Probing Deposit-Driven Age-Related Macular Degeneration Via Thicknesses of Outer Retinal Bands and Choroid: ALSTAR2 Baseline.

Purpose: We aimed to identify structural differences in normal eyes, early age-related macular degeneration (AMD), and intermediate AMD eyes using optical coherence tomography (OCT) in a well-characterized, large cross-sectional cohort. Methods: Subjects ≥ 60 years with healthy normal eyes, as well as early or intermediate AMD were enrolled in the Alabama Study on Age-related Macular Degeneration 2 (ALSTAR2; NCT04112667). Using Spectralis HRA + OCT2, we obtained macular volumes for each participant. An auto-segmentation software was used to segment six layers and sublayers: photoreceptor inner and outer segments, subretinal drusenoid deposits (SDDs), retinal pigment epithelium + basal lamina (RPE + BL), drusen, and choroid. After manually refining the segmentations of all B-scans, mean thicknesses in whole, central, inner and outer rings of the ETDRS grid were calculated and compared among groups. Results: This study involved 502 patients, 252 were healthy, 147 had early AMD, and 103 had intermediate AMD eyes (per Age-Related Eye Disease Study [AREDS] 9-step). Intermediate AMD eyes exhibited thicker SDD and drusen, thinner photoreceptor inner segments, and RPE compared to healthy and early AMD eyes. They also had thicker photoreceptor outer segments than early AMD eyes. Early AMD eyes had thinner photoreceptor outer segments than normal eyes but a thicker choroid than intermediate AMD eyes. Using the Beckman scale, 42% of the eyes initially classified as early AMD shifted to intermediate AMD, making thickness differences for photoreceptor outer segments and choroid insignificant. Conclusions: With AMD stages, the most consistent structural differences involve appearance of drusen and SDD, followed by RPE + BL thickness, and then thickness of photoreceptor inner and outer segments. Structural changes in the transition from aging to intermediate AMD include alterations in the outer retinal bands, including the appearance of deposits on either side of the RPE.

An improved class of estimators for estimation of population distribution functions under stratified random sampling.

The main objective of the current study is to suggest an enhanced family of log ratio-exponential type estimators for population distribution function (DF) using auxiliary information under stratified random sampling. Putting different choices in our suggested generalized class of estimators, we found some Specific estimators. The bias and MSE expressions of the estimators have been approximated up to the first order. By using the actual and simulated data sets, we measured the performance of estimators. Based on the results, the suggested estimators for DF show better performance as compared to the preliminary estimators considered here. The suggested estimators have a advanced efficiency than the other estimators examined with the estimators F‾ˆlogPR(st)2, and F‾ˆlogPR(st)4 for both the actual and simulated data sets. The magnitude of the improvement in efficiency is noteworthy, indicating the superiority of the proposed estimators in terms of MSE.

Enhanced exponential ratio-cum-ratio estimator in ranked set sampling using transformed auxiliary information.

Estimation of population mean is a determined subject issue in sampling surveys and many efforts have been paid by various researchers to enhance the precision of the estimates by utilizing the correlated auxiliary information. In connection with this, we suggest an improved exponential ratio-cum-ratio estimator using transformed auxiliary variables under ranked set sampling scheme. Theoretical comparison between estimators is made in terms of mean square errors (MSEs), percentage relative efficiencies (PREs), and percentage relative root mean squared error (PRRMSE). The numerical expression for the bias and MSE of the suggested estimator is derived up to first order of approximation. Based on the results of actual data sets and a simulation study, it is found that the suggested estimator perform well as compared to its existing counterparts.

Improved estimation of population distribution function using twofold auxiliary information under simple random sampling.

