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Background With recent advances in microscopy, recordings of cell behaviour can result in terabyte-size datasets. The lattice light sheet microscope (LLSM) images cells at high speed and high 3D resolution, accumulating data at 100 frames/second over hours, presenting a major challenge for interrogating these datasets. The surfaces of vertebrate cells can rapidly deform to create projections that interact with the microenvironment. Such surface projections include spike-like filopodia and wave-like ruffles on the surface of macrophages as they engage in immune surveillance. LLSM imaging has provided new insights into the complex surface behaviours of immune cells, including revealing new types of ruffles. However, full use of these data requires systematic and quantitative analysis of thousands of projections over hundreds of time steps, and an effective system for analysis of individual structures at this scale requires efficient and robust methods with minimal user intervention. Results We present LLAMA, a platform to enable systematic analysis of terabyte-scale 4D microscopy datasets. We use a machine learning method for semantic segmentation, followed by a robust and configurable object separation and tracking algorithm, generating detailed object level statistics. Our system is designed to run on high-performance computing to achieve high throughput, with outputs suitable for visualisation and statistical analysis. Advanced visualisation is a key element of LLAMA: we provide a specialised tool which supports interactive quality control, optimisation, and output visualisation processes to complement the processing pipeline. LLAMA is demonstrated in an analysis of macrophage surface projections, in which it is used to i) discriminate ruffles induced by lipopolysaccharide (LPS) and macrophage colony stimulating factor (CSF-1) and ii) determine the autonomy of ruffle morphologies. Conclusions LLAMA provides an effective open source tool for running a cell microscopy analysis pipeline based on semantic segmentation, object analysis and tracking. Detailed numerical and visual outputs enable effective statistical analysis, identifying distinct patterns of increased activity under the two interventions considered in our example analysis. Our system provides the capacity to screen large datasets for specific structural configurations. LLAMA identified distinct features of LPS and CSF-1 induced ruffles and it identified a continuity of behaviour between tent pole ruffling, wave-like ruffling and filopodia deployment.

Conservation efforts often focus on umbrella species whose distributions overlap with many other flora and fauna. However, because biodiversity is affected by different threats that are spatially variable, focusing only on the geographic range overlap of species may not be sufficient in allocating the necessary actions needed to efficiently abate threats. We developed a problem‐based method for prioritizing conservation actions for umbrella species that maximizes the total number of flora and fauna benefiting from management while considering threats, actions, and costs. We tested our new method by assessing the performance of the Australian federal government's umbrella prioritization list, which identifies 73 umbrella species as priorities for conservation attention. Our results show that the federal government priority list benefits only 6% of all Australia's threatened terrestrial species. This could be increased to benefit nearly half (or 46%) of all threatened terrestrial species for the same budget of AU$550 million/year if more suitable umbrella species were chosen. This results in a 7‐fold increase in management efficiency. We believe nations around the world can markedly improve the selection of prioritized umbrella species for conservation action with this transparent, quantitative, and objective prioritization approach., Article impact statement: Considering spatially overlapping species, threats, actions, and costs in conservation prioritization yields 7‐fold increase in efficiency.

Isolated right ventricular acute myocardial infarction is rare and its presentation can sometimes mimic an anterior ST-segment elevation myocardial infarction. We reported two cases of isolated right ventricular acute myocardial infarction presenting with a ST-elevation in anterior leads. The first case was admitted for an out-of-hospital cardiac arrest due to ventricular fibrillation. The patient died from neurologic consequences of the cardiac arrest, despite a successful prehospital thrombolysis, followed by a percutaneous angioplasty of the right coronary artery. The second case occurred after a complex percutaneous angioplasty of the right coronary artery, complicated by a total occlusion of a right marginal branch. These two cases illustrate the limits of the ECG for the diagnosis of isolated right ventricular acute infarction, and the difficulties of the differential diagnosis with anterior infarction, which may determine the treatment and the prognosis.

