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Space debris is an increasing problem. Unlike terrestrial debris, there are no natural systems, other than exponentially diminishing atmospheric drag, to self-correct. This creates a self-perpetuat...

Supplementary Figure 6 (A) Survival curve comparing patients with high expression of FLT3, the FLT3LG receptor, to patients with low expression of FLT3 expression. (B) Survival curve comparing patients with high expression of FLT3LG to patients with low expression of FLT3LG.

Supplementary Figure 5 (A) IL-15 amounts in serum of Balb/c mice treated with RT, anti-CD25, anti-asialoGM1 to deplete NK cells, and FLT3L; **** p{less than or equal to}0.0001; n=6. (B) Flow cytometric analysis of DCs MOC2 tumors after treatment with radiation therapy and anti-CD25; n=5. (C) growth curves of MOC2 tumors in individual mice treated with radiation therapy, anti-CD25, and anti-CD137.

Supplementary Figure 3 (A) MOC2 tumor volumes of mice treated with RT, anti-CD25, and pLEV vehicle control (black line); RT, anti-CD25, and pLEV FLT3L plasmid (green line), and RT + anti-CD25 (red line). n=7. (B) Flow Cytometry analysis of CD8 T cell populations in MOC2 tumors and lymph nodes (LN) of C57 BL/6 mice. MOC2 tumors were harvested 3 days after RT, NK cell depletion and FLT3L therapy; n=6.

Purpose:Natural killer (NK) cells are type I innate lymphoid cells that are known for their role in killing virally infected cells or cancer cells through direct cytotoxicity. In addition to direct tumor cell killing, NK cells are known to play fundamental roles in the tumor microenvironment through secretion of key cytokines, such as FMS-like tyrosine kinase 3 ligand (FLT3L). Although radiotherapy is the mainstay treatment in most cancers, the role of radiotherapy on NK cells is not well characterized.Experimental Design:This study combines radiation, immunotherapies, genetic mouse models, and antibody depletion experiments to identify the role of NK cells in overcoming resistance to radiotherapy in orthotopic models of head and neck squamous cell carcinoma.Results:We have found that NK cells are a crucial component in the development of an antitumor response, as depleting them removes efficacy of the previously successful combination treatment of radiotherapy, anti-CD25, and anti-CD137. However, in the absence of NK cells, the effect can be rescued through treatment with FLT3L. But neither radiotherapy with FLT3L therapy alone nor radiotherapy with anti-NKG2A yields any meaningful tumor growth delay. We also identify a role for IL2 in activating NK cells to secrete FLT3L. This activity, we show, is mediated through CD122, the intermediate affinity IL2 receptor, and can be targeted with anti-CD25 therapy.Conclusions:These findings highlight the complexity of using radio-immunotherapies to activate NK cells within the tumor microenvironment, and the importance of NK cells in activating dendritic cells for increased tumor surveillance.

Supplementary Figure 1 (A) Flow cytometry analysis of NK cell population expression of NKG2A in MOC2 tumors 3 days after RT; n=3. (B). Flow cytometry analysis of NK cell populations in MOC2 tumors 3 days after RT and anti-NKG2A therapy; n=6. (C) Flow cytometry analysis of CD4 T cell populations in MOC2 tumors 3 days after RT, anti-NKG2A therapy and NK cell depletion with NK1.1 antibody; n=6. (D) MOC2 tumor volumes of C57BL/6 mice treated with RT and isotype control (red line), anti-CD137, anti-CD25, and anti-NKG2A (blue line), anti-CD17 and antiCD25 (black line); n=7.

Supplementary Figure 4 (A) Gating strategy used in flow cytometry analysis analyzing NK46+ CD3-NK cells, CD11c+ MHCII+ DCs, CD3+ CD4+ T cells, and CD3+ CD8+ T cells. (B) Flow cytometry analysis of NK cell populations in blood from WT C57BL/6 mice treated with RT, anti-CD25, and anti-CD137; n=4. (C) Flow cytometry of CD4 T cell populations in tumors from WT C57BL/6 mice treated with RT, anti-CD25, and anti-CD137 and from DEREG mice treated with RT, anti-CD25, antiCD137, and diphtheria toxin (DT); *p{less than or equal to}0.05, ** p{less than or equal to}0.01; n=6. (D) FLT3L present in serum of C57BL6 treated with radiation therapy, anti-CD25, and anti-CD137, and DEREG mice treated with radiation therapy, anti-CD25, anti-CD137, and diphtheria toxin (DT); ** p{less than or equal to}0.01; n=6

Supplementary Figure 2 (A) Flow cytometry analysis of LY2 tumors analyzing DC populations; n=6. (B) Analysis of FLT3L present in the serum of LY2 bearing mice treated with radiation therapy and isotype antibodies, radiation therapy and anti-CD25 antibody, radiation therapy and anti-CD25 antibody and anti-asialoGM1 antibody to deplete NK cells, and radiation therapy, anti-CD25 antibody, anti-asialoGM1 antibody to deplete NK cells, and FLT3L therapy; n=5.

Purpose:Natural killer (NK) cells are type I innate lymphoid cells that are known for their role in killing virally infected cells or cancer cells through direct cytotoxicity. In addition to direct tumor cell killing, NK cells are known to play fundamental roles in the tumor microenvironment through secretion of key cytokines, such as FMS-like tyrosine kinase 3 ligand (FLT3L). Although radiotherapy is the mainstay treatment in most cancers, the role of radiotherapy on NK cells is not well characterized.Experimental Design:This study combines radiation, immunotherapies, genetic mouse models, and antibody depletion experiments to identify the role of NK cells in overcoming resistance to radiotherapy in orthotopic models of head and neck squamous cell carcinoma.Results:We have found that NK cells are a crucial component in the development of an antitumor response, as depleting them removes efficacy of the previously successful combination treatment of radiotherapy, anti-CD25, and anti-CD137. However, in the absence of NK cells, the effect can be rescued through treatment with FLT3L. But neither radiotherapy with FLT3L therapy alone nor radiotherapy with anti-NKG2A yields any meaningful tumor growth delay. We also identify a role for IL2 in activating NK cells to secrete FLT3L. This activity, we show, is mediated through CD122, the intermediate affinity IL2 receptor, and can be targeted with anti-CD25 therapy.Conclusions:These findings highlight the complexity of using radio-immunotherapies to activate NK cells within the tumor microenvironment, and the importance of NK cells in activating dendritic cells for increased tumor surveillance.

Background The current sparsity of surgical trainees’ exposure to training in operative trauma surgery is multifactorial. This concern has been addressed in the revised Intercollegiate Surgical Curriculum Programme (ISCP) for general and vascular surgery (2021). In the lead up to its implementation, we aimed to assess both trainee and consultant confidence levels as a surrogate reflection in the core competency operative skills in general emergency trauma surgery, identify individual experience in commonly performed trauma procedures and gauge interest in a career in trauma surgery. Method An online survey was circulated to general surgery and vascular surgery trainees and consultants. Self-reported competencies were assessed using a 1–10 confidence rating scale. Most questions were based on competencies in emergency trauma surgery as set out by the ISCP. Results Out of 251 surgical trainees and consultants, 119 responded to our survey (47.4% response rate). Less than half (44.1%; n = 52) of respondents had experienced a trauma thoracotomy. Respondents scored ‘somewhat’ or ‘not at all’ competent in the majority of competencies assessed. Conclusion Self-reported competencies in operative trauma skills across all subgroups were sub-standard with incremental levels of perceived competence proportional to years of surgical training. Our data supports the necessity of the new curriculum, in addition to modern training pathways with direct exposure to operative trauma surgery involving dedicated trauma centres and networks, and responsibility of training pathways in the provision of training trauma surgery.

In the Republic of Ireland (ROI), BRCA1/BRCA2 genetic testing has been traditionally undertaken in eligible individuals, after pre-test counselling by a Clinical Geneticist/Genetic Counsellor. Clinical Genetics services in ROI are poorly resourced, with routine waiting times for appointments at the time of this pilot often extending beyond a year. The consequent prolonged waiting times are unacceptable where therapeutic decision-making depends on the patient's BRCA status. "Mainstreaming" BRCA1/BRCA2 testing through routine oncology/surgical clinics has been implemented successfully in other centres in the UK and internationally. We aimed to pilot this pathway in three Irish tertiary centres. A service evaluation project was undertaken over a 6-month period between January and July 2017. Eligible patients, fulfilling pathology and age-based inclusion criteria defined by TGL clinical, were identified, and offered constitutional BRCA1/BRCA2 testing after pre-test counselling by treating clinicians. Tests were undertaken by TGL Clinical. Results were returned to clinicians by secure email. Onward referrals of patients with uncertain/pathogenic results, or suspicious family histories, to Clinical Genetics were made by the treating team. Surveys assessing patient and clinician satisfaction were sent to participating clinicians and a sample of participating patients. Data was collected with respect to diagnostic yield, turnaround time, onward referral rates, and patient and clinician feedback. A total of 101 patients underwent diagnostic germline BRCA1/BRCA2 tests through this pathway. Pathogenic variants were identified in 12 patients (12%). All patients in whom variants were identified were appropriately referred to Clinical Genetics. At least 12 additional patients with uninformative BRCA1/BRCA2 tests were also referred for formal assessment by Clinical Geneticist or Genetic Counsellor. Issues were noted in terms of time pressures and communication of results to patients. Results from a representative sample of participants completing the satisfaction survey indicated that the pathway was acceptable to patients and clinicians. Mainstreaming of constitutional BRCA1/BRCA2 testing guided by age- and pathology-based criteria is potentially feasible for patients with breast cancer as well as patients with ovarian cancer in Ireland.

Background: Mural thickening (MT) on computed tomography (CT) poses a diagnostic dilemma in the absence of clear reporting guidelines. The aim of this study was to analyse CT reports, identifying patients in whom gastrointestinal wall MT was observed, and to correlate these reports with subsequent endoscopic evaluation. Methods: Patients with MT who had follow-up endoscopy were included in the study (n = 308). The cohort was subdivided into upper gastrointestinal mural thickening (UGIMT) & lower gastrointestinal mural thickening (LGIMT). Results: In total, 55.71% (n = 122) of colonoscopies and 61.8% (n = 55) of gastroscopies were found to be normal. Haemoglobin (HB) level in combination with MT was a predictor of neoplasia in both arms (p = 0.04 UGIMT cohort, p < 0.001 LGIMT cohort). In addition to this, age was a significant correlative parameter in both UGIMT and LGIMT cohorts (p = 0.003, p < 0.001 respectively). Dysphagia and weight loss were associated with UGI malignancies (38 and 63% respectively) and rectal bleeding was correlative in 20% of patients with LGI malignancies. Conclusion: HB, advancing age, and red flag symptoms are potentially useful adjuncts to MT in predicting upper and lower gastrointestinal malignancies. We propose the adoption of a streamlined pathway to delineate patients who should undergo endoscopic investigation following CT identification of MT.

For the past two decades, BTK a tyrosine kinase and member of the Tec family has been a drug target of significant interest due to its potential to selectively treat various B cell-mediated diseases such as CLL, MCL, RA, and MS. Owning to the challenges encountered in identifying drug candidates exhibiting the potency block B cell activation via BTK inhibition, the pharmaceutical industry has relied on the use of covalent/irreversible inhibitors to address this unmet medical need. Herein, we describe a medicinal chemistry campaign to identify structurally diverse reversible BTK inhibitors originating from HITS identified using a fragment base screen. The leads were optimized to improve the potency and in vivo ADME properties resulting in a structurally distinct chemical series used to develop and validate a novel in vivo CD69 and CD86 PD assay in rodents.

Historically, high negative appendicectomy rates (NAR) were acceptable to offset the risks of perforation, previously exceeding 20%. With improved imaging and clinical scoring algorithms, there is growing demand for lower negative appendicectomy rates. The objectives were to (1) establish the NAR in our institution and (2) correlate clinical parameters and imaging modalities with histological findings. Patients undergoing an appendicectomy between January 2012 and June 2018 were identified using a prospectively maintained pathology database. Histology findings were cross referenced against our radiology system, and anonymised data was collected for gender, age, WCC, Neutrophil and CRP level. One thousand one hundred fifty-three patients met the inclusion criteria. Fifty-three percent were males (n = 610), with 81% (n = 933) of histology reports classified as appendicitis. Sixty patients had a histologically normal appendix equating to a 5.2% NAR. If lymphoid hyperplasia, fibrosis and atrophy are included, it equates to a NAR of 14.57%. (p < 0.0001). Sixty-six percent of patients had no pre-operative imaging. CT imaging demonstrated a higher sensitivity (93.33%) and positive predictive value (99.60%) compared to ultrasonography. WCC and CRP are statistically significant in predicting appendicitis (p < 0.0001). There is no consensus on defining a negative appendicectomy or for imaging modality utilisation. CT imaging is the most sensitive and should be used in cases of diagnostic uncertainty. A standardised algorithm regarding the workup of patients with RIF pain along with a consensus on the use of imaging will further reduce negative appendicectomy rates.

Background In recent decades the management of acute appendicitis has evolved significantly. Improved access to early imaging and better clinical scoring algorithms have resulted in less negative appendicectomy rates. In addition, non-operative management has become increasingly utilized. The aim of this study was to assess the variability of management of acute appendicitis globally. Methods This was a multi-national targeted survey of general surgeons across 39 countries. A structured set of questions was utilized to delineate nuances between management styles of consultants and trainees. Opinions on the pathological diagnosis of appendicitis, acceptable negative appendicectomy rates, and the role of non-operative treatment of appendicitis (NOTA) were surveyed. Results A total of 304 general surgeons responded to this survey, 42% of which were consultants/attendings. Sixty-nine percent advocated that a histologically normal appendix was the most appropriate definition of a negative appendicectomy, while 29% felt that anything other than inflammation, necrosis, gangrene, or perforation was more appropriate. Forty-three percent felt that negative appendicectomy rates should be less than 10%, with 41% reporting that their own negative appendicectomy rate was

Tumour budding (TB) is an adverse histological feature in many epithelial cancers. It is thought to represent epithelial–mesenchymal transition, a key step in the metastatic process. The significance of TB in breast carcinoma (BC) remains unclear. The aim of this study is to investigate the relationship between TB and other histological and molecular features of BC. A systematic search was performed to identify studies that compared features of BC based on the presence or absence of high-grade TB. Dichotomous variables were pooled as odds ratios (OR) using the Der Simonian–Laird method. Quality assessment of the included studies was performed using the Newcastle–Ottawa scale (NOS). Seven studies with a total of 1040 patients (high-grade TB n = 519, 49.9%; low-grade/absent TB n = 521, 50.1%) were included. A moderate to high risk of bias was noted. The median NOS was 7 (range 6–8). High-grade TB was significantly associated with lymph node metastasis (OR 2.32, 95% c.i. 1.77 to 3.03, P

Laparoscopic Cholecystectomy (LC) is currently considered the gold standard for the management of symptomatic gallbladder stones disease. Specific complications remain challenging, particularly postoperative bleeding, bile leak, and bile duct injury. We report a rare case of a giant intrahepatic subcapsular haematoma (ISH) complicating LC. Case Presentation A 59-year-old female presented with symptomatic biliary colic. Her past medical history was noted for obesity (BMI>50). She underwent an elective LC with an uncomplicated intraoperative course; however, post-operatively she developed hypovolaemic shock with an acute haemoglobin drop requiring fluid resuscitation and blood transfusion. Emergency CT revealed a massive subcapsular haematoma measuring 21cm×3.1cm× 17cm at the right liver margin without evidence of ongoing bleeding. She was managed conservatively- as per a tertiary hepatobiliary surgery centre’s advice- with meticulous clinical observations, serial monitoring of haemoglobin, and repeat CT to assess for interval progressions. She progressed well with conservative management and did not require surgical or radiological intervention. A follow-up liver sonography performed eight weeks post-discharge confirmed a complete resolution. Conclusion Giant ISH is an exceedingly rare but life-threatening complication following LC which merits special attention. Our case demonstrates the necessity of close postoperative monitoring of patients undergoing LC and considering the possibility of ISH in those who experience refractory postoperative hypotension. It also highlights the decisive role of diagnostic imaging in securing a timely and accurate diagnosis of post-LC ISH.

Despite recent medical advances, surgery remains the mainstay treatment in colon cancer. It is well established that better patient outcomes are achieved when complex surgery including pancreatic, oesophageal and rectal surgeries are carried out in high-volume centres. However, it is unclear as to whether or not colon cancer patients receive the same benefit. Lymph node adequacy is a key performance indicator of successful oncological colonic resection which impacts on patient outcome. To assess the adequacy of lymph node clearance during colonic resection performed with curative intent in a non-specialist centre post introduction of the National Cancer Strategy. Retrospective analysis was performed of a prospectively maintained database examining the lymph node clearance of all oncological resections for colon cancer over a 7-year period (Nov 2010–Dec 2017) at a satellite unit with links to a regional specialist centre. Primary outcome measured was the number of lymph nodes retrieved. Secondary outcomes included resection margins, 30-day complication rate and survival at 1 year. Statistical analysis was performed using SPSS Statistics for Windows, version 24.0 (IBM Corp, Armonk, N.Y., USA). One hundred sixty-seven patients were included. Mean age was 71.0 ± 11.6 years. Majority were male (n = 90, 53.6%). The majority of resections was right sided (n = 112.66.7%) with 78.6% of all resections being undertaken electively. All margins were free of tumour. The average lymph node count was 19.93 ± 8.63 (4.62) with only 17 (10.2%) of specimens containing