In this article, our main aim is to suggest enhanced families of estimators for estimating the population distribution function (DF) using twofold auxiliary evidence within the framework of simple random sampling. Numerical analysis is performed on four different actual data sets. The precision of the estimators is further investigated exhausting a simulation study. As equated with existing estimators, the suggested families of estimators have minimum mean square error (MSE) and higher percentage relative efficiency (PRE). The succeeding recommended family of estimators outperforms the first family of estimators across all data sets. These are positive indicators of its performance. The theoretical result shows that the recommended family of estimators performs better than the existing estimators. The extent of improvement in efficiency is noteworthy, indicating the superiority of the suggested estimators in terms of minimum MSE.

Hepatopathy in Scrub Typhus: Clinical Presentation, Association With Morbidity and Impact on Outcome.

INTRODUCTION: Acute liver injury accompanies tropical fevers like scrub typhus. This study was undertaken to evaluate liver injury in scrub typhus and its association with the disease severity. METHODS: This was a single-centre prospective, observational study on in-patients of scrub typhus from north India. All patients were categorized on basis of elevation of transaminases as having normal or abnormal liver function. Those with hepatopathy were sub-categorized as having mild, moderate, severe or very severe liver injury. RESULTS: Liver dysfunction was present in 76/109 of the patients and was significantly associated with eschar, clinically discernible hepatomegaly and splenomegaly. Shock, renal and respiratory insufficiency, need for intensive care and oxygen supplementation were also significantly associated with hepatopathy. Duration of hospitalization and mortality were comparable in patients with/without liver injury; however delayed defervescence (6.2+3.8 vs. 4.5+2.5 days; p=0.025) was observed with hepatopathy. Icterus (p=0.001), hepatomegaly (p=0.015), thrombocytopenia (p<0.001) and raised erythrocyte sedimentation rate (ESR) (p=0.003) were significantly observed with increasing grade of liver injury.  Conclusion: Liver dysfunction and its increased severity in scrub typhus did not translate into increased morbidity and/or poor outcomes.

Potential Structural Biomarkers in 3D Images Validated by the First Functional Biomarker for Early Age-Related Macular Degeneration - ALSTAR2 Baseline.

Purpose: Lack of valid end points impedes developing therapeutic strategies for early age-related macular degeneration (AMD). Delayed rod-mediated dark adaptation (RMDA) is the first functional biomarker for incident early AMD. The relationship between RMDA and the status of outer retinal bands on optical coherence tomography (OCT) have not been well defined. This study aims to characterize these relationships in early and intermediate AMD. Methods: Baseline data from 476 participants was assessed including eyes with early AMD (n = 138), intermediate AMD (n = 101), and normal aging (n = 237). Participants underwent volume OCT imaging of the macula and rod intercept time (RIT) was measured. The ellipsoid zone (EZ) and interdigitation zone (IZ) on all OCT B-scans of the volumes were segmented. The area of detectable EZ and IZ, and mean thickness of IZ within the Early Treatment Diabetic Retinopathy Study (ETDRS) grid were computed and associations with RIT were assessed by Spearman's correlation coefficient and age adjusted. Results: Delayed RMDA (longer RIT) was most strongly associated with less preserved IZ area (r = -0.591; P < 0.001), followed by decreased IZ thickness (r = -0.434; P < 0.001), and EZ area (r = -0.334; P < 0.001). This correlation between RIT and IZ integrity was not apparent when considering normal eyes alone within 1.5 mm of the fovea. Conclusions: RMDA is correlated with the status of outer retinal bands in early and intermediate AMD eyes, particularly, the status of the IZ. This correlation is consistent with a previous analysis of only foveal B-scans and is biologically plausible given that retinoid availability, involving transfer at the interface attributed to the IZ, is rate-limiting for RMDA.

SLIViT: a general AI framework for clinical-feature diagnosis from limited 3D biomedical-imaging data.

We present SLIViT, a deep-learning framework that accurately measures disease-related risk factors in volumetric biomedical imaging, such as magnetic resonance imaging (MRI) scans, optical coherence tomography (OCT) scans, and ultrasound videos. To evaluate SLIViT, we applied it to five different datasets of these three different data modalities tackling seven learning tasks (including both classification and regression) and found that it consistently and significantly outperforms domain-specific state-of-the-art models, typically improving performance (ROC AUC or correlation) by 0.1-0.4. Notably, compared to existing approaches, SLIViT can be applied even when only a small number of annotated training samples is available, which is often a constraint in medical applications. When trained on less than 700 annotated volumes, SLIViT obtained accuracy comparable to trained clinical specialists while reducing annotation time by a factor of 5,000 demonstrating its utility to automate and expedite ongoing research and other practical clinical scenarios.

An enhanced estimator of finite population variance using two auxiliary variables under simple random sampling.

In this article, we have suggested a new improved estimator for estimation of finite population variance under simple random sampling. We use two auxiliary variables to improve the efficiency of estimator. The numerical expressions for the bias and mean square error are derived up to the first order approximation. To evaluate the efficiency of the new estimator, we conduct a numerical study using four real data sets and a simulation study. The result shows that the suggested estimator has a minimum mean square error and higher percentage relative efficiency as compared to all the existing estimators. These findings demonstrate the significance of our suggested estimator and highlight its potential applications in various fields. Theoretical and numerical analyses show that our suggested estimator outperforms all existing estimators in terms of efficiency. This demonstrates the practical value of incorporating auxiliary variables into the estimation process and the potential for future research in this area.

A new approach for estimating variance of a population employing information obtained from a stratified random sampling.

In this article, we suggest an enhanced estimator for the estimation of finite population variance using twofold auxiliary variable under stratified random sampling. The numerical expressions for the bias and MSE are determined up to the first order of approximation. In order to effectively validate the theoretical findings, three actual data sets are included. Additionally, the application of the suggested estimators is demonstrated using a simulation study. Results of an empirical comparison among the suggested and existing estimators were investigated. To determine how good the suggested estimator, in comparison to the preliminary estimators, the MSE criterion is used. The suggested estimator has a smaller MSE and better PRE than existing estimators, according to numerical results utilizing actual data sets and a simulation analysis.

New generalized class of estimators for estimation of finite population mean based on probability proportional to size sampling using two auxiliary variables: A simulation study.

This article aims to suggest a new generalized class of estimators based on probability proportional to size sampling using two auxiliary variables. The numerical expressions for the bias and mean squared error (MSE) are derived up to the first order of approximation. Four actual data sets are used to examine the performances of a new improved generalized class of estimators. From the results of real data sets, it is examined that the suggested estimator gives the minimum MSE and the percentage relative efficiency is higher than all existing estimators, which shows the importance of the new generalized class of estimators. To check the strength and generalizability of our proposed class of estimators, a simulation study is also accompanied. The consequence of the simulation study shows the worth of newly found proposed class estimators. Overall, we get to the conclusion that the proposed estimator outperforms as compared to all other estimators taken into account in this study.

Estimation of finite population mean using double sampling under probability proportional to size sampling in the presence of extreme values.

Values that are too large or small enough can be found in many data sets. Therefore, the estimator can yield ambiguous findings if several of the incredible deals are picked for the sample. When such extreme values occur, we propose improved estimators to determine the finite population means using double sampling based on probability proportional to size sampling (PPS). The properties of estimators are obtained up to the first order of approximations. When the size of the units varies widely, the PPS sampling technique may be employed. To determine the values of Pi when using PPS, we must be acquainted with the aggregate of the auxiliary variable Xi. However the designs and estimation techniques we have looked at so far are unsuccessful and are less effective when this information is difficult to locate or when other information is missing. The two-phase approach is preferable and more feasible in these kinds of circumstances. To demonstrate how effectively the recommended estimators performed, we used three actual data sets. We show mathematically and theoretically that the suggested estimators outperform alternative estimators.

Potential Structural Biomarkers in 3D Images Validated by the First Functional Biomarker for Early Age-Related Macular Degeneration - ALSTAR2 Baseline.

