled by the lamination approach. This is the highest reported PCE for any laminated PSC encapsulated between glass substrates. We further show that this approach expands the processing window beyond traditional fabrication processes and is adaptable for different transport layer compositions. The laminated PSCs retained >75% of their initial PCE after 1000 h of 1-sun illumination at 40 °C in air using an all-inorganic transport layer configuration without additional encapsulation. Furthermore, a laminated 1 cm2 device maintained a Voc of 1.16 V. The scalable lamination strategy in this study enables the implementation of new transport layers and interfacial engineering approaches for improving performance and stability.

Seroepidemological investigation of Toxoplasma gondii and Trichinella spp. in pigs reared by tribal communities and small-holder livestock farmers in Northeastern India.

Toxoplasma gondii and Trichinella spp. are critical tissue-dwelling foodborne zoonotic parasites associated with pork consumption and pig rearing. Despite being a major pig-rearing region in the country, Northeastern India has not undergone any investigation regarding the presence of T. gondii and Trichinella spp. in pigs. Therefore, this study aims to determine the seroprevalence of T. gondii and Trichinella spp. and identify associated risk factors in pigs reared by tribal communities and small-holder livestock farmers in the northeastern region of India. In a cross-sectional serological survey, 400 pigs from 400 households across five northeastern states of India underwent testing for the seroprevalence of porcine toxoplasmosis and trichinellosis. Serum samples (80 from each state) were analyzed using commercially available ELISA assays. Data on backyard farm characteristics and various management aspects were collected, and risk factors linked with prevalence were analyzed through univariate and multivariate logistic regression analysis. The findings revealed that the apparent and true prevalence of anti-T. gondii antibodies were 45% (40.12-49.88, 95% CI) and 45.7% (40.7-50.69, 95% CI), respectively. As for anti- Trichinella antibodies, both the apparent and true prevalence were 0.75% (-0.1-1.6, 95% CI). The univariate and multivariate analyses indicated that age above 24 months (OR 7.20, 95% CI 2.45-23.71), exposure to cats (OR = 5.87, 95% CI 2.55-14.05), and farms operating for breeding purposes (OR = 5.60, 95% CI 3.01-11.04) were significant risk factors associated with the seroprevalence of T. gondii. This study marks the initial documentation of the seroprevalence of T. gondii and Trichinella spp. in pigs reared by tribal communities in Northeastern India. The results emphasize the significance of these parasites as foodborne zoonotic threats in the region, potentially posing substantial public health risks, especially within tribal and rural communities. The insights derived from this research could be valuable in formulating targeted preventive and control strategies against T. gondii and Trichinella spp. in pigs, not only in this region but also in areas with similar rearing practices.

Disinfection Efficacy of Laser Activation on Different Forms and Concentrations of Sodium Hypochlorite Root Canal Irrigant against Enterococcus faecalis in Primary Teeth.

Photoactivated disinfection with sodium hypochlorite (NaOCl) has improved primary root canal treatment outcomes. This in vitro study aims to assess and compare the disinfecting efficacy of 2.5% sodium hypochlorite solution and 5.25% sodium hypochlorite gel, without laser activation and accompanied by laser activation, on Enterococcus faecalis-contaminated primary teeth root canals. After one month of incubating extracted teeth specimens with E. faecalis, 36 specimens were randomly divided into two groups: Group A (conventional method without laser-activated irrigation) and Group B (with laser-activated irrigation). Each group was further divided into three subgroups, with six samples in each subgroup. Subgroup 1 received irrigation with normal saline, Subgroup 2 with 2.5% sodium hypochlorite solution, and Subgroup 3 with 5.25% sodium hypochlorite gel. Diode laser activation at 810 nm was used in Group B. Bacterial colony counts were measured before and after the intervention. Student's t-test and one-way analysis of variance (ANOVA) with Tukey's post hoc test were used for statistical analysis. The significance level was set at p < 0.05. Microbial analysis revealed no bacterial growth in samples irrigated with 5.25% sodium hypochlorite gel activated with the laser. Activation with the laser significantly (p = 0.02) improved the disinfection ability of the irrigant compared to the non-activation group. The disinfection ability of sodium hypochlorite gel was better than that of saline (p = 0.02); however, it was comparable to that of sodium hypochlorite solution (p = 0.67). Conclusion: Root canal irrigation with 5.25% sodium hypochlorite gel activated with an 810 nm diode laser resulted in complete eradication of Enterococcus faecalis, indicating its effectiveness as an endodontic disinfection treatment modality.

Novel helix loop-mediated isothermal amplification (HAMP) assay for colorimetric detection of Staphylococcus aureus in milk.

Staphylococcus aureus is an important and leading cause of foodborne diseases worldwide. Prompt detection and recall of contaminated foods are crucial to prevent untoward health consequences caused by S. aureus. Helix loop-mediated isothermal amplification (HAMP) is an exciting recent addition to the array of available isothermal-based nucleic acid amplification techniques. This study aimed to develop and evaluate a HAMP assay for detecting S. aureus in milk and milk products. The assay is completed in 75 minutes of isothermal temperature incubation (64 ˚C) and dye-based visual interpretation of results based on colour change. The specificity of the developed assay was ascertained using 27 S. aureus and 17 non S. aureus bacterial strains. The analytical sensitivity of the developed HAMP assay was 9.7 fg/µL of pure S. aureus DNA. The detection limit of the HAMP assay in milk (86 CFU/mL) was 1000x greater than the routinely used endpoint PCR (86 × 103 CFU/mL). The practicality of applying the HAMP assay was also assessed by analysing milk and milk product samples (n = 95) obtained from different dairy farms and retail outlets. The developed test is a more rapid, sensitive, and user-friendly method for the high-throughput screening of S. aureus in food samples and may therefore be suitable for field laboratories. To our knowledge, this is the first study to develop and evaluate the HAMP platform for detecting S. aureus.

Biofilm-forming antimicrobial-resistant pathogenic Escherichia coli: A one health challenge in Northeast India.

This study aimed to investigate the prevalence of Shiga toxin-producing Escherichia coli (STEC), Enteropathogenic E. coli (EPEC), and Enterotoxigenic E. coli (ETEC) in common food animals (cattle, goats, and pigs) reared by tribal communities and smallholder farmers in Northeast India. The isolates were characterized for the presence of virulence genes, extended-spectrum beta-lactamases (ESBL) production, antimicrobial resistance, and biofilm production, and the results were statistically interpreted. In pathotyping 141 E. coli isolates, 10 (7.09%, 95% CI: 3.45%-12.66%) were identified as STEC, 2 (1.42%, 95% CI: 0.17%-5.03%) as atypical-EPEC, and 1 (0.71%, 95% CI: 0.02%-3.89%) as typical-EPEC. None of the isolates were classified as ETEC. Additionally, using the phenotypic combination disc method (ceftazidime with and without clavulanic acid), six isolates (46.1%, 95% CI: 19.22%-74.87%) were determined to be ESBL producers. Among the STEC/EPEC strains, eleven (84.6%, 95% CI: 54.55%-98.08%) and one (7.7%, 95% CI: 0.19%-36.03%) strains were capable of producing strong or moderate biofilms, respectively. PFGE analysis revealed indistinguishable patterns for certain isolates, suggesting clonal relationships. These findings highlight the potential role of food animals reared by tribal communities and smallholder farmers as reservoirs of virulent biofilm-forming E. coli pathotypes, with implications for food contamination and zoonotic infections. Therefore, monitoring these pathogens in food animals is crucial for optimizing public health through one health strategy.

First Seroepidemiological Investigation of Hepatitis E Virus Infection in Backyard Pigs from Northeastern India: Prevalence and Associated Risk Factors.

Hepatitis E virus (HEV) is the leading cause of acute viral hepatitis globally, with zoonotic potential, and pigs are considered the major reservoir. To determine the seroprevalence of HEV infection in pigs reared in backyard conditions in the northeastern region of India, blood samples were collected from 400 pigs from five northeastern states (80 samples from each state) and tested for IgG antibodies against HEV using an ELISA assay. Questionnaires on farm characteristics and management practices were completed, and risk factors associated with HEV were studied using univariate and multivariate analysis. The apparent seroprevalence of HEV infection was 51% (46.1-55.9, 95% CI), with a true prevalence of 52.98% (47.22-58.75, 95% CI). The risk factors significantly associated with higher HEV seropositivity were as follows: lack of disinfection (OR 4.65), feeding swill (restaurant and bakery waste) (OR 2.55), failure to follow the all-in-all-out production system (OR 3.47), and medium holding size (OR 9.83), which refers to mixed rearing of younger and older age groups. This study demonstrates that HEV is widespread among pigs reared in northeastern India. The risk factor analysis conducted in this study provides valuable insights into the prevalence of HEV in the region.

Establishment of ex vivo calibration curve for X-ray induced "dicentric + ring" and micronuclei in human peripheral lymphocytes for biodosimetry during radiological emergencies, and validation with dose blinded samples.

In the modern developing society, application of radiation has increased extensively. With significant improvement in the radiation protection practices, exposure to human could be minimized substantially, but cannot be avoided completely. Assessment of exposure is essential for regulatory decision and medical management as applicable. Until now, cytogenetic changes have served as surrogate marker of radiation exposure and have been extensively employed for biological dose estimation of various planned and unplanned exposures. Dicentric Chromosomal Aberration (DCA) is radiation specific and is considered as gold standard, micronucleus is not very specific to radiation and is considered as an alternative method for biodosimetry. In this study dose response curves were generated for X-ray induced "dicentric + ring" and micronuclei, in lymphocytes of three healthy volunteers [2 females (age 22, 23 years) and 1 male (24 year)]. The blood samples were irradiated with X-ray using LINAC (energy 6 MV, dose rate 6 Gy/min), in the dose range of 0-5Gy. Irradiated blood samples were cultured and processed to harvest metaphases, as per standard procedures recommended by International Atomic Energy Agency. Pooled data obtained from all the three volunteers, were in agreement with Poisson distribution for "dicentric + ring", however over dispersion was observed for micronuclei. Data ("dicentric + ring" and micronuclei) were fitted by linear quadratic model of the expression Y[bond, double bond]C + αD + ßD2 using Dose Estimate software, version 5.2. The data fit has resulted in linear coefficient α = 0.0006 (±0.0068) "dicentric + ring" cell-1 Gy-1 and quadratic coefficient ß = 0.0619 (±0.0043) "dicentric + ring" cell-1 Gy-2 for "dicentric + ring" and linear coefficient α = 0.0459 ± (0.0038) micronuclei cell-1 Gy-1 and quadratic coefficient ß = 0.0185 ± (0.0010) micronuclei cell-1 Gy-2 for micronuclei, respectively. Background frequencies for "dicentric + ring" and micronuclei were 0.0006 ± 0.0004 and 0.0077 ± 0.0012 cell-1, respectively. Established curves were validated, by reconstructing the doses of 8 dose blinded samples (4 by DCA and 4 by CBMN) using coefficients generated here. Estimated doses were within the variation of 0.9-16% for "dicentric + ring" and 21.7-31.2% for micronuclei respectively. These established curves have potential to be employed for biodosimetry of occupational, clinical and accidental exposures, for initial triage and medical management.

COVID-19 prediction based on hybrid Inception V3 with VGG16 using chest X-ray images.

The Corona Virus was first started in the Wuhan city, China in December of 2019. It belongs to the Coronaviridae family, which can infect both animals and humans. The diagnosis of coronavirus disease-2019 (COVID-19) is typically detected by Serology, Genetic Real-Time reverse transcription-Polymerase Chain Reaction (RT-PCR), and Antigen testing. These testing methods have limitations like limited sensitivity, high cost, and long turn-around time. It is necessary to develop an automatic detection system for COVID-19 prediction. Chest X-ray is a lower-cost process in comparison to chest Computed tomography (CT). Deep learning is the best fruitful technique of machine learning, which provides useful investigation for learning and screening a large amount of chest X-ray images with COVID-19 and normal. There are many deep learning methods for prediction, but these methods have a few limitations like overfitting, misclassification, and false predictions for poor-quality chest X-rays. In order to overcome these limitations, the novel hybrid model called "Inception V3 with VGG16 (Visual Geometry Group)" is proposed for the prediction of COVID-19 using chest X-rays. It is a combination of two deep learning models, Inception V3 and VGG16 (IV3-VGG). To build the hybrid model, collected 243 images from the COVID-19 Radiography Database. Out of 243 X-rays, 121 are COVID-19 positive and 122 are normal images. The hybrid model is divided into two modules namely pre-processing and the IV3-VGG. In the dataset, some of the images with different sizes and different color intensities are identified and pre-processed. The second module i.e., IV3-VGG consists of four blocks. The first block is considered for VGG-16 and blocks 2 and 3 are considered for Inception V3 networks and final block 4 consists of four layers namely Avg pooling, dropout, fully connected, and Softmax layers. The experimental results show that the IV3-VGG model achieves the highest accuracy of 98% compared to the existing five prominent deep learning models such as Inception V3, VGG16, ResNet50, DenseNet121, and MobileNet.

Ocular surface staining: Current concepts and techniques.

The health of the ocular surface is vital for clear vision and comfort. Various factors can adversely influence the ocular surface and tear film homeostasis, and these include procedures like cataract and corneal refractive surgery. It is, therefore, important to assess the integrity of the ocular surface in a rapid, predictable, and consistent manner in the clinic. Various tests and devices have been described, and while these are useful, this article highlights the importance of using fluorescein staining of the ocular surface in detecting changes. This is a simple, inexpensive, rapidly performed test that is available in most eye clinics. However, a proper technique of dye instillation and assessment is important to recognize the changes that can occur. Once detected, these changes can be quantified, and the location and patterns can be used to diagnose the diseases that are present; these changes can also be used to monitor treatment outcomes and disease progression. The article discusses the technique, assessment, and interpretation of fluorescein staining of the ocular surface, along with the role of the two other vital dyes - rose bengal and lissamine green.

Pest scenario of Helicoverpa armigera (Hub.) on pigeonpea during future climate change periods under RCP based projections in India.

Gram pod borer, Helicoverpa armigera (Hub.) is the major insect pest of pigeonpea and prediction of number of generations (no. of gen.) and generation time (gen. time) using growing degree days (GDD) approach during three future climate change periods viz., Near (NP), Distant (DP) and Far Distant (FDP) periods at eleven major pigeonpea growing locations of India was attempted. Multi-model ensemble of Maximum (Tmax) and Minimum (Tmin) temperature data of four Representative Concentration Pathways viz., RCP 2.6, 4.5, 6.0 and 8.5 of Coupled Model Inter comparison Project 5 (CMIP5) models was adopted here. The increase in projected Tmax and Tmin are significant during 3 climate change periods (CCPs) viz., the NP, DP and FDP over base line (BL) period under four RCP scenarios at all locations and would be higher (4.7-5.1 °C) in RCP 8.5 and in FDP. More number of annual (10-17) and seasonal (5-8) gens. are expected to occur with greater percent increase in FDP (8 to 38%) over base line followed by DP (7 to 22%) and NP (5to 10%) periods with shortened annual gen. time (4 to 27%) across 4 RCPs. The reduction of crop duration was substantial in short, medium and long duration pigeonpeas at all locations across 4 RCPs and 3 CCPs. The seasonal no.of gen. is expected to increase (5 to 35%) with shortened gen. time (4 to 26%) even with reduced crop duration across DP and FDP climate periods of 6.0 and 8.5 RCPs in LD pigeonpea. More no. of gen. of H. armigera with reduced gen. time are expected to occur at Ludhiana, Coimbatore, Mohanpur, Warangal and Akola locations over BL period in 4 RCPs when normal duration of pigeonpeas is considered. Geographical location (66 to 72%), climate period (11 to 19%), RCPs (5-7%) and their interaction (0.04-1%) is vital and together explained more than 90% of the total variation in future pest scenario. The findings indicate that the incidence of H. armigera would be higher on pigeonpea during ensuing CCPs in India under global warming context.

Development of a novel visual isothermal amplification assay for rapid detection of Brucella spp.

Brucellosis is an economically important livestock disease worldwide besides having a noteworthy impact on human health. In this study, a rapid, simple, and ultra-sensitive nuclei-acid diagnostic technique was developed for the detection of brucellosis harnessing saltatory rolling circle amplification (SRCA). The diagnostic method was developed using World Organization for Animal Health (WOAH) approved primers targeting the bcsp31 gene of the Brucella genome. The assay can be accomplished within 90 min at a temperature of 65 °C without the requirement of sophisticated instrumentation. The result interpretation can be done with the naked eye with the aid of SYBR green dye. The developed technique displayed 100% specificity by amplifying only 10 reference and field strains of Brucella spp. and there was no cross-reactivity with the other tested pathogens. The lower limit of detections of SRCA and end-point PCR assays were 9.7 fg/µL (2.7 genome copies of Brucella) and 970 fg/µL, respectively. Thus, the developed SRCA assay was found to be 100× more sensitive than the end-point PCR assay. To the best of our knowledge, our study is the first one to develop an SRCA-based assay for the detection of brucellosis and it can be a diagnostic tool for resource-constrained laboratories and veterinary hospitals.

Impact of academic medical center access on outcomes in multiple myeloma.

Treatment at academic cancer centers (ACs) is associated with improved survival across hematologic malignancies, though the benefit in multiple myeloma (MM) has not been examined. This study aims to evaluate survival outcomes at Commission on Cancer accredited ACs compared to non-academic centers (NACs) for patients receiving MM-directed therapy. The National Cancer Database (NCDB) was used to identify demographics and overall survival (OS) of MM patients diagnosed from 2004 to 2017 and to compare outcomes by facility type. Survival analysis was repeated in a propensity score matched cohort, with NACs matched 1:1 to ACs by age, race, comorbidity score, insurance, year of diagnosis, distance traveled, and income. Of 163 375 MM patients, 44.5% were treated at ACs. Patients at ACs were more likely to receive MM-directed therapy compared to NACs (81% vs. 73%, p < .001). For patients receiving treatment, median OS at ACs was 71.3 months versus 41.2 months at NACs (p < .001). When adjusted for baseline demographics, patients treated at ACs had reduced mortality; hazard ratio (HR) 0.79 (95% CI 0.78-0.81, p < .001). The propensity score matched cohort maintained this survival benefit with a median OS of 59.9 months at ACs versus 37.0 months at NACs (p < .001), HR of 0.66 (95% CI 0.64-0.67, p < .001). ACs treated younger patients with fewer comorbidities and were more likely to treat racial minorities and patients with Medicaid or private insurance, and the uninsured. In this analysis, MM patients treated at ACs have significantly improved survival. While potentially related to access to specialized care, socioeconomic factors that drive facility selection may also contribute.

Chromosome length ratio as a biomarker of DNA damage in cells exposed to high dose ionizing radiation.

The premature chromosome condensation (PCC) assay is considered as complementary bio-dosimetry tool for chromosome aberration assay and the PCC assay can be used to estimate high dose exposure. Though the PCC ring is considered as prospective biomarker, chromosome length ratio (ratio of longest and shortest chromosome length in PCC spreads) of chemically induced PCC is shown to be very good indicator of ionizing radiation. In view of this, an in-vitro study has been performed using PCC assay to suggest chromosome length ratio (LR) as potential bio-dosimeter induced by high dose ionizing radiation. Blood samples were collected from healthy subjects (n = 3) after prior consent and irradiated to ten different doses ranging between 0 and 20 Gy using 6 MV LINAC X-rays with dose rate of 5.6 Gy/min. Irradiated lymphocytes were cultured and calyculin induced PCC spreads were prepared. PCC spreads were captured using image analysis system and chromosome lengths were measured using open-source ImageJ software. For each dose, LR for 50 chromosome spreads were computed and mean LR value was calculated. LR varies between 6.0 ± 0.08 and 23.6 ± 0.55 for the dose range between 2 and 20 Gy. The dose response curve for LR was observed to be linear with y = 1.02x + 3.36, R2 = 0.97. Linear dose response relationship obtained in the present study confirms the prospective use of LR measurement. This study is first of its kind to examine chromosome length ratio as a biomarker of DNA damage in cells exposed to high dose X-ray exposure.

Factors affecting relationship issues among clients attending youth mental health promotion services in India.

BACKGROUND: India today is home for the largest youth population in the world. Youth is a formative phase transitioning from childhood to adulthood. Relationship is fundamental for a healthy and satisfactory life. Relationships assume importance and maturity during adolescence and youth. Relationships and mental health have a bidirectional effect. The effect of relationships on mental health is stronger than vice versa. MATERIALS AND METHODS: Two-year case record analysis of 8595 beneficiaries aged 15-35 years attending youth guidance centers (Yuva Spandana Kendras) in Karnataka, India, was undertaken to understand factors affecting relationship issues among them. Multivariate logistic regression was performed with any beneficiary having a relationship issue as outcome. RESULTS: Being a student (adjusted odds ratio [AOR] = 1.49; 95% confidence interval [CI] = 1.18-1.89), occupation (AORbusiness/salaried = 3.04; 95% CI = 2.10-4.40 and AORothers = 1.72; 95% CI = 1.22-2.44), marital status (AORmarried = 1.42; 95% CI = 1.06-1.90 and AORothers = 3.44; 95% CI = 1.45-8.15), having health and lifestyle issues (AOR = 3.61; 95% CI = 3.05-4.27), personality issues (AOR = 2.88; 95% CI = 2.43-3.41), safety issues (AOR = 6.28; 95% CI = 5.01-7.87), gender, sex, and sexuality issues (AOR = 3.10; 95% CI = 1.93-4.98), suicidality (AOR = 1.82; 95% CI = 1.17-2.85), alcohol use (AOR = 5.43; 95% CI = 3.92-7.41), and different emotions experienced (AOR ranging from 0.37 to 3.50), had significant association with relationship issues. CONCLUSION: Investing in health promotion interventions focusing on these precursors of relationship issues among youth seems strategic. Our findings have implications for other states in India and other low-middle-income countries like India.

Evaluation of ocular surface and tear function - A review of current approaches for dry eye.

An increasing prevalence of dry eye disease in the past decade has resulted in a greater focus on diagnostic methods for this condition. There has been a proliferation of technologies that attempt to quantify various aspects of tear function and ocular surface health. However, a cost-effective, simple, and efficient method remains elusive. In the Indian context, the majority of these patients present to the general ophthalmologist, and a clinical approach that is quick and easy to perform would allow widespread usage for accurate diagnosis. This article reviews currently available methods and their relevance to the general ophthalmologist.

Addition of navitoclax to ongoing ruxolitinib treatment in patients with myelofibrosis (REFINE): a post-hoc analysis of molecular biomarkers in a phase 2 study.

BACKGROUND: Primary analyses of cohort 1a of the REFINE trial showed that addition of navitoclax to ruxolitinib induced a 35% or greater reduction in spleen volume (SVR35) and reduced symptoms in patients with myelofibrosis no longer benefiting from ruxolitinib. Here, we report the exploratory post-hoc biomarker analyses from cohort 1a. METHODS: REFINE is a phase 2, multicentre, open-label trial designed to assess the activity and safety of navitoclax alone or in combination with ruxolitinib in patients with primary or secondary (post-polycythaemia vera or post-essential thrombocythaemia) myelofibrosis. Cohort 1a of the study included patients who had disease progression or suboptimal response on stable ruxolitinib monotherapy. Patients in cohort 1a, who had previously received ruxolitinib for 12 weeks or more, continued their current stable dose, and navitoclax was orally administered at 50 mg per day and escalated weekly to a maximum of 300 mg per day, based on tolerability. The primary activity endpoint was SVR35 at week 24 from baseline. Secondary endpoints were a 50% or greater reduction in total symptom score (TSS50) at week 24 from baseline as measured by the Myelofibrosis Symptom Assessment Form (version 4.0), anaemia response assessed according to International Working Group-Myeloproliferative Neoplasms Research and European LeukemiaNet criteria, and change in grade of bone marrow fibrosis according to the European consensus grading system; and exploratory endpoints included overall survival and changes in inflammatory cytokines. Exploratory analyses investigated potential prognostic biomarkers of the benefit of navitoclax-based combination treatment, including bone marrow fibrosis and variant allele frequency, in patients with a suboptimal response to ruxolitinib. This study is registered with ClinicalTrials.gov (NCT03222609) and is ongoing. FINDINGS: Between Nov 14, 2017, and April 10, 2019, 34 patients in cohort 1a received at least one dose of navitoclax plus ruxolitinib. 23 (68%) patients were male, with 32 (94%) being White. At data cutoff (May 6, 2021), the median follow-up for survivors was 26·2 months (IQR 21·9-32·3). 33 patients were evaluable for biomarker analyses; 19 (58%) had high molecular risk mutations. Five (31%) of 16 patients had SVR35 at week 24 in the high molecular risk group, as did four (31%) of 13 in the non-high molecular risk group. Four (36%) of 11 patients in the high molecular risk group had TSS50 at week 24 compared with two (25%) of eight in the non-high molecular risk group; seven (39%) of 18 in the high molecular risk group had an improvement in fibrosis by at least one grade compared with five (36%) of 14 in the non-high molecular risk group; and four (28%) of 14 had reductions in variant allele frequency of 20% or greater in the high molecular risk group compared with two (17%) of 12 in the non-high molecular risk group. Patients with improvements in fibrosis of one grade or more and a reduction of 20% of more in variant allele frequency had improved overall survival (median overall survival not reached) compared with those who did not achieve fibrosis improvement or a reduction in variant allele frequency (median overall survival 28·5 months [95% CI 19·6-not estimable] for both), suggesting potential disease modification. Additionally, changes in concentrations of ß-2-microglobulin (week 12: r=0·57; week 24: r=0·57), TIMP metallopeptidase inhibitor 1 (week 12: r=0·47; week 24: r=0·54), TNF receptor type II (r=0·55; week 24: r=0·40), and vascular cell adhesion molecule-1 (r=0·58; week 24: r=0·50) were positively associated with changes in spleen volume. INTERPRETATION: These biomarker analyses reveal clinically meaningful splenic responses independent of high molecular risk mutation status in patients treated with navitoclax plus ruxolitinib who were not benefiting from ruxolitinib monotherapy. Furthermore, the overall survival benefit observed in those with an improvement in fibrosis or a reduction in variant allele frequency is suggestive of disease modification, implying the therapeutic potential of adding navitoclax to ruxolitinib for patients with myelofibrosis who had disease progression or suboptimal response to ruxolitinib monotherapy. FUNDING: AbbVie.

Inflammation and dry eye disease-where are we?

The presence of inflammation in dry eye disease (DED) results in increased patient symptomatology, ocular surface damage and worsening tear dysfunction. It also affects the health of meibomian glands and their secretions which further aggravates ocular surface disease. This article reviews current knowledge regarding ocular surface inflammation in DED and explores the relationships between the vicious cycles of DED, inflammation and meibomian gland dysfunction (MGD). The clinical evaluation of eyes with such changes, markers that identify the presence of inflammation on the ocular surface and current treatment options are discussed.