Acute CO2 tolerance in fishes is associated with air breathing but not the Root effect, red cell ßNHE, or habitat.

High CO2 (hypercapnia) can impose significant physiological challenges associated with acid-base regulation in fishes, impairing whole animal performance and survival. Unlike other environmental conditions such as temperature and O2, the acute CO2 tolerance thresholds of fishes are not understood. While some fish species are highly tolerant, the extent of acute CO2 tolerance and the associated physiological and ecological traits remain largely unknown. To investigate this, we used a recently developed ramping assay, termed the Carbon Dioxide maximum (CDmax), that increases CO2 exposure until loss of equilibrium (LOE) is observed. We investigated if there was a relationship between CO2 tolerance and the Root effect, ß-adrenergic sodium proton exchanger (ßNHE), air-breathing, and fish habitat in 17 species. We hypothesized that CO2 tolerance would be higher in fishes that lack both a Root effect and ßNHE, breathe air, and reside in tropical habitats. Our results showed that CDmax ranged from 2.7 to 26.7 kPa, while LOE was never reached in four species at the maximum PCO2 we could measure (26.7 kPa); CO2 tolerance was only associated with air-breathing, but not the presence of a Root effect or a red blood cell (RBC) ßNHE, or fish habitat. This study demonstrates that the diverse group of fishes investigated here are incredibly tolerant of CO2 and that although this tolerance is associated with air-breathing, further investigations are required to understand the basis for CO2 tolerance.

Preferential intracellular pH regulation is a common trait amongst fishes exposed to high environmental CO2.

Acute (<96 h) exposure to elevated environmental CO2 (hypercarbia) induces a pH disturbance in fishes that is often compensated by concurrent recovery of intracellular and extracellular pH (pHi and pHe, respectively; coupled pH regulation). However, coupled pH regulation may be limited at CO2 partial pressure (PCO2 ) tensions far below levels that some fishes naturally encounter. Previously, four hypercarbia-tolerant fishes had been shown to completely and rapidly regulate heart, brain, liver and white muscle pHi during acute exposure to >4 kPa PCO2  (preferential pHi regulation) before pHe compensation was observed. Here, we test the hypothesis that preferential pHi regulation is a widespread strategy of acid-base regulation among fish by measuring pHi regulation in 10 different fish species that are broadly phylogenetically separated, spanning six orders, eight families and 10 genera. Contrary to previous views, we show that preferential pHi regulation is the most common strategy for acid-base regulation within these fishes during exposure to severe acute hypercarbia and that this strategy is associated with increased hypercarbia tolerance. This suggests that preferential pHi regulation may confer tolerance to the respiratory acidosis associated with hypercarbia, and we propose that it is an exaptation that facilitated key evolutionary transitions in vertebrate evolution, such as the evolution of air breathing.

Economic costs of using tailwater recovery systems for maintaining water quality and irrigation.

Best management practices (BMPs) are conservation efforts implemented to address environmental challenges associated with agricultural production. One such BMP, a tailwater recovery (TWR) system, has a dual purpose aimed at mitigating solids and nutrient losses from agricultural landscapes and creating an additional surface water source for irrigation. This study analyzes the costs of using five TWR systems to reduce solids, nutrients, and retain water. All systems were located in the Lower Mississippi Alluvial Valley and were used to irrigate crops including rice (Oryza sativa), corn (Zea mays), and soybeans (Glycine max). Costs to reduce solids and nutrients were calculated using annual payments and revenue losses due to lost tillable area from implementation of TWR systems. Similarly, cost to save and irrigate a mega-liter (ML) of water was determined as the annual payment for TWR systems, revenue losses and measured pumping cost. The range of mean total cost to reduce solids using TWR systems was $0 to $0.77 per kg; P was $0.61 to $3315.72 per kg; and N was $0.13 to $396.44 per kg. The range of mean total cost to retain water using TWR systems was $189.73 to $628.23 per ML, compared to a range of mean cost of groundwater of $13.99 to $36.17 per ML. Compared to other BMPs, TWR systems are one of the least expensive ways to reduce solid losses but remain an expensive way to reduce nutrient losses. The costs of using TWR systems to provide an additional irrigation water source range from less expensive than common conservation practices used to improve water use efficiency to more expensive and comparable to practices such as desalination. Therefore, TWR systems may be a prohibitively more expensive BMP to retain nutrients and water on some agricultural landscapes than other solutions.

Genetic And Morphological Evaluation (GAME) score for patients with colorectal liver metastases.

BACKGROUND: This study sought to develop a clinical risk score for resectable colorectal liver metastasis (CRLM) by combining clinicopathological and clinically available biological indicators, including KRAS. METHODS: A cohort of patients who underwent resection for CRLM at the Johns Hopkins Hospital (JHH) was analysed to identify independent predictors of overall survival (OS) that can be assessed before operation; these factors were combined into the Genetic And Morphological Evaluation (GAME) score. The score was compared with the current standard (Fong score) and validated in an external cohort of patients from the Memorial Sloan Kettering Cancer Center (MSKCC). RESULTS: Six preoperative predictors of worse OS were identified on multivariable Cox regression analysis in the JHH cohort (502 patients). The GAME score was calculated by allocating points to each patient according to the presence of these predictive factors: KRAS-mutated tumours (1 point); carcinoembryonic antigen level 20 ng/ml or more (1 point), primary tumour lymph node metastasis (1 point); Tumour Burden Score between 3 and 8 (1 point) or 9 and over (2 points); and extrahepatic disease (2 points). The high-risk group in the JHH cohort (GAME score at least 4 points) had a 5-year OS rate of 11 per cent, compared with 73·4 per cent for those in the low-risk group (score 0-1 point). Importantly, in cohorts from both the JHH and MSKCC (747 patients), the discriminatory capacity of the GAME score was superior to that of the Fong score, as demonstrated by the C-index and the Akaike information criterion. CONCLUSION: The GAME score is a preoperative prognostic tool that can be used to inform treatment selection.

Proteomic approach to characterize biochemistry of meat quality defects.

Proteomics can be used to characterize quality defects including pale, soft, and exudative (PSE) meat (pork and poultry), woody broiler breast meat, reddish catfish fillets, meat toughness, and beef myoglobin oxidation. PSE broiler meat was characterized by 15 proteins that differed in abundance in comparison to normal broiler breast meat, and eight proteins were differentially expressed in woody breast meat in comparison to normal breast meat. Hemoglobin was the only protein that was differentially expressed between red and normal catfish fillets. However, inducing low oxygen and/or heat stress conditions to catfish fillets did not lead to the production of red fillets. Proteomic data provided information pertaining to the protein differences that exist in meat quality defects. However, these data need to be evaluated in conjunction with information pertaining to genetics, nutrition, environment of the live animal, muscle to meat conversion, meat quality analyses and sensory attributes to understand causality, protein biomarkers, and ultimately how to prevent quality defects.

Several types of groupoids induced by two-variable functions.

In this paper, we introduce the concept of several types of groupoids related to semigroups, viz., twisted semigroups for which twisted versions of the associative law hold. Thus, if [Formula: see text] is a groupoid and if [Formula: see text] is a function [Formula: see text], then [Formula: see text] is a left-twisted semigroup with respect to [Formula: see text] if for all [Formula: see text], [Formula: see text]. Other types are right-twisted, middle-twisted and their duals, a dual left-twisted semigroup obeying the rule [Formula: see text] for all [Formula: see text]. Besides a number of examples and a discussion of homomorphisms, a class of groupoids of interest is the class of groupoids defined over a field [Formula: see text] via a formula [Formula: see text], with [Formula: see text], fixed structure constants. Properties of these groupoids as twisted semigroups are discussed with several results of interest obtained, e.g., that in this setting simultaneous left-twistedness and right-twistedness of [Formula: see text] implies the fact that [Formula: see text] is a semigroup.

