Breast density effect on the sensitivity of digital screening mammography in a UK cohort.

OBJECTIVES: To assess the performance of breast cancer screening by category of breast density and age in a UK screening cohort. METHODS: Raw full-field digital mammography data from a single site in the UK, forming a consecutive 3-year cohort of women aged 50 to 70 years from 2016 to 2018, were obtained retrospectively. Breast density was assessed using Volpara software. Examinations were grouped by density category and age group (50-60 and 61-70 years) to analyse screening performance. Statistical analysis was performed to determine the association between density categories and age groups. Volumetric breast density was assessed as a binary classifier of interval cancers (ICs) to find an optimal density threshold. RESULTS: Forty-nine thousand nine-hundred forty-eight screening examinations (409 screen-detected cancers (SDCs) and 205 ICs) were included in the analysis. Mammographic sensitivity, SDC/(SDC + IC), decreased with increasing breast density from 75.0% for density a (p = 0.839, comparisons made to category b), to 73.5%, 59.8% (p = 0.001), and 51.3% (p < 0.001) in categories b, c, and d, respectively. IC rates were highest in the densest categories with rates of 1.8 (p = 0.039), 3.2, 5.7 (p < 0.001), and 7.9 (p < 0.001) per thousand for categories a, b, c, and d, respectively. The recall rate increased with breast density, leading to more false positive recalls, especially in the younger age group. There was no significant difference between the optimal density threshold found, 6.85, and that Volpara defined as the b/c boundary, 7.5. CONCLUSIONS: The performance of screening is significantly reduced with increasing density with IC rates in the densest category four times higher than in women with fatty breasts. False positives are a particular issue for the younger subgroup without prior examinations. CLINICAL RELEVANCE STATEMENT: In women attending screening there is significant underdiagnosis of breast cancer in those with dense breasts, most marked in the highest density category but still three times higher than in women with fatty breasts in the second highest category. KEY POINTS: Breast density can mask cancers leading to underdiagnosis on mammography. Interval cancer rate increased with breast density categories 'a' to 'd'; 1.8 to 7.9 per thousand. Recall rates increased with increasing breast density, leading to more false positive recalls.

Mammography Breast Cancer Screening Triage Using Deep Learning: A UK Retrospective Study.

Background Breast screening enables early detection of cancers; however, most women have normal mammograms, resulting in repetitive and resource-intensive reading tasks. Purpose To investigate if deep learning (DL) algorithms can be used to triage mammograms by identifying normal results to reduce workload or flag cancers that may be overlooked. Materials and Methods In this retrospective study, three commercial DL algorithms were investigated using consecutive mammograms from two UK Breast Screening Program sites from January 2015 to December 2017 and January 2017 to December 2018 on devices from two mammography vendors. Normal mammograms with a 3-year follow-up and histopathologically proven cancer detected at screening, the subsequent round, or in the 3-year interval were included. Two algorithm thresholds were set: in scenario A, 99.0% sensitivity for rule-out triage to a lone reader, and in scenario B, approximately 1.0% additional recall providing a rule-in triage for further assessment. Both thresholds were then applied to the screening workflow in scenario C. The sensitivity and specificity were used to assess the overall predictive performance of each DL algorithm. Results The data set comprised 78 849 patients (median age, 59 years [IQR, 53-63 years]) and 887 screening-detected, 439 interval, and 688 subsequent screening round-detected cancers. In scenario A (rule-out triage), models DL-1, DL-2, and DL-3 triaged 35.0% (27 565 of 78 849), 53.2% (41 937 of 78 849), and 55.6% (43 869 of 78 849) of mammograms, respectively, with 0.0% (0 of 887) to 0.1% (one of 887) of screening-detected cancers undetected. In scenario B, DL algorithms triaged in 4.6% (20 of 439) to 8.2% (36 of 439) of interval and 5.2% (36 of 688) to 6.1% (42 of 688) of subsequent-round cancers when applied after the routine double-reading workflow. Combining both approaches in scenario C resulted in an overall noninferior specificity (difference, -0.9%; P < .001) and superior sensitivity (difference, 2.7%; P < .001) for the adaptive workflow compared with routine double reading for all three algorithms. Conclusion Rule-out and rule-in DL-adapted triage workflows can improve the efficiency and efficacy of mammography breast cancer screening. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Nishikawa and Lu in this issue.

Optimized 18F-FDG PET-CT Method to Improve Accuracy of Diagnosis of Metastatic Cancer.