The promise of machine learning methods to act as decision support systems for pathologists continues to grow. However, central to their successful adoption must be interpretable implementations so that people can trust and learn from them effectively. Generative modeling, most notable in the form of adversarial generative models, is a naturally interpretable technique because the quality of the model is explicit from the quality of images it generates. Such a model can be further assessed by exploring its latent space, using human-meaningful concepts by defining concept vectors. Motivated by these ideas, we apply for the first time generative methods to histological images of basal cell carcinoma (BCC). By simultaneously learning to generate and encode realistic image patches, we extract feature rich latent vectors that correspond to various tissue morphologies, namely BCC, epidermis, keratin, papillary dermis and inflammation. We show that a logistic regression model trained on these latent vectors can achieve high classification accuracies across 6 binary tasks (86–98%). Further, by projecting the latent vectors onto learned concept vectors we can generate a score for the absence or degree of presence for a given concept, providing semantically accurate “conceptual summaries” of the various tissues types within a patch. This can be extended to generate multi-dimensional heat maps for whole-image specimens, which characterizes the tissue in a similar way to a pathologist. We additionally find that accurate concept vectors can be defined using a small labeled dataset.

We present LLAMA, a pipeline for systematic analysis of terabyte scale 4D microscopy datasets. Analysis of individual biological structures in imaging at this scale requires efficient and robust methods which do not require human micromanagement or editing of outputs. To meet this challenge, we use a machine learning method for semantic segmentation, followed by a robust and configurable object separation and tracking algorithm, and the generation of detailed object level statistics. Advanced visualisation is a key element of LLAMA: we provide a specialised software tool which supports quality control and optimisation as well as visualisation of outputs. LLAMA was used in a quantitative analysis of macrophage surface membrane projections (filopodia, ruffles, tent-pole ruffles) examining the differential effects of two interventions: lipopolysaccharide (LPS) and macrophage colony stimulating factor (CSF-1). Distinct patterns of increased activity were identified. In addition, a continuity of behaviour was found between tent pole ruffling and wave-like ruffling, further defining the role of filopodia in ruffling.

Densely labelled segmentation data for digital pathology images is costly to produce but is invaluable to training effective machine learning models. We make available 290 hand-annotated histopathology tissue sections of the 3 most common skin cancers; basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and intraepidermal carcinoma (IEC). These non-melanoma skin cancers constitute over 90% of all skin cancer diagnoses and hence this dataset gives an opportunity to the scientific community to benchmark analytic methodologies on a significant portion of the dermatopathology workflow. The data represents typical cases of the three cancer types (not requiring a differential diagnosis) across shave, punch and excision biopsy contexts. Each image is accompanied with a segmentation mask which characterizes the section into 12 tissue types, specifically: keratin, epidermis, papillary dermis, reticular dermis, hypodermis, inflammation, glands, hair follicles and background, as well as BCC, SCC and IEC. Included also are cancer margin measurements to work towards automated assessment of surgical margin clearance and tumour invasion. This leaves open many opportunities for researchers to utilize or extend the dataset, building upon recent work on image analysis problems in skin cancer (Thomas et al., 2021).

We apply for the first-time interpretable deep learning methods simultaneously to the most common skin cancers (basal cell carcinoma, squamous cell carcinoma and intraepidermal carcinoma) in a histological setting. As these three cancer types constitute more than 90% of diagnoses, we demonstrate that the majority of dermatopathology work is amenable to automatic machine analysis. A major feature of this work is characterising the tissue by classifying it into 12 meaningful dermatological classes, including hair follicles, sweat glands as well as identifying the well-defined stratified layers of the skin. These provide highly interpretable outputs as the network is trained to represent the problem domain in the same way a pathologist would. While this enables a high accuracy of whole image classification (93.6-97.9%), by characterising the full context of the tissue we can also work towards performing routine pathologist tasks, for instance, orientating sections and automatically assessing and measuring surgical margins. This work seeks to inform ways in which future computer aided diagnosis systems could be applied usefully in a clinical setting with human interpretable outcomes.

