Caudate lobe resections: a single-center experience and evaluation of factors predictive of outcomes

BACKGROUND: Despite the increasing frequency of liver resection for multiple types of disease, caudate lobe resection remains a rare surgical event. The goal of this study is to review our experience and evaluate possible predictors of adverse outcomes in patients undergoing caudate lobectomy. METHODS: We reviewed a 1,900-patient prospective hepato-pancreatico-biliary database from January 2000 to December 2011, identifying 36 hepatectomy patients undergoing caudate lobe resection. Clinicopathologic characteristic and outcome data were compared using chi-square, T-test, ANOVA, Kaplan-Meier, and Cox regression analysis. Primary endpoints were the incidence and severity of complications, and secondary endpoints were blood loss, hospital stay, and transfusion requirements. Patients were also divided in two groups with group A being patients operated on before December 2007 and group B after 2007. We compared the demographics, risk factors, complication rates, and operative details between the two groups. RESULTS: Thirty-six patients underwent caudate lobe resection for cholangiocarcinoma (47.2%), metastatic colorectal cancer (36.1%), hepatocellular carcinoma (8.3%), or benign disease (8.3%). Nine patients (29%) had additional liver resection. Median overall survival (OS) was 21 months. Complications occurred in 52.7% (19/36) of patients with a median grade of 2. Tobacco abuse was associated with an increased risk of operative complications (73.3% vs. 38.9%, p = 0.03). Prior history of cardiac disease was associated with a higher complication rate (87% vs. 42%, p = 0.03). Neoadjuvant chemotherapy, biliary procedures, hepatitis, and prior major abdominal surgery were not predictive of complications. Major complication was also predicted by the volume of RBC transfusion (2.7 vs. 4.1 units, p = 0.003). In our subgroup analysis of the patients undergoing surgery before and after 2007, the two groups were well matched based on age, comorbidities, and risk factors. The complication rates and rates of high-grade complications were similar, but blood loss (600 ml vs. 400 ml, p = 0.03), inflow occlusion time (Pringle time 12.6 vs. 6, p = 0.00), and hospital stay (9.5 vs. 7 days, p = 0.01) were significantly lower in group B. CONCLUSIONS: With appropriate patient selection, caudate lobe resection is an effective component of surgery for hepatic disease. Tobacco use and prior cardiac history increase the risk of complications

Splice variants of Na(V)1.7 sodium channels have distinct β subunit-dependent biophysical properties.

Genes encoding the α subunits of neuronal sodium channels have evolutionarily conserved sites of alternative splicing but no functional differences have been attributed to the splice variants. Here, using Na(V)1.7 as an exemplar, we show that the sodium channel isoforms are functionally distinct when co-expressed with β subunits. The gene, SCN9A, encodes the α subunit of the Na(V)1.7 channel, and contains both sites of alternative splicing that are highly conserved. In conditions where the intrinsic properties of the Na(V)1.7 splice variants were similar when expressed alone, co-expression of β1 subunits had different effects on channel availability that were determined by splicing at either site in the α subunit. While the identity of exon 5 determined the degree to which β1 subunits altered voltage-dependence of activation (P = 0.027), the length of exon 11 regulated how far β1 subunits depolarised voltage-dependence of inactivation (P = 0.00012). The results could have a significant impact on channel availability, for example with the long version of exon 11, the co-expression of β1 subunits could lead to nearly twice as large an increase in channel availability compared to channels containing the short version. Our data suggest that splicing can change the way that Na(V) channels interact with β subunits. Because splicing is conserved, its unexpected role in regulating the functional impact of β subunits may apply to multiple voltage-gated sodium channels, and the full repertoire of β subunit function may depend on splicing in α subunits

Maximal aerobic and anaerobic power generation in large crocodiles versus mammals: implications for dinosaur gigantothermy

Inertial homeothermy, the maintenance of a relatively constant body temperature that occurs simply because of large size, is often applied to large dinosaurs. Moreover, biophysical modelling and actual measurements show that large crocodiles can behaviourally achieve body temperatures above 30°C. Therefore it is possible that some dinosaurs could achieve high and stable body temperatures without the high energy cost of typical endotherms. However it is not known whether an ectothermic dinosaur could produce the equivalent amount of muscular power as an endothermic one. To address this question, this study analyses maximal power output from measured aerobic and anaerobic metabolism in burst exercising estuarine crocodiles, Crocodylus porosus, weighing up to 200 kg. These results are compared with similar data from endothermic mammals. A 1 kg crocodile at 30°C produces about 16 watts from aerobic and anaerobic energy sources during the first 10% of exhaustive activity, which is 57% of that expected for a similarly sized mammal. A 200 kg crocodile produces about 400 watts, or only 14% of that for a mammal. Phosphocreatine is a minor energy source, used only in the first seconds of exercise and of similar concentrations in reptiles and mammals. Ectothermic crocodiles lack not only the absolute power for exercise, but also the endurance, that are evident in endothermic mammals. Despite the ability to achieve high and fairly constant body temperatures, therefore, large, ectothermic, crocodile-like dinosaurs would have been competitively inferior to endothermic, mammal-like dinosaurs with high aerobic power. Endothermy in dinosaurs is likely to explain their dominance over mammals in terrestrial ecosystems throughout the Mesozoic.Roger S. Seymou

Development of 'synthetic lethal' strategies to target BRCA1-deficient breast cancer

Recent clinical trials demonstrating the efficacy of poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of BRCA1-deficient breast cancer have provided support for the 'synthetic lethal' concept of targeted cancer therapeutics. A new study provides further preclinical validation of this concept by demonstrating that BRCA1-deficient mouse mammary tumor cells are selectively sensitive to an inhibitor of the polycomb gene EZH2. The development of polycomb gene inhibitors may provide a novel approach to selectively exploit the molecular alterations in BRCA1-deficient breast tumors