Highlights • Obscure GI bleeding can be a challenging diagnosis and is well acknowledged. • Perseverance is required to achieve the correct diagnosis in obscured GI bleeding. • Diagnostic overshadowing can halt investigations and delay diagnosis. • Multidisciplinary team input is important in the diagnosis of obscured GI bleeding., Introduction Undiagnosed gastrointestinal bleeding may originate in the small bowel. This presents a diagnostic challenge despite the advancement in contemporary imaging. We report two cases which highlight the limitations of routine investigation for obscure gastrointestinal bleeding. Presentation of case Patient A presented with a history of rectal bleeding, treated with interventional embolisation of caecal angiodysplasia. A diagnosis of neuroendocrine tumour (NET) was reached two years after presentation following intraoperative right hemicolectomy resection of a presumed recurrent angiodysplastic bleed. Patient B presented with recurrent melaena labelled as non-steroidal anti-inflammatory drug (NSAID) induced gastritis. After multiple endoscopic and radiological investigations, a 4.5 cm mass was visualised on imaging after three years, which was histologically proven as gastrointestinal stromal tumour (GIST) of the small bowel. Both patients experienced a delayed diagnosis despite multiple investigations and careful follow-up. Discussion Our case series discusses the benefits and limitations of investigation for gastrointestinal bleeding and suggests a need for continued multidisciplinary input in situations where the patient presumed diagnosis remains in question. Conclusion OGIB remains a diagnostic challenge and is attributable to small bowel pathology in 75% of cases. This suggests a need for continued investigation in situations where the patient presents multiple times despite adequate treatment for the presumed underlying condition.

The single-ion anisotropy and magnetic interactions in spin-ice systems give rise to unusual non-collinear spin textures, such as Pauling states and magnetic monopoles. The effective spin correlation strength ($J_{eff}$) determines the relative energies of the different spin-ice states. With this work, we display the capability of capacitive torque magnetometry in characterizing the magneto-chemical potential associated with monopole formation. We build a magnetic phase diagram of Ho$_2$Ti$_2$O$_7$, and show that the magneto-chemical potential depends on the spin-sublattice ($\alpha$ or $\beta$), i.e., the Pauling state, involved in the transition. Monte-Carlo simulations using the dipolar-spin-ice Hamiltonian support our findings of a sublattice-dependent magneto-chemical potential, but the model underestimates the $J_{eff}$ for the $\beta$-sublattice. Additional simulations, including next-nearest neighbor interactions ($J_2$), show that long-range exchange terms in the Hamiltonian are needed to describe the measurements. This demonstrates that torque magnetometry provides a sensitive test for $J_{eff}$ and the spin-spin interactions that contribute to it., Comment: Main text: 12 pages, 5 figures, 1 table; Supplemental Materials: 12 pages, 7 figures, 6 tables

Background As genomic profiling of constitutional and tumour-derived DNA becomes increasingly critical in cancer risk estimation, prognostication and treatment, there is a growing need for clinicians involved in cancer care to up-skill in Cancer Genetics. In the Republic of Ireland (ROI), this is particularly crucial, given a paucity of vocationally trained Clinical Geneticists per capita compared to other European countries. Aims We aimed to assess the self-reported confidence of postgraduate medical/surgical trainees in ROI in requesting, interpreting, and managing genomic data in patients with cancer, and to assess their selfreported experience, and demand for future training in this area. Methods A cross-sectional survey of postgraduate trainees in four specialties (Medical and Radiation Oncology, Surgery, and Obstetrics and Gynaecology (O&G)), training in ROI, was undertaken. A bespoke electronic questionnaire was designed to capture data regarding preceding experience, and confidence across several hypothetical clinical scenarios involving genomic testing. The survey was circulated to eligible participants by training programme administrators, after relevant institutional ethical approval. Data was collected anonymously. Results The study cohort included 62 respondents. A paucity of cancer genetics training at every level was demonstrated, with “hardly any” or “none at all” reported by 47(76%), 62(100%), and 50(81%) during undergraduate, core specialty, and higher specialist training, respectively. A relative lack of confidence in all clinical scenarios was apparent, particularly among Surgery/O&G trainees. Most respondents would value more training in Cancer Genetics. Conclusions This study demonstrates an unmet need in dedicated Cancer Genetics training for postgraduate specialty trainees in ROI.