Topotecan has demonstrated activity in ovarian carcinomas. In order to increase the tumour response rate and to define the maximum tolerated dose (MTD) of topotecan, we decided to develop a high-dose phase I regimen supported by stem cell support. High-doses schedules using a 1-day single administration have MTDs of 10.5 (24 h continuous infusion (CI)) or 22.5 mg/m2 (30 min infusion). Five-day CI induces grade IV mucositis at high doses (MTD12 mg/m2). We chose to administer topotecan in a 5-day schedule with a 30 min daily infusion. Patients were scheduled to receive one cycle of therapy. The first dose level was 4.0 mg/m2/day x 5 days. Limiting toxicities were defined as toxic death, grade IV non-haematopoietic or haematopoietic toxicity6 weeks. From August 1998 to April 2002, 49 patients were included. Forty-three patients have completed one course and 15 have received two cycles. One patient treated at level 7 mg/m2/day died of sepsis. Median duration of grade IV neutropenia was 9 days. Two episodes of grade IV diarrhoea were observed at level 9.5 mg/m2/day. Pharmacokinetic data were linear within the dose range of 4-9.0 mg/m2/day. The MTD was reached at 9 mg/m2/day x 5 days.

A coordinated initiative for patients with heart failure was planned and implemented across this healthcare system to: (1) incorporate best evidence-based practice to rapidly stabilize the patient, and (2) establish early, coordinated patient education to promote self-care at home with the support of appropriate resources. Length of stay, readmission frequency, ACE inhibitor and beta blocker prescribing patterns at discharge were the outcomes selected for ongoing study and cross-site efforts toward improvement. These outcomes did improve following cross-site implementation with the collaboration of all appropriate disciplines and the coordination of new and existing services to serve this population.

In order to evaluate the feasibility of the autologous transfusion in an alloimmunized sickle cell patient, changes in the hematologic and biochemical characteristics of erythrocytes stored for 42 days from two patients with sickle cell SC anemia were compared with control subjects' (Hb A) red blood cells. Erythrocytes were stored in Saline Adenosine Dextrose Mannitol at +4 degrees C. The cryopreservation storage was made and 51Cr red cell survival was measured in one patient. No significant difference in the hematologic and biochemical parameters of the SC red blood cells and the control subjects was observed during the storage at +4 degrees C. Red cell survivals determined in fresh cells, cells stored for 42 days at +4 degrees C and thawed cells from one patient demonstrate much shorter half-life values than those of normal red blood cells. Before application, our results need to be confirmed by the same protocol with another patient with sickle cell SC.

Objectifs Le but de notre etude etait d’evaluer la prise en charge des prolapsus genitaux chez les patientes greffees renales. Methodes Nous avons realise une etude retrospective multicentrique incluant les patientes transplantees ayant eu une cure de prolapsus entre 2008 et 2016 en interrogeant tous les centres francais de transplantation renale. L’identification des patientes reposait sur une analyse du PMSI avec les codes CCAM relatifs a la promontofixation. Les criteres etudies etaient l’âge, le BMI, les antecedents, les facteurs de risques et le type de prolapsus selon la classification de Baden et Walker, l’incontinence urinaire associee, le site de la greffe, le type d’anastomose urinaire, le traitement immunosuppresseur, les donnees urodynamiques, le type de chirurgie, les complications selon Clavien et le suivi avec les complications tardives. Resultats Quatorze patientes ont ete identifiees dans seulement 3 des 23 centres. Les caracteristiques cliniques, les details des transplantations et traitements immunosuppresseurs sont exposes dans le Tableau 1 . Le traitement etait une promontofixation (n = 7) (double bandelettes dans 6 cas et uniquement anterieure dans 1 cas) ou une cure de cystocele par voie basse (n = 7) (4 sacrospinofixation, 2 sans prothese, 1 avec prothese synthetique Elevate®). Une seule patiente a presente une complication peroperatoire sans rapport avec la presence du greffon (plaie de vessie par voie basse). Deux complications Clavien 1 ont ete decrites en postoperatoire. Apres un suivi moyen de 24 mois, 2 patientes ont presente une vulvovaginite et 4 ont demasque une incontinence. Il n’y a eu aucune erosion, suppuration chronique, ni ablation de materiel. Aucun prolapsus n’a recidive. Conclusion Dans notre etude, aucune complication en rapport avec le transplant renal ou en rapport avec un defaut de cicatrisation n’a ete rapportee confirmant l’absence de specificite dans la prise en charge du prolapsus des patientes transplantees renales.

The purpose of this study was to investigate circulating polymorphonuclear leucocyte (PMNL) oxidative metabolism and lipid peroxidation in patients with adult respiratory distress syndrome (ARDS) who were treated with low- frequency, positive-pressure ventilation with extracorporeal carbon dioxide removal.