Purpose: While intermediate and late age-Related Macular Degeneration (AMD) have been widely investigated, rare studies were focused on the pathophysiologic mechanism of early AMD. Delayed rod-mediated dark adaptation (RMDA) is the first functional biomarker for incident early AMD. The status of outer retinal bands on optical coherence tomography (OCT) may be potential imaging biomarkers and the purpose is to investigate the hypothesis that the integrity of interdigitation zone (IZ) may provide insight into the health of photoreceptors and retinal pigment epithelium (RPE) in early AMD. Methods: We establish the structure-function relationship between ellipsoid zone (EZ) integrity and RMDA, and IZ integrity and RMDA in a large-scale OCT dataset from eyes with normal aging (n=237), early AMD (n=138), and intermediate AMD (n=101) by utilizing a novel deep-learning-derived algorithm with manual correction when needed to segment the EZ and IZ on OCT B-scans (57,596 B-scans), and utilizing the AdaptDx device to measure RMDA. Results: Our data demonstrates that slower RMDA is associated with less preserved EZ (r = -0.334; p<0.001) and IZ area (r = -0.591; p<0.001), and decreased IZ thickness (r = -0.434; p<0.001). These associations are not apparent when considering normal eyes alone. Conclusions: The association with IZ area and RMDA in large-scale data is biologically plausible because retinoid availability and transfer at the interface attributed to IZ is rate-limiting for RMDA. This study supports the hypothesis that the IZ integrity provides insight into the health of photoreceptors and RPE in early AMD and is a potential new imaging biomarker.

Green synthesised AuNps using Ajuga Bracteosa extract and AuNps-Free supernatant exhibited equivalent antibacterial and anticancerous efficacies.

The current study is designed to synthesize gold nanoparticles using Ajuga bracteosa extract, which is a highly known medicinal herb found in the northern Himalayas. The synthesized gold nanoparticles were initially characterized by UV-Vis spectrophotometer, SEM, FTIR, pXRD, and, GC-MS. Antibacterial efficacy of A. bracteosa extract, AuNps, and AuNps-free supernatant activity was checked against highly pathogenic clinical isolates of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa via agar well diffusion method, assuming that supernatant might have active compounds. The Nps-free supernatant showed the maximum antibacterial activity against E. coli (20.8±0.3 mm), Staphylococcus aureus (16.5±0.5), and Pseudomonas aeruginosa (13±0.6). While green synthesized AuNps showed effective antibacterial activity (Escherichia coli (16.4±0.3mm), Staphylococcus aureus (15.05±0.5mm), and Pseudomonas aeruginosa (11.07±0.6mm)) which was high compared to A. bracteosa extract. Anticancer activity was assessed by MTT assay on U87 and HEK293 cell lines. Aj-AuNps have an antigrowth effect on both the cell lines however Aj-AuNps-free supernatant which was also evaluated along with the Aj-AuNps, showed high toxicity toward HEK293 cell line compared to U87. Further, the GC-MS analysis of supernatant showed the presence of resultant toxic compounds after the reduction of gold salt, which include Trichloromethane, Propanoic acid, 2-methyl-, methyl ester, Methyl isovalerate, Pentanoic acid, 2-hydroxy-4-methyl-, Benzene-propanoic acid, and alpha-hydroxy. Based on the observation small molecular weight ligands of Ajuga bracteosa were analyzed in-silico for their binding efficacy towards selected membrane proteins of our target pathogens. RMSD is also calculated for the best docked protein ligand pose. The results revealed that among all listed ligands, Ergosterol and Decacetylajugrin IV have high virtuous binding affinities towards the membrane proteins of targeted pathogens. The current findings revealed that the Aj-AuNps are good antibacterial as well as anticancerous agents while the Nps-free supernatant is also exceedingly effective against resistant pathogens and cancer cell lines.

A simulation study: An enhanced generalized class of estimators for estimation of population proportion using twofold auxiliary attribute.