Freshwater influences on embryos, hatching and larval survival of euryhaline Gulf killifish Fundulus grandis and potential constraints on habitat distribution.

The influence of fresh water on potential habitat occupancy of early life-history stages of euryhaline Gulf killifish Fundulus grandis was determined by evaluating fertilization of freshwater-spawned eggs and subsequent survival of embryos and larvae in comparison with saline water (salinity 7). Overall per cent fertilization of eggs was low (mean ± s.e. = 20·21 ± 0·03%). Embryo survival was greater in saline water, but hatching rate (mean ± s.e. = 81·6 ± 0·1%) and post-hatch survival of larvae in fresh water (mean ± s.e. = 74·5 ± 0·1%) was relatively high. Therefore, the relative limitation of fresh water on habitat distribution of F. grandis changes with development, stimulating further questions on factors that may constrain habitat distribution of euryhaline fishes.

Survival after resection of perihilar cholangiocarcinoma-development and external validation of a prognostic nomogram.

BACKGROUND: The objective of this study was to derive and validate a prognostic nomogram to predict disease-specific survival (DSS) after a curative intent resection of perihilar cholangiocarcinoma (PHC). PATIENTS AND METHODS: A nomogram was developed from 173 patients treated at Memorial Sloan Kettering Cancer Center (MSKCC), New York, USA. The nomogram was externally validated in 133 patients treated at the Academic Medical Center (AMC), Amsterdam, The Netherlands. Prognostic accuracy was assessed with concordance estimates and calibration, and compared with the American Joint Committee on Cancer (AJCC) staging system. The nomogram will be available as web-based calculator at mskcc.org/nomograms. RESULTS: For all 306 patients, the median overall survival (OS) was 40 months and the median DSS 41 months. Median follow-up for patients alive at last follow-up was 48 months. Lymph node involvement, resection margin status, and tumor differentiation were independent prognostic factors in the derivation cohort (MSKCC). A nomogram with these prognostic factors had a concordance index of 0.73 compared with 0.66 for the AJCC staging system. In the validation cohort (AMC), the concordance index was 0.72, compared with 0.60 for the AJCC staging system. Calibration was good in the derivation cohort; in the validation cohort patients had a better median DSS than predicted by the model. CONCLUSIONS: The proposed nomogram to predict DSS after curative intent resection of PHC had a better prognostic accuracy than the AJCC staging system. Calibration was suboptimal because DSS differed between the two institutions. The nomogram can inform patients and physicians, guide shared decision making for adjuvant therapy, and stratify patients in future randomized, controlled trials.

Long-term outcomes following microwave ablation for liver malignancies.

BACKGROUND: Microwave ablation has emerged as a promising treatment for liver malignancies, but there are scant long-term follow-up data. This study evaluated long-term outcomes, with a comparison of 915-MHz and 2.4-GHz ablation systems. METHODS: This was a retrospective review of patients with malignant liver tumours undergoing operative microwave ablation with or without liver resection between 2008 and 2013. Regional or systemic (neo)adjuvant therapy was given selectively. Local recurrence was analysed using competing-risk methods with clustering, and overall survival was determined from Kaplan-Meier curves. RESULTS: A total of 176 patients with 416 tumours were analysed. Colorectal liver metastases (CRLM) comprised 81.0 per cent of tumours, hepatocellular carcinoma 8.4 per cent, primary biliary cancer 1.7 per cent and non-CRLM 8.9 per cent. Median follow-up was 20.5 months. Local recurrence developed after treatment of 33 tumours (7.9 per cent) in 31 patients (17.6 per cent). Recurrence rates increased with tumour size, and were 1.0, 9.3 and 33 per cent for lesions smaller than 1 cm, 1-3 cm and larger than 3 cm respectively. On univariable analysis, the local recurrence rate was higher after ablation of larger tumours (hazard ratio (HR) 2.05 per cm; P < 0.001), in those with a perivascular (HR 3.71; P = 0.001) or subcapsular (HR 2.71; P = 0.008) location, or biliary or non-CRLM histology (HