The site of breast cancer metastases dictates their clonal composition and reversible transcriptomic profile.

Intratumoral heterogeneity is a driver of breast cancer progression, but the nature of the clonal interactive network involved in this process remains unclear. Here, we optimized the use of optical barcoding to visualize and characterize 31 cancer subclones in vivo. By mapping the clonal composition of thousands of metastases in two clinically relevant sites, the lungs and liver, we found that metastases were highly polyclonal in lungs but not in the liver. Furthermore, the transcriptome of the subclones varied according to their metastatic niche. We also identified a reversible niche-driven signature that was conserved in lung and liver metastases collected during patient autopsies. Among this signature, we found that the tumor necrosis factor-α pathway was up-regulated in lung compared to liver metastases, and inhibition of this pathway affected metastasis diversity. These results highlight that the cellular and molecular heterogeneity observed in metastases is largely dictated by the tumor microenvironment.

Rule-based algorithm for the classification of sitting postures in the sagittal plane from the Cardiff Body Match measurement system.

The purpose of this paper is to present the design and implementation of a novel rule-based algorithm for the classification of sitting postures in the sagittal plane. The research focused on individuals with severe musculoskeletal problems and, thus, specific requirements for posture and pressure management. Clients' body shapes were captured using the Cardiff Body Match system developed by the Rehabilitation Engineering Unit, Cardiff and Vale University Health Board. The algorithm consists of four main steps: the first step is the symmetry line detection, the second step involves the mathematical analysis of the curvature of the backrest profile, the third step is the sitting posture classification and the fourth step is the extraction of the geometric parameters from the curve. The results show the classification system was successful in identifying four types of curves characterizing sitting postures using local derivatives as curve descriptors with an overall accuracy of 93.9%.

Pelvis feature extraction and classification of Cardiff body match rig base measurements for input into a knowledge-based system.

The purpose of this paper is to determine whether it is possible to use an automated measurement tool to clinically classify clients who are wheelchair users with severe musculoskeletal deformities, replacing the current process which relies upon clinical engineers with advanced knowledge and skills. Clients' body shapes were captured using the Cardiff Body Match (CBM) Rig developed by the Rehabilitation Engineering Unit (REU) at Rookwood Hospital in Cardiff. A bespoke feature extraction algorithm was developed that estimates the position of external landmarks on clients' pelvises so that useful measurements can be obtained. The outputs of the feature extraction algorithms were compared to CBM measurements where the positions of the client's pelvis landmarks were known. The results show that using the extracted features facilitated classification. Qualitative analysis showed that the estimated positions of the landmark points were close enough to their actual positions to be useful to clinicians undertaking clinical assessments.

The link between intravenous multiple pump flow errors and infusion system mechanical compliance.

IV drug delivery in intensive care often takes the form of simultaneous multiple infusions from separate infusion devices via either shared or individual fluid pathways. Because of the potency of the drugs administered and the acuity of the patients, accurate drug delivery is required. Instances of unexpected and unacceptable accuracy degradation have been reported when the equilibrium of the infusion system is disturbed. We describe a mathematical model of a simple infusion system used to investigate and verify results reported from a simple experimental multiple pump fault scenario. The results suggest that flow degradation is attributable to small changes in infusion system extracorporeal volume, referred to as "compliance." The model may, by expansion, be used to determine the nature of fluid flow within other multiple pump systems, be applied to the design of future IV systems, and explain the need for small-volume infusion systems with small mechanical compliance.

Excess mortality, hospital stay, and cost due to candidemia: a case-control study using data from population-based candidemia surveillance.

OBJECTIVE: To determine the mortality, hospital stay, and total hospital charges and cost of hospitalization attributable to candidemia by comparing patients with candidemia with control-patients who have otherwise similar illnesses. Prior studies lack broad patient and hospital representation or cost-related information that accurately reflects current medical practices. DESIGN: Our case-control study included case-patients with candidemia and their cost-related data, ascertained from laboratory-based candidemia surveillance conducted among all residents of Connecticut and Baltimore and Baltimore County, Maryland, during 1998 to 2000. Control-patients were matched on age, hospital type, admission year, discharge diagnoses, and duration of hospitalization prior to candidemia onset. RESULTS: We identified 214 and 529 sets of matched case-patients and control-patients from the two locations, respectively. Mortality attributable to candidemia ranged between 19% and 24%. On multivariable analysis, candidemia was associated with mortality (OR, 5.3 for Connecticut and 8.5 for Baltimore and Baltimore County; P < .05), whereas receiving adequate treatment was protective (OR, 0.5 and 0.4 for the two locations, respectively; P < .05). Candidemia itself did not increase the total hospital charges and cost of hospitalization; when treatment status was accounted for, having received adequate treatment for candidemia significantly increased the total hospital charges and cost of hospitalization ($6,000 to $29,000 and $3,000 to $22,000, respectively) and the length of stay (3 to 13 days). CONCLUSION: Our findings underscore the burden of candidemia, particularly regarding the risk of death, length of hospitalization, and cost associated with treatment.