The article introduces a novel class of estimators designed for estimating finite population proportions. These estimators utilize dual auxiliary attributes and are applicable under simple random sampling. The proposed class of estimators includes various members with distinct characteristics. The article provides numerical terminologies for the bias and MSE of the estimators, acquire up to first order of approximation. Four actual data sets are used. Additionally, a simulation study is accompanied to perceive the presentations of estimators. The MSE criterion is used to assess how well the proposed estimator performed as likened to the preliminary estimators. The simulation analysis revealed that, in contrast to other examined estimators, the suggested class of estimators provided better results. The empirical investigation offers evidence to substantiate the findings of the argument. Theoretical research also displays that the suggested class of estimators outperforms its competitors.

Pure Red Cell Aplasia Encountered in a Tertiary Care Hematology Laboratory: A Series of Nine Distinctive Cases.

Pure red cell aplasia (PRCA) is characterized by severe anemia with reticulocytopenia and bone marrow erythroblastopenia. The early erythroblasts are markedly decreased; however, in rare instances, they may be normal or raised in number. There are varied etiologies, namely congenital or acquired and primary or secondary. The congenital PRCA is known as "Diamond-Blackfan anemia." Thymomas, autoimmune disease, lymphomas, infections, and drugs also may be familiar associates. However, the etiologies of PRCA are numerous, and many diseases/infections can be associated with PRCA. The diagnosis rests on clinical suspicion and appropriate laboratory workup. We evaluated nine cases of red cell aplasia, having severe anemia with reticulocytopenia. Nearly half of the cases showed adequate erythroid (> 5% of the differential count) but with a maturation arrest. The adequacy of the erythroid could confuse the hematologist and may even delay the diagnosis. Hence, it is empirical that PRCA could be considered a differential in every case of severe anemia with reticulocytopenia, even in the presence of adequate erythroid precursors in the bone marrow.

Improved family of estimators for the population mean using supplementary variables under PPS sampling.

In this article, we suggest an enhanced family of estimators for estimation of population mean employing the supplementary variables under probability proportional to size sampling. Up to the first order of approximation, numerical formulations of the bias and mean square error of estimators are obtained. From our suggested improved family of estimators, we give sixteen different members. The recommended family of estimators has specifically been used to derive the characteristics of sixteen estimators based on the known population parameters of the study as well as auxiliary variables. The performances of the suggested estimators have been assessed using three actual data. Furthermore, a simulation investigation is also accompanied to evaluate the effectiveness of estimators. The proposed estimators have a smaller MSE and an advanced PRE when linked to existing estimators, which are based on actual data sets and simulation studies. Theoretically and empirically studies also reveal that the suggested estimators accomplish well than the usual estimators.

Haematological factors and anaemia in acute malaria: A prospective hospital-based cross-sectional observational study.

This prospective, observational, cross-sectional study was undertaken to estimate the burden of anaemia in malaria and to evaluate the contribution of haematogenic factors and haemolysis in its pathogenesis. Haematogenic factors (vitamin B12, folic acid, lactate dehydrogenase, ferritin, total iron binding capacity, direct Coombs test) were estimated in patients with malaria at the time of admission. They were categorized as anaemics or non-anaemics and their complications and outcomes were recorded. P. vivax (97/112) and P. falciparum (13/112) mono-infections dominated; anaemia was seen in 63.3%. Patients with and without anaemia were comparable in terms of haemolysis and the haematogenic factors evaluated. Bleeding events, acute kidney injury and acute liver injury were comparable; however, the need for mechanical ventilation and transfusion of blood products was significantly higher amongst the anaemics. We concluded that haemolysis and presumably transient bone marrow suppression contribute to anaemia in malaria. Pre-existing nutritional deficiencies do not, however, predispose to severe malaria.

A case series of 2,4 diethylamine poisoning - what the future holds for us.

2,4-Diethylamine (2,4-D) is a chlorphenoxy herbicide widely used in north India, marketed as 'Sohna' and 'Zura'. Multi-organ dysfunction and mortality is high in cases of accidental or suicidal ingestion owing to the lack of any antidote. We report a case series of 2,4-D poisoning from a single tertiary centre of north India managed with variable outcomes.