Synthesis and Characterization of [(PbSe)1+δ]4[TiSe2]4 Isomers.

This work presents the preparation of a series of [(PbSe)1+δ]4[TiSe2]4 isomers via a low temperature synthesis approach that exploits precursor nanoarchitecture to direct formation of specific isomers. The targeted isomers formed even when the precursors did not have the correct amount of each element to make a unit cell from each repeating sequence of elemental layers deposited. This suggests that the exact composition of the precursors is less important than the nanoarchitecture in directing the formation of the compounds. The as-deposited diffraction data show that the isomers begin to form during the deposition, and Ti2Se, in addition to PbSe and TiSe2, are present in the specular diffraction patterns. HAADF-STEM images reveal impurity layers above and below an integer number of targeted isomer unit cells. The structural data suggest that Ti2Se forms as Se is deposited on the initial Ti layers and remains throughout isomer self-assembly. During growth, the isomers deplete the local supply of Ti and Pb, creating diffusion gradients that drive additional cations toward the growth front, which leaves surface impurity layers of TiSe2 and TiO2 after the supply of Pb is exhausted. The deposited stacking sequences direct formation of the targeted isomers, but fewer repeating units form than intended due to the lack of material per layer in the precursor and formation of impurity layers. All isomers have negative Hall and Seebeck coefficients, indicating that electrons are the majority carrier. The carrier concentration and conductivity of the isomers increase with the number of interfaces in the unit cell, resulting from charge donation between adjacent layers. The opposite variation of the carrier concentration and mobility with temperature result in minima in the resistivity between 50 and 100 K. The very weak temperature dependence of the carrier concentration likely results from changes in the amount of charge transfer between the layers with temperature.

Kinetics of the Topochemical Transformation of (PbSe) m(TiSe2) n(SnSe2) m(TiSe2) n to (Pb0.5Sn0.5Se) m(TiSe2) n.

Solid-state reaction kinetics on atomic length scales have not been heavily investigated due to the long times, high reaction temperatures, and small reaction volumes at interfaces in solid-state reactions. All of these conditions present significant analytical challenges in following reaction pathways. Herein we use in situ and ex situ X-ray diffraction, in situ X-ray reflectivity, high-angle annular dark field scanning transmission electron microscopy, and energy-dispersive X-ray spectroscopy to investigate the mechanistic pathways for the formation of a layered (Pb0.5Sn0.5Se)1+δ(TiSe2) m heterostructure, where m is the varying number of TiSe2 layers in the repeating structure. Thin film precursors were vapor deposited as elemental-modulated layers into an artificial superlattice with Pb and Sn in independent layers, creating a repeating unit with twice the size of the final structure. At low temperatures, the precursor undergoes only a crystallization event to form an intermediate (SnSe2)1+γ(TiSe2) m(PbSe)1+δ(TiSe2) m superstructure. At higher temperatures, this superstructure transforms into a (Pb0.5Sn0.5Se)1+δ(TiSe2) m alloyed structure. The rate of decay of superlattice reflections of the (SnSe2)1+γ(TiSe2) m(PbSe)1+δ(TiSe2) m superstructure was used as the indicator of the progress of the reaction. We show that increasing the number of TiSe2 layers does not decrease the rate at which the SnSe2 and PbSe layers alloy, suggesting that at these temperatures it is reduction of the SnSe2 to SnSe and Se that is rate limiting in the formation of the alloy and not the associated diffusion of Sn and Pb through the TiSe2 layers.

Kinetically Controlled Formation and Decomposition of Metastable [(BiSe)1+δ] m[TiSe2] m Compounds.

Preparing homologous series of compounds allows chemists to rapidly discover new compounds with predictable structure and properties. Synthesizing compounds within such a series involves navigating a free energy landscape defined by the interactions within and between constituent atoms. Historically, synthesis approaches are typically limited to forming only the most thermodynamically stable compound under the reaction conditions. Presented here is the synthesis, via self-assembly of designed precursors, of isocompositional incommensurate layered compounds [(BiSe)1+δ] m[TiSe2] m with m = 1, 2, and 3. The structure of the BiSe bilayer in the m = 1 compound is not that of the binary compound, and this is the first example of compounds where a BiSe layer thicker than a bilayer in heterostructures has been prepared. Specular and in-plane X-ray diffraction combined with high-resolution electron microscopy data was used to follow the formation of the compounds during low-temperature annealing and the subsequent decomposition of the m = 2 and 3 compounds into [(BiSe)1+δ]1[TiSe2]1 at elevated temperatures. These results show that the structure of the precursor can be used to control reaction kinetics, enabling the synthesis of kinetically stable compounds that are not accessible via traditional techniques. The data collected as a function of temperature and time enabled us to schematically construct the topology of the free energy landscape about the local free energy minima for each of the products.

An objective assessment of the variability in number of drops per bottle of glaucoma medication.

BACKGROUND: The purpose of this study is to evaluate the number of eyedrops available per bottle of a variety of commonly prescribed glaucoma medications. METHODS: Six bottles of each glaucoma medication were tested: three each in the vertical and horizontal orientations. Bottles were housed in a customized force gauge apparatus designed to mimic ballpoint fingertip contact with a bottle. At a standard rate, all drops were expressed from each bottle and counted with an automated drop counter. Simultaneously, bottle volume was measured and drop size and number were also estimated. The main outcome measures were: total number of drops, volume per bottle and drops per milliliter (mL) of glaucoma medication. RESULTS: A total of 192 bottles from 32 bottle designs and manufacturers were tested. Twenty-two of the 32 bottle designs had a significantly different mean number of drops in the vertical and horizontal positions, with 10 designs have more drops dispensed in the horizontal orientation and 12 in the vertical orientation. Six of the 32 bottle designs had a significantly different mean total bottle volume in the vertical and horizontal positions, with all designs having greater volume in the vertical position. An adjusted ratio of mean number of drops/mean bottle volume demonstrated a range from 20.9 drops/mL to 40.8 drops/mL. CONCLUSIONS: There is significant variability in drops and volume available per bottle of glaucoma medication depending on both the bottle position and manufacturer. These data point to the need for circumspection in prescribing glaucoma medications and caution in evaluating therapeutic outcomes.

Retinal nerve fiber layer thickness measurements: uveitis, a major confounding factor.

OBJECTIVE: To evaluate optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) measurements in patients with active and quiescent uveitis with and without glaucoma and compare results to the published age-adjusted normative data. DESIGN: Comparative, retrospective pilot study. PARTICIPANTS: Consecutive patients with uveitis who underwent OCT RNFL measurements between December 2011 and October 2012 were identified: 76 uveitic eyes without glaucoma and 135 uveitic eyes with glaucoma. INTERVENTION: We conducted OCT of the RNFL. MAIN OUTCOME MEASURES: Global and sectoral RNFL thickness measurements. RESULTS: In 19 nonglaucomatous, uveitic eyes with active inflammation, mean global and all sectoral RNFL measurements were greater than the normative 95th percentile. The mean global RNFL OCT measurement was 140.5 microns in such eyes compared with 107.8 microns in the 57 nonglaucomatous, quiescent, uveitic eyes (P=0.008). These measurements were significantly higher than the average of 95.3 microns reported in normal eyes (P<0.001). All mean sectoral measurements except superonasal were significantly higher in active compared with quiescent uveitic eyes (P=0.002-0.05). In glaucomatous eyes with both quiescent and active uveitis, the mean global RNFL measurements on OCT were 92.3 and 95.7 microns, respectively. These measurements were significantly higher than the mean global RNFL thickness (65.3 microns) reported in eyes with the same stage (moderate) of nonuveitic glaucoma. CONCLUSIONS: Uveitis is a major confounding factor in assessing the thickness of the RNFL. A significant thickening of the RNFL was found in patients with active uveitis and a greater RNFL thickness than anticipated in patients with uveitic glaucoma. These data raise concerns about the comparative value of RNFL scans as a method to detect and monitor glaucoma in uveitic eyes.

Prevalence of self-reported early glaucoma eye drop bottle exhaustion and associated risk factors: a patient survey.

BACKGROUND: One barrier to patient adherence with chronic topical glaucoma treatment is an inadequate amount of medication available between prescription refills. We examined the self-reported prevalence of early exhaustion of glaucoma eye drops prior to a scheduled refill, and associated risk factors. METHODS: This cross-sectional survey was performed at a University-based clinical practice. Glaucoma patients at the University of Washington who were experienced with eye drop application and were on a steady regimen of self-administered glaucoma drops in both eyes took a survey at the time of clinic examination. The main outcome measure was self-reported early eye drop bottle exhaustion. RESULTS: 236 patients were eligible and chose to participate. In general, patients included were relatively healthy (mean 2.3 comorbid medical conditions). Sixty patients (25.4%) reported any problem with early exhaustion of eye drop bottles, and this was associated with visual acuity ≤ 20/70 in the better eye (P = .049). Twelve patients (5.1%) reported that they "often" (5-7 times per year), "usually" (8-11 times per year) or "always" ran out of eye drops prior to a scheduled refill. Patients affected by this higher level (≥ 5 times yearly) of eye drop bottle exhaustion were more likely to have poor visual acuity in their worse eye ≤ 20/70 (P = .015) and had significantly lower worse-eye logMAR (P = .043). CONCLUSIONS: Self-reported early glaucoma bottle exhaustion regularly affected 5% of patients in our population and 25% reported early exhaustion at least once; the main risk factor was poor vision in at least one eye. These results may not be generalizable to a broad patient population, or to those inexperienced with eye drop self-administration. However, this pilot study compels further evaluation and consideration of early eye drop bottle exhaustion in glaucoma patients.

Telluride misfit layer compounds: [(PbTe)1.17]m(TiTe2)n.

Telluride misfit layer compounds are reported for the first time. These compounds were synthesized using a novel approach of structurally designing a precursor that would form the desired product upon low-temperature annealing, which allows the synthesis of kinetically stable products that do not appear on the equilibrium phase diagram. Four new compounds of the [(PbTe)(1.17)]m(TiTe2)n family are reported, and their structures were examined by a variety of X-ray diffraction techniques.

Prevalence of xerophthalmia among malnourished children in rural Ethiopia.

To assess the prevalence of eye disease among malnourished children in a rural Ethiopian health center and evaluate correlations between xerophthalmia and grades of malnutrition. A retrospective, cross-sectional survey. An institution-based cross-sectional prospective study was performed at Bushulo Health Center in rural south Ethiopia and included all children age 6 months to 14 years receiving care for malnourishment from June 1st to July 30th, 2008. Data collection involved a combination of interviews with caretakers, ocular examination by a pediatric ophthalmologist and anthropometric measurements. One hundred and seventy-three children (average age at examination 2.9 ± 0.2 years) were treated for malnutrition (97 female, 76 male). One hundred and forty-nine patients had moderate malnutrition (86.03 %) and 24 had severe malnutrition (13.9 %). The following eye diseases were diagnosed--trachoma (12.1 %), blepharitis (13.3 %) and xerophthalmia (20.8 %). Severely malnourished children were more likely to suffer from xerophthalmia than moderately malnourished children (p < 0.0001). When comparing anthropometric measurements to the diagnosis of xerophthalmia, only weight percentile showed significance (p = 0.008). Xerophthalmia is a common global cause of pediatric blindness and is highly correlated with severe malnutrition. Continued efforts are necessary to improve nutrition and outcomes in these patients.

The Matthew Effect: Prevalence of Doctor and Physician Parents among Ophthalmology Applicants.

Objective This article determines the prevalence of physician parents among ophthalmology residency applications. Design Retrospective, single-center cohort study. Subjects All applicants to the University of Kentucky Ophthalmology Residency between 2018 and 2023. Methods Residency applications were reviewed, with data collection including applicant gender, self-identified Under-Represented in Medicine (URiM) status, United States Medical Licensing Examination (USMLE) Step 1 score, USMLE Step 2 score, and whether the application identified a doctor or physician as a parent. Doctor was defined as a profession requiring a doctorate degree, and similarly, physician as a profession requiring a medical degree. Results A total of 2,057 applications were reviewed, representing 54% of all match participants during the study period. Fourteen percent (296) of applications indicated a parent was a doctor and 12% (253) a parent was a physician. There were no differences between gender, URiM, USMLE Step 1, and Step 2 scores between applicants indicating a doctor or physician as a parent and those that did not ( p all > 0.4 and Cohen's d all < 0.02). Of the type of doctors, 85% (253) were physicians, 6% (17) optometrists, 6% (17) Doctors of Philosophy, 3% (8) dentists, 1% (1) pharmacist, and 1% (1) veterinarian. Eighty-six percent (217) of applications with a physician parent provided the type of physician, with ophthalmologist the most common (93, 43%). Ninety-eight percent (249) of applications with a physician parent provided the gender of the parent, with father (168, 68%) more common than mother (42, 17%) or both parents (39, 16%). Conclusion Physician parents are substantially overrepresented in ophthalmology residency applicants. This raises concerns regarding diversity and inclusion efforts for recruitment in medicine.

