Early increases in plasminogen activator activity following partial hepatectomy in humans

Background Increases in urokinase-like plasminogen activator (uPA) activity are reported to be amongst the earliest events occurring in remnant liver following partial hepatectomy in rats, and have been proposed as a key component of the regenerative response. Remodelling of the extracellular matrix, conversion of single chain hepatocyte growth factor to the active two-chain form and a possible activation of a mitogenic signalling pathway have all been ascribed to the increased uPA activity. The present study aimed to determine whether similar early increases in uPA activity could be detected in the remnant liver following resection of metastatic tumours in surgical patients. Results Eighteen patients undergoing partial hepatectomy for the removal of hepatic metastases secondary to primary colonic tumours were studied. Increased plasminogen activator activity was found in the final liver samples for the group of patients in whom the resection size was at least 50%. For smaller resections, the increased activity was not observed. The increased activity did not correlate with the age of the patient or with the time between the start of resection and the end of the operation. There was, however, a negative correlation between plasminogen activator activity and the time for which blood supply to the liver was clamped. Conclusions Our findings are in accordance with those from experimental animal models and show, for the first time, that rapid increases in plasminogen activator activity can occur following similarly large liver resection in humans. Thus, increases in plasminogen activator activity are an early event in the remnant liver following major liver resection in man. Our observations provide support for the contention that increases in plasminogen activators play a key role in the initiation of hepatic regeneration in man

A Pointwise Method for Identifying Biomechanical Heterogeneity of the Human Gallbladder

Identifying the heterogeneous biomechanical property of human gallbladder (GB) walls from non-invasive measurements can have clinical significance in patient-specific modeling and acalculous biliary pain diagnosis. In this article, a pointwise method was proposed to measure the heterogeneity of ten samples of human GB during refilling. Three different points, two on the equator of GB body 90◦ apart and one on the apex of GB fundus, were chosen to represent the typical regions of interest. The stretches at these points were estimated from ultrasound images of the GB during the bile emptying phase based on an analytical model. The model was validated against the experimental data of a lamb GB. The material parameters at the different points were determined inversely by making use of a structure-based anisotropic constitutive model. This anisotropic model yielded much better accuracy when compared to a number of phenomenologically-based constitutive laws, as demonstrated by its significantly reduced least-square errors in stress curve fitting. The results confirmed that the human GB wall material was heterogeneous, particularly toward the apex region. Our study also suggested that non-uniform wall thickness of the GB was important in determining the material parameters, in particular, on the parameters associated with the properties of the matrix and the longitudinal fibers—the difference could be as large as 20–30% compared to that of the uniform thickness model

Correlation of mechanical factors and gallbladder pain

Acalculous biliary pain occurs in patients with no gallstones, but is similar to that experienced by patients with gallstones. Surgical removal of the gallbladder (GB) in these patients is only successful in providing relief of symptoms to about half of those operated on, so a reliable pain-prediction model is needed. In this paper, a mechanical model is developed for the human biliary system during the emptying phase, based on a clinical test in which GB volume changes are measured in response to a standard stimulus and a recorded pain profile. The model can describe the bile emptying behaviour, the flow resistance in the biliary ducts, the peak total stress, including the passive and active stresses experienced by the GB during emptying. This model is used to explore the potential link between GB pain and mechanical factors. It is found that the peak total normal stress may be used as an effective pain indicator for GB pain. When this model is applied to clinical data of volume changes due to Cholecystokinin stimulation and pain from 37 patients, it shows a promising success rate of 88.2% in positive pain prediction

Low copper levels measured in the aortic wall of New Zealand patients with non-syndromic ascending thoracic aortic aneurysm

OBJECTIVES: Studies in animals have shown causal relationships between copper (Cu) deficiency and the development of thoracic aortic aneurysms (TAAs) [1, 2]. Cu deficiency is widespread in New Zealand (NZ) soils; the high soil pH from the use of lime fertilizers reduces the bioavailability of Cu for grazing animals and growing plants; this, in turn, reduces Cu availability in the NZ human food chain. Our study is a pilot study to explore associations between Cu and TAA. We measured Cu levels in aneurysmal aortic tissues in patients undergoing Bentall procedures and non-aneurysmal aortic tissue from coronary artery bypass graft patients. METHODS: Aortic samples were collected from 2 groups of patients during elective open-heart surgery over 4 months between November 2017 and February 2018. The groups were a TAA group, patients with non-syndromic aortic aneurysm and without the bicuspid aortic valve or known infectious or inflammatory condition (ANEURYSM; n = 13), and a control coronary artery bypass graft group (CONTROL; n = 44). Standardized digested dry tissue weighed samples were analysed from both groups. Tissue extraction of trace elements was carried out using HCl-H2O2 digestion and a highly sensitive analytical technique, inductively coupled plasma mass spectrometry-used to measure elemental concentrations. RESULTS: Cu concentration (mean ± SD) was significantly lower in ANEURYSM (3.34 ± 0.16 µg/g) when compared to the CONTROL group tissues (4.33 ± 0.20 µg/g) (dry weight; mean ± SD; Student's t-test, P < 0.05). Over 46% of the Aneurysm patients were Maori and live in a geographically Cu-deficient NZ territory. CONCLUSIONS: Cu deficiency may play a role in the development or progression of non-syndromic ascending aortic aneurysms in NZ. Maori patients are more at risk as they commonly live in rural NZ, dependent on locally grown nutritional sources. Further studies are required to confirm this exciting finding and to establish cause and effect relationship

Soft-mode anisotropy in the negative thermal expansion material ReO3

We use a symmetry-motivated approach to analyse neutron pair distribution function data to investigate the character of the soft phonon modes in negative thermal expansion (NTE) material ReO3. This analysis shows that its local structure is dominated by an in-phase octahedral tilting mode and that the octahedral units are far less flexible to scissoring type deformations than in the related NTE compound ScF3. The lack of flexibility in ReO3 restricts the NTE-driving phonons to a smaller region of reciprocal space, limiting the magnitude and temperature range of NTE. These results support the idea that structural flexibility is an important factor in NTE materials. Surprisingly, our results show that the local fluctuations, even at elevated temperatures, respect the symmetry and order parameter direction of the initial pressure induced phase transition in ReO3. The result indicates that the dynamic motions associated with rigid unit modes are highly anisotropic in these systems

Antarctic ice sheet discharge driven by atmosphere-ocean feedbacks at the Last Glacial Termination

Reconstructing the dynamic response of the Antarctic ice sheets to warming during the Last Glacial Termination (LGT; 18,000–11,650 yrs ago) allows us to disentangle ice-climate feedbacks that are key to improving future projections. Whilst the sequence of events during this period is reasonably well-known, relatively poor chronological control has precluded precise alignment of ice, atmospheric and marine records, making it difficult to assess relationships between Antarctic ice-sheet (AIS) dynamics, climate change and sea level. Here we present results from a highly-resolved ‘horizontal ice core’ from the Weddell Sea Embayment, which records millennial-scale AIS dynamics across this extensive region. Counterintuitively, we find AIS mass-loss across the full duration of the Antarctic Cold Reversal (ACR; 14,600–12,700 yrs ago), with stabilisation during the subsequent millennia of atmospheric warming. Earth-system and ice-sheet modelling suggests these contrasting trends were likely Antarctic-wide, sustained by feedbacks amplified by the delivery of Circumpolar Deep Water onto the continental shelf. Given the anti-phase relationship between inter-hemispheric climate trends across the LGT our findings demonstrate that Southern Ocean-AIS feedbacks were controlled by global atmospheric teleconnections. With increasing stratification of the Southern Ocean and intensification of mid-latitude westerly winds today, such teleconnections could amplify AIS mass loss and accelerate global sea-level rise

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM