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Contemporary computational accounts of instrumental conditioning have emphasized a role for a model-based system in which values are computed with reference to a rich model of the structure of the world, and a model-free system in which values are updated without encoding such structure. Much less studied is the possibility of a similar distinction operating at the level of Pavlovian conditioning. In the present study, we scanned human participants while they participated in a Pavlovian conditioning task with a simple structure while measuring activity in the human amygdala using a high-resolution fMRI protocol. After fitting a model-based algorithm and a variety of model-free algorithms to the fMRI data, we found evidence for the superiority of a model-based algorithm in accounting for activity in the amygdala compared to the model-free counterparts. These findings support an important role for model-based algorithms in describing the processes underpinning Pavlovian conditioning, as well as providing evidence of a role for the human amygdala in model-based inference.

A sample preparation method was developed for the screening of deoxynivalenol (DON) in wheat and wheat dust. Extraction was carried out with water and was successful due to the polar character of DON. For detection, an enzyme-linked immunosorbent assay (ELISA) was compared to the sensor-based techniques of surface plasmon resonance (SPR) and biolayer interferometry (BLI) in terms of sensitivity, affinity and matrix effect. The matrix effects from wheat and wheat dust using SPR were too high to further use this screenings method. The preferred ELISA and BLI methods were validated according to the criteria established in Commission Regulation 519/2014/EC and Commission Decision 2002/657/EC. A small survey was executed on 16 wheat lots and their corresponding dust samples using the validated ELISA method. A linear correlation (r = 0.889) was found for the DON concentration in dust versus the DON concentration in wheat (LOD wheat: 233 μg/kg, LOD wheat dust: 458 μg/kg).

Antibody-mediated imaging of amyloid β (Aβ) in Alzheimer's disease (AD) offers a promising strategy to detect and monitor specific Aβ species, such as oligomers, that have important pathological and therapeutic relevance. The major current limitation of antibodies as a diagnostic and imaging device is poor blood-brain-barrier permeability. A classical anti-Aβ antibody, 6E10, is modified with 10 kDa polyethylene glycol (PEG) and a positron emitting isotope, Copper-64 (t(½) = 12.7 h), and intravenously delivered to the TgCRND8 mouse model of Alzheimer's disease. Modification of 6E10 with PEG (6E10-PEG) increases accumulation of 6E10 in brain tissue in both TgCRND8 and wild type control animals. 6E10-PEG differentiates TgCRND8 animals from wild type controls using positron emission tomography (PET) and provides a framework for using antibodies to detect pathology using non-invasive medical imaging techniques.

It is increasingly accepted that the development of the academic writing required to succeed in higher education is most effective when embedded within the discipline in which students are studying and when integrated with formal teaching. The many initiatives and programmes discussed in this journal suggest a variety of models and collaborations in the move from generic study skills to the integration of writing in the disciplines. As a contribution to this, we discuss the evaluation of an academic writing module for Masters students in the School for International Development at the University of East Anglia. The module was devised collaboratively by the learning developer, subject specialist and postgraduate research students from the department. It was delivered by postgraduate research students, who also participated in its evaluation. The evaluation led to changes not only in the writing module itself but to the main Masters programme. We argue that the post graduate research students played a key role in these changes and that through dialogue between students and the department, academics who were only peripherally involved, nonetheless gained insights about students experience, potentially informing their future practice.

Tropical forests in developing countries are increasingly being valued for their role in carbon sequestration. Such interest is reflected in the emergence of international initiatives for Reducing Emissions from Deforestation and Forest Degradation (REDD+). REDD+ requires addressing both tropical forests as complex social-ecological systems and the multiple sectors involved in tropical forest resources, which may necessitate transformational change away from business-as-usual approaches to forest governance. We studied the potential for REDD+ to mobilize an influential coalition of actors promoting transformational change in forest governance in Papua New Guinea (PNG), a leading proponent of REDD+ internationally. Combining policy network approaches with the advocacy coalition framework, we identified four advocacy coalitions in the REDD+ policy domain in PNG and estimated the influence of each coalition. We found the most influential advocacy coalition is promoting the status quo rather than governance reforms capable of reducing deforestations and forest degradation, leading us to suggest that business as usual is the dominant perspective in the REDD+ policy domain in PNG. This may explain why, despite the large amount of REDD+ rhetoric, there has been only modest change in formal policy or practice in PNG to date. However, we did find influential coalitions calling for transformational change. Although these are currently minority coalitions, we identified several pathways through which they could increase their power to realize transformational change

Woodland caribou habitat management in northwestern Ontario is a complex spatial problem. The Strategic Forest Management Model (SFMM), a linear programming PC-based planning tool being developed in Ontario, was used to examine the impacts of alternative management strategies on caribou habitat. The management alternatives investigated included the cessation of timber management and maximising the present value of wood production without any explicit concern (in the model) for caribou. Three major findings are worth noting: 1) trying to maintain prime caribou habitat within active Forest Management Units will come at a cost to wood supply but the cost will depend on the absolute amount of area affected and the spatial configuration of that land in relation to mills. The cost of maintaining caribou habitat in one management unit at a level about 25 000 hectares is roughly $324 000 per year (about 3 cents for each Ontario resident). The imposition of an even-flow constraint on wood production is in fact potentially more costly; 2) Given the region is heavily dominated by spruce aged 90 years and over, forest succession and fire disturbance will likely cause large declines in prime caribou habitat in the near to medium term (20 to 40 years) even if no timber harvesting occurs; 3) The complexities of the trade-offs in this resource management problem highlight the limitations of any single modelling tool to satisfactorily address all issues. Planners need to take advantage of a wide range of analytical techniques to quantify the issues and formulate integrated policies.

We calculate the impedance and wake functions for laminated structures with parallel-plane and circular geometries in the ultrarelativistic limit. We critically examine the approximations used in the literature for the coupling impedance in laminated chambers and find that most of them are not justified because the wall surface impedance is large. A comparison between flat and circular geometry impedances is presented. We apply our calculation in a state-of-the-art beam dynamics simulation of the Fermilab Booster which includes nonlinear optics, laminated wakefields, and space charge impedance. The latter can have a significant effect away from the ultrarelativistic limit. Even though the simulations and the comparison with the experiment are done at the Booster injection energy, where the relativistic factor γ=1.42, we find good agreement between our calculation of the coherent tune shift and recent experimental measurements.

Although international comparisons of average student performance are a staple of U.S. educational debate, little attention has been paid to cross-national differences in the variability of performance. It is often assumed that the performance of U.S. students is unusually variable or that the distribution of U.S. scores is left-skewed – that is, that it has an unusually long ‘tail' of low-scoring students – but data from international studies are rarely brought to bear on these questions. This study used data from the Third International Mathematics and Science Study (TIMSS) to compare the variability of performance in the U.S., Australia, France, Germany, Hong Kong, Korea, and Japan; investigate how this performance variation is distributed within and between classrooms; and explore how well background variables predict performance at both levels. TIMSS shows that the U.S. is not anomalous in terms of the amount, distribution, or prediction of performance variation. Nonetheless, some striking differences appear between countries that are potentially important for both research and policy. In the U.S., Germany, Hong Kong, and Australia, between 42 and 47 percent of score variance was between classrooms. At the other extreme, Japan and Korea both had less than 10 percent of score variance between classrooms. Two-level models (student and classroom) were used to explore the prediction of performance by social background variables in four of these countries (the U.S., Hong Kong, France, and Korea). The final models included only a few variables; TIMSS lacked some important background variables, such as income, and other variables were dropped either because of problems revealed by exploratory data analysis or because of a lack of significance in the models. In all four countries, these sparse models predicted most of the between-classroom score variance (from 59 to 94 percent) but very little of the within-classroom variance. Korea was the only country in which the models predicted more than 5 percent of the within-classroom variance in scores. In the U.S. and Hong Kong, the models predicted about one-third of the total score variance, and almost all of this prediction was attributable to between-classroom differences in background variables. In Korea, only 19 percent of total score variance was predicted by the model, and most of this most of this was attributable to within-classroom variables. Thus, in some instances, countries differ more in terms of the structure and prediction of performance variance than in the simple amount of variance. TIMSS does not provide a clear explanation of these differences, but this paper suggests hypotheses that warrant further investigation.

H vessels are an essential link in angiogenic-osteogenic coupling and orchestrate the process of bone healing. H vessels are critically deficient in the setting of radiation-induced fractures, which have been reported to occur in up to 25% of patients undergoing radiotherapy. By increasing H-vessel proliferation, Deferoxamine (DFO) revitalizes the physiologic response to skeletal injury and accelerates irradiated fracture repair. H-vessel quantification is therefore an important outcome measure in histologic analysis of bone healing. However, an optimized protocol for staining H vessels in formalin-fixed paraffin-embedded (FFPE) tissue sections has not been reported. With this protocol, we describe a method of staining FFPE bone samples with minimal background fluorescence and high signal-to-noise ratio. We examined mandibular specimens in a rat model of bone healing from a range of fracture conditions, including healthy bone (Fx), irradiated bone (XFx), and irradiated bone with DFO treatment (XFx-DFO). Quantitative analysis revealed a significant increase of H vessels in the XFxDFO group compared to both the Fx and XFx groups. By optimizing immunofluorescent staining of H vessels in FFPE samples across a range of fracture conditions, we offer investigators an efficacious means of producing reliable imaging for quantitative analysis of H vessels in an irradiated fracture callus.

The Jatropha curcas cake, a protein-rich by-product of biofuel production, was the subject of our study. We identified and quantified the ACE inhibitory, antioxidant, and antidiabetic activities of bioactive peptides from a Jatropha curcas L. var Sevangel protein isolate. The protein isolate (20.44% recovered dry matter, 38.75% protein content, and 34.98% protein yield) was subjected to two enzyme systems for hydrolysis: alcalase (PEJA) and flavourzyme (PEJF), recording every 2 h until 8 h had passed. The highest proteolytic capacity in PEJA was reached at 2 h (4041.38 ± 50.89), while in PEJF, it was reached at 6 h (3435.16 ± 59.31). Gel electrophoresis of the PEJA and PEJF samples showed bands corresponding to peptides smaller than 10 kDa in both systems studied. The highest values for the antioxidant capacity (DPPH) were obtained at 4 h for PEJA (56.17 ± 1.14), while they were obtained at 6 h for PEJF (26.64 ± 0.52). The highest values for the antihypertensive capacity were recorded at 6 h (86.46 ± 1.85) in PEJF. The highest antidiabetic capacity obtained for PEJA and PEJF was observed at 6 h, 68.86 ± 8.27 and 52.75 ± 2.23, respectively. This is the first report of their antidiabetic activity. Notably, alcalase hydrolysate outperformed flavourzyme hydrolysate and the cereals reported in other studies, confirming its better multi-bioactivity.

The hardware utilized for rigid internal fixation of the craniofacial skeleton has evolved over time. Thus, the reasons for the unplanned removal of hardware continue to change. The purpose of this study is to compare past (1989-1995) and present (2000-2020) patient cohorts to establish trends related to unplanned removal of craniofacial hardware. A retrospective review study was designed. Data from our institution's original publication describing the unplanned removal of craniofacial hardware (1989-1995) was obtained. Data related to patients who underwent unplanned removal of hardware from 2000 to 2020 was collected from the electronic medical record. A descriptive statistical analysis was performed to compare demographics, reasons for hardware placement, and reasons for unplanned hardware removal between cohorts. This study includes 55 patients treated from 1989 to 1995 and 184 patients treated from 2000 to 2020. The average age at hardware placement decreased from 32 years (1989-1995) to 28 years (2000-2020). The most common reason for hardware placement changed from motor vehicle accident (1989-1995) to congenital deformity (2000-2020). The length of time with hardware in situ increased from 13 months (1989-1995) to 25 months (2000-2020). The most common reason for hardware removal changed from prominent hardware (1989-1995) to hardware exposure (2000-2020). In summary, patients who underwent rigid internal fixation of the craniofacial skeleton from 2000 to 2020 retained their hardware 2 times longer than patients treated from 1989 to 1995. Factors potentially contributing to increased retention include improved surgical technique, decreased profile of hardware, and increased surgeon experience. Further studies are warranted to define preoperative risk factors for unplanned hardware removal., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Background: Cleft palatoplasty commonly results in denuded maxillary bone in the lateral gutter(s) and a posterior void between oral and nasal closures. Bony exposure of the anterior palate subjects the maxilla to scarring and growth restriction, while scar contracture of the posterior void may result in velopharyngeal insufficiency (VPI) and fistula formation. Utilization of the buccal fat pad flap (BFPF) at the time of palatoplasty provides vascularized tissue over these critical areas, thereby reducing the rate of secondary surgery for speech and fistula revision., Methods: A single-center, retrospective review identified patients who underwent palatoplasty with or without BFPF between 1995-2015. Data collected included cleft type, surgical technique, follow-up duration, and complications. Outcomes included rate of speech surgery and palatal fistula development. Veau phenotype index was computed on a scale of 2-4 as a weighted mean to reflect the frequency of cleft type (Veau II-IV) in BFPF and non-BFPF groups., Results: Charts of 866 patients were reviewed; 212 met inclusion criteria. Of these, 101 received a BFPF. Mean follow-up duration was 11.4 years. Despite a selection bias for more severe clefts, the BFPF group had lower incidence of speech surgery (9.9% vs. 36.9%, p=0.0072). The BFPF group had more mild cases treatable with fat injection (7.9% vs. 2.7%, p=0.0346) and developed fewer fistulas (6.9% vs. 18.0%, p=0.0280)., Conclusion: Despite the presence of more severe clefts, the BFPF group had a significantly lower rate of speech surgery. The BFPF is a valuable adjunct in primary palatoplasty, reducing VPI and fistula formation., (Copyright © 2024 by the American Society of Plastic Surgeons.)

Dendronized nanoparticles, also called nanoparticle-cored dendrimers, combine the advantages of nanoparticles and dendrimers. These very stable and polyvalent nanoparticles can be used for diverse applications. One such application is drug delivery, because the dendrons can enhance the density of the payload. In this report, we describe the design of multifunctional gold nanoparticles (AuNPs) coated with poly(propylene imine) (PPI) dendrons that contain both prostate cancer active targeting and chemotherapeutic drugs. The PPI dendron is a good candidate for the design of drug delivery vehicles because of its ability to induce a proton sponge effect that will enhance lysosomal escape and intracellular therapeutic delivery. The chemotherapeutic drug used is doxorubicin (DOX), and it was linked to the dendron through a hydrazone acid-sensitive bond. Subsequent acidification of the AuNP system to a pH of 4-5 resulted in the release of 140 DOX drugs per nanoparticles. In addition, the PPI dendron was conjugated via "click" chemistry to an EphA2-targeting antibody fragment that has been shown to target prostate cancer cells. In vitro cell viability assays revealed an IC50 of 0.9 nM for the targeted DOX-bearing AuNPs after 48 h incubation with PC3 cells. These results are very promising upon optimization of the system.

Background: Surgical procedures in ophthalmology are subject to fluctuations in their application and are dependent on new developments, availability, and success rates. In the field of glaucoma surgery in particular, numerous new procedures have been introduced over the last few years. So far, hardly any analyses have been done on the current application of these newer procedures. In this paper, we present the extent to which different glaucoma surgery procedures were used in German hospitals in 2019., Methods: The quality reports of German hospitals from 2019 were evaluated regarding all glaucoma-specific procedure codes. In particular, laser procedures, "classic" glaucoma procedures, and "modern" procedures such as MIGS (minimally invasive glaucoma surgery) are compared below., Results: In 2019, 49,031 glaucoma procedures were performed in German hospitals. Numerically, cyclodestructive procedures were used most frequently. MIGS accounted for approximately 10% of procedures according to the available data. Among filtering procedures, about 40% were implant-assisted., Discussion and Conclusion: On the one hand, the data analyzed show a mixed expansion of the spectrum with newer procedures such as the MIGS and implants; on the other hand, classic procedures such as cyclodestruction are still used. It can be assumed that further shifts in surgical methods will be seen in the coming years., Competing Interests: Lübke: Vortragstätigkeit für Allergan/Abbvie, MST./The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Favorable functional outcomes have been reported after excimer laser-assisted penetrating keratoplasty (EXL PKP). But this technique has not been widely adopted, and there are reports on EXL PKP from only a very limited number of institutions. Some of these results refer to operations carried out with laser systems that are not commercially available. In this retrospective case series, we report the long-term outcome of EXL PKP using the Schwind Amaris 500E laser system., Material and Methods: This retrospective consecutive case series included 30 eyes of 29 patients who had undergone EXL PKP between 2010 and 2013. Primary outcome measures were topographic astigmatism and visual acuity. Secondary outcome measures were the rates of graft rejection and graft failure, and the rate of grafts with an endothelial cell density below 500 cells/mm 2 . Survival analyses were carried out for the following endpoints: visual acuity, rate of graft rejection, and rate of grafts with endothelial cell densities higher than 500 cells/mm 2 ., Results: The median interquartile range (IQR) duration of follow-up was 45 (36) months. The indications for PKP were keratoconus (n = 21), corneal scarring (n = 6), Fuchs endothelial dystrophy (n = 1), and corneal dystrophy other than Fuchs endothelial dystrophy (n = 2). The median (IQR) topographic astigmatism at the end of the follow-up period was 5.3 (2.9) D. Forty-five months after surgery, 73% of all eyes had a visual acuity better than 0.3 LogMAR. The rate of graft rejection after 45 months of follow-up was 32%. All eyes maintained endothelial cell densities higher than 500 cells/mm 2 . There was no graft failure., Conclusions: EXL PKP is a safe and effective surgical procedure. No general conclusions can be drawn on the refractive outcome of EXL PKP. Potential advantages, such as a higher degree of graft-host congruity, that could possibly improve the refractive outcome should be weighed against the higher costs of EXL PKP., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

The shorter synthesis of a novel poly(propylene imine) (PPI) dendron that can be quantitatively conjugated in good yields in a modular fashion to various modified Michael acceptors is reported herein. The focal point of the PPI dendron was coupled to an ester-linked thioctic acid-modified spacer to allow for an improved scalable synthesis and to allow attachment to other suitable systems, such as nanoparticle surfaces. The two modified Michael acceptors reported here are an acyl hydrazine Michael acceptor as well as an azide Michael acceptor. The acyl hydrazine modified third generation PPI dendron was further conjugated to doxorubicin (DOX) as a model system to test acid-sensitive drug delivery. The PPI-DOX conjugate displayed fast release of DOX at pH 4.5 while remaining stable at pH 7.4 and the PPI-DOX conjugate showed low in vitro cytotoxicity against PC3 prostate cancer cells. This modular platform represents a powerful dendronized system for incorporation onto nanoparticles or other systems to allow for multifunctional drug delivery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Noninvasive ventilation (NIV) has become more studied in immunocompromised patients. However, it has not been studied in hematopoietic cell transplantation (HCT) recipients, who have higher mortality and higher pulmonary complication rates than other immunocompromised patients. This population may be prone to negative effects from this treatment modality. The aim of this study was to determine whether NIV use is associated with worse outcomes in this vulnerable patient population., Methods: A secondary analysis of a retrospective multi-center database was performed. Twelve pediatric ICUs across the United States enrolled HCT subjects from 2009-2014 that were admitted to the pediatric ICU (PICU) with the diagnosis of acute respiratory failure. Subjects exposed to NIV prior to intubation were compared against those not exposed to NIV. Our primary outcome was all-cause mortality at 90 d; secondary outcomes included ventilator-free days (VFD) at 28 d and development of pediatric ARDS. Multivariable logistic and linear regression models were constructed using variables significant on univariable analysis., Results: Two-hundred eleven subjects were included. Of these, 82 (39%) received NIV prior to intubation. Those that received NIV prior to intubation were older (13 vs 6 y, P < .001) and more commonly diagnosed with respiratory distress (90% vs 74%, P = .004). On multivariable analysis, NIV use prior to intubation was associated with a higher PICU mortality (hazard ratio 1.51 [95% CI 1.18-2.28], P = .02) and fewer VFD at 28 d (β -3.50 [95% CI -6.09 to 0.91], P = .008). Those with NIV exposure prior to intubation also had higher rates of development of pediatric ARDS (95% vs 78%, P = .001)., Conclusions: In this cohort of children post-HCT, NIV use prior to intubation was associated with worse outcomes. The benefits and risks of NIV in this patient population should be carefully evaluated prior to its use, and careful patient selection is crucial for its optimal utilization., Competing Interests: Dr Rowan is funded by the NIH (1K23HL150244-01A21) The remaining authors have disclosed no conflicts of interest., (Copyright © 2022 by Daedalus Enterprises.)

Background: Especially in rural areas, access of visually impaired people to ophthalmic care and counselling can be limited. The Eye Van is a project supported by the Ministry for Rural Affairs and Consumer Protection Baden-Württemberg which offers visually impaired people an on-the-spot ophthalmological examination and counselling on low-vision aids and social support services. The aim of this project was to evaluate the quality of care provided to visually impaired people in the rural areas of South Baden., Materials and Methods: Between 2016 and 2019, 45 villages in South Baden participated in this project. The visits were advertised in the local press. Appointments were assigned and participant eligibility was assessed over the telephone by the local Federation of the Blind and Partially Sighted in South Baden. During the on-site visits, a medical history was obtained from participants, who then received a comprehensive ophthalmological examination and counselling on low-vision aids and social support services. Interviews were conducted in order to determine the expectations of the participants and to assess their quality of life. A second interview, focused on the measures that had been implemented and changes in the participants' quality of life, was carried out three months later., Results: In total, 264 participants were examined. Of these, 101 participants fulfilled the criteria of moderate/severe visual impairment or blindness defined by the WHO (World Health Organization). The mean age of the visually impaired participants was 85 years. The median decimal visual acuity was 0.08. The median length of time since the participants' last ophthalmological examination was one year. Among the visually impaired participants, 13% did not have any low-vision aids. Their use was recommended to 62% of the visually impaired participants. The main expectation of participants was counselling on low-vision aids and support services. Among all the participants, 42 did one interview and 28 did two interviews. In the second interview, 72% of the participants claimed to have implemented the recommendations. There was no statistically significant change in their quality of life., Conclusion: The access of visually impaired people to ophthalmic care does not seem to be limited in the rural areas of South Baden. Nevertheless, there was a high demand for counselling on low-vision aids and social support services., Competing Interests: The authors declare that they have no conflict of interest./Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

This work discusses in vivo experiments that were performed to evaluate whether local or whole-body heating to 40 °C reduced interstitial fluid pressures (IFPs) and enhanced nanoparticle delivery to subcutaneous PC3 human prostate cancer xenograft tumors in mice. After heating, 0.2 mL of a previously developed nanofluid containing gold nanoparticles (10 mg Au/mL) was injected via the tail vein. The induced whole-body hyperthermia led to increases in tumor and mouse body blood perfusion rates of more than 50% and 25%, respectively, while the increases were much smaller in the local heating group. In the whole-body hyperthermia groups, the IFP reduction from the baseline at the tumor center immediately after heating was found to be statistically significant when compared to the control group. The 1 h of local heating group showed IFP reductions at the tumor center, while the IFPs increased in the periphery of the tumor. The intratumoral gold nanoparticle accumulation was quantified using inductively coupled plasma mass spectrometry (ICP-MS). Compared to the control group, 1 h or 4 h of experiencing whole-body hyperthermia resulted in an average increase of 51% or 67% in the gold deposition in tumors, respectively. In the 1 h of local heating group, the increase in the gold deposition was 34%. Our results suggest that 1 h of mild whole-body hyperthermia may be a cost-effective and readily implementable strategy for facilitating nanoparticle delivery to PC3 tumors in mice., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.

Objectives: To evaluate the associations between early cumulative fluid balance (CFB) and outcomes among critically ill pediatric allogeneic hematopoietic cell transplant (HCT) recipients with acute respiratory failure, and determine if these associations vary by treatment with renal replacement therapy (RRT)., Methods: We performed a secondary analysis of a multicenter retrospective cohort of patients (1mo - 21yrs) post-allogeneic HCT with acute respiratory failure treated with invasive mechanical ventilation (IMV) from 2009 to 2014. Fluid intake and output were measured daily for the first week of IMV (day 0 = day of intubation). The exposure, day 3 CFB (CFB from day 0 through day 3 of IMV), was calculated using the equation [Fluid in - Fluid out] (liters)/[PICU admission weight](kg)*100. We measured the association between day 3 CFB and PICU mortality with logistic regression, and the rate of extubation at 28 and 60 days with competing risk regression (PICU mortality = competing risk)., Results: 198 patients were included in the study. Mean % CFB for the cohort was positive on day 0 of IMV, and increased further on days 1-7 of IMV. For each 1% increase in day 3 CFB, the odds of PICU mortality were 3% higher (adjusted odds ratio (aOR) 1.03, 95% CI 1.00-1.07), and the rate of extubation was 3% lower at 28 days (adjusted subdistribution hazard ratio (aSHR) 0.97, 95% CI 0.95-0.98) and 3% lower at 60 days (aSHR 0.97, 95% CI 0.95-0.98). When day 3 CFB was dichotomized, 161 (81%) had positive and 37 (19%) had negative day 3 CFB. Positive day 3 CFB was associated with higher PICU mortality (aOR 3.42, 95% CI 1.48-7.87) and a lower rate of extubation at 28 days (aSHR 0.30, 95% CI 0.18-0.48) and 60 days (aSHR 0.30, 95% 0.19-0.48). On stratified analysis, the association between positive day 3 CFB and PICU mortality was significantly stronger in those not treated with RRT (no RRT: aOR 9.11, 95% CI 2.29-36.22; RRT: aOR 1.40, 95% CI 0.42-4.74)., Conclusions: Among critically ill pediatric allogeneic HCT recipients with acute respiratory failure, positive and increasing early CFB were independently associated with adverse outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sallee, Smith, Rowan, Heckbert, Angelo, Daniel, Gertz, Hsing, Mahadeo, McArthur and Fitzgerald.)

Prcis: Cyclodiode as a primary treatment for childhood glaucoma patients younger than 8 years has a 12-month success rate of 55.24%. It can delay the need for penetrating glaucoma surgery., Purpose: The purpose of this study was to evaluate the treatment outcome of cyclodiode laser in childhood glaucoma for patients under the age of 8 years., Design: This was a retrospective, consecutive, noncomparative case series., Participants: All childhood glaucoma patients who underwent cyclodiode from March 2005 to January 2017 as a primary surgical treatment under the age of 8 years., Methods: A retrospective review of the medical records of consecutive patients who underwent cyclodiode by a single surgeon., Main Outcome Measures: Success for single-diode intervention was defined as intraocular pressure (IOP) (>6 wk postoperative) ≤21 mm Hg with antiglaucoma medications and ≥20% IOP reduction, no further glaucoma surgery including cyclodiode, no loss of perception of light, and no major complications. Success for multiple-diode interventions was defined similar to the single diode, except that repeated cyclodiode is not considered a failure., Results: In all, 59 eyes of 43 patients were studied. The most common diagnosis was aphakic glaucoma. The mean age at cyclodiode treatment was 2.7 years (SD=2.2). Fifty-six percent of the patients were under 3 years. Success rates at 12 months after the procedure were 46.67% and 55.24% for single-diode and multiple-diode interventions, respectively. An IOP of >20 mm Hg 6 weeks after a cyclodiode session is a significant risk factor for failure with an hazard ratio of 2.41 (95% confidence interval: 1.00-5.81; P=0.05). Among the operated eyes, the surgeon could avoid further glaucoma surgery in 67.8% of the eyes during the first year after single or multiple cyclodiode sessions. None of the eyes experienced phthisis bulbi, hypotony, and severe uveitis., Conclusions: Cyclodiode laser in childhood glaucoma patients under the age of 8 years can be considered a safe alternative for glaucoma patients who can have a high risk of surgical complications. Performing cyclodiode laser can delay the need for penetrating glaucoma surgery. The IOP at 6 weeks may be a good predictor for the treatment outcome., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Keratoplasty is considered the most frequently performed type of transplantation in humans. Traditionally, penetrating keratoplasty has been the most common procedure. However, over the last 15 years, the importance of posterior lamellar keratoplasty has increased for the treatment of Fuchs endothelial dystrophy and bullous keratopathy. In Germany, based on national surveys, it was suggested that there was a trend towards lamellar keratoplasty., Objective: The main objective of this study was to determine whether the proportion of lamellar keratoplasties carried out in Germany between 2006 and 2017 had increased. Furthermore, the number of keratoplasties carried out as HLA-matched (HLA: human leukocyte antigen) keratoplasties should be calculated., Materials and Methods: The numbers of all keratoplasties carried out as lamellar/penetrating and HLA-matched keratoplasties was extracted from the hospital quality reports published between 2006 and 2017. Descriptive statistical analysis was carried out in R (www.r-project.org)., Results: Between 2006 and 2017, 43,021 keratoplasties were carried out in Germany. The number of keratoplasties increased from 2,849 (2006) to 8,231 (2017). The number of penetrating keratoplasties remained stable. The proportion of lamellar keratoplasties increased from 6.5% (2006) to 61.4% (2017). The proportion of HLA-matched keratoplasties was below 20% and declined between 2010 and 2017 (2010: 19.7%; 2017: 9.8%)., Discussion: In Germany, posterior lamellar keratoplasty has become increasingly important. Since 2014, the number of lamellar keratoplasties has exceeded the number of penetrating keratoplasties. However, the number of penetrating keratoplasties remained stable between 2006 and 2017 and still plays an important role in the management of patients with predominantly stromal or corneal defects affecting all layers. The decreasing number of HLA-matched keratoplasties is most likely due to the lack of clear evidence of a significant reduction in the rejection rates in cases of normal risk keratoplasty., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Purpose: To describe the transition from conventional angle surgery (CAS), trabeculotomy with rigid probe or goniotomy, to 360-degree trabeculotomy assisted with microcatheter (MCT)., Design: Retrospective comparative interventional case series., Methods: Review of consecutive children with glaucoma undergoing angle surgery, including cases with previous surgery, from January 2012 until March 2018 at Moorfields Eye Hospital. Main outcome measure was success rate, defined as intraocular pressure (IOP) ≤21 mm Hg with a minimum of 20% of IOP reduction and no further glaucoma surgery (complete success: without the need of glaucoma drops; qualified success: drops were needed to keep the IOP under control)., Results: Among the 106 eyes (77 patients) included were 54 MCT and 52 CAS eyes. At last visit, after a single surgery, qualified success was 85% (46 eyes) in MCT and 37% (19 eyes) in CAS. Complete success was 69% (37 cases) in MCT and 23% (12 cases) in CAS. The mean (95% confidence interval) change in axial length after surgery was -0.03 mm (-0.34 to 0.40) for MCT and +1.35 mm (-0.64 to 1.62) for CAS (P < .001). The percentage of IOP reduction was 52.1% in MCT and 45.5% in CAS (P = .1616). Further glaucoma surgery was required in 5.5% (3) in MCT and 63.4% (33) in CAS. At 1 year, 94.3% of MCT cases achieved qualified success compared to 34.6% of CAS (P < .0001). No significant complications were found on either group., Conclusion: MCT achieved better results with significantly lower reoperation rates. The transition from CAS to MCT can be easily achieved, even in difficult cases or those previously operated., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Scleral buckling and pars-plana vitrectomy are therapeutic options for the treatment of rhegmatogenous retinal detachment. Comparative studies still support the value of scleral buckling in phakic eyes. Nevertheless, the number of sceral buckling procedures may be continuously decreasing over time. The study aims to analyse the incidence of scleral buckling procedures for the treatment of patients with retinal detachment in Germany over time., Material and Methods: The numbers of scleral buckling procedures (OPS 5-152) and rhegmatogenous retinal detachment (ICD H33.0) in Germany are analysed on the basis of data from the quality reports published by the Federal Joint Committee and secondary analyses of the DRG-based billing system (DRG-Statistik) of the Federal Statistical Office between 2006 and 2017., Results: Based on the quality reports, numbers of scleral buckling procedures performed between 2006 and 2017 dropped by 49% from 8841 to 4510. During this period of time, the number of rhegmatogenous retinal detachments, identified by the ICD code H33.0, rose by 102% from 11 507 to 23 314. A decrease in scleral buckling procedures of 42% between 2006 and 2017 was also observed in the DRG Statistics. Regional and age-dependent subgroup analyses suggests that there are both regional and age-dependent differences in the practice of scleral buckling., Conclusions: Our analysis clearly illustrates that scleral buckling procedures are now less commonly performed in Germany than in 2006. However, the total of ~ 4500 billed procedures in 2017 in Germany shows that scleral buckling is still an important and current therapeutic option in the treatment of retinal detachment., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Crotamine is a basic, 42-residue polypeptide from snake venom that has been shown to possess cell-penetrating properties. Here we describe the preparation, purification, biochemical and biophysical analysis of venom-derived, recombinant, chemically synthesized, and fluorescent-labeled crotamine. We also describe the formation and characterization of crotamine-DNA and crotamine-RNA nanoparticles; and the delivery of these nanoparticles into cells and animals. Crotamine forms nanoparticles with a variety of DNA and RNA molecules, and crotamine-plasmid DNA nanoparticles are selectively delivered into actively proliferating cells in culture or in living organisms such as mice, Plasmodium, and worms. As such, these nanoparticles could form the basis for a nucleic acid drug-delivery system. We also describe here the design and characterization of crotamine-functionalized gold nanoparticles, and the delivery of these nanoparticles into cells. We also evaluated the viability of using the combination of crotamine with silica nanoparticles in animal models, aiming to provide slow delivery, and to decrease the crotamine doses needed for the biological effects. In addition, the efficacy of administering crotamine orally was also demonstrated.