Methods for predicting service reliability of passive fiber optic interconnections have not developed to the same extent as they have for fiber. Much progress has been made in the understanding of failure modes, however, it has not been extended to the estimation of mean life or failure rate as a function of time. The most critical need is the development of appropriate life-stress models which include test acceleration factors and statistical analysis methods. In this paper, simple models are proposed for three distinct failure modes: (1) flexural fatigue of a connector bend limiting assembly, (2) static fatigue of a ceramic connector alignment sleeve, and (3) torsional fatigue of fibers in splices. The more general problem is discussed in the context of these examples.© (1994) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Methods have not yet been developed for predicting the reliability of fiber optic connectors and splices even though they have been installed in increasing numbers over the last decade. There is a need for failure rate prediction methods as these components move into new areas of existing networks and new applications where they will be subjected to a broad range of service environments. These methods must be based on accelerated tests derived in many cases from life-stress models and on statistical models appropriate for the known failure modes. This paper deals with the application of these basic principles to fiber optic connectors and splices. Guidelines are proposed for developing prediction methods.

Although the service reliability of passive optical components has been quite good, methods for predicting reliability have not been developed for them as they have for fiber. There is a growing need for methods of predicting failure rates as these components move into new areas of existing networks and new applications where they will be subjected to a broad range of service environments. The methods will have to be based on accelerated tests derived from life-stress models appropriate for the known failure modes. This paper deals with the application of these basic principles to fiber optic connectors and splices. The common failure modes are reviewed and guidelines are proposed for developing reliability prediction methods.

Fiber optic connectors and splices have been in service for over a decade and now number in the tens of millions. Although the reliability level ascertained from Performance is quite good, there are presently no well defined testing and analytical methods in place for predicting reliability. This is due in large part to the variety of potential failure modes and service environments. As fiber expands in the telecommunications network and into other applications such as private LANs, data links, and control systems, the need for reliability prediction methodologies has become increasingly important. This paper addresses the issues related to this problem.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Based on previous experience with air deployable fiber-optic systems, a ruggedized single- fiber cable has been developed to meet new requirements presented by such applications as robotics and radar remoting. Both multimode and single-mode versions of the cable were developed. They are terminated with a militarized connector whose design built upon previous commercial developments. To minimize the size of the termination, an adaptation of the commercial ST TM connector was inserted into a protective housing that provides mechanical and environmental performance stability dictated by system designers. In addition, the challenging requirement of hermaphrodicity was attained. Assemblies were fully tested in accordance with an approved test plan.

A rugged simplex hermaphroditic connector has been developed for use in tactical fiber-optic applications such as radar and radio remoting, and various robotic systems. The single-terminus connector is intended for use wherever bi-directional transmission is required. It was designed to operate while meeting severe environmental and mechanical conditions experienced in the field. Both multimode and single-mode designs of the connector have been developed. Connectors have insertion loss of less than 1 dB when installed on either 50/125 pm multimode fiber or single-mode fiber. In addition to low loss and ruggedness, connector design features include cable retention hardware which requires neither special tools nor adhesives, waterproofing seals, and ease of cleaning without special kits. The connector was designed to accommodate existing tactical cables whose diameters range from 2.5 to 4.0 mm, and is capable of withstanding tensile loads up to 1335 newtons. Operating temperature range is from -46°C to 71°C; storage temperature extremes are -57°C and 85°C. The new connector is small, being only 1.4 cm in diameter and 8.6 cm long, including bend limiter. It weights less than 30 gm. A complementary bulkhead receptacle is equally rugged and may be mounted on panels up to 6.4 mm thick. EMI shielding has been incorporated in the unit.

A small simplex hermaphroditic connector has been designed for use in tactical fiber-optic communications systems and robotic vehicle applications. The rugged connector is intended for use wherever bi-directional transmission is required. It was designed to operate while meeting environmental and mechanical conditions typically encountered in tactical applications. This single-fiber connector is available in both multimode and single-mode versions. Measurements of prototype connectors show insertion loss of less than 1 dB when installed on either 50/125 im multimode fiber or singlemode fiber. This connector was designed to include some of the features of the TFOCA connector. In particular, these comprise cable retention hardware which requires neither special tools nor adhesives, waterproofing seals, and ease of cleaning without special kits. However, the simplex unit employs ST® connector technology whereas the TFOCA included biconic components. The connector was designed to accommodate cable diameters ranging from 2 to 4 mm, and is capable of withstanding tensile loads up to 1335 newtons. Operating temperature range is from -46° to +71°C. The new connector is 1.4 cm in diameter and 8.6 cm long, including bend limiter, and weighs less than 30 gm. A complementary bulkhead receptacle shares the same hermaphroditic interface and may be mounted on panels up to 6.4 mm thick. EMI shielding has been incorporated in the unit.

