Intraperitoneal rupture of ectopic varices--a rare complication of portal hypertension

A 50 year old man presented with sudden abdominal pain, abdominal distension and shock. At emergency laparotomy a large amount of blood was found in the peritoneal cavity. There was micronodular cirrhosis of the liver and the spleen was enlarged. The bleeding was traced to distended veins in the right paracolic gutter which were oversewn and the abdomen closed. A coagulopathy was diagnosed and treatment including high dose aprotinin commenced. However, he continued to bleed and at a second laparotomy the area of previous haemorrhage was packed. Further deterioration continued until death 12 hours later. Intraperitoneal haemorrhage from ectopic varices is a rare occurrence. There is a high mortality rate usually due to an advanced coagulopathy. This is the first report of aprotinin being used in an attempt to treat this. On the basis of this report aprotinin would not seem to be of benefit for this condition.     

Benchmarking of electricity networks: Practical problems with its use for regulation

Benchmarking is a technique derived for management purposes, intended to identify outliers in any population as possible problems for resolution. Several regulatory agencies have tried to use benchmarking to define the degree of inefficiency of regulated companies, by reference to some target or frontier. This paper identifies the main problem inherent in trying to adapt a management technique to a regulatory purpose – namely that it requires the exercise of subjective judgements. The resulting lack of predictability and objectivity is not conducive to the provision of efficient regulatory incentives.This paper explains where subjective judgement enters into regulatory applications of benchmarking, which is not always apparent. The choice of model and selection of data sets are two obvious areas, but the main problem arises over the assumption that any costs not explained by the model must be due to inefficiency. Such assumptions are simply unsupported by evidence and lead to cost targets (or cost reduction targets defined over several years) that are little better than subjective guesses. There are other, superior ways to set cost reduction targets, based on long-term trends in total factor productivity for the regulated sector, which are used in the US and in other countries. However, some regulators feel obliged to use benchmarking and the paper concludes with recommendations as to how benchmarking should support further and more objective investigations into the costs of regulated utilities.     

New energy transfer dyes for DNA sequencing

We have synthesized a set of four energy transfer dyes and demonstrated their use in automated DNA sequencing. The donor dyes are the 5- or 6-carboxy isomers of 4'-aminomethylfluorescein and the acceptor dyes are a novel set of four 4,7-dichloro-substituted rhodamine dyes which have narrower emission spectra than the standard, unsubstituted rhodamines. A rigid amino acid linker, 4-aminomethylbenzoic acid, was used to separate the dyes. The brightness of each dye in an automated sequencing instrument equipped with a dual line argon ion laser (488 and 514 nm excitation) was 2-2.5 times greater than the standard dye-primers with a 2 times reduction in multicomponent noise. The overall improvement in signal-to-noise was 4- to 5-fold. The utility of the new dye set was demonstrated by sequencing of a BAC DNA with an 80 kb insert. Measurement of the extinction coefficients and the relative quantum yields of the dichlororhodamine components of the energy transfer dyes showed their values were reduced by 20-25% compared with the dichlororhodamine dyes alone.     

An object design framework for structural engineering

Object-oriented principles have introduced several useful concepts for developing complex software systems. As a result, several methodologies have been suggested for the overall design of software systems based on these concepts. Methodologies and frameworks for designing objects that are to be part of the software systems are currently lacking. This paper proposes anobject design framework andmethodology, which utilizes the object-oriented concepts, for planning, organizing and designing structural engineering design objects. Design objects in an integrated structural engineering system are complex and often related to each other in various different ways. The paper also identifies several important relationships among structural engineering design objects. These relationships serve as communication channels through wich design objects send messages to and receive responses from each other. Several examples, drawn from reinforced concrete structures, will be presented to demonstrate the object design methodology and to illustrate how the framework is effective in reducing the complexity of design objects in an integrated structural engineering system.     

Performance optimization of multidisciplinary mechanical systems subject to uncertainties

This paper presents a methodology to solve a new class of stochastic optimization problems for multidisciplinary systems (multidisciplinary stochastic optimization or MSO) wherein the objective is to maximize system mechanical performance (e.g. aerodynamic efficiency) while satisfying reliability-based constraints (e.g. structural safety). Multidisciplinary problems require a different solution approach than those solved in earlier research in reliability-based structural optimization (single discipline) wherein the goal is usually to minimize weight (or cost) for a structural configuration subject to a limiting probability of failure or to minimize probability of failure subject to a limiting weight (or cost). For the problems solved herein, the objective is to maximize performance over the range of operating conditions, while satisfying constraints that ensure safe and reliable operation. Because the objective is performance based and because the constraints are reliability based, the random variables used in the objective must model variability in operating conditions, while the random variables used in the constraints must model uncertainty in extreme values (to ensure safety). Thus, the problem must be formulated to treat these two different types of variables at the same time, including the case when the same physical quantity (e.g. a particular load) appears in both the objective function and the constraints. In addition, the problem must be formulated to treat multiple load cases, which can again require modeling the same physical quantity with different random variables. Deterministic multidisciplinary optimization (MDO) problems have advanced to the stage where they are now commonly formulated with multiple load cases and multiple disciplines governing the objective and constraints. This advancement has enabled MDO to solve more realistic problems of much more practical interest. The formulation used herein solves stochastic optimization problems that are posed in this same way, enabling similar practical benefits but, in addition, producing optimum designs that are more robust than the deterministic optimum designs (since uncertainties are accounted for during the optimization process). The methodology has been implemented in the form of a baseline MSO shell that executes on both a massively parallel computer and a network of workstations. The MSO shell is demonstrated herein by a stochastic shape optimization of an axial compressor blade involving fully coupled aero-structural analysis.     

