Resection of the liver for colorectal carcinoma metastases - A multi-institutional study of long-term survivors

In this review of a collected series of patients undergoing hepatic resection for colorectal metastases, 100 patients were found to have survived greater than five years from the time of resection. Of these 100 long-term survivors, 71 remain disease-free through the last follow-up, 19 recurred prior to five years, and ten recurred after five years. Patient characteristics that may have contributed to survival were examined. Procedures performed included five trisegmentectomies, 32 lobectomies, 16 left lateral segmentectomies, and 45 wedge resections. The margin of resection was recorded in 27 patients, one of whom had a positive margin, nine of whom had a less than or equal to 1-cm margin, and 17 of whom had a greater than 1-cm margin. Eighty-one patients had a solitary metastasis to the liver, 11 patients had two metastases, one patient had three metastases, and four patients had four metastases. Thirty patients had Stage C primary carcinoma, 40 had Stage B primary carcinoma, and one had Stage A primarycarcinoma. The disease-free interval from the time of colon resection to the time of liver resection was less than one year in 65 patients, and greater than one year in 34 patients. Three patients had bilobar metastases. Four of the patients had extrahepatic disease resected simultaneously with the liver resection. Though several contraindications to hepatic resection have been proposed in the past, five-year survival has been found in patients with extrahepatic disease resected simultaneously, patients with bilobar metastases, patients with multiple metastases, and patients with positive margins. Five-year disease-free survivors are also present in each of these subsets. It is concluded that five-year survival is possible in the presence of reported contraindications to resection, and therefore that the decision to resect the liver must be individualized. © 1988 American Society of Colon and Rectal Surgeons

Acupuncture for dyspnea in advanced cancer: a randomized, placebo-controlled pilot trial [ISRCTN89462491]

BACKGROUND: Dyspnea, or shortness of breath, is a common symptom in patients with advanced cancer. Pharmacologic management is of proven benefit, but it does not help all patients. Preliminary data suggest that acupuncture can relieve dyspnea in a variety of populations, including cancer patients. We conducted a pilot study (ISRCTN89462491) preparatory to a fully powered randomized, placebo-controlled trial to determine whether acupuncture reduces dyspnea in patients with lung or breast cancer. METHODS: The study sample was comprised of forty-seven patients with lung or breast cancer presenting with dyspnea. Patients receiving symptomatic treatments were not excluded as long as no changes in management were planned during the trial. Patients were randomized to receive a single session of true or placebo acupuncture in addition to their existing dyspnea treatments. Semi-permanent acupuncture "studs" were then inserted: patients applied pressure to these studs twice a day to provide ongoing stimulation to acupuncture points. The subjective sensation of dyspnea was assessed with a 0 – 10 numerical rating scale immediately before and after acupuncture treatment and daily for a week thereafter. RESULTS: All but two of 47 randomized patients provided follow-up data. Dyspnea scores were slightly higher for patients receiving true versus placebo acupuncture, for both the period immediately following acupuncture treatment and for the daily one week follow-up (differences between means of 0.34, 95% C.I. -0.33, 1.02 and 0.56, 95% C.I. -0.39, 1.51). The 95% confidence interval excludes the prespecified minimum clinically significant difference of a 20% greater improvement in dyspnea for patients receiving acupuncture. CONCLUSION: The acupuncture technique used in this trial is unlikely to have effects on dyspnea importantly larger than placebo for patients with advanced cancer

Impact of the Resident Microbiota on the Nutritional Phenotype of Drosophila melanogaster

Background: Animals are chronically infected by benign and beneficial microorganisms that generally promote animal health through their effects on the nutrition, immune function and other physiological systems of the host. Insight into the host-microbial interactions can be obtained by comparing the traits of animals experimentally deprived of their microbiota and untreated animals. Drosophila melanogaster is an experimentally tractable system to study host-microbial interactions. Methodology/Principal Findings: The nutritional significance of the microbiota was investigated in D. melanogaster bearing unmanipulated microbiota, demonstrated by 454 sequencing of 16S rRNA amplicons to be dominated by the a-proteobacterium Acetobacter, and experimentally deprived of the microbiota by egg dechorionation (conventional and axenic flies, respectively). In axenic flies, larval development rate was depressed with no effect on adult size relative to conventional flies, indicating that the microbiota promotes larval growth rates. Female fecundity did not differ significantly between conventional and axenic flies, but axenic flies had significantly reduced metabolic rate and altered carbohydrate allocation, including elevated glucose levels. Conclusions/Significance: We have shown that elimination of the resident microbiota extends larval development and perturbs energy homeostasis and carbohydrate allocation patterns of of D. melanogaster. Our results indicate that th

Thermal Variability Increases the Impact of Autumnal Warming and Drives Metabolic Depression in an Overwintering Butterfly

Increases in thermal variability elevate metabolic rate due to Jensen's inequality, and increased metabolic rate decreases the fitness of dormant ectotherms by increasing consumption of stored energy reserves. Theory predicts that ectotherms should respond to increased thermal variability by lowering the thermal sensitivity of metabolism, which will reduce the impact of the warm portion of thermal variability. We examined the thermal sensitivity of metabolic rate of overwintering Erynnis propertius (Lepidoptera: Hesperiidae) larvae from a stable or variable environment reared in the laboratory in a reciprocal common garden design, and used these data to model energy use during the winters of 1973–2010 using meteorological data to predict the energetic outcomes of metabolic compensation and phenological shifts. Larvae that experienced variable temperatures had decreased thermal sensitivity of metabolic rate, and were larger than those reared at stable temperatures, which could partially compensate for the increased energetic demands. Even with depressed thermal sensitivity, the variable environment was more energy-demanding than the stable, with the majority of this demand occurring in autumn. Autumn phenology changes thus had disproportionate influence on energy consumption in variable environments, and variable-reared larvae were most susceptible to overwinter energy drain. Therefore the energetic impacts of the timing of entry into winter dormancy will strongly influence ectotherm fitness in northern temperate environments. We conclude that thermal variability drives the expression of metabolic suppression in this species; that phenological shifts will have a greater impact on ectotherms in variable thermal environments; and that E. propertius will be more sensitive to shifts in phenology in autumn than in spring. This suggests that increases in overwinter thermal variability and/or extended, warm autumns, will negatively impact all non-feeding dormant ectotherms which lack the ability to suppress their overwinter metabolic thermal sensitivity

Cracking the BAFF code.

The tumour necrosis factor (TNF) family members B cell activating factor (BAFF) and APRIL (a proliferation-inducing ligand) are crucial survival factors for peripheral B cells. An excess of BAFF leads to the development of autoimmune disorders in animal models, and high levels of BAFF have been detected in the serum of patients with various autoimmune conditions. In this Review, we consider the possibility that in mice autoimmunity induced by BAFF is linked to T cell-independent B cell activation rather than to a severe breakdown of B cell tolerance. We also outline the mechanisms of BAFF signalling, the impact of ligand oligomerization on receptor activation and the progress of BAFF-depleting agents in the clinical setting

Analysis of osteoarthritis in a mouse model of the progeroid human DNA repair syndrome trichothiodystrophy

The increasing average age in developed societies is paralleled by an increase in the prevalence of many age-related diseases such as osteoarthritis (OA), which is characterized by deformation of the joint due to cartilage damage and increased turnover of subchondral bone. Consequently, deficiency in DNA repair, often associated with premature aging, may lead to increased pathology of these two tissues. To examine this possibility, we analyzed the bone and cartilage phenotype of male and female knee joints derived from 52- to 104-week-old WT C57Bl/6 and trichothiodystrophy (TTD) mice, who carry a defect in the nucleotide excision repair pathway and display many features of premature aging. Using micro-CT, we found bone loss in all groups of 104-week-old compared to 52-week-old mice. Cartilage damage was mild to moderate in all mice. Surprisingly, female TTD mice had less cartilage damage, proteoglycan depletion, and osteophytosis compared to WT controls. OA severity in males did not significantly differ between genotypes, although TTD males had less osteophytosis. These results indicate that in premature aging TTD mice age-related changes in cartilage were not more severe compared to WT mice, in striking contrast with bone and many other tissues. This segmental aging character may be explained by a difference in vasculature and thereby oxygen load in cartilage and bone. Alternatively, a difference in impact of an anti-aging response, previously found to be triggered by accumulation of DNA damage, might help explain why female mice were protected from cartilage damage. These findings underline the exceptional segmental nature of progeroid conditions and provide an explanation for pro- and anti-aging features occurring in the same individual

Large-scale unit commitment under uncertainty: an updated literature survey

The Unit Commitment problem in energy management aims at finding the optimal production schedule of a set of generation units, while meeting various system-wide constraints. It has always been a large-scale, non-convex, difficult problem, especially in view of the fact that, due to operational requirements, it has to be solved in an unreasonably small time for its size. Recently, growing renewable energy shares have strongly increased the level of uncertainty in the system, making the (ideal) Unit Commitment model a large-scale, non-convex and uncertain (stochastic, robust, chance-constrained) program. We provide a survey of the literature on methods for the Uncertain Unit Commitment problem, in all its variants. We start with a review of the main contributions on solution methods for the deterministic versions of the problem, focussing on those based on mathematical programming techniques that are more relevant for the uncertain versions of the problem. We then present and categorize the approaches to the latter, while providing entry points to the relevant literature on optimization under uncertainty. This is an updated version of the paper "Large-scale Unit Commitment under uncertainty: a literature survey" that appeared in 4OR 13(2), 115--171 (2015); this version has over 170 more citations, most of which appeared in the last three years, proving how fast the literature on uncertain Unit Commitment evolves, and therefore the interest in this subject

Variability in organic carbon reactivity across lake residence time and trophic gradients

The transport of dissolved organic carbon from land to ocean is a large dynamic component of the global carbon cycle. Inland waters are hotspots for organic matter turnover, via both biological and photochemical processes, and mediate carbon transfer between land, oceans and atmosphere. However, predicting dissolved organic carbon reactivity remains problematic. Here we present in situ dissolved organic carbon budget data from 82 predominantly European and North American water bodies with varying nutrient concentrations and water residence times ranging from one week to 700 years. We find that trophic status strongly regulates whether water bodies act as net dissolved organic carbon sources or sinks, and that rates of both dissolved organic carbon production and consumption can be predicted from water residence time. Our results suggest a dominant role of rapid light-driven removal in water bodies with a short water residence time, whereas in water bodies with longer residence times, slower biotic production and consumption processes are dominant and counterbalance one another. Eutrophication caused lakes to transition from sinks to sources of dissolved organic carbon. We conclude that rates and locations of dissolved organic carbon processing and associated CO2 emissions in inland waters may be misrepresented in global carbon budgets if temporal and spatial reactivity gradients are not accounted for