Search

Ageing is associated with altered neuroendocrine function. In the context of the hypothalamic supraoptic nucleus, which makes the antidiuretic hormone vasopressin, ageing alters acute responses to hyperosmotic cues, rendering the elderly more susceptible to dehydration. Chronically, vasopressin has been associated with numerous diseases of old age, including type 2 diabetes and metabolic syndrome. Bulk RNAseq transcriptome analysis has been used to catalogue the polyadenylated supraoptic nucleus transcriptomes of adult (3 months) and aged (18 months) rats in basal euhydrated and stimulated dehydrated conditions. Gene ontology and Weighted Correlation Network Analysis revealed that ageing is associated with alterations in the expression of extracellular matrix genes. Interestingly, whilst the transcriptomic response to dehydration is overall blunted in aged animals compared to adults, there is a specific enrichment of differentially expressed genes related to neurodegenerative processes in the aged cohort, suggesting that dehydration itself may provoke degenerative consequences in aged rats.

Recent advances in machine learning (ML) methods have led to substantial improvement in materials property prediction against community benchmarks, but an excellent benchmark score may not imply good generalization of performance. Here we show that ML models trained on the Materials Project 2018 (MP18) dataset can have severely degraded prediction performance on new compounds in the Materials Project 2021 (MP21) dataset. We document performance degradation in graph neural networks and traditional descriptor-based ML models for both quantitative and qualitative predictions. We find the source of the predictive degradation is due to the distribution shift between the MP18 and MP21 versions. This is revealed by the uniform manifold approximation and projection (UMAP) of the feature space. We then show that the performance degradation issue can be foreseen using a few simple tools. Firstly, the UMAP can be used to investigate the connectivity and relative proximity of the training and test data within feature space. Secondly, the disagreement between multiple ML models on the test data can illuminate out-of-distribution samples. We demonstrate that the simple yet efficient UMAP-guided and query-by-committee acquisition strategies can greatly improve prediction accuracy through adding only 1~\% of the test data. We believe this work provides valuable insights for building materials databases and ML models that enable better prediction robustness and generalizability.

The kidney of the one-humped camel has a remarkable capacity to preserve water and solute during extremes of long-term dehydration. We investigated the effects of dehydration and subsequent rehydration on camel kidney morphology at the ultrastructural level and the expression of aquaporins and solute carrier proteins. In light microscopy, dehydration induced few degenerative and necrotic changes in cells of the cortical tubules with little effect on medullary cells. Ultrastructural changes were mainly observed in some of the glomerular and tubular cells with insignificant changes in the collecting ducts of medulla. These changes included condensation of nuclear chromatin, vacuolization of cytoplasm, swelling of mitochondria, degradation or loss of brush borders of proximal tubules, cracking of major processes of some podocytes and degeneration of lysosomes and endoplasmic reticulum. Cell death, apoptotic-like bodies and changes in the basolateral membranes were infrequent and nephrolithiasis was not detected. Chronic nephropathy, mainly interstitial fibrosis and glomerular sclerosis induced by recurrent dehydration in human and animal models were not observed. Modulation of SLC proteins, AQP 1, 2, 3, 4, 9 and regulation of gene mRNAs expression levels during dehydration/rehydration play important role in water conservation and cell protection favoring kidney cellular restoration to near normal.

Opsin 3 (Opn3) is a light-sensitive protein present throughout the mammalian brain, although its functions in this organ are currently unknown. Since Opn3 encoded mRNA increases in the supraoptic nucleus (SON) of the hypothalamus in response to hyperosmotic stimuli, we have explored the role of Opn3 in this nucleus. By in situ hybridization, we have demonstrated that Opn3 is expressed in neurones expressing both arginine vasopressin and oxytocin in the rat SON, suggesting that OPN3 functions in both neuronal types. Gene profiling analysis by RNA-seq suggested that neuropeptide production is impaired when knocking down Opn3 in the rat SON, as confirmed by quantitative PCR and immunolabelling. Knocking down Opn3 in the rat SON altered physiological parameters including water intake, body temperature and motor activity. Altogether the data indicates that Opn3 in the SON is involved in the regulation of a number of neuropeptides and other proteins that participate in water homeostasis, body temperature and motor activity.

The performance in hydro-electric turbine casting and repair requires understanding of how process parameters and chemistry selection affect solidification microstructures. The aim of this study is to provide a quantitative phase-field formulation for process-microstructure relationships that seeks to model stainless steels. We have developed a phase-field model to simulate austenitic stainless steel solidification under experimental thermal histories. To this end we look at a pseudo-binary approximations for numerical efficiency. The pseudo-binary formulation is underpinned by the alloying element equivalent value, a metallurgical tool used to analyze the microstructural impact of “minor” alloying elements in stainless steels. For model validation we develop thin wall casting experiments to measure the thermal history and chemistry controlled microstructure. The models incorporate a thermodynamic parameterization and are linked to a thermal-phase transformation model which represents the experimentally measured thermal history. The results display a good agreement with the primary branch spacing and cellular to dendritic transition of the casting experiments. These models and software provide the basis for future expansion to include more complex microstructures.

Water conservation is vital for life in the desert. The dromedary camel (Camelus dromedarius) produces low volumes of highly concentrated urine, more so when water is scarce, to conserve body water. Two hormones, arginine vasopressin (AVP) and oxytocin (OXT), both produced in the supraoptic nucleus (SON), the core hypothalamic osmoregulatory control centre, are vital for this adaptive process, but the mechanisms that enable the camel SON to cope with osmotic stress are not known. To investigate the central control of water homeostasis in the camel, we first built three dimensional models of the camel SON based on the expression of the AVP and OXT mRNAs in order to facilitate sampling. We then compared the transcriptomes of the SON under control and WD conditions and identified genes that change in expression due to hyperosmotic stress. By comparing camel and rat datasets, we have identified common elements of the WD transcriptomic response network, as well as elements, such as extracellular matrix remodelling and upregulation of angiotensinogen expression, that appear to be unique to the dromedary camel and that may be essential adaptations necessary for life in the desert.

Introduction This study evaluates the effects of the multi-pressure dial (MPD) on steady-state pattern electroretinography (ss-pERG) parameters. The study is a randomized, controlled, prospective, pilot trial in a private practice setting with ocular hypertensive (OHT), glaucoma suspect, and open-angle glaucoma (OAG) subjects. Methods This study included nine patients (64 ± 9.0 years, nine female) with OHT, glaucoma suspect, or mild OAG. One eye of each subject was randomized to receive negative periocular pressure, while the contralateral eye served as the intrasubject control through the goggle without negative pressure. The Diopsys High Contrast Sensitivity ss-pERG protocol was conducted on both eyes of each subject while wearing the MPD device. Application of negative periocular pressure was set at 50% of baseline intraocular pressure for each study eye. Results Following 2 h of negative periocular pressure application, the difference in MagnitudeD (MagD) from baseline for eyes randomized to receive negative periocular pressure (+ 0.17 versus − 0.26) was statistically significant (p = 0.023). Over the same period, the change in MagD/Magnitude (MagD/Mag ratio) from baseline for eyes randomized to receive negative periocular pressure was also higher (+ 0.14 versus − 0.16), compared to the control eyes, approached significance (p = 0.059). Conclusions Following 2 h of MPD wear, the measured MagD and MagD/Mag ratio improved compared to control, suggesting that negative periocular pressure application to the anterior globe can lead to short-term improvement in one measure of retinal ganglion cell function.

In this article, we review the latest research related to presbyopia management at the time of cataract surgery with attention focused on available options in the USA. With refractive cataract surgery, patient satisfaction is largely dependent on preoperative expectations with regard to spectacle independence and photic phenomena. Monovision with monofocal intraocular lenses have the highest rates of spectacle dependence but the lowest rate of photic phenomena. Extended depth of focus lenses provides excellent distance and intermediate vision, but patients often require glasses for near vision in addition to having mild glare and halos. Refractive multifocal lenses tend to have the highest rates of photic phenomena. Both diffractive and refractive multifocal lenses had excellent near and distance visual acuity but difficulty with intermediate vision. Trifocal lenses provided the most consistent vision at near, intermediate, and distance and only had moderate amounts of glare and halos with excellent patient satisfaction. The current market of intraocular lenses provides patients with the opportunity to experience spectacle independence following refractive cataract surgery. Current options include monovision with monofocal lenses, multifocal intraocular lenses, extended depth of focus intraocular lenses, and pseudo-accomodative intraocular lenses. Future technology is focusing on accommodation, pinhole apertures, and improved multifocality.

The advancement of analytical methods for nanoparticle measurements is critical both for the growing industrial exploitation of engineered nanoparticles and for developing robust strategies to understand and control the concentration of nanomaterials in humans and the environment. For high value nanoparticles, the measurement of nanoparticle number concentration in a liquid directly impacts the ability to assess the scale and reproducibility of the production process, it allows optimisation of efficiency and supports regulatory compliance. This measurement is also useful to monitor and control the intentional or accidental release of engineered nanoparticles into the environment at the production plant, as well as by end-users., peer-reviewed

Despite their proven level of safety and patient satisfaction, laser-assisted in situ keratomileusis (LASIK) and other corneal refractive surgeries have faced scrutiny in the media recently as they have been linked to suicides following poor outcomes. Between 1998 and 2006, the Food and Drug Administration (FDA) received 140 official complaints linked to LASIK surgery, spurring the development of a Patient-Reported Outcomes With LASIK (PROWL) questionnaire to measure quality of life-related outcomes after LASIK. Dry eye symptoms are the most common complication after LASIK, but the overall patient satisfaction rate after surgery remains around 95 percent with around 1 million surgeries performed in the U.S. each year. Three cases involving completed or attempted suicide after corneal refractive surgery are discussed. Considerations and recommendations including preoperative screening and counseling to help prevent similar outcomes in the future are provided.We seek to discuss the facts surrounding LASIK surgery, and the factors that may contribute to a purported connection between corneal refractive surgery and mental illness.Patients will continue to pursue refractive surgery with high expectations. Prevention by proper screening and setting of realistic expectations paired with early recognition and treatment may help minimize the effect of complications. Less-than-perfect cases must be reported to build a more robust body of literature on the topic. This will help highlight the procedures' safety and efficacy while improving management when complications occur. Performed for the right patient, at the right time, refractive surgery has the potential for consistently transformative results.

Ophthalmic manifestations of disseminated intravascular coagulation (DIC) in a newborn are rare. Ocular involvement typically involves the posterior segment bilaterally and manifests as choroidal and/or retinal hemorrhages associated with fibrin thrombi in the choriocapillaris. We present the case of a newborn girl with DIC secondary to sepsis who subsequently developed nonclearing hyphema, related secondary cataract, 360° posterior synechiae, and nonclearing vitreous hemorrhage in the right eye and diffuse retinal hemorrhage in the left eye. The right fundus was not visible because of intraocular bleeding. The patient underwent cataract surgery at 39 days of life and was left aphakic. Two weeks later, she required subsequent vitrectomy because of a nonclearing vitreous hemorrhage. She developed amblyopia of the right eye and a right esotropia that required strabismus surgery. At 7 years of age, the patient's visual acuity was 20/50 in the right eye and 20/20 in the left eye.

Magnesium silicide-based thermoelectric materials have several attractive attributes, including high performance, low cost, and low toxicity. In contrast to prior work which relied on powder metallurgy methods, this work reports on the solidification process of a potentially high-throughput method to synthesize Sn-substituted magnesium silicide with Bi dopants (Mg2Si1−x−ySnxBiy) via solidification from melt. This approach yields material with relatively good thermoelectric properties (maximum ZT ~ 1.0), with greatly increased throughput in comparison to powder metallurgy processes. The microstructure and composition were characterized, and the solidification process was elucidated by comparing phase-field simulation to experimentally observed morphologies.

Background The EORTC QLQ-MY20 is a widely used myeloma-specific patient-reported outcome measure originally developed in 1999. It consists of 20 items covering Disease Symptoms (DS), Side Effects (SE), Future Perspectives (FP) and Body Image (BI). Novel treatments and multiple lines of therapy mean the treatment for myeloma patients and life expectancy has changed dramatically and there is a need to ensure the measurement of health-related quality of life remains current for these patients. The original validation study was almost exclusively in newly diagnosed patients reflecting the nature of clinical trials at the time. This review was conducted as part of an EORTC funded grant to update the QLQ-MY20, with the aim of summarising the published literature from the QLQ-MY20 to date including any further validation results for the QLQ-MY20. Methods Literature search was conducted using the Ovid SP platform (Medline, EMBASE and PsycINFO) from 1996 (first release of the questionnaire). Abstracts were included if they were reporting: a clinical study using the QLQ-MY20 or validation studies. Information about the study design was extracted alongside whether the population were newly diagnosed or relapsed, and the supplementary instruments used alongside the QLQ-MY20. For randomised control trials, information on the type of analysis and results were also extracted. For validation studies data on the instrument structure and data distribution, reliability, validity and ability to detect change/interpretation of change scores was extracted. Results 656 abstracts were screened to 74 included papers (65 clinical studies, of which 21 were interventional clinical trials, and 9 validation studies). Supplementary instruments used alongside QLQ-C30 and MY20 included BPI-SF (Brief pain inventory short form), EQ-5D-5L (generic preference-based measure), FACT-GOG-Ntx (neurotoxicity) and the EORTC QLQ-CIPN20 (chemotherapy induced peripheral neuropathy). In contrast with the original validation study, 34 out of 43 clinical studies included either exclusively relapsed patients (n=24) or a mix of newly diagnosed and relapsed (n=9). DS and SE were the most commonly reported results from the QLQ-MY20. Further validation studies supported the factor structure, reliability and validity, with the only potential issue being observed ceiling effects for the BI subscale. Conclusions The shift in HRQOL measurement to patients experiencing multiple lines of treatment and novel treatments, highlights the need for updating the conceptual model for the QLQ-MY20. Interviews are currently underway internationally with 90 patients and 20 healthcare professionals to identify the issues relevant to myeloma patients today. The current questionnaire has been shown to be psychometrically valid and can be supplemented in the interim using item banks or existing questionnaires to cover new side effects specific to novel treatments.

In this paper, we develop a mean-field model for simulating the microstructure evolution of crystalline materials during static recrystallization. The model considers a population of individual cells (i.e. grains and subgrains) growing in a homogeneous medium representing the average microstructure properties. The average boundary properties of the individual cells and of the medium, required to compute growth rates, are estimated statistically as a function of the microstructure topology and of the distribution of crystallographic orientations. Recrystallized grains arise from the competitive growth between cells. After a presentation of the algorithm, the model is compared to full-field simulations of recrystallization performed with a 2D Vertex model. It is shown that the mean-field model predicts accurately the evolution of boundary properties with time, as well as several recrystallization parameters including kinetics and grain orientations. The results allow one to investigate the role of orientation spreads on the determination of boundary properties, the formation of recrystallized grains and recrystallization kinetics. The model can be used with experimentally obtained inputs to investigate the relationship between deformation and recrystallization microstructures.

Michael D Greenwood,1 Richard A Gorham,2 Keeley R Boever2,3 1Vance Thompson Vision, West Fargo, ND, USA; 2Ektropia Solutions LLC, Laguna Beach, CA, USA; 3Vance Thompson Vision, Sioux Falls, SD, USACorrespondence: Michael D GreenwoodVance Thompson Vision, 505 32nd Ave E, Suite B, West Fargo, ND 58078, USATel +1 701-566-5390Fax +1 701-639-7199Email Michael.Greenwood@VanceThompsonVision.comPurpose: To determine the preference of patients undergoing bilateral LASIK for either the dexamethasone intracanalicular insert or topical prednisolone acetate for control of postoperative symptoms and ocular surface signs.Methods: In this randomized clinical trial, one eye was randomized to receive the dexamethasone insert or topical prednisolone acetate 1% four times daily for one week and 2 times daily for a second week; the fellow eye received the alternate therapy. One month postoperatively, patient preference for these two therapies was assessed using an adapted COMTOL questionnaire. Ocular comfort was assessed using the SPEED questionnaire. Corneal staining and uncorrected distance visual acuity (UDVA) were also assessed.Results: Twenty patients participated. At Month 1, 80% of patients preferred the dexamethasone insert, 10% preferred prednisolone acetate, and 10% expressed no preference (p< 0.001). SPEED scores measuring ocular comfort/discomfort related to dry eye symptoms were similar between groups (p=0.72), and both the incidence of patient-reported ocular dryness and the corneal staining scores were similar between groups. Both groups attained the same final UDVA.Conclusion: Patients undergoing elective bilateral femtosecond LASIK surgery overwhelmingly (by an 8-to-1 margin) preferred the dexamethasone insert to topical prednisolone acetate for postoperative treatment. The insert produced comparable ocular comfort, corneal staining, and visual acuity outcomes to topical prednisolone. The insert is an appropriate means of postoperative symptom control in this quality of life-conscious population.Keywords: dexamethasone, Dextenza, LASIK, randomized trial, patient preference, ocular surface symptoms

In this work, we numerically investigate the effect of building direction on the solidification behaviour and microstructure evolution of direct metal laser sintered (DMLS) AlSi10Mg. The building direction, as previously proved in experimental studies, can influence the solidification behavior and promote morphological transitions in cellular dendritic microstructures such as columnar-to-equiaxed transition (CET). We develop a thermal model to systemically address the impact of laser processing conditions and building direction on time-dependent solidification parameters including pulling velocity, thermal gradients, and cooling rates of the molten pool during DMLS of AlSi10Mg alloy. We then study the microstructure evolution of DLMS-AlSi10Mg for horizontal and vertical building directions. The present model includes heterogenous nucleation on inoculant particles that triggers the CET, and its results are consistent with the predictions of a previously developed model. In addition, findings are compared with experimental observations to ensure the accuracy of obtained numerical results.

To understand the current and new technology surrounding episcleral venous pressure (EVP). Episcleral venous pressure plays a vital role in calculating intraocular pressure based on the formula IOP = (Q − U)/c + EVP where Q is the aqueous flow rate, U is the pressure-insensitive uveoscleral outflow rate, c is the outflow facility, and EVP is episcleral venous pressure. Various methods for measuring EVP, including direct, indirect, and non-invasive methods, have been explored. These methods have great variability, with findings ranging between 5.1 and 11.4 mmHg. The effect of various medications on EVP has also been examined, and newer medications that aim to lower EVP are being developed. Future studies and techniques are needed to develop more reliable and accurate measurements of EVP. With these improved diagnostics, we will be able to identify an individual’s EVP, which will allow for targeted therapy with medications or surgery.

Phase field (PF) models are one of the most popular methods for simulating solidification microstructures due to their fundamental connections to the physics of phase transformations. However, these methods are numerically very stiff due to the multiple length scales in a solidifying material, from the nanoscopic solid-liquid interface, to dendritic structures on the order of hundreds of microns. While this problem can be greatly alleviated by thin-interface analytical treatments of the PF equations, additional numerical methods are required to explore experimentally relevant sample sizes and times scales. It was shown about 18 years ago that the use of dynamic adaptive mesh refinement (AMR) can alleviate this problem by exploiting the simple fact that the majority of the solidification kinetics occur at the solid-liquid interface, which scales with a lower dimensionality than the embedding system itself. AMR methods, together with asymptotic analysis, nowadays provide one of the most efficient numerical strategies for self-consistent quantitative PF modelling of solidification microstructure processes. This paper highlights the latest developments in the AMR technique for 3D modelling of solidification using classical phase field equations. This includes a move away from finite element techniques to faster finite differencing through the use of dynamic mini-meshes which are each associated with each node of a 3D Octree data structure, and distributed MPI parallelism that uses a new communication algorithm to decompose a 3D domain into multiple adaptive meshes that are spawned on separate cores. The numerical technique is discussed, followed by demonstrations of the new AMR algorithm on select benchmark solidification problems, as well as some illustrations of multi-phase modelling using a recently developed multi-order parameter phase field model.