Molecular and geographic patterns of tuberculosis transmission after 15 years of directly observed therapy

Stevioside is a sweet-tasting glycoside, composed of stevia, a diterpenic carboxylic alcohol with three glucose molecules, mainly used as a substitute for non-alcoholic sweetener. It has previously been shown to reduce blood pressure in studies in animals and human. The effect of intravenous stevioside on the blood pressure was studied in spontaneously hypertensive rats (SHR). The hypotensive effect on both systolic and diastolic blood pressure was dose-dependent for intravenous doses of 50, 100 and 200 mg/kg in conscious SHR. The maximum reductions in systolic and diastolic blood pressure were 31.4 +/- 4.2% and 40.8 +/- 5.6% (mean +/- SEM) respectively and the hypotensive effect lasted for more than 60 min with a dose of 200 mg/kg. Serum dopamine, norepinephrine and epinephrine levels were not changed significantly 60 min after intravenous injection of stevioside 100 mg/kg in anesthetized SHR. The present data show that stevioside given intravenously to conscious SHR was effective in blood pressure reduction and there was no change in serum catecholamines in anaesthetized animals with this natural compound.     

The association of intra-abdominal infection and abdominal wound dehiscence

Concurrent infection is a risk factor for abdominal wound dehiscence. We reviewed our experience with fascial dehiscence to determine the incidence and to identify prognostic factors for associated intra-abdominal infection. Over a 7-year period, 107 patients with abdominal wound dehiscence were identified. Seventeen were managed nonoperatively, and 90 underwent exploratory laparotomy, 43 of whom had no intra-abdominal pathology and 47 of whom had intra-abdominal infections. Demographic factors, comorbid diseases, and potential indicators of systemic infection did not distinguish patients with intra-abdominal infection from those without. Patients with an intra-abdominal infection were more likely to have undergone an emergency operation (74% vs 48%; P < 0.02), an operation on the colon (55% vs 25%; P < 0.005), or an operation with a higher wound classification (P < 0.02). Mortality was higher in patients with intra-abdominal infection than in those without (44% vs 20%; P < 0.02). Wound dehiscence after emergent operations, and operations with a higher wound classification, especially those involving the colon, should raise concern for intra-abdominal infection. Thorough abdominal exploration should be performed at the time of dehiscence repair. Before nonoperative management is chosen, intra-abdominal infection should be excluded.     

Investigating T Cell Immunity in Cancer: Achievements and Prospects

T cells play a key role in tumour surveillance, both identifying and eliminating transformed cells. However, as tumours become established they form their own suppressive microenvironments capable of shutting down T cell function, and allowing tumours to persist and grow. To further understand the tumour microenvironment, including the interplay between different immune cells and their role in anti-tumour immune responses, a number of studies from mouse models to clinical trials have been performed. In this review, we examine mechanisms utilized by tumour cells to reduce their visibility to CD8⁺ Cytotoxic T lymphocytes (CTL), as well as therapeutic strategies trialled to overcome these tumour-evasion mechanisms. Next, we summarize recent advances in approaches to enhance CAR T cell activity and persistence over the past 10 years, including bispecific CAR T cell design and early evidence of efficacy. Lastly, we examine mechanisms of T cell infiltration and tumour regression, and discuss the strengths and weaknesses of different strategies to investigate T cell function in murine tumour models.     

A formal approach to specifying assembly operations

Experience has proved that exploiting robots for assembly tasks is much more difficult than manufacturing engineers had expected and many attempts at implementing robotic assembly have failed. Our research has led us to believe that a formal approach to specifying the steps required for assembly would be of great benefit in developing the required software for a specific task, and in adaptively controlling and monitoring the execution of robotic assembly steps. The US National Bureau of Standards has developed a formal system, called ABC (for Assembly By Constraints) for specifying the steps required for assembly. The system is based on the reduction in the degrees of freedom of objects as they are assembled. Using this basic concept, we have developed 14 primitive operations which can be used to completely specify assembly steps for a large class of problems. This paper initially outlines the historical development of the system, then describes two pieces of software developed to allow easy definition of assembly tasks using the ABC system, and finally presents two practical examples.