To investigate disturbances in the coronary circulation and myocardial metabolism during septic shock, we examined coronary sinus blood flow and myocardial substrate extraction in 40 patients with septic shock and 13 control patients. Patients with coronary artery disease were excluded from this study. The global hemodynamic pattern of the septic patients was characterized by a lower stroke volume, despite an elevated cardiac index. Coronary sinus blood flow was high (187 +/- 47 vs 130 +/- 21 ml/min in the control group, p less than .001) due to marked coronary vasodilation, especially in the subgroup of nonsurvivors. In contrast to the control group, myocardial lactate uptake was elevated, while that of free fatty acids, glucose, and ketone bodies was diminished in patients with septic shock. These findings were especially prominent in the nonsurvivors. Expressed as oxygen equivalents, the contribution of free fatty acids as an energy source of the myocardium was markedly diminished in septic patients (12% vs 54% in the control group, p less than .005), while that of lactate was increased (36% vs 12%, p less than .01). The observed shift in myocardial substrate extraction was associated with a discrepancy between measured myocardial oxygen consumption and that calculated chemically from commonly available exogenous substrates: 41% of myocardial oxygen consumption was not explained by the utilization of commonly available substrates extracted from coronary circulation in all patients with septic shock.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary haemodynamics and myocardial metabolism of non-esterified fatty acids (NEFA) and lactate were studied in 11 patients with severe sepsis, and compared to 10 control subjects. Coronary sinus blood flow was evaluated by thermodilution. Arterial and coronary sinus blood samples were collected for the measurement of lactate and total and individual NEFA concentrations both in septic and control patients. There was an increase in lactate and total NEFA arterial concentrations with a marked increase in palmitic and linolenic acids. The uptake of the main NEFA (C14:0 to C18:2) was significantly decreased. In the control group, individual NEFA uptake was proportional to their arterial concentrations. This relationship was not observed in patients with sepsis: there was no preferential extraction of any particular NEFA. Furthermore, in patients with sepsis, myocardial oxygen consumption did not correlate with NEFA, but only with lactate uptake. Alterations in NEFA uptake were found to be constant during severe sepsis and are consistent with major disturbances in myocardial metabolism.

Superposed dark-zone patterns in field-ion images of ordered Ni4Mo have been observed to exhibit the symmetry of the disordered f.c.c. cell as well as that of the ordered b.c.t. cell. The behaviour of these two patterns at domain boundaries and crystal interfaces is demonstrated, and a possible interpretation is presented.

To preserve a good resolution at high counting rates we studied and realized a charge-sensitive preamplifier (P.A.C.) operating until 300 000 counts per second. Then, we observed in which conditions it was possible to change a conventional P.A.C. without failure of its intrinsic resolution.

1. The characteristics of the threshold excitation behavior of the squid giant axon were investigated with condenser discharges, exponentially blunted D. c. shocks, sinusoidal currents, and brief condenser-discharge test shocks superimposed at either electrode at controlled brief intervals following the closing of a constant current. 2. Data obtained by the use of condenser discharges and exponentially blunted currents followed theoretical patterns separately, but could not be mutually reconciled, under the system of the two-factor theories of excitation, since the accommodation was so rapid that the apparent ratio between the two time factors was incompatible with certain previously neglected theoretical limitations. 3. Data obtained with the other procedures indicated similarly rapid accommodation, but usually showed an imaginary component in the values of the time constants, associated with a capacity of the threshold to exhibit damped oscillatory behavior. 4. The anodal threshold behavior did not parallel that at the cathode, showing neither oscillation nor accommodation at ordinary current intensities. 5. The digressions from predictions of the two-factor theories of excitation are partly analyzed and compared with other reported deviations.