Background: Transformation into a standardised code system such as ICD-10 or Alpha-ID is required before medical reports can be scientifically analysed. This is due to the use of different terminologies and the frequent use of synonyms. The so-called "word vector embedding" seems to be suitable for the generation of the required thesaurus, because synonymous diagnoses can be identified independently of the spelling - after suitable training of the underlying neural network., Methods: All letters from a total of 50,000 patients were extracted anonymously. Diagnoses consisting of several words were merged into single words by means of phrase recognition and the "word2vec" model was trained on the text corpus of 352 megabytes. A total of 3742 diagnoses and ophthalmological interventions were extracted semi-automatically. The ophthalmological ICD and Alpha-ID codes were downloaded together with the official descriptions from the DIMDI website and the ophthalmological diagnoses/interventions were automatically linked with the nearest ICD- and Alpha-ID codes in the "word2vec" model., Results: The "word2vec" model assigned 90% of the doctor's letter diagnoses correctly to appropriate ICD-10 codes. At the finer level of Alpha-ID, the rate of correct assignments was only 76%. The interventions were assigned to the correct indication in 92% of cases. Rare diseases, unusual designations and code degeneration in the official DIMDI file were identified as sources of error for incorrect or missing allocations., Discussion: A diagnostic thesaurus can be generated with the "word2vec" method from a corpus of anonymised medical reports and the official Alpha-ID file from the DIMDI website. This thesaurus could be used for automatic extraction of diagnoses from doctor's letters in the future, given appropriate manual revision., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Human corneal grafts from organ culture need to have more than 2000 endothelial cells/mm 2 to be suitable for transplantation. Measurement of the endothelial cell density is complicated by invisible cell borders in phase contrast microscopy, as well as by limited areas for counting due to folds in the Descemet membrane of the swollen corneal grafts. To date, no automated counting method for measuring the endothelial cell density exists. The neuronal network U-Net has already proven itself in automated segmentation of specular microscopy images of human corneal endothelium. The aim of this study was the application of the U-Net in the quality control of human corneal grafts., Material and Methods: Training of the U-Net was performed using 100 manually tagged endothelial cell images of corneal grafts from the Lions eye bank in Baden-Württemberg. Another 100 images were obtained for testing the precision of measurements of the U-Net. These were adjudged manually by a) an experienced investigator and b) a less experienced ophthalmologist. The endothelial cells in identical images were then counted automatically by the trained U-Net. Comparison with the manually counted results was drawn by Pearson correlation., Results: The correlation coefficient between the U-Net and the experienced investigator as gold standard was 0.9. The correlation coefficient between the less experienced ophthalmologist and the gold standard was only 0.81. Both correlations were statistically highly significant (p < 0.0001)., Discussion: The strong correlation between the U-Net and the gold standard points out that, given medical approval, effective assistance for eye banks is possible in quality control by automated counting. This could improve objectivity and efficiency of work flow., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

PRéCIS:: Glaucoma drainage device (GDD) implantation within the first 2 years of life yields an overall success rate of 59.0% at 5 years. It is safe and requires a relatively low number of postoperative interventions., Purpose: The purpose of this study was to evaluate the long-term outcomes of the treatment of childhood glaucoma with GDDs within the first 2 years of life., Methods: A total of 43 children (60 eyes) having undergone GDD implantation within the first 2 years of life at Moorfields Eye Hospital between July 2005 and November 2014 were included in this retrospective case series. Kaplan-Meier survival curves were created for the evaluation of surgical success. Log-rank analysis was performed for the detection of risk factors for failure., Main Outcome Measures: Overall success rates at 1, 5, and 7 years after surgery. Surgical success: intraocular pressure ≥5/≤21 mm Hg, no further glaucoma surgery required, nonoccurrence of loss of perception of light or devastating complications., Results: The results are listed as follows: Median duration of follow-up was 48.0 months. Median age at surgery was 11.5 months. Seventy-three percentage of children were white. Most common types of glaucoma were primary congenital glaucoma [(PCG); 67%], glaucoma following cataract surgery (18%), and anterior segment dysgenesis (10%). Overall success rates were 93%, 59%, and 59%, respectively. There were no differences in the survival rates as a function of PCG/non-PCG, sex, and removal of intraluminal stent suture. Mean number of general anesthesia administrations during the first postoperative year was 1.8., Conclusions: GDD implantation within the first 2 years of life is effective and safe. The low number of general anesthesia administrations required during the first postoperative year could help to reduce the burden placed on children and carers. Further research is required to directly compare the efficiency of GDD implantation with other surgical options.

Purpose: To explore the impact of childhood lensectomy on posterior segment development., Methods: Cross-sectional observational study at children's eye clinics at a tertiary referral center in London, UK. We included 45 children age 4 to 16 years with healthy eyes and 38 who had undergone lensectomy. We acquired posterior segment optical coherence tomography scans of both eyes. We used parametric and nonparametric tests in SPSS24 for the comparison of parameters between groups and within individuals; a P value less than 0.05 was considered significant. The main outcome measures were foveal pit depth and subfoveal choroidal thickness (CT). Secondary outcomes were inner and outer ring CT and photoreceptor layer parameters, macular and peripapillary retinal nerve fiber layer thickness., Results: Foveal pit depth and subfoveal CT are significantly reduced in eyes that have undergone lensectomy compared with nonoperated eyes. Inner ring CT and outer ring CT are reduced. Foveal inner retinal layer thickness is increased. Mean inner retinal and outer nuclear layer thickness are not affected., Conclusions: Childhood lensectomy is associated with a reduction in developmental foveal pit deepening and lack of developmental thickening of the posterior choroid. Mechanical and optical disruption of foveal and subfoveal choroidal development may affect structural foveal development after childhood lensectomy.

Background: Cataract is one of the most prevalent eye diseases in Germany. According to the German Ophthalmological Society, its prevalence will increase significantly in the coming years. It has been suggested that most cataract operations are carried out in an outpatient setting. However, there still seems to be a need for inpatient cataract surgery., Objective: The main objective of this study was to determine the total number of cataract operations carried out in German hospitals over the last 12 years and to investigate whether the proportion of cataract operations carried out as outpatient procedures has increased in recent years., Material and Methods: The numbers of cataract operations carried out as outpatient and inpatient procedures were extracted from the quality reports published by the Federal Joint Committee between 2006 and 2016. The total number, the number of cataract operations per 1000 residents (inpatient and outpatient procedures) and the proportion of complex cataract operations carried out as inpatient procedures were calculated. The descriptive statistical analysis was carried out in R (www.r-project.org)., Results: Between 2006 and 2016, 1,884,506 cataract operations were carried out in German hospitals. There was an increase in the total number of cataract operations (2006: 223,070; 2016: 279,331). The proportion of outpatient procedures increased between 2006 (44%) and 2010 (48.9%) and remained stable between 2010 and 2016 (2016: 48.5%). Between 2006 and 2016, the proportion of complex cataract operations carried out as inpatient procedures ranged from 56 to 86%., Discussion: A stable and significant proportion of cataract operations in Germany is still carried out in hospitals. The total number of cataract operations has increased. After increasing between 2006 and 2010, the proportion of cataract operations carried out as outpatient procedures remained stable. This sustained demand may be triggered by a group of patients who, due to medical and/or social reasons, require treatment under inpatient conditions., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Monitoring the density of corneal endothelial cells (CEC) is essential in the management of corneal diseases. Its manual calculation is time consuming and prone to errors. U-Net, a neural network for biomedical image segmentation, has shown promising results in the automated segmentation of images of healthy corneas and good quality. The purpose of this study was to assess its performance in "real-world" CEC images (variable quality, different ophthalmologic diseases). The outcome measures were: precision and recall of the extraction of CEC, correctness of CEC density estimation, detection of ungradable images. A classical approach based on grayscale morphology and water shedding was pursued for comparison. There was good agreement between the automated image analysis and the manual annotation from the U-Net. R-square from Pearson's correlation was 0.96. Recall of CEC averaged 0.34 and precision 0.84. The U-Net correctly predicted the CEC density in a large set of images of healthy and diseased corneas, including images of poor quality. It robustly ignored image regions with poor visibility of CEC. The classical approach, however, did not provide acceptable results. R-square from Pearson's correlation with the ground truth was as low as 0.35.

The synthesis of a novel poly(propyleneimine) (PPI) dendron in gram scale as well as its use in the formation of a highly stable, dendronized gold nanoparticle (AuNP)-based drug delivery platform is described herein. The AuNP-based platform is composed of three complementary parts: (i) a 15 nm AuNP core, (ii) a heterofunctional thioctic acid-terminated tetraethylene glycol spacer, and (iii) a third-generation PPI dendron with a unique protonation profile and diverse end-group functionalization that allows for further derivatization. The prepared dendronized AuNPs are able to withstand several rounds of lyophilization cycles with no sign of aggregation, are stable in phosphate-buffered saline and Hanks' buffer as well as in serum, and are resistant to degradation by glutathione exchange reactions. This nanocarrier platform displays a dense coating, with >1400 dendrons/AuNPs, which will enable very high payload. Furthermore, while amine-terminated AuNPs expectedly showed cytotoxicity against the MCF-7 breast cancer cell line from a NP concentration of 1 nM, the mixed monolayer AuNPs (coated with 40/60 amine/carboxylate dendrons) interestingly did not exhibit any sign of toxicity at concentrations as high as 15 nM, similar to the carboxylate-terminated AuNPs. The described dendronized AuNPs address the current practical need for a stable NP-based drug delivery platform which is scalable and easily conjugable, has long-term stability in solution, and can be conveniently formulated as a powder and redispersed in desired buffer or serum.

Purpose: To compare Schlemm canal (SC) and trabecular meshwork (TM) in children with healthy eyes and those with and without glaucoma after lensectomy., Design: Cross-sectional observational study., Participants: Fifty children 4 to 16 years of age with healthy eyes and 48 children who underwent lensectomy (124 healthy and 72 postlensectomy eyes)., Methods: Anterior segment (AS) OCT (Tomey SS-1000 CASIA; Tomey, Nagoya, Japan) of the nasal iridocorneal angle at 2 levels of accommodative effort (2.5 diopters [D] and 15 D). For each parameter and state of accommodation, a random effects model was fitted to estimate differences between healthy eyes and eyes with history of lensectomy., Main Outcome Measures: Dimensions of SC and TM and conventional AS OCT iridocorneal angle measurements., Results: The horizontal diameter of SC and its cross-sectional area (CSA) are significantly smaller in eyes that have undergone lensectomy versus healthy eyes. Accommodative effort increases SC size in healthy eyes, but not in eyes that have undergone lensectomy., Conclusions: Lensectomy is associated with a reduction in SC size and a loss of physiologic SC dilatation during accommodative effort, which may reflect a reduction in outflow facility and may contribute to the development of glaucoma after lensectomy., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To report the surgical outcomes of children with cataract associated with microphthalmia, microcornea, or persistent fetal vasculature (MMP) and children with isolated cataract., Methods: The study included 111 children (cataract associated with MMP: n = 25) who underwent cataract surgery at younger than 16 years. Exclusion criteria were duration of follow-up less than 5 years, intraindividual differences in age at surgery, eye disorders other than MMP, secondary cataract, and syndromal diseases. Main outcome measures were proportion of eyes with glaucoma and best corrected visual acuity (BCVA). Both groups were dichotomized by age at surgery (early intervention group: ≤ 48 days). Descriptive analysis was performed throughout., Results: Median age at surgery was 3.9 months for cataract associated with MMP and 23.3 months for isolated cataract. The median (interquartile range [IQR]) duration of follow-up was 95.9 months (range: 76.0 to 154.5 months). In children with bilateral cataract associated with MMP, the proportion of eyes with final BCVA worse than 0.3 logMAR was similar regardless of age at surgery (early intervention: 80%, later intervention: 78%). In bilateral isolated cataract, the proportions were 56% and 33%, respectively. Children with cataract associated with MMP had a high prevalence of glaucoma (28%). Glaucoma prevalence was lower in the later intervention group., Conclusions: In the presence of MMP, early cataract surgery is associated with a high risk of post-lensectomy glaucoma, but does not offer the benefit of better visual outcomes. [J Pediatr Ophthalmol Strabismus. 2019;56(1):43-49.]., (Copyright 2018, SLACK Incorporated.)

Zinc oxide (ZnO) nanomaterials have been used as desulfurizing sorbents for gaseous streams, zinc sulfide (ZnS)-forming template lattices in nanomaterial synthesis, and agriculturally produced sulfur (S)-removing reagents from the environment. Although various nanoscale forms of ZnO have already been utilized widely for such purposes, there is currently a lack of fundamental insight into the sulfidation of ZnO nanomaterials at the single nanocrystal level. We demonstrate that position-resolved confocal Raman spectroscopy can be successfully used to reveal the sulfidation process of ZnO NRs occurring at the single nanomaterial level. We attained a single crystal level understanding of the facet-dependent sulfidation reactivity of ZnO NRs by tracking the same NRs with Raman spectroscopy before and after the sulfidation reaction and quantitatively analyzing various ZnS-induced phonon scattering intensities from different positions on the NRs. The trend in NR facet-dependent sulfidation reactivity is further substantiated by correlating it with the electron microscopy and fluorescence data measured from the same NRs. The insight obtained from this study may provide the much-needed fundamental knowledge base for designing optimal ZnO nanostructures beneficial to many technological and industrial applications exploiting the ZnO-to-ZnS conversion. Taken together with the well-established methods to synthesize ZnO nanomaterials of specific crystal shapes and structures, our findings from this study may be broadly applicable in formulating and optimizing more advanced, low-dimensional ZnO sorbents and scrubbers for highly effective S removal.

Coherent coupling between plasmons and transition dipole moments in emitters can lead to two distinct spectral effects: vacuum Rabi splitting at strong coupling strengths, and induced transparency (also known as Fano interference) at intermediate coupling strengths. Achieving either strong or intermediate coupling between a single emitter and a localized plasmon resonance has the potential to enable single-photon nonlinearities and other extreme light-matter interactions, at room temperature and on the nanometer scale. Both effects produce two peaks in the spectrum of scattering from the plasmon resonance, and can thus be confused if scattering measurements alone are performed. Here we report measurements of scattering and photoluminescence from individual coupled plasmon-emitter systems that consist of a single colloidal quantum dot in the gap between a gold nanoparticle and a silver film. The measurements unambiguously demonstrate weak coupling (the Purcell effect), intermediate coupling (Fano interference), and strong coupling (Rabi splitting) at room temperature.

While gold nanorods (AuNRs) have found many applications due to their unique optical properties, a few challenges persist in their synthesis. Namely, it is often difficult to reproducibly synthesize AuNRs with specific and monodisperse sizes, especially at shorter aspect ratios. Here, we report a method of post-synthesis precise tailoring of AuNRs by etching with cysteamine. Cysteamine selectively etches AuNRs from their ends while preserving the initial rod shape and monodispersity, making this a viable means of obtaining highly monodisperse short AuNRs down to aspect ratio 2.3. Further, we explore the effect of this etching method on two types of silica-coated AuNRs: silica side-coated and silica end-coated AuNRs. We find that the etching process is cysteamine concentration-dependent and can lead to different degrees of sharpening of the silica-coated AuNRs, forming elongated tips. We also find that cysteamine behaves only as a ligand at concentrations above 200 mM, as no etching of the AuNRs is observed in this condition. Simulations show that excitation of plasmon resonances in these sharpened AuNRs produces local electric fields twice as strong as those produced by conventional AuNRs. Thus, cysteamine etching of AuNRs is shown to be an effective means of tailoring both the size and shape of AuNRs along with their corresponding optical properties. At the same time, the resulting cysteamine coating on the etched AuNRs displays terminal amino groups that allow for further functionalization of the nanorods.

Purpose: The purpose of this study was to explore changes in Schlemm canal (SC), trabecular meshwork (TM), and iridocorneal angle (ICA) morphology during accommodative effort in children and young adults., Methods: We acquired anterior segment optical coherence tomography images (AS-OCT) of the ICA and ciliary muscle (CM) of both eyes of 50 children age 4 to 16 years with healthy eyes, at two levels of accommodation: 2.5 and 15 diopters (D). Semiautomated nasal ICA measurements were as follows: angle opening distance at 500/750 μm (AOD-500, -750), trabecular iris space area at 500/750 μm (TISA-500, -750), and trabecular iris angle at 500/750 μm (TIA-500, -750). Manual measurements were as follows: anteroposterior and radial SC diameter (SC-APD, SC-RD), cross-sectional area of SC (SC-CSA) and TM height (TMH), TM length (TML), and TM density (TMD). CM width was measured at 1, 2, and 3 mm from the scleral spur (CM-1, CM-2, CM-3). For each parameter, a three-level random-effects model was fitted to estimate differences between the two levels of accommodation., Results: With accommodative effort, SC diameters and CSA increase significantly, as do TM length and iridocorneal angle parameters. With increasing age, SC dimensions reduce. Angle parameters are smaller in eyes with greater spherical equivalent (hypermetropia)., Conclusions: AS-OCT can be used to visualize dynamic morphologic changes in outflow structures with physiologic accommodation. The increase in SC dimensions with accommodative effort may contribute to the regulation of IOP in children.

We demonstrate a straightforward and effective method to synthesize vertically oriented, Cu-doped ZnO nanorods (NRs) using a novel multipurpose platform of copper silicide nanoblocks (Cu₃Si NBs) preformed laterally in well-defined directions on Si. The use of the surface-organized Cu₃Si NBs for ZnO NR growth successfully results in densely assembled Cu-doped ZnO NRs on each NB platform, whose overall structures resemble thick bristles on a brush head. We show that Cu₃Si NBs can uniquely serve as a catalyst for ZnO NRs, a local dopant source of Cu, and a prepatterned guide to aid the local assembly of the NRs on the growth substrate. We also ascertain the crystalline structures, optical properties, and spectroscopic signatures of the Cu-doped ZnO NRs produced on the NBs, both at each module of NRs/NB and at their ensemble level. Subsequently, we determine their augmented properties relative to the pristine form of undoped ZnO NRs and the source material of Cu₃Si NBs. We provide spatially correlated structural and optical data for individual modules of Cu-doped ZnO NRs assembled on a Cu₃Si NB by resolving them along the different positions on the NB. Ensemble-averaged versus individual behaviors of Cu-doped ZnO NRs on Cu₃Si NBs are then compared. We further discuss the potential impact of such ZnO-derived NRs on their relatively unexplored biological and biomedical applications. Our efforts will be particularly useful when exploiting each integrated module of self-aligned, Cu-doped ZnO NRs on a NB as a discretely addressable, active element in solid-state sensors and miniaturized luminescent bioprobes., Competing Interests: The authors declare no conflict of interest.

This paper describes the development of a facile and environmentally friendly strategy for supporting crotamine on gold nanoparticles (GNPs). Our approach was based on the covalent binding interaction between the cell penetrating peptide crotamine, which is a snake venom polypeptide with preference to penetrate dividing cells, and a polyethylene glycol (PEG) ligand, which is a nontoxic, water-soluble and easily obtainable commercial polymer. Crotamine was derivatized with ortho-pyridyldisulfide-polyethyleneglycol-N-hydroxysuccinimide (OPSS-PEG-SVA) cross-linker to produce OPSS-PEG-crotamine as the surface modifier of GNP. OPSS-PEG-SVA can serve not only as a surface modifier, but also as a stabilizing agent for GNPs. The successful PEGylation of the nanoparticles was demonstrated using different physicochemical techniques, while the grafting densities of the PEG ligands and crotamine on the surface of the nanoparticles were estimated using a combination of electron microscopy and mass spectrometry analysis. In vitro assays confirmed the internalization of these GNPs, into living HeLa cells. The results described herein suggest that our approach may serve as a simple platform for the synthesis of GNPs decorated with crotamine with well-defined morphologies and uniform dispersion, opening new roads for crotamine biomedical applications., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Following high-profile cases, referrals for evaluation of 'suspicious optic discs' to eye clinics in the UK have sharply increased, asking ophthalmologists to reliably distinguish between true and pseudopapilloedema. Optic nerve sheath dilatation (ONSD) on ocular ultrasound (US) is considered a reliable sign of true papilloedema, but this test is not widely available. Recently, anterior bowing of Bruch's membrane (BM) and increased retinal nerve fibre layer thickness on optical coherence tomography (OCT) have emerged as indicators of intracranial hypertension, and OCT is widely available. We aimed to evaluate safety and efficacy of the diagnostic workup in our service, with particular emphasis of diagnostic reliability of US and OCT., Methods: Retrospective service evaluation/cohort study of children and young people younger than 16 years investigated for 'suspicious discs' over a 7-month period in 2016 at a single eye care provider in London, UK. 61 children and young people underwent clinical assessment, US scan and OCT., Results: Of 61 cases, 3 had intracranial pathology. At presentation, only one had ONSD on US and anterior bowing of BM on OCT. Increased nerve fibre layer thickness in at least one of three relevant sectors was observed in two cases. All three cases of intracranial pathology, however, had significant points in their presenting or medical history., Conclusion: Ophthalmologists and optometrists must not rely on funduscopy and ocular imaging when assessing a child for possible intracranial disease; history and basic neurological assessment are critical in the diagnostic workup., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

This chapter reviews the use of dendronized systems as nanocarriers for the delivery of chemotherapeutic drugs. Dendronized systems include dendrimers prepared through convergent methods as well as other systems containing dendrons (e.g., polymers, nanoparticles, liposomes). The preparation of such systems is detailed, followed by the various conjugation techniques used for the transport of chemotherapeutic drugs and their specific delivery to tumor cells. In addition, the ability of dendronized systems to provide passive and active targeting to tumors is discussed. The efficacy of drug delivery using dendronized systems is also illustrated through specific examples of kinetic and biological studies. Finally, the newest trends in conjugation of the most common chemotherapeutics to dendronized systems are described. Overall, this chapter highlights dendronized systems as a way to improve the therapeutic efficiency of drugs for the treatment of cancer. All the recent developments in areas, such as biodegradable dendrimers, modifications to enhance biocompatibility, selectively cleavable drug conjugations, ligand-mediated targeting, and the potential for multifunctional properties, show promises for future advances in cancer therapy., (© 2018 Elsevier Inc. All rights reserved.)

Studies of the plasmon resonances in individual and coupled metal nanoparticles often involve imaging of the nanostructures of interest in an electron microscope. We show that this process can dramatically modify the optical spectra of coupled plasmonic nanoparticles, illustrated here with the case of gold nanorod-nanosphere dimers. The spectral changes are due to the thin, partially conductive carbonaceous layer that deposits onto the particles during imaging. These changes are particularly significant for coupled nanoparticles with subnanometer interparticle gaps but have largely been neglected in previous studies of such structures, including studies intended to probe quantum-mechanical effects in plasmon coupling. Accounting for the effects of the carbonaceous layer will lead to a more accurate understanding of such systems.

PurposeTo determine the incidence of medically unexplained visual loss (MUVL) in children in an open access children's eye casualty.Patients and methodsWe collated demographic and clinical data of consecutive patients younger than 16 years who presented to the children's eye casualty at Moorfields Eye Hospital over a 12-month period and were diagnosed with MUVL or suspected MUVL. We reviewed the clinical records at least 3 months after initial presentation. We calculated the incidence using the number of 'new patient' attendances over the same period as denominator (n=2397). We used descriptive analysis., Main Outcome Measures: number of patients diagnosed with MUVL, proportion of patients with a history of or present psychological problems, recovery rate, and improvement in visual acuity.ResultsWe identified 85 cases of MUVL (54 females; median age: 9 years (IQR 7-12)). The median duration of follow-up was 1.2 months (IQR 0-4.3). The estimated annual incidence was 3.5% (95% confidence interval 2.9-4.4%). Thirty-three per cent of children had a history of psychiatric disorders, reported a stressful life event, or showed signs of psychiatric disorder at the time of first presentation. The recovery rate was 25%. Median improvement in best-corrected visual acuity from presentation to last appointment was 0.22 (IQR 0.06-0.43) logMAR.ConclusionThe incidence of MUVL is higher and the rate of resolution lower than previously reported. MUVL may be associated with mental health problems. We recommend screening for psychological problems to facilitate access to psychological treatment.

Purpose: To describe a pragmatic approach to the medical management of blepharokeratoconjunctivitis in children, based on published evidence and clinical experience., Methods: The authors used the Delphi consensus method to explore the preferred management patterns of four senior clinicians at one institution to reach agreement on indications and dosage schedules for commonly used treatments. Four iterations were created, with electronic questionnaires distributed via an online survey platform. Initial questions were based on recent systematic reviews and clinical experience. After each round, a facilitator summarized the responses and fed these back to the expert participants, together with an invitation to complete the next round of questions., Results: Typical and specific eyelid, corneal, and conjunctival disease features influenced management decisions, and treatments were targeted toward specific findings in these tissues rather than to overall disease severity. Active keratitis was considered the main indication for high potency steroids, systemic antibiotics, and possibly systemic immunomodulators. Other indications for systemic antibiotics were chronic active blepharitis and recurrent troublesome chalazia. Oral antibiotics were used for their anti-inflammatory and antimicrobial properties. There was little agreement on the role of dietary modification, topical lubricants, and preference for oral or topical antibiotics., Conclusions: Detailed clinical assessment of eyelids and ocular surface allows targeted treatment. Research is needed to clarify disease mechanisms and to optimize treatment strategies. [J Pediatr Ophthalmol Strabismus. 2017;54(3):156-162.]., (Copyright 2017, SLACK Incorporated.)

Purpose: Astigmatism is a significant problem in penetrating keratoplasty. Lower astigmatism and better visual outcomes had been expected from laser-assisted penetrating keratoplasty, that is, from the top-hat, mushroom, or zig-zag cutting profiles. We report the long-term outcomes of 141 femtosecond laser-assisted penetrating keratoplasties retrospectively. We compare these outcomes with those of penetrating keratoplasty using the guided trephine system (GTS)., Methods: In all, 141 femtosecond laser-assisted penetrating keratoplasties had been performed in 119 patients. The results were compared with those of conventional keratoplasty (n = 1254; visual and refractive outcomes, graft rejections, and graft failure)., Results: Follow-up averaged 33 months. In eyes with keratoconus, the time to achieve a visual acuity of 10/20 (Snellen) was shorter in the mushroom than in the GTS group. However, there was no relevant long-term difference. Graft astigmatism was higher in the laser groups [keratometric astigmatism at the end of follow-up: -4.5 ± 4 (GTS), -5.8 ± 3.3 (top-hat), -5.9 ± 3.2 D (mushroom); P < 0.01]. In eyes with keratoconus, rates of graft rejection were highest in the mushroom group (55%). In the other groups, top-hat keratoplasty resulted in lower rates of rejection than GTS keratoplasty (31%)., Conclusions: There is no significant difference in the refractive and visual outcomes after femtosecond laser-assisted penetrating keratoplasty compared with GTS keratoplasty. The benefits from the use of the femtosecond laser may be limited and should be weighed against an increased risk of immune reactions, higher surgical complexity, and higher costs.

Characterizing biomolecular interactions is crucial to the understanding of biological processes. Existing characterization methods have low spatial resolution, poor specificity, and some lack the capability for deep tissue imaging. We describe a novel technique that relies on small-angle X-ray scattering signatures from high-contrast molecular probes that correlate with the presence of biomolecular interactions. We describe a proof-of-concept study that uses a model system consisting of mixtures of monomer solutions of gold nanoparticles (GNPs) as the non-interacting species and solutions of GNP dimers linked with an organic molecule (dimethyl suberimidate) as the interacting species. We report estimates of the interaction fraction obtained with the proposed small-angle X-ray scattering characterization method exhibiting strong correlation with the known relative concentration of interacting and non-interacting species.