The diagnosis of cancer by FDG PET-CT is often inaccurate owing to subjectivity of interpretation. We compared the accuracy of a novel normalized (standardized) method of interpretation with conventional non-normalized SUV. Patients (n = 393) with various malignancies were studied with FDG PET/CT to determine the presence or absence of cancer. Target lesions were assessed by two methods: (1) conventional SUVmax (conSUVmax) and (2) a novel method that combined multiple factors to optimize SUV (optSUVmax), including the patient's normal liver SUVmax, a liver constant (k) derived from a review of the literature, and use of site-specific thresholds for malignancy. The two methods were compared to pathology findings in 154 patients being evaluated for mediastinal and/or hilar lymph node (MHLNs) metastases, 143 evaluated for extra-thoracic lymph node (ETLNs) metastases, and 96 evaluated for liver metastases. OptSUVmax was superior to conSUVmax for all patient groups. For MHLNs, sensitivity was 83.8% vs. 80.7% and specificity 88.7% vs. 9.6%, respectively; for ETLNs, sensitivity was 92.1% vs. 77.8% and specificity 80.1% vs. 27.6%, respectively; and for lesions in the liver parenchyma, sensitivity was 96.1% vs. 82.3% and specificity 88.8% vs. 23.0%, respectively. Optimized SUVmax increased diagnostic accuracy of FDG PET-CT for cancer when compared with conventional SUVmax interpretation.

Three-dimensional biofabrication of nanosecond laser micromachined nanofibre meshes for tissue engineered scaffolds.

There is a high demand for bespoke grafts to replace damaged or malformed bone and cartilage tissue. Three-dimensional (3D) printing offers a method of fabricating complex anatomical features of clinically relevant sizes. However, the construction of a scaffold to replicate the complex hierarchical structure of natural tissues remains challenging. This paper reports a novel biofabrication method that is capable of creating intricately designed structures of anatomically relevant dimensions. The beneficial properties of the electrospun fibre meshes can finally be realised in 3D rather than the current promising breakthroughs in two-dimensional (2D). The 3D model was created from commercially available computer-aided design software packages in order to slice the model down into many layers of slices, which were arrayed. These 2D slices with each layer of a defined pattern were laser cut, and then successfully assembled with varying thicknesses of 100 µm or 200 µm. It is demonstrated in this study that this new biofabrication technique can be used to reproduce very complex computer-aided design models into hierarchical constructs with micro and nano resolutions, where the clinically relevant sizes ranging from a simple cube of 20 mm dimension, to a more complex, 50 mm-tall human ears were created. In-vitro cell-contact studies were also carried out to investigate the biocompatibility of this hierarchal structure. The cell viability on a micromachined electrospun polylactic-co-glycolic acid fibre mesh slice, where a range of hole diameters from 200 µm to 500 µm were laser cut in an array where cell confluence values of at least 85% were found at three weeks. Cells were also seeded onto a simpler stacked construct, albeit made with micromachined poly fibre mesh, where cells can be found to migrate through the stack better with collagen as bioadhesives. This new method for biofabricating hierarchical constructs can be further developed for tissue repair applications such as maxillofacial bone injury or nose/ear cartilage replacement in the future.

Migration drivers and migration choice: interrogating responses to migration and development interventions in West Africa.

The notion of migration as being at least partly about 'choice' is deeply rooted in both academic thought and public policy. Recent contributions have considered migration choice as step-wise in nature, involving a separation between 'aspiration' and 'ability' to migrate, whilst stressing a range of non-economic factors that influence migration choices. But such nuances have not prevented the emergence of a significant area of public policy that seeks to influence choices to migrate from Africa through 'irregular' channels, or at all, through a range of development interventions. This paper explores evidence from West Africa on how young people formulate the boundaries of such choice. Drawing on approaches in anthropology and elsewhere that stress the value of a 'future-orientated' lens, we show how present uncertainty is a central framing that fundamentally limits the value of thinking about migration as a choice. This has important implications for policy on 'migration and development'.

A Progressive Nutrient Profiling System to Guide Improvements in Nutrient Density of Foods and Beverages.

Improving the nutrient density of processed foods is one way to bring the global food supply closer to the WHO Sustainable Development Goals. Nutrient profiling (NP) has emerged as the preferred method of monitoring the progress toward product innovation and reformulation. This paper presents PepsiCo Nutrition Criteria (PNC), a new internal NP model that was designed to guide and monitor improvements in nutrient density and overall nutritional quality of foods and beverages. The new PNC NP model assigns food products into four classes of increasing nutritional value, based on the content of nutrients to limit, along with nutrients and ingredients to encourage. The nutrient standards used for category assignment followed those developed by global dietary authorities. Standards are proposed for calories, sodium, added sugars, saturated, and industrially produced trans fats. Also included are minimum values for food groups to encourage, low-fat dairy, and for country-specific gap nutrients. Internal use of the NP model has spurred product changes that are consistent with WHO goals for industry transparency. An audited review of company products showed that 48% met added sugar, 65% met sodium, and 71% met saturated fat goals. By the end of 2020, in the top 26 regions in which products are sold, 48% of the total sales volume of global beverages had 100 kcal or less from added sugars per 355 ml serving representing 80% of beverage volume and over 90% of food volume sold globally. The PNC NP model is not consumer-facing but is specifically intended for internal use to motivate stepwise and incremental product innovation and reformulation. Transparent and published NP models further WHO goals of engaging industry stakeholders in the (re)formulation of processed foods and beverages consistent with public health goals.

An improved process for the fabrication and surface treatment of custom-made titanium cranioplasty implants informed by surface analysis.

Cranioplasty implants are routinely fabricated from commercially pure titanium plates by maxillofacial prosthetists. The differing fabrication protocols adopted by prosthetists working at different hospital sites gives rise to considerable variations in surface topography and composition of cranioplasty implants, with residues from the fabrication processes having been found to become incorporated into the surface of the implant. There is a growing recognition among maxillofacial prosthetists of the need to standardise these protocols to ensure quality and consistency of practice within the profession. In an effort to identify and eliminate the source of the inclusions associated with one such fabrication protocol, the present study examined the surfaces of samples subjected to each of the manufacturing steps involved. Surface and elemental analysis techniques identified the main constituent of the surface inclusions to be silicon from the glass beads used to texture the surface of the implant during fabrication. Subsequent analysis of samples prepared according to a revised protocol resulted in a more homogeneous titanium dioxide surface as evidenced by the reduction in area occupied by surface inclusions (from 8.51% ± 2.60% to 0.93% ± 0.62%). These findings may inform the development of improved protocols for the fabrication of titanium cranioplasty plates.

Low-Cost Eye Phantom for Stereophotogrammetry-Based Optic Nerve Head Topographical 3D Imaging.

Glaucoma is the second leading cause of blindness globally. Stereophotogrammetry-based optic nerve head topographical imaging systems could potentially allow for objective glaucoma assessment in settings where technologies such as optical coherence tomography and the Heidelberg Retinal Tomograph are prohibitively expensive. In the development of such systems, eye phantoms are invaluable tools for both system calibration and performance evaluation. Eye phantoms developed for this purpose need to replicate the optical configuration of the eye, the related causes of measurement artefacts, and give the possibility to present to the imaging system the targets required for system calibration. The phantoms in the literature that show promise of meeting these requirements rely on custom lenses to be fabricated, making them very costly. Here, we propose a low-cost eye phantom comprising a vacuum formed cornea and commercially available stock bi-convex lens, that is optically similar to a gold-standard reference wide-angle schematic eye model and meets all the compliance and configurability requirements for use with stereo-photogrammetry-based ONH topographical imaging systems. Moreover, its modular design, being fabricated largely from 3D-printed components, lends itself to modification for other applications. The use of the phantom is successfully demonstrated in an ONH imager.

Probing fibronectin adsorption on chemically defined surfaces by means of single molecule force microscopy.

Atomic force microscope (AFM) based single molecule force spectroscopy (SMFS) and a quartz crystal microbalance (QCM) were respectively employed to probe interfacial characteristics of fibronectin fragment FNIII8-14 and full-length fibronectin (FN) on CH3-, OH-, COOH-, and NH2-terminated alkane-thiol self-assembled monolayers (SAMs). Force-distance curves acquired between hexahistidine-tagged FNIII8-14 immobilised on trisNTA-Ni2+ functionalized AFM cantilevers and the OH and COOH SAM surfaces were predominantly 'loop-like' (76% and 94% respectively), suggesting domain unfolding and preference for 'end-on' oriented binding, while those generated with NH2 and CH3 SAMs were largely 'mixed type' (81% and 86%, respectively) commensurate with unravelling and desorption, and 'side-on' binding. Time-dependent binding of FN to SAM-coated QCM crystals occurred in at least two phases: initial rapid coverage over the first 5 min; and variably diminishing adsorption thereafter (5-70 min). Loading profiles and the final hydrated surface concentrations reached (~ 950, ~ 1200, ~ 1400, ~ 1500 ng cm-2 for CH3, OH, COOH and NH2 SAMs) were consistent with: space-filling 'side-on' orientation and unfolding on CH3 SAM; greater numbers of FN molecules arranged 'end-on' on OH and especially COOH SAMs; and initial 'side-on' contact, followed by either (1) gradual tilting to a space-saving 'end-on' configuration, or (2) bi-/multi-layer adsorption on NH2 SAM.

3D Reconstruction of the Optic Nerve Head of a Phantom Eye from Images Obtained using a Slit Lamp Fitted with Low Cost Add-Ons.