Introduction: Novel triplet regimens containing immunomodulatory drugs and proteasome inhibitors (PIs) have improved outcomes and extended survival for patients (pts) with RRMM. However, use of combination therapies (tx) over an extended period may increase tx-related symptom burden and impact health-related quality of life (HRQoL). In the randomized phase 2 ELOQUENT-3 trial (NCT02654132), the efficacy and safety of elotuzumab (ELO) + pomalidomide + dexamethasone (EPd) vs pomalidomide + dexamethasone (Pd) were assessed in pts with RRMM previously treated with lenalidomide (LEN) and a PI. EPd had a 46% reduction in the risk of death vs Pd, without increasing toxicity or affecting HRQoL through 18.3 months (mo) follow-up (f/u) (Dimopoulos MA, et al. N Engl J Med 2018;379:1811-1822; Weisel K, et al. Blood 2019;134[suppl 1];Abstract 3480). To inform tx decision-making, it is important to measure how effective tx can preserve HRQoL without a negative impact. Here we evaluate updated HRQoL findings from ELOQUENT-3 after 4 years of EPd tx (data cutoff, February 2021), including the first report of responder analyses. Methods: Pt-reported outcomes (PROs) were exploratory endpoints, assessed using the EuroQoL 5 dimension 3 level (EQ-5D-3L) instrument and the MD Anderson Symptom Inventory MM module (MDASI-MM). EQ-5D-3L incorporates a global health visual analog scale (VAS; score range 0-100) and a descriptive system consisting of 5 dimensions to which UK empirically derived weights were applied to generate a utility index (UI; score range −0.59 to −1); MDASI-MM measures total symptom severity (20 items) and symptom interference (6 items) (score range 0-10). Minimally important differences (MIDs)/responder definitions were 0.08 (UI), 7 (VAS), or based on the standard error of the mean (MDASI-MM). Higher scores indicate better health for EQ-5D-3L, but more severe symptoms for MDASI-MM. PRO data were collected at baseline (BL), the start of every 28-day tx cycle, the end of tx, and during f/u every 3 mo. All randomized pts with BL and ≥ 1 post-BL assessment were included in the PRO analysis. Completion rates are presented out of the expected population. Changes from BL were evaluated descriptively and using a mixed model for repeated measures. Time to first deterioration was defined as time to first change from BL that was at least the responder definition threshold; hazard ratios (HR) were calculated using a Cox proportional hazard model. Responder analyses present the proportion of improved/stable/worsened pts at each time point based on responder definition. Results: Of 117 randomized pts, 106 (EPd n=55; Pd n=51) were included in PRO analyses. BL characteristics of the PRO population were balanced between arms and representative of the entire study population. Except for 2 cycles, PRO completion rates were ≥ 80% for both PROs for all on-tx time points where ≥ 10 pts remained on study. Although 11 pts remained on EPd until cycle 29, between-tx arm HRQoL analysis was not feasible after cycle 13 due to low Pd pt numbers. After end of tx, f/u PRO data were available for a longer period for EPd vs Pd (for ≥ 10 pts up to f/u visit 6 (18 mo) for EPd and up to f/u visit 2 (6 mo) for Pd). Mean BL scores were similar between EPd and Pd arms, and least squares mean change from BL data showed no overall clinically meaningful differences between tx arms for EQ-5D-3L UI or VAS, or MDASI-MM total symptom severity, symptom interference, or items of pain, fatigue, or bone pain. For the EPd tx arm, the proportion of pts who either improved or maintained stable HRQoL based on responder analyses up until cycle 13 ranged 82%-96% for MDASI total symptom score and 64%-85% for MDASI symptom interference (Fig. 1). There were no statistically significant differences in time to first deterioration between arms for key EQ-5D-3L and MDASI-MM scales. Kaplan-Meier plots presenting f/u data up to 48 mo were overlapping, indicating no HRQoL differences between EPd and Pd (Fig. 2). Conclusions: HRQoL was similar between pts who received triplet EPd and doublet Pd in ELOQUENT-3, thus the addition of ELO to Pd did not significantly impact time to deterioration in HRQoL over an extended f/u period. These pt-reported findings complement existing f/u data showing that EPd tx resulted in clinically meaningful improvements in survival without detriment to HRQoL, further supporting the clinical value of EPd in adult pts with RRMM who have received ≥ 2 prior tx including LEN and a PI. Figure 1 Figure 1. Disclosures Weisel: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy; Novartis: Honoraria; Pfizer: Honoraria. Dimopoulos: BMS: Honoraria; Takeda: Honoraria; Beigene: Honoraria; Janssen: Honoraria; Amgen: Honoraria. San-Miguel: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Karyopharm, Merck Sharpe & Dohme, Novartis, Regeneron, Roche, Sanofi, SecuraBio, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Paner: Adaptive Biotechnologies: Consultancy; Amgen: Consultancy; GSK: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy; Oncopeptides: Consultancy; Rush University Medical Center: Consultancy, Current Employment; Sanofi: Consultancy; BMS: Consultancy. Taylor: Adelphi Values: Current Employment; BMS: Consultancy. Lord-Bessen: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Yao: BMS: Current Employment. Yip: Adelphi Values: Current Employment. Greenwood: Adelphi Values: Current Employment. Tang: BMS: Consultancy. Cavo: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Accommodations, Speakers Bureau; Novartis: Honoraria; Adaptive Biotechnologies: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithKline: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau; Bristol-Myers Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Additive manufacturing experiments using the laser powder bed fusion (LPBF) method reveal that changing the build direction can stimulate morphological transitions in the solidification microstructure. As a result, the final texture and material properties can be altered. In this work, we conduct numerical investigations to explore the effect of building direction on the microstructure evolution of dilute Al-Si alloy produced by the LPBF process. A finite element thermal model is developed to incorporate the effect of build direction on the thermal characteristics of the melt pool for a vertically and horizontally printed Al-Si powder layer. We then utilize a multi-order parameter phase-field model to probe the microstructure evolution of LPBF Al-Si alloy in the dilute limit under the aforementioned thermal conditions for horizontal and vertical printing strategies. The phase-field model described here can self-consistently emulate spontaneous formation of nuclei from inoculant particles and simulate morphological transitions. The accuracy of the phase-field model is validated through the numerical examination of morphological transitions under directional solidification conditions of a dilute Al-Si alloy and compared to the predictions of the analytical CET theory of Hunt [1]. The phase-field simulations and subsequent grain analysis of the microstructure under transient thermal conditions reveal that the nucleation rate and hence equiaxed to columnar microstructure ratio is notably higher in the horizontally built samples. These results are in consistence with experimental observations.