Taxonomic Chauvinism Revisited: Insight from Parental Care Research

Parental care (any non-genetic contribution by a parent that appears likely to increase the fitness of its offspring) is a widespread trait exhibited by a broad range of animal taxa. In addition to influencing the fitness of parent(s) and offspring, parental care may be inextricably involved in other evolutionary processes, such as sexual selection and the evolution of endothermy. Yet, recent work has demonstrated that bias related to taxonomy is prevalent across many biological disciplines, and research in parental care may be similarly burdened. Thus, I used parental care articles published in six leading journals of fundamental behavioral sciences (Animal Behaviour, Behavioral Ecology, Behavioral Ecology and Sociobiology, Ethology, Hormones and Behavior, and Physiology & Behavior) from 2001–2010 (n = 712) to examine the year-to-year dynamics of two types of bias related to taxonomy across animals: (1) taxonomic bias, which exists when research output is not proportional to the frequency of organisms in nature, and (2) taxonomic citation bias, which is a proxy for the breadth of a given article—specifically, the proportion of articles cited that refer solely to the studied taxon. I demonstrate that research on birds likely represents a disproportionate amount of parental care research and, thus, exhibits taxonomic bias. Parental care research on birds and mammals also refers to a relatively narrow range of taxonomic groups when discussing its context and, thus, exhibits taxonomic citation bias. Further, the levels of taxonomic bias and taxonomic citation bias have not declined over the past decade despite cautionary messages about similar bias in related disciplines— in fact, taxonomic bias may have increased. As in Bonnet et al. (2002), my results should not be interpreted as evidence of an ‘ornithological Mafia’ conspiring to suppress other taxonomic groups. Rather, I generate several rational hypotheses to determine why bias persists and to guide future work

Exhaustive exercise training enhances aerobic capacity in American alligator (Alligator mississippiensis)

The oxygen transport system in mammals is extensively remodelled in response to repeated bouts of activity, but many reptiles appear to be ‘metabolically inflexible’ in response to exercise training. A recent report showed that estuarine crocodiles (Crocodylus porosus) increase their maximum metabolic rate in response to exhaustive treadmill training, and in the present study, we confirm this response in another crocodilian, American alligator (Alligator mississippiensis). We further specify the nature of the crocodilian training response by analysing effects of training on aerobic [citrate synthase (CS)] and anaerobic [lactate dehydrogenase (LDH)] enzyme activities in selected skeletal muscles, ventricular and skeletal muscle masses and haematocrit. Compared to sedentary control animals, alligators regularly trained for 15 months on a treadmill (run group) or in a flume (swim group) exhibited peak oxygen consumption rates higher by 27 and 16%, respectively. Run and swim exercise training significantly increased ventricular mass (~11%) and haematocrit (~11%), but not the mass of skeletal muscles. However, exercise training did not alter CS or LDH activities of skeletal muscles. Similar to mammals, alligators respond to exercise training by increasing convective oxygen transport mechanisms, specifically heart size (potentially greater stroke volume) and haematocrit (increased oxygen carrying-capacity of the blood). Unlike mammals, but similar to squamate reptiles, alligators do not also increase citrate synthase activity of the skeletal muscles in response to exercise

Respiratory Evolution Facilitated the Origin of Pterosaur Flight and Aerial Gigantism

Pterosaurs, enigmatic extinct Mesozoic reptiles, were the first vertebrates to achieve true flapping flight. Various lines of evidence provide strong support for highly efficient wing design, control, and flight capabilities. However, little is known of the pulmonary system that powered flight in pterosaurs. We investigated the structure and function of the pterosaurian breathing apparatus through a broad scale comparative study of respiratory structure and function in living and extinct archosaurs, using computer-assisted tomographic (CT) scanning of pterosaur and bird skeletal remains, cineradiographic (X-ray film) studies of the skeletal breathing pump in extant birds and alligators, and study of skeletal structure in historic fossil specimens. In this report we present various lines of skeletal evidence that indicate that pterosaurs had a highly effective flow-through respiratory system, capable of sustaining powered flight, predating the appearance of an analogous breathing system in birds by approximately seventy million years. Convergent evolution of gigantism in several Cretaceous pterosaur lineages was made possible through body density reduction by expansion of the pulmonary air sac system throughout the trunk and the distal limb girdle skeleton, highlighting the importance of respiratory adaptations in pterosaur evolution, and the dramatic effect of the release of physical constraints on morphological diversification and evolutionary radiation

Boolean Dynamics with Random Couplings

This paper reviews a class of generic dissipative dynamical systems called N-K models. In these models, the dynamics of N elements, defined as Boolean variables, develop step by step, clocked by a discrete time variable. Each of the N Boolean elements at a given time is given a value which depends upon K elements in the previous time step. We review the work of many authors on the behavior of the models, looking particularly at the structure and lengths of their cycles, the sizes of their basins of attraction, and the flow of information through the systems. In the limit of infinite N, there is a phase transition between a chaotic and an ordered phase, with a critical phase in between. We argue that the behavior of this system depends significantly on the topology of the network connections. If the elements are placed upon a lattice with dimension d, the system shows correlations related to the standard percolation or directed percolation phase transition on such a lattice. On the other hand, a very different behavior is seen in the Kauffman net in which all spins are equally likely to be coupled to a given spin. In this situation, coupling loops are mostly suppressed, and the behavior of the system is much more like that of a mean field theory. We also describe possible applications of the models to, for example, genetic networks, cell differentiation, evolution, democracy in social systems and neural networks.Comment: 69 pages, 16 figures, Submitted to Springer Applied Mathematical Sciences Serie