'IHPBA-APHPBA clinical practice guidelines': international Delphi consensus recommendations for gallbladder cancer.

BACKGROUND: The Delphi consensus study was carried out under the auspices of the International and Asia-Pacific Hepato-Pancreato-Biliary Associations (IHPBA-APHPBA) to develop practice guidelines for management of gallbladder cancer (GBC) globally. METHOD: GBC experts from 17 countries, spanning 6 continents, participated in a hybrid four-round Delphi consensus development process. The methodology involved email, online consultations, and in-person discussions. Sixty eight clinical questions (CQs) covering various domains related to GBC, were administered to the experts. A consensus recommendation was accepted only when endorsed by more than 75% of the participating experts. RESULTS: Out of the sixty experts invited initially to participate in the consensus process 45 (75%) responded to the invitation. The consensus was achieved in 92.6% (63/68) of the CQs. Consensus covers epidemiological aspects of GBC, early, incidental and advanced GBC management, definitions for radical GBC resections, the extent of liver resection, lymph node dissection, and definitions of borderline resectable and locally advanced GBC. CONCLUSIONS: This is the first international Delphi consensus on GBC. These recommendations provide uniform terminology and practical clinical guidelines on the current management of GBC. Unresolved contentious issues like borderline resectable/locally advanced GBC need to be addressed by future clinical studies.

Deciphering microbial communities involved in marine steel corrosion using high-throughput amplicon sequencing.

To characterize the source and effects of bacterial communities on corrosion of intertidal structures, three different UK coastal sites were sampled for corrosion materials, sediment and seawater. Chemical analyses indicate the activity of sulfate-reducing microbes (SRBs) at 2 sites (Shoreham and Newhaven), but not at the third (Southend-on-Sea). Microbial communities in the deep sediment and corrosion samples are similar. The phylum Proteobacteria is dominant (40.4% of the total ASV), followed by Campilobacterota (11.3%), Desulfobacterota and Firmicutes (4%-5%). At lower taxonomic levels, corrosion causing bacteria, such as Shewanella sp. (6%), Colwellia sp. (7%) and Mariprofundus sp. (1%), are present. At Southend-on-sea, the relative abundance of Campilobacterota is higher compared to the other two sites. The mechanism of action of microorganisms at Shoreham and Newhaven involves biogenic sulfuric acid corrosion of iron by the combined action of SRBs and sulfur-oxidizing microbes. However, at Southend-on-sea, sulfur compounds are not implicated in corrosion, but SRBs and other electroactive microbes may play a role in which cathodic reactions (electrical MIC) and microbial enzymes (chemical MIC) are involved. To contribute to diagnosis of accelerated intertidal corrosion types, we developed a rapid identification method for SRBs using quantitative polymerase chain reaction high-resolution melt curve analysis of the dsrB gene.

Comparative immune profiling of pancreatic ductal adenocarcinoma progression among South African patients.

BACKGROUND: Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive cancer characterized by an immunosuppressive microenvironment. Patients from specific ethnicities and population groups have poorer prognoses than others. Therefore, a better understanding of the immune landscape in such groups is necessary for disease elucidation, predicting patient outcomes and therapeutic targeting. This study investigated the expression of circulating key immune cell markers in South African PDAC patients of African ancestry. METHODS: Blood samples were obtained from a total of 6 healthy volunteers (HC), 6 Chronic Pancreatitis (CP) and 34 PDAC patients consisting of 22 resectable (RPC), 8 locally advanced (LAPC) and 4 metastatic (MPC). Real-time Quantitative Polymerase Chain reactions (RT-qPCR), Metabolomics, Enzyme-Linked Immunosorbent Assay (ELISA), Reactive Oxygen Species (ROS), and Immunophenotyping assays were conducted. Statistical analysis was conducted in R (v 4.3.2). Additional analysis of single-cell RNA data from 20 patients (16 PDAC and 4 controls) was conducted to interrogate the distribution of T-cell and Natural Killer cell populations. RESULTS: Granulocyte and neutrophil levels were significantly elevated while lymphocytes decreased with PDAC severity. The total percentages of CD3 T-cell subpopulations (helper and double negative T-cells) decreased when compared to HC. Although both NK (p = 0.014) and NKT (p < 0.001) cell levels increased as the disease progressed, their subsets: NK CD56dimCD16- (p = 0.024) and NKTs CD56+ (p = 0.008) cell levels reduced significantly. Of note is the negative association of NK CD56dimCD16- (p < 0.001) cell levels with survival time. The gene expression analyses showed no statistically significant correlation when comparing the PDAC groups with the controls. The inflammatory status of PDAC was assessed by ROS levels of serum which were elevated in CP (p = 0.025), (RPC (p = 0.003) and LAPC (p = 0.008)) while no significant change was observed in MPC, compared to the HC group. ROS was shown to be positively correlated with GlycA (R = 0.45, p = 0.0096). Single-cell analyses showed a significant difference in the ratio of NKT cells per total cell counts in LAPC (p < 0.001) and MPC (p < 0.001) groups compared with HC, confirming observations in our sample group. CONCLUSION: The expression of these immune cell markers observed in this pilot study provides insight into their potential roles in tumour progression in the patient group and suggests their potential utility in the development of immunotherapeutic strategies.

Organ systems of a Cambrian euarthropod larva.

The Cambrian radiation of euarthropods can be attributed to an adaptable body plan. Sophisticated brains and specialized feeding appendages, which are elaborations of serially repeated organ systems and jointed appendages, underpin the dominance of Euarthropoda in a broad suite of ecological settings. The origin of the euarthropod body plan from a grade of vermiform taxa with hydrostatic lobopodous appendages ('lobopodian worms')1,2 is founded on data from Burgess Shale-type fossils. However, the compaction associated with such preservation obscures internal anatomy3-6. Phosphatized microfossils provide a complementary three-dimensional perspective on early crown group euarthropods7, but few lobopodians8,9. Here we describe the internal and external anatomy of a three-dimensionally preserved euarthropod larva with lobopods, midgut glands and a sophisticated head. The architecture of the nervous system informs the early configuration of the euarthropod brain and its associated appendages and sensory organs, clarifying homologies across Panarthropoda. The deep evolutionary position of Youti yuanshi gen. et sp. nov. informs the sequence of character acquisition during arthropod evolution, demonstrating a deep origin of sophisticated haemolymph circulatory systems, and illuminating the internal anatomical changes that propelled the rise and diversification of this enduringly successful group.

Tropical root responses to global changes: A synthesis.

Tropical ecosystems face escalating global change. These shifts can disrupt tropical forests' carbon (C) balance and impact root dynamics. Since roots perform essential functions such as resource acquisition and tissue protection, root responses can inform about the strategies and vulnerabilities of ecosystems facing present and future global changes. However, root trait dynamics are poorly understood, especially in tropical ecosystems. We analyzed existing research on tropical root responses to key global change drivers: warming, drought, flooding, cyclones, nitrogen (N) deposition, elevated (e) CO2, and fires. Based on tree species- and community-level literature, we obtained 266 root trait observations from 93 studies across 24 tropical countries. We found differences in the proportion of root responsiveness to global change among different global change drivers but not among root categories. In particular, we observed that tropical root systems responded to warming and eCO2 by increasing root biomass in species-scale studies. Drought increased the root: shoot ratio with no change in root biomass, indicating a decline in aboveground biomass. Despite N deposition being the most studied global change driver, it had some of the most variable effects on root characteristics, with few predictable responses. Episodic disturbances such as cyclones, fires, and flooding consistently resulted in a change in root trait expressions, with cyclones and fires increasing root production, potentially due to shifts in plant community and nutrient inputs, while flooding changed plant regulatory metabolisms due to low oxygen conditions. The data available to date clearly show that tropical forest root characteristics and dynamics are responding to global change, although in ways that are not always predictable. This synthesis indicates the need for replicated studies across root characteristics at species and community scales under different global change factors.

The need for research targeting the link between occupational carcinogens and hepatopancreatobiliary cancers in Africa: A systematic review.

INTRODUCTION: Hepatopancreatobiliary (HPB) cancers encompassing malignancies of the liver, pancreas, gall bladder, and bile ducts pose a significant health burden in Africa. While the association of certain occupational carcinogens in cancer is well established globally, their potential role in HPB cancers remains understudied, especially in an African context. AIM: This systematic review delves into the association between occupational carcinogens and HPB cancer in Africa. It examines the current state of research on occupational carcinogens and HPB cancers in Africa, identifying key challenges and knowledge gaps. METHODS: This systematic review examined publications (published between 01 January 2012 and 31 May 2023) that highlight occupational carcinogens and HBP cancers in Africa. The search was conducted on electronic databases namely PubMed, Web of Science, and Africa Wide Information. RESULT: Due to the lack of information on the association between occupational carcinogens and HPB cancers in Africa, as a result of the paucity of published studies, only four articles were included in this study. Hepatocellular carcinoma (HCC) was the predominant cancer associated with the occupational carcinogen, aflatoxin. Agricultural workers, especially those involved in the production and processing of maize and peanuts, appear to be the most exposed to aflatoxin. CONCLUSION: Despite the sample size limitations due to the paucity of research studies on occupational carcinogens and HPB cancers in Africa, this study provides a reasonable tool for subsequent epidemiological studies. There is a need for more research on the association of occupational carcinogens and HPB cancers in Africa, especially with the growing industrialization.

Functional group tolerant hydrogen borrowing C-alkylation.

Hydrogen borrowing is an attractive and sustainable strategy for carbon-carbon bond formation that enables alcohols to be used as alkylating reagents in place of alkyl halides. However, despite intensive efforts, limited functional group tolerance is observed in this methodology, which we hypothesize is due to the high temperatures and harsh basic conditions often employed. Here we demonstrate that room temperature and functional group tolerant hydrogen borrowing can be achieved with a simple iridium catalyst in the presence of substoichiometric base without an excess of reagents. Achieving high yields necessitates the application of anaerobic conditions to counteract the oxygen sensitivity of the catalytic iridium hydride intermediate, which otherwise leads to catalyst degradation. Substrates containing heteroatoms capable of complexing the catalyst exhibit limited room temperature reactivity, but the application of moderately higher temperatures enables extension to a broad range of medicinally relevant nitrogen rich heterocycles. These newly developed conditions allow alcohols possessing functional groups that were previously incompatible with hydrogen borrowing reactions to be employed.

Novel applications of Convolutional Neural Networks in the age of Transformers.

Convolutional Neural Networks (CNNs) have been central to the Deep Learning revolution and played a key role in initiating the new age of Artificial Intelligence. However, in recent years newer architectures such as Transformers have dominated both research and practical applications. While CNNs still play critical roles in many of the newer developments such as Generative AI, they are far from being thoroughly understood and utilised to their full potential. Here we show that CNNs can recognise patterns in images with scattered pixels and can be used to analyse complex datasets by transforming them into pseudo images with minimal processing for any high dimensional dataset, representing a more general approach to the application of CNNs to datasets such as in molecular biology, text, and speech. We introduce a pipeline called DeepMapper, which allows analysis of very high dimensional datasets without intermediate filtering and dimension reduction, thus preserving the full texture of the data, enabling detection of small variations normally deemed 'noise'. We demonstrate that DeepMapper can identify very small perturbations in large datasets with mostly random variables, and that it is superior in speed and on par in accuracy to prior work in processing large datasets with large numbers of features.

Policy and market forces delay real estate price declines on the US coast.

Despite increasing risks from sea-level rise (SLR) and storms, US coastal communities continue to attract relatively high-income residents, and coastal property values continue to rise. To understand this seeming paradox and explore policy responses, we develop the Coastal Home Ownership Model (C-HOM) and analyze the long-term evolution of coastal real estate markets. C-HOM incorporates changing physical attributes of the coast, economic values of these attributes, and dynamic risks associated with storms and flooding. Resident owners, renters, and non-resident investors jointly determine coastal property values and the policy choices that influence the physical evolution of the coast. In the coupled system, we find that subsidies for coastal management, such as beach nourishment, tax advantages for high-income property owners, and stable or increasing property values outside the coastal zone all dampen the effects of SLR on coastal property values. The effects, however, are temporary and only delay precipitous declines as total inundation approaches. By removing subsidies, prices would more accurately reflect risks from SLR but also trigger more coastal gentrification, as relatively high-income owners enter the market and self-finance nourishment. Our results suggest a policy tradeoff between slowing demographic transitions in coastal communities and allowing property markets to adjust smoothly to risks from climate change.

The equivalence of psychodynamic therapy and cognitive behavioral therapy for depressive disorders in adults: A meta-analytic review.

BACKGROUND: Meta-analyses on the relative efficacy of psychodynamic psychotherapy (PDT) and cognitive behavioral therapy (CBT) for depressive disorders are limited by heterogeneity in diagnostic samples and comparators and a lack of equivalence testing. OBJECTIVE: We addressed this through a meta-analytic test of the equivalence of manualized PDT and CBT in treating adults with depressive disorders as determined by diagnostic interviews. Sensitivity analyses evaluated the impact of pretreatment differences, mixed diagnostic samples, author allegiance, study quality, year of publication and outliers on findings. METHOD: A comprehensive literature search across multiple databases using reliable screening methods identified nine randomized controlled trials directly comparing manualized PDT and CBT for diagnosed depressive disorders in adults. Following pre-registration, we employed random effect models for our meta-analyses and two one-sided test procedures for equivalence testing. RESULTS: Independent raters determined that all studies were of adequate quality. Immediately posttreatment, depressive symptoms were statistically equivalent across PDT and CBT (k = 9; g = -0.11, 90% confidence interval [90% CI]: -0.24 to 0.02, pequivalence = .048, pNHST = .212, I2 = 32.7). At follow-up, the longest time point within a year, depressive symptoms were neither statistically equivalent nor statistically different (k = 6; g = -0.16, 90% CI: -0.31 to -0.02, pequivalence = .184, pNHST = .126, I2 = 0.00). CONCLUSION: The efficacy of manualized PDT is equal to manualized CBT immediately at posttreatment for depressive disorders in the adult general population. Nevertheless, insufficient data exists to reach a conclusion regarding equivalence at follow-up.

A comparison of the effect of two types of brief psychodynamic group therapy on perfectionism-related attitudes, self-relatedness, and self-esteem.

Objective: This randomized controlled trial investigated the efficacy of dynamic relational group therapy (DRT) relative to group psychodynamic supportive therapy (PST) in improving perfectionism-related attitudes and components of the perfectionistic self-relationship. Method: Based on a comprehensive conceptualization of perfectionism, 80 community-recruited, highly perfectionistic individuals were randomly allocated to 12 sessions of group DRT (n = 41; 5 groups) or group PST (n = 39; 5 groups). Patients completed measures of dysfunctional attitudes, self-criticism, self-esteem, and self-reassurance at pre-, mid-, and post-treatment, and six months post-treatment. Results: Multigroup latent growth curve modeling revealed significant (p < .05) decreases in dysfunctional attitudes, concern over mistakes, two types of self-criticism, and self-esteem problems, along with a significant increase in self-reassurance, from pre-treatment to six-month follow-up in both DRT and PST. Moderate-to-large between-group differences favoring DRT over PST were found for dysfunctional attitudes and self-reassurance. A majority of patients in both conditions maintained reliable improvement at six-month follow-up in dysfunctional attitudes, concern over mistakes, and self-criticism focused on inadequacy. Conclusion: Findings provide evidence for the use of psychodynamic group therapy approaches in treating perfectionism-related attitudes and self-relational elements of perfectionism, and support the relative efficacy of DRT for dysfunctional attitudes and self-reassurance.

Toward a coordinated understanding of hydro-biogeochemical root functions in tropical forests for application in vegetation models.

Tropical forest root characteristics and resource acquisition strategies are underrepresented in vegetation and global models, hampering the prediction of forest-climate feedbacks for these carbon-rich ecosystems. Lowland tropical forests often have globally unique combinations of high taxonomic and functional biodiversity, rainfall seasonality, and strongly weathered infertile soils, giving rise to distinct patterns in root traits and functions compared with higher latitude ecosystems. We provide a roadmap for integrating recent advances in our understanding of tropical forest belowground function into vegetation models, focusing on water and nutrient acquisition. We offer comparisons of recent advances in empirical and model understanding of root characteristics that represent important functional processes in tropical forests. We focus on: (1) fine-root strategies for soil resource exploration, (2) coupling and trade-offs in fine-root water vs nutrient acquisition, and (3) aboveground-belowground linkages in plant resource acquisition and use. We suggest avenues for representing these extremely diverse plant communities in computationally manageable and ecologically meaningful groups in models for linked aboveground-belowground hydro-nutrient functions. Tropical forests are undergoing warming, shifting rainfall regimes, and exacerbation of soil nutrient scarcity caused by elevated atmospheric CO2. The accurate model representation of tropical forest functions is crucial for understanding the interactions of this biome with the climate.