To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of a single-use dual blade (Kahook) in patients with mild to end-stage glaucoma.International multicenter ophthalmic care centers.Prospective interventional case series.Consecutive patients with glaucoma who had phacoemulsification plus goniotomy with the single-use dual blade were enrolled in this study. Each center collected deidentified clinical data, including preoperative and postoperative IOP, medication use, adverse events, and whether additional surgery was required during a 6-month follow-up.Of the 71 eyes included in this study, 70% had primary open-angle glaucoma. Other diagnoses included angle-closure, pigmentary, pseudoexfoliative, and normal-tension glaucoma. Sixty-five percent of eyes were classified as having mild to moderate glaucoma and 35%, severe glaucoma. The mean baseline IOP decreased from 17.4 mm Hg ± 5.2 (SD) to 12.8 ± 2.6 mm Hg 6 months postoperatively and the hypotensive medication use decreased from 1.6 ± 1.3 to 0.9 ± 1.0, respectively (P .001 and P = .005, respectively). The most common observation was blood reflux during surgery (39.4%).Single-use dual blade goniotomy plus phacoemulsification resulted in a significant and sustained reduction in IOP and a decrease in glaucoma medications after 6 months of follow-up.

Purpose of Review Glaucoma is the second leading cause of blindness worldwide and remains a disease with a complex underlying pathophysiology. Primary open-angle glaucoma (POAG) is glaucoma in the absence of known causes and often is associated with elevated intraocular pressure (IOP).

