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Abstract While optical microscopy inspection of blood films and bone marrow aspirates by a hematologist is a crucial step in establishing diagnosis of acute leukemia, especially in low-resource settings where other diagnostic modalities are not available, the task remains time-consuming and prone to human inconsistencies. This has an impact especially in cases of Acute Promyelocytic Leukemia (APL) that require urgent treatment. Integration of automated computational hematopathology into clinical workflows can improve the throughput of these services and reduce cognitive human error. However, a major bottleneck in deploying such systems is a lack of sufficient cell morphological object-labels annotations to train deep learning models. We overcome this by leveraging patient diagnostic labels to train weakly-supervised models that detect different types of acute leukemia. We introduce a deep learning approach, Multiple Instance Learning for Leukocyte Identification (MILLIE), able to perform automated reliable analysis of blood films with minimal supervision. Without being trained to classify individual cells, MILLIE differentiates between acute lymphoblastic and myeloblastic leukemia in blood films. More importantly, MILLIE detects APL in blood films (AUC 0.94 ± 0.04) and in bone marrow aspirates (AUC 0.99 ± 0.01). MILLIE is a viable solution to augment the throughput of clinical pathways that require assessment of blood film microscopy.

Abstract How do we best constrain social interactions to decrease transmission of communicable diseases? Indiscriminate suppression is unsustainable long term and presupposes that all interactions carry equal importance. Instead, transmission within a social network has been shown to be determined by its topology. In this paper, we deploy simulations to understand and quantify the impact on disease transmission of a set of topological network features, building a dataset of 9000 interaction graphs using generators of different types of synthetic social networks. Independently of the topology of the network, we maintain constant the total volume of social interactions in our simulations, to show how even with the same social contact some network structures are more or less resilient to the spread. We find a suitable intervention to be specific suppression of unfamiliar and casual interactions that contribute to the network’s global efficiency. This is, pathogen spread is significantly reduced by limiting specific kinds of contact rather than their global number. Our numerical studies might inspire further investigation in connection to public health, as an integrative framework to craft and evaluate social interventions in communicable diseases with different social graphs or as a highlight of network metrics that should be captured in social studies.

The SEM-EDX method was used to investigate the structure and morphology of organic–inorganic hybrids containing zirconium, boron and phosphorus compounds, synthesized by the sol–gel method. We started by using, for the first time together, zirconyl chloride hexa-hydrate (ZrOCl2·6H2O), phenyl phosphinic acid and triethyl borate as precursors and reagents, at different molar ratios. The obtained hybrids showed a very high thermal stability and are not soluble in water or in organic solvents. As a consequence, such hybrid solid materials are suitable for applications at high temperatures. The obtained hybrids have complex 3D structures and form organic–inorganic networks containing Zr-O-Zr, Zr-O-P and Zr-O-B bridges. Such organic–inorganic networks are also expected to form supramolecular structures and to have many potential applications in different fields of great interest such as catalysis, medicine, agriculture, energy storage, fuel cells, sensors, electrochemical devices and supramolecular chemistry.

BackgroundPerforator flaps account for a fraction of reconstructive procedures despite their growing popularity. Specific microsurgical skills are required for successful harvesting of perforator flaps, which are difficult to attain through direct operating room training. Cadaver and small animal dissection cannot simulate human perforator dissection, lacking either bleeding and vessel feedback or providing too small calibers. Thus, we have developed and refined over the last ten years five perforator flaps models in living pig, described their harvesting technique and provided evidence for their effectiveness as perforator flap training models.MethodCT angiography data from ten living pigs was used for detailed examination of the integument's vascular anatomy. Microsurgical techniques were used to standardize and harvest the perforator flaps in acute models. The same operator-assistant team, with no prior perforator flap harvesting experience, raised all flaps in a sequential manner, one animal per day, during a 7 weeks timespan. Porcine flaps were compared to human counterparts in terms of vessel caliber, dissection times. Immediate flap survival was measured as duration of perforator pulsation after completion of flap harvesting, measured every 10 minutes for up to two hours.ResultsFive perforator flaps were standardized, based on the deep cranial epigastric, thoracodorsal, lateral intercostal, cranial gluteal and dorsal cervical arteries and the operative technique was described in detail. Mean pig perforator size was 1.24±0.36 mm and mean pedicle diameter was 2.78±0.8 mm, which matched closely the human calibers for each flap. Total harvesting time increased 22.4% between the first two experiments due to a more cautious approach following the lack of perforator pulsation in all flaps in the first experimental animal. A total decrease of 44.4% harvesting time between second and last experiment was observed, as expected with all repetitive surgical procedures. Post-operative perforator pulsation time revealed a steep learning curve, with no or short-term pulsatile perforators in the first five pigs, followed by a 275% increase in total perforator pulsation time between 5th and 6th experimental animal. Based on these findings we provide a description of the most common mistakes, their consequences and gestures which can be trained using the pig perforator flaps, in order to overcome these mistakes.ConclusionThese five pig perforator flap models provide a fast and efficient learning tool to develop perforator flap harvesting skills safely. Surgical training using these five experimental models offers a similar hands-on perforator flap dissection experience as with human tissue, based on the similar sized calibers of both perforators and pedicles with their human counterparts.

Background Perforator flaps account for a fraction of reconstructive procedures despite their growing popularity. Specific microsurgical skills are required for successful harvesting of perforator flaps, which are difficult to attain through direct operating room training. Cadaver and small animal dissection cannot simulate human perforator dissection, lacking either bleeding and vessel feedback or providing too small calibers. Thus, we have developed and refined over the last ten years five perforator flaps models in living pig, described their harvesting technique and provided evidence for their effectiveness as perforator flap training models. Method CT angiography data from ten living pigs was used for detailed examination of the integument’s vascular anatomy. Microsurgical techniques were used to standardize and harvest the perforator flaps in acute models. The same operator-assistant team, with no prior perforator flap harvesting experience, raised all flaps in a sequential manner, one animal per day, during a 7 weeks timespan. Porcine flaps were compared to human counterparts in terms of vessel caliber, dissection times. Immediate flap survival was measured as duration of perforator pulsation after completion of flap harvesting, measured every 10 minutes for up to two hours. Results Five perforator flaps were standardized, based on the deep cranial epigastric, thoracodorsal, lateral intercostal, cranial gluteal and dorsal cervical arteries and the operative technique was described in detail. Mean pig perforator size was 1.24±0.36 mm and mean pedicle diameter was 2.78±0.8 mm, which matched closely the human calibers for each flap. Total harvesting time increased 22.4% between the first two experiments due to a more cautious approach following the lack of perforator pulsation in all flaps in the first experimental animal. A total decrease of 44.4% harvesting time between second and last experiment was observed, as expected with all repetitive surgical procedures. Post-operative perforator pulsation time revealed a steep learning curve, with no or short-term pulsatile perforators in the first five pigs, followed by a 275% increase in total perforator pulsation time between 5th and 6th experimental animal. Based on these findings we provide a description of the most common mistakes, their consequences and gestures which can be trained using the pig perforator flaps, in order to overcome these mistakes. Conclusion These five pig perforator flap models provide a fast and efficient learning tool to develop perforator flap harvesting skills safely. Surgical training using these five experimental models offers a similar hands-on perforator flap dissection experience as with human tissue, based on the similar sized calibers of both perforators and pedicles with their human counterparts.

In the present work, novel organic–inorganic hybrid materials containing boron, zirconium, and phosphorus were synthesized at different molar ratios, using the sol–gel method, starting from zirconyl chloride hexa-hydrate, triethyl borate, and phenyl phosphonic acid as the precursors. The sol–gel process is used for the first time in the present work in order to obtain organic–inorganic hybrids (or the so-called inorganic polymers) containing together boron, zirconium, and phosphorus. The sol–gel syntheses were performed at room temperature in ethanol. Zirconium containing compounds are already well known for their applications in medicine in restorative or prosthetic devices, including dental implants, knee and hip replacements, middle-ear ossicular chain reconstruction, and so on. Zirconium is a strong transition metal, which started to replace hafnium and titanium in the last decade in important applications. On the other hand, boron has the capability (similar to carbon) to form stable covalently bonded molecular networks. In addition to this capability, boron also offers mixed metallic and nonmetallic properties, because of its place on the periodic table, at the border between metals and nonmetals. Boron is responsible for the higher thermal stability of synthesized hybrid compounds. In the structure of those hybrid compounds, zirconium, boron, and phosphorus atoms are always connected via an oxygen atom, by P-O-Zr, Zr-O-Zr, or Zr-O-B bridges.