Fishing-related ocular trauma in the Pacific Northwest: hook, line and sinker.

Traumatic injuries are a worldwide major cause of blindness and ocular morbidity. We report a series of four cases of fishing-related ocular trauma from the Pacific Northwest demonstrating the varied presentation and visual consequences of these injuries, including open and closed globe injuries, retained foreign bodies and retinal and subretinal hemorrhage. More efforts are needed to increase awareness and use of preventative measures.

Accuracy of Ophthalmology Clinic Follow-Up in the Incarcerated Patient Population.

Purpose Incarcerated patients represent a uniquely vulnerable population in the outpatient ophthalmology setting, and the reliability of follow-up in this group is undetermined. Methods This was a retrospective, observational chart review of consecutive incarcerated patients evaluated at the ophthalmology clinic of a single academic medical center between July 2012 and September 2016. For each encounter the following were recorded: patient age, gender, incarcerated status at the time of encounter (a subset of patients had encounters before/after incarceration), interventions performed, follow-up interval requested, urgency of follow-up, and actual time to subsequent follow-up. Primary outcome measures were no-show rate and timeliness, which was defined as follow-up within 1.5× the requested period. Results There were 489 patients included during the study period, representing a total of 2,014 clinical encounters. Of the 489 patients, 189 (38.7%) were seen once. Of the remaining 300 patients with more than one encounter, 184 (61.3%) ultimately did not return and only 24 (8%) were always on time for every encounter. Of 1,747 encounters with specific follow-up requested, 1,072 were considered timely (61.3%). Factors significantly associated with subsequent loss to follow-up include whether a procedure was performed ( p < 0.0001), urgency of follow-up ( p < 0.0001), incarcerated status ( p = 0.0408), and whether follow-up was requested ( p < 0.0001). Conclusion Almost two-thirds of incarcerated patients in our population requiring repeat examination were lost to follow-up, particularly those who underwent an intervention or required more urgent follow-up. Patients entering and exiting the penal system were less likely to follow-up while incarcerated. Further work is needed to understand how these gaps compare to those in the general population and to identify means of improving these outcomes.

Confined acoustic line modes within a glide-symmetric waveguide.

Confined coupled acoustic line-modes supported by two parallel lines of periodic holes on opposite surfaces of a glide-symmetric waveguide have a hybrid character combining symmetric and anti-symmetric properties. These hybrid coupled acoustic line-modes have a near constant group velocity over a broad frequency range as no band gap is formed at the first Brillouin zone boundary. We show that the hybrid character of these confined modes is tuneable as a function of the spacing between the two surfaces. Further we explore how the band-gap reappears as the glide symmetry is broken.

Surgical results in the management of advanced primary congenital glaucoma in a rural pediatric population.

OBJECTIVE: To present the anatomic and functional results of surgical treatment for advanced primary congenital glaucoma (PCG) in a rural setting. DESIGN: Retrospective, observational case series. PARTICIPANTS: Forty eyes of 22 consecutive patients diagnosed with PCG and who underwent surgical treatment. METHODS: All eyes underwent surgical treatment for PCG. Type of surgery and postoperative complications were noted. We examined anatomic and functional indices before and after the operation. MAIN OUTCOME MEASURES: Visual acuity (VA), intraocular pressure (IOP), refractive spherical error, cup-to-disc ratio (CDR), and horizontal corneal diameter (HCD). RESULTS: Average age at the time of surgery was 3.3 years (range, 0.4-10) and the mean follow-up was 6 months (range, 1-11). 15% showed marked lens dislocation owing to the severe buphthalmos at presentation. Preoperative IOP was 54 ± 2 mmHg, HCD was 15.1 ± 0.3 mm, and CDR (when visible) was 0.8 ± 0.02. Surgical intervention included 31 trabeculotomies, 6 Ahmed Glaucoma Valve implants, 1 goniotomy, and 2 eviscerations. Serious complications were noted in 4 eyes. Final postoperative IOP was 23 ± 2 mmHg (P < 0.0001). Patients were significantly more likely to have ambulatory VA (following objects or better) after operation (18% vs 64%; P < 0.0001). CONCLUSIONS: Our surgical outcomes in children with advanced PCG demonstrated moderate overall improvement in IOP and modest improvement of VA. Deep deprivation amblyopia, severe disease manifestation at presentation, opaque corneas, and frequent lens dislocation limited the possible success. These data further signify the need for effective, timely screening of children and prompt recognition by health care workers to reduce the rate of avoidable blindness in developing countries.

Bilateral primary congenital glaucoma in monozygotic twins.

Primary congenital glaucoma is an uncommon pediatric ocular disease contributing to a disproportionately high percentage of childhood blindness worldwide. This case report describes bilateral primary congenital glaucoma in monozygotic twins who first presented to an ophthalmologist in Ethiopia at 6 years of age. Both had severe, protracted disease, with only moderate improvement after surgical intervention.

Reporting of Race and Ethnicity in the Ophthalmology Literature in 2019.

Importance: The description of racial and ethnic data in human trials is relatively unregulated, leading to potential confusion with and inconsistent reporting of these data. Objective: To determine the frequency and use of racial and ethnic data in the ophthalmology literature in 2019. Design, Setting, and Participants: This cross-sectional study included all full-length human studies published between January and December 2019 in the American Journal of Ophthalmology, JAMA Ophthalmology, and Ophthalmology. Main Outcomes and Measures: Whether race or ethnicity was included in the data or analysis, how the categorization was described in the methods and results, specific racial and ethnic categories used, and whether and how the categories were determined. Results: A total of 547 articles were identified during the study period, 484 (88% ± 2.7%) of which reported background demographic information, including patient age and sex. Only 233 (43% ± 4.1%) reported race and/or ethnicity. Of those articles, 72 (31% ± 5.9%) categorized it as race, 51 (22% ± 5.3%) ethnicity, 56 (24% ± 5.4%) race/ethnicity, 21 (9% ± 3.7%) race and ethnicity, 12 (5% ± 3.0%) descent, 12 (5% ± 2.9%) population, and 5 (2% ± 2.0%) ancestry; in 21 (9% ± 3.8%) it was not defined. Only 30 studies (13% ± 4.4%) described how it was determined in the methods or results, most frequently by self-report (77% ± 3.9%). A total of 78 races and/or ethnicities were defined. Conclusions and Relevance: While most articles during the study period reported background demographic information, few included race and ethnicity and only a fraction of those described how these data were determined. The categories used were heterogeneous and often inconsistent. These findings suggest the need for increased and more standardized reporting of ethnic and racial demographic data in the ophthalmology literature.

Age-related ocular vascular changes.

BACKGROUND: The global society is aging at an increasing rate, with a continually larger proportion of the population consisting of those over the age of 65. Age-related vascular changes have been demonstrated in ocular tissue, and the incidence and prevalence of diseases such as macular degeneration, glaucoma and vascular occlusive diseases increase significantly with age. METHODS: This article reviews the current body of literature examining age-associated ocular vascular changes, and summarizes the aggregate findings. We discuss the potential role of the aging vasculature in the etiology of age-associated ocular disease, focusing on glaucoma. RESULTS: Our working hypothesis is that although advancing age is a physiological phenomenon, there are stepwise hemodynamic and vascular changes that occur, predisposing the eye and other tissue beds to pathological conditions. Advancing age does not independently give rise to disease, but does generate increasingly vulnerable vascular beds that are susceptible to further insults. CONCLUSIONS: These results compel a need for further investigation of age-related changes in ocular physiology and pathophysiology.

Effect of glaucoma on identification of bottle cap color in ophthalmic medications.

A prospective, nonrandomized, observational trial of 60 glaucoma patients to correlate visual acuity and visual field with ability to distinguish bottle cap color of commonly used ophthalmic medications was conducted. A total of 103 eyes from 60 patients (30 women) were evaluated. The mean logMAR acuity was 0.34±0.54 (approximately 20/45 Snellen acuity), average Humphrey Visual Field (HVF) mean deviation was -8.58±8.69 dB, mean Ishihara plates (out of 14) were 11.78±4.15, and bottle cap color score (out of 10) was 8.56±2.51. Multiple linear regression analysis revealed an independent correlation of visual acuity (P=0.0137) and Ishihara score (P<0.001) with cap color score, but no significant effect with visual field mean deviation (P>0.05). Glaucoma patients with poor visual acuity, but not necessarily advanced visual field loss, are likely to have difficultly identifying the color of their bottle caps. Physicians should be cognizant of this potential issue when reviewing medications with patients.

Accuracy of biometry in pediatric cataract extraction with primary intraocular lens implantation.

PURPOSE: To determine the accuracy of predicted postoperative refractive outcomes in pediatric patients having cataract surgery with intraocular lens (IOL) implantation and to compare them with other variables historically considered important in cataract surgery. SETTING: Tertiary care referral hospital. METHODS: This retrospective review comprised 203 eyes of 153 consecutive pediatric patients (< or = 18 years old) having cataract extraction with primary posterior chamber IOL implantation in the capsular bag. All cases were performed by 1 of 2 surgeons, and all refractions were performed manually by an experienced pediatric ophthalmologist using a retinoscope. RESULTS: In all patients, the mean absolute value (MAE) of the prediction error was 1.08 diopters (D) +/- 0.93 (SD). Age at time of surgery and corneal (K) mean curvature were significantly correlated with the absolute value of the prediction error (P = .0006 and P = .0088, respectively). A multiple regression model showed that age at time of surgery and K mean curvature were the only 2 variables significantly associated with MAE; axial length, formula, surgeon, and A-scan type were not significantly associated with prediction error. CONCLUSIONS: Data from 203 consecutive primary pediatric IOL implantations showed the heterogeneous nature of the variables involved in predictions of refractive outcomes in this population. The complexities of this issue support the need for specific methods of measurement and an IOL calculation formula for the pediatric population.

Squeeze Me if You Can: Variability in Force Requirements to Extract a Drop From Common Glaucoma Bottles.

PURPOSE: To determine the force requirements to dispense a single drop from commonly prescribed brand and generic topical glaucoma medications and correlate these findings with pinch strength in a representative patient population. PATIENTS AND METHODS: Four bottles of each medication were tested: 2 in the vertical and 2 in the horizontal orientation. Bottles were housed in a customized force gauge apparatus designed to mimic ballpoint fingertip contact with a bottle tip. For all bottles, each of the first 10 dispensed drops was tested and then tests were performed in increments of 10 until the bottle was empty. For each tested drop, the maximum force and displacement were electronically measured. Concurrently, maximum pinch strength was measured on consecutive glaucoma patients. RESULTS: A total of 84 bottles from 21 bottle designs were tested. There was significant variability across the designs, with roughly a 7-fold (0.67 to 4.49 kgf) and 4-fold (0.81 to 3.00 kgf) difference in force requirements in the vertical and horizontal positions, respectively. Of 53 enrolled patients in the glaucoma clinic, the mean pinch strength was 5.05 (range, 1.23 to 10.4 kgf) and 4.82 (range, 1.47 to 10.67 kgf) kgf for the right and left hands, respectively. CONCLUSIONS: There is statistically significant variability in the force required to squeeze a drop from common glaucoma medications, and a representative sampling of clinic patients suggests that many likely struggle with the force requirements of several bottle designs. These data further support standardization of topical glaucoma drug delivery and design.

The synthesis of [(PbSe)1+δ]m(TiSe2)n[(SnSe2)1+γ]m(TiSe2)n heterostructures with designed nanoarchitectures by self assembly of amorphous precursors.

Targeted heterostructures containing intergrown two dimensional (2D) layers of 3 different constituent layers, SnSe2, PbSe and TiSe2, were prepared by controlling the composition and sequence of elemental bilayers within a designed precursor. Varying the structure of the precursor enabled the number of structural units of each constituent and the sequence of crystalline 2D layers to be precisely controlled. The stacking of the 2D layers, their structures, and the segregation of the elements between them were determined using X-ray diffraction and electron microscopy techniques, with the observed sequence of the 2D layers consistent with the targeted intergrowth. This ability to prepare targeted heterostructures is critical, since the number of possible configurations in the final compound increases rapidly as the number of constituents increases, from almost 60 000 with two constituents to over 130 million with three constituents and to over 35 billion with four constituents for 20 or fewer distinct layers in the unit cell. This general route for synthesizing specific multiple component heterostructures will accelerate the feedback loop in this growing research area, permitting theorists to assume specific structures in the search for enhanced properties and providing experimentalists with crystallographically aligned samples to test these predictions.