Early detection and treatment are key in limiting vision loss from glaucoma, the second leading cause of blindness worldwide. Morphological alteration of the optic nerve head (ONH), detectable early in the condition, is a key clinical indicator. The mainstay for evaluation in clinics is the subjective assessment of stereoscopic ONH images. If quantitative diagnostic devices, which extract 3D information and use this to make an objective assessment, could be made affordable, it could mean greater diagnostic capability in primary/community care. A potentially cost-effective solution is to extract, using computer stereo vision, 3D information from stereo images obtained through a slit lamp, a mainstay of eye diagnostics, present in practically all ophthalmology and optometry practices. This work shows 3D ONH reconstruction in an eye phantom through a common slit lamp fitted with low cost cameras. Quantitative reconstructions, in close agreement with ground truths, were obtained.

Adsorption of Fibronectin Fragment on Surfaces Using Fully Atomistic Molecular Dynamics Simulations.

The effect of surface chemistry on the adsorption characteristics of a fibronectin fragment (FNIII8⁻10) was investigated using fully atomistic molecular dynamics simulations. Model surfaces were constructed to replicate self-assembled monolayers terminated with methyl, hydroxyl, amine, and carboxyl moieties. It was found that adsorption of FNIII8⁻10 on charged surfaces is rapid, specific, and driven by electrostatic interactions, and that the anchoring residues are either polar uncharged or of opposing charge to that of the targeted surfaces. On charged surfaces the presence of a strongly bound layer of water molecules and ions hinders FNIII8⁻10 adsorption. In contrast, adsorption kinetics on uncharged surfaces are slow and non-specific, as they are driven by van der Waals interactions, and the anchoring residues are polar uncharged. Due to existence of a positively charged area around its cell-binding region, FNIII8⁻10 is available for subsequent cell binding when adsorbed on a positively charged surface, but not when adsorbed on a negatively charged surface. On uncharged surfaces, the availability of the fibronectin fragment's cell-binding region is not clearly distinguished because adsorption is much less specific.

Fostering Strategies to Expand the Consumption of Edible Insects: The Value of a Tripartite Coalition between Academia, Industry, and Government.

Although many insect-based foods are nutritious and often an inexpensive option for human and domesticated animal consumption, there remains a negligible market for such foods in many countries. Several environmental and economic considerations underscore the potential value of insect-based foods, and emerging science suggests that diets incorporating such foods might also convey some genuine health benefits. However, if expanded markets for insect-based foods in cultures naïve to entomophagy are to be pursued, it will be important to develop multifaceted and coordinated strategies to 1) delineate authentic health benefits, 2) explore means of optimizing insect husbandry and food processing, 3) examine cultural barriers to acceptance, 4) formulate workable approaches to marketing, and 5) address relevant food regulations. We sought to construct a multidisciplinary coalition whose goals are to investigate the above-mentioned 5 issues. Eighteen individuals from government, industry, and academia, with collective expertise in the fields of entomology, insect husbandry, human nutrition, sustainable agriculture, entomophagy, consumer product development and marketing, food-processing technologies, food regulatory affairs, and the anthropology of food selection, convened a 1-d summit and formed a tripartite organization to integrate their varied perspectives. Collaborative efforts are underway among members of this coalition to accomplish these multiple goals. Coordinating efforts between accomplished experts in relevant fields of academia, government, and industry will greatly expand our knowledge of and appreciation for the potential benefits of insect-based foodstuffs to individuals, to society, and to the sustainability of the global food supply, and thereby inform us as to how to proceed in a judicious and intelligent manner.

Mammographic density and breast cancer risk in breast screening assessment cases and women with a family history of breast cancer.

BACKGROUND: Mammographic density has been shown to be a strong independent predictor of breast cancer and a causative factor in reducing the sensitivity of mammography. There remain questions as to the use of mammographic density information in the context of screening and risk management, and of the association with cancer in populations known to be at increased risk of breast cancer. AIM: To assess the association of breast density with presence of cancer by measuring mammographic density visually as a percentage, and with two automated volumetric methods, Quantra™ and VolparaDensity™. METHODS: The TOMosynthesis with digital MammographY (TOMMY) study of digital breast tomosynthesis in the Breast Screening Programme of the National Health Service (NHS) of the United Kingdom (UK) included 6020 breast screening assessment cases (of whom 1158 had breast cancer) and 1040 screened women with a family history of breast cancer (of whom two had breast cancer). We assessed the association of each measure with breast cancer risk in these populations at enhanced risk, using logistic regression adjusted for age and total breast volume as a surrogate for body mass index (BMI). RESULTS: All density measures showed a positive association with presence of cancer and all declined with age. The strongest effect was seen with Volpara absolute density, with a significant 3% (95% CI 1-5%) increase in risk per 10 cm3 of dense tissue. The effect of Volpara volumetric density on risk was stronger for large and grade 3 tumours. CONCLUSIONS: Automated absolute breast density is a predictor of breast cancer risk in populations at enhanced risk due to either positive mammographic findings or family history. In the screening context, density could be a trigger for more intensive imaging.