Background Tumour budding (TB) is an adverse histological feature in many cancers. It is thought to represent epithelial-to-mesenchymal transition, a key step in the metastatic process. The role of TB in breast carcinoma (BC) remains unclear. Aim To investigate the relationship between TB and other histological and molecular features of BC. Method A systematic search was performed to identify studies that compared features of BC based on the presence or absence of high-grade TB. Dichotomous variables were pooled as odds ratios (OR) using the Cochran–Mantel–Haenszel method. Quality assessment of the included studies was performed using the Newcastle-Ottawa scale (NOS). Result Seven studies with a total of 1040 patients (high grade TB n=519, 49.9%; low grade TB n=521, 50.1%) were included. A moderate- to high-risk of bias was noted. The median NOS was 7 (range 6-8). High-grade TB was significantly associated with lymph node involvement (OR 2.28, 95% c.i. 1.74 to 2.98, P Conclusion High-grade TB is enriched in hormone-positive BC and is associated with known adverse prognostic variables. TB may offer new insights into the metastatic processes of luminal BC. Take-home message High-grade TB is enriched in hormone-positive BC and is associated with known adverse prognostic variables. TB may offer new insights into the metastatic processes of luminal BC.

Introduction Sarcopenia in cancer may confer negative outcomes, but its prevalence and impact in the modern multimodal management of locally advanced breast cancer have not been systematically studied. Method Patients undergoing neoadjuvant therapy and surgery for locally advanced breast cancer between 2010 and 2015 were studied. Skeletal muscle index (SMI) and lean body mass (LBM) were determined. Sarcopenia was defined by computed tomography (CT) at L3 as SMI Result 258 patients were studied. Sarcopenia was present in 23.0%, 7.8% and 0.0% of patients with normal weight, overweight and obesity, respectively (P=0.001). Sarcopenia was not associated with baseline cT and cN stage, tumour grade, histologic type or receptor status. Patients with sarcopenia exhibited equivalent indices of neoadjuvant therapy response including ypT and ypN stage, pathologic complete response and Sataloff grade following surgical resection. Postoperatively, sarcopenia was not independently associated with comprehensive complications index (P=0.242), length of stay (P=0.716) or overall morbidity (P=0.365). However, on multivariable analysis, lower LBM independently predicted reduced invasive disease-free (P=0.049,HR0.93[95%CI0.87-1.00]) and overall (P=0.028,HR0.92[0.85-0.99]), but not disease-specific survival (P=0.070). Conclusion Consistent with a lack of association with baseline and post-treatment pathologic features, sarcopenia in locally advanced breast cancer is associated with reduced overall, but not disease-specific, survival. These data indicate that the prognostic impact of sarcopenia may be mediated by impaired performance status and increased non-cancer mortality. Take-home message Consistent with a lack of association with baseline and post-treatment pathologic features, sarcopenia in locally advanced breast cancer is associated with reduced overall, but not disease-specific, survival. These data indicate that the prognostic impact of sarcopenia may be mediated by impaired performance status and increased non-cancer mortality.

This work presents fundamental understanding of the correlation between nanoindentation hardness and practical scratch resistance for mechanically tunable anti-reflective (AR) hardcoatings. These coatings exhibit a unique design freedom, allowing quasi-continuous variation in the thickness of a central hardcoat layer in the multilayer design, with minimal impact on anti-reflective optical performance. This allows detailed study of anti-reflection coating durability based on variations in hardness vs. depth profiles, without the durability results being confounded by variations in optics. Finite element modeling is shown to be a useful tool for the design and analysis of hardness vs. depth profiles in these multilayer films. Using samples fabricated by reactive sputtering, nanoindentation hardness depth profiles were correlated with practical scratch resistance using three different scratch and abrasion test methods, simulating real world scratch events. Scratch depths from these experiments are shown to correlate to scratches observed in the field from consumer electronics devices with chemically strengthened glass covers. For high practical scratch resistance, coating designs with hardness &gt, 15 GPa maintained over depths of 200–800 nm were found to be particularly excellent, which is a substantially greater depth of high hardness than can be achieved using previously common AR coating designs.