Las características de las raíces de los bosques tropicales y las estrategias de adquisición de recursos están subrepresentadas en modelos de vegetación, lo que dificulta la predicción del efecto de cambio de clima para estos ecosistemas ricos en carbono. Los bosques tropicales a menudo tienen combinaciones únicas a nivel mundial de alta biodiversidad taxonómica y funcional, estacionalidad de precipitación, y suelos infértiles, dando lugar a patrones distintos en los rasgos y funciones de las raíces en comparación con los ecosistemas de latitudes más altas. Integramos los avances recientes en nuestra comprensión de la función subterránea de los bosques tropicales en modelos de vegetación, centrándonos en la adquisición de agua y nutrientes. Ofrecemos comparaciones de avances recientes en la comprensión empírica y de modelos de las características de las raíces que representan procesos funcionales importantes en los bosques tropicales. Nos centramos en: (1) estrategias de raíces finas para adquisición de recursos del suelo, (2) acoplamiento y compensaciones entre adquisición del agua y de nutrientes, y (3) vínculos entre funciones sobre tierra y debajo del superficie en bosques tropicales. Sugerimos vías para representar estas comunidades de plantas extremadamente diversas en grupos computacionalmente manejables y ecológicamente significativos en modelos. Los bosques tropicales se están calentando, tienen cambios en los regímenes de lluvias, y tienen una exacerbación de la escasez de nutrientes del suelo causada por el elevado CO2 atmosférico. La representación precisa de las funciones de los bosques tropicales en modelos es crucial para comprender las interacciones de este bioma con el clima.

Automatic Self Recriminations: Development and Validation of a Measure of Self-Condemnatory Internal Dialogue.

This article introduces a measure of self-condemnatory internal dialogue as an element of the relationship with the self: The Automatic Self-Recrimination Scale (ASRS). Using the construct validation approach to test construction, we describe the initial development of items and report on findings from a clinical and nonclinical sample showing the ASRS is best understood as a multidimensional measure of self-critical internal dialogue composed of one higher-order factor and four lower-order facets: Not Mattering, Self as Failure, Undeserving Self, and Loathsomeness. The overall scale and four subscales demonstrated acceptable internal consistency and test-retest reliability. Moreover, there was evidence of good convergent and incremental validity of the ASRS subscales with measures of perfectionism, self-criticism, and dysfunctional attitudes. Overall, the ASRS appears to be a reliable and valid measure of an automatic self-recriminatory internal dialogue.

The influence of carbon dioxide on cerebral metabolism and oxygen consumption: combining multimodal monitoring with dynamic systems modelling.

Hypercapnia increases cerebral blood flow. The effects on cerebral metabolism remain incompletely understood although studies show an oxidation of cytochrome c oxidase, Complex IV of the mitochondrial respiratory chain. Systems modelling was combined with previously published non-invasive measurements of cerebral tissue oxygenation, cerebral blood flow, and cytochrome c oxidase redox state to evaluate any metabolic effects of hypercapnia. Cerebral tissue oxygen saturation and cytochrome oxidase redox state were measured with broadband near infrared spectroscopy and cerebral blood flow velocity with transcranial Doppler ultrasound. Data collected during 5-min hypercapnia in awake human volunteers were analysed using a Fick model to determine changes in brain oxygen consumption and a mathematical model of cerebral hemodynamics and metabolism (BrainSignals) to inform on mechanisms. Either a decrease in metabolic substrate supply or an increase in metabolic demand modelled the cytochrome oxidation in hypercapnia. However, only the decrease in substrate supply explained both the enzyme redox state changes and the Fick-calculated drop in brain oxygen consumption. These modelled outputs are consistent with previous reports of CO2 inhibition of mitochondrial succinate dehydrogenase and isocitrate dehydrogenase. Hypercapnia may have physiologically significant effects suppressing oxidative metabolism in humans and perturbing mitochondrial signalling pathways in health and disease.

CBFA2T3::GLIS2 pediatric acute megakaryoblastic leukemia is sensitive to BCL-XL inhibition by navitoclax and DT2216.

ABSTRACT: Acute megakaryoblastic leukemia (AMKL) is a rare, developmentally restricted, and highly lethal cancer of early childhood. The paucity and hypocellularity (due to myelofibrosis) of primary patient samples hamper the discovery of cell- and genotype-specific treatments. AMKL is driven by mutually exclusive chimeric fusion oncogenes in two-thirds of the cases, with CBFA2T3::GLIS2 (CG2) and NUP98 fusions (NUP98r) representing the highest-fatality subgroups. We established CD34+ cord blood-derived CG2 models (n = 6) that sustain serial transplantation and recapitulate human leukemia regarding immunophenotype, leukemia-initiating cell frequencies, comutational landscape, and gene expression signature, with distinct upregulation of the prosurvival factor B-cell lymphoma 2 (BCL2). Cell membrane proteomic analyses highlighted CG2 surface markers preferentially expressed on leukemic cells compared with CD34+ cells (eg, NCAM1 and CD151). AMKL differentiation block in the mega-erythroid progenitor space was confirmed by single-cell profiling. Although CG2 cells were rather resistant to BCL2 genetic knockdown or selective pharmacological inhibition with venetoclax, they were vulnerable to strategies that target the megakaryocytic prosurvival factor BCL-XL (BCL2L1), including in vitro and in vivo treatment with BCL2/BCL-XL/BCL-W inhibitor navitoclax and DT2216, a selective BCL-XL proteolysis-targeting chimera degrader developed to limit thrombocytopenia in patients. NUP98r AMKL were also sensitive to BCL-XL inhibition but not the NUP98r monocytic leukemia, pointing to a lineage-specific dependency. Navitoclax or DT2216 treatment in combination with low-dose cytarabine further reduced leukemic burden in mice. This work extends the cellular and molecular diversity set of human AMKL models and uncovers BCL-XL as a therapeutic vulnerability in CG2 and NUP98r AMKL.

Lumbar Bone Stress Injuries and Nonunited Defects in Elite Australian Cricket Players.

OBJECTIVE: To describe the presentation and management of lumbar bone stress injuries (LBSI), recurrent LBSI, and lumbar nonunited defects in elite Australian male and female cricket players. DESIGN: Retrospective case series. SETTING: Professional domestic and international cricket teams over 13 seasons. PARTICIPANTS: Elite Australian cricket players. INDEPENDENT VARIABLES: Symptomatic LBSI requiring time off cricket and lumbar nonunited defects, both confirmed by imaging. MAIN OUTCOME MEASURES: Incidence, presentation, history, healing, and management. RESULTS: 211 LBSI were identified at an average incidence of 5.4 per 100 players per season. LBSI were most common in male pace bowlers younger than 20 years of age (58.1 per 100 players per season), however, were also observed in older players, females, and non-pace bowlers. Recurrent LBSI accounted for 33% (27%-40%) of all LBSI. Median days to return to match availability was 182 (128-251) days for all LBSI, with a shorter time frame observed for new and less severe injuries, and male spin bowlers. Healing was demonstrated in 87% (81%-91%) of all LBSI cases. 29 nonunited defects were identified and predisposed subsequent pain, LBSI, and spondylolisthesis. CONCLUSIONS: LBSI are experienced by approximately 5.4 in every 100 elite Australian cricket players per season, with a high time cost of approximately 4 to 8 months. Nonunited defects also have a high time cost with associated subsequent lumbar spine issues. The findings of this study reinforce the importance of early detection and conservative management of LBSI, particularly for younger male pace bowlers and players with recurrent LBSI, which may be supported by MRI.

Topical ivermectin 1.0% cream in the treatment of ocular demodicosis.

PURPOSE: Ocular demodicosis can cause debilitating ocular surface disease. As ivermectin is effective at reducing Demodex proliferation in rosacea, this study investigated the efficacy of topical ivermectin 1.0% cream in treating ocular demodicosis. METHODS: This retrospective single-centre clinical practice chart analysis involved the off-label treatment of patients who had ocular demodicosis with topical ivermectin 1.0 % cream (Soolantra, Galderma Ltd, UK) applied nightly to the lid margins of both eyes for 3 months. Ocular surface health was assessed at baseline when the treatment was prescribed and followed up at 3 and 12 months after baseline. Slit lamp biomicroscopy was used to take digital images of the upper eyelid lashes. Manual image analysis with ImageJ was conducted by a masked assessor to quantify signs of ocular demodicosis including the number of lashes with collarettes, with visible Demodex tails and with follicle pouting. RESULTS: Data from a total of 75 patients with ocular demodicosis were analysed for this study (mean age 66.6 ± 13.9 years, 44 female). The numbers of lashes with collarettes (Median [Interquartile range]: 8 [4-13] at baseline to 0 [0-2] at the final visit, p < 0.001) and lashes with follicle pouting (3 [1-5] at baseline to 0 [0-1.8] at the final visit, p < 0.001) decreased with treatment. Any sign of lashes with visible tails was eliminated by the final visit (p < 0.007). Fluorescein staining severity score also improved, particularly from baseline (1 [0-2]) to the second visit (0 [0-1], p < 0.001). CONCLUSIONS: The findings of this study show evidence for the efficacy of a 3-month course of topical ivermectin 1.0% cream in treating ocular demodicosis as indicated by reduction in collarettes, follicle pouting and visible Demodex tails. More research is warranted to improve the diagnosis, management and monitoring of this condition which is often overlooked or misdiagnosed.