Trabecular microbypass stents are effective at lowering intraocular pressure in patients with mild to moderate glaucoma. Corneal hysteresis has been shown to correlate with reduction in intraocular pressure in patients using topical prostaglandin analogues and selective laser trabeculoplasty to treat glaucoma. The purpose of this study was to investigate whether baseline corneal hysteresis measurements were predictive of effectiveness of trabecular microbypass stents in treating glaucoma.This was a retrospective chart review of 163 eyes from 109 patients with primary open angle glaucoma that underwent simultaneous trabecular microbypass stenting and cataract surgery. This was a single center study with one surgeon performing all procedures.The eyes were grouped into quartiles according to baseline corneal hysteresis measurements. Baseline intraocular pressures among the four quartiles of baseline corneal hysteresis groups were similar (p=0.082, ANOVA). The average intraocular pressure reduction at 3 months post-operative visits were 3.67, 1.51, 2.83, and 2.09 mmHg for the first through fourth quartiles respectively, and these differences are insignificant overall (p=0.34, ANOVA). Likewise, no significant difference was detected in terms of reduction in glaucoma medications among the quartiles three months after surgery (p=0.78, ANOVA).Baseline corneal hysteresis does not appear to show any value in predicting intraocular pressure reduction in response to placement of a trabecular microbypass stent for treating glaucoma.

Keegan B Mechels,1 Michael D Greenwood,2 Ramu G Sudhagoni,3 John P Berdahl2 1Sanford School of Medicine, University of South Dakota, Vermillion, SD, 2Vance Thompson Vision, Sioux Falls, SD, 3School of Health Sciences, University of South Dakota, Vermillion, SD, USA Purpose: Descemet’s membrane endothelial keratoplasty (DMEK) is a minimally invasive partial corneal transplant procedure used in patients with failing endothelial membranes. This study aims to identify those factors which influence the need for a rebubble of the corneal graft. Methods: A total of 94 eyes that received DMEK between March 2014 and January 2016 at Vance Thompson Vision were used in the study. Demographic and graft data were collected from the patients and donors, and perioperative statistics of the procedures. A logistical regression was used to compare eyes that did and did not require a rebubble. Results: Among those characteristics that were included (patient age/sex, donor age/sex, death to processing time, donation to surgery time, death to procurement time, specular cell count density, burping procedure, postoperative day 1 intraocular pressure [IOP], and postoperative week 1 IOP, concurrent phacoemulsification, and how well the Descemet graft was centered), only a lower specular cell count density of the corneal graft, and a graft that was not well-centered correlated with needing a rebubble due to partial graft detachment (p=0.021) and (p=0.023), respectively. Conclusion: An increased specular cell count density may allow for better placement of the corneal graft by allowing for better unfolding in DMEK procedures. A well-centered graft may decrease postoperative complications by increasing adherence. Additionally, postoperative management of IOP may not affect the rebubble rate, and therefore should be left to the discretion of the provider to determine whether it is necessary. Keywords: descemet, rebubble, keratoplasty, DMEK

Introduction: Next-generation-sequencing (NGS) is increasingly used in clinical and research protocols for patients with cancer. NGS assays are routinely used in clinical laboratories to detect mutations bearing on cancer diagnosis, prognosis and personalized therapy. A typical assay may interrogate 50 or more gene targets that encompass many thousands of possible gene variants. Analysis of NGS data in cancer is a labor-intensive process that can become overwhelming to the molecular pathologist or research scientist. Although commercial tools for NGS data analysis and interpretation are available, they are often costly, lack key functionality or cannot be customized by the end user. Methods: To facilitate NGS data analysis in our clinical molecular diagnostics laboratory, we created a custom bioinformatics tool termed Houston Methodist Variant Viewer (HMVV). HMVV is a Java-based solution that integrates sequencing instrument output, bioinformatics analysis, storage resources and end user interface. Results: Compared to the predicate method used in our clinical laboratory, HMVV markedly simplifies the bioinformatics workflow for the molecular technologist and facilitates the variant review by the molecular pathologist. Importantly, HMVV reduces time spent researching the biological significance of the variants detected, standardizes the online resources used to perform the variant investigation and assists generation of the annotated report for the electronic medical record. HMVV also maintains a searchable variant database, including the variant annotations generated by the pathologist, which is useful for downstream quality improvement and research projects. Conclusions: HMVV is a clinical grade, low-cost, feature-rich, highly customizable platform that we have made available for continued development by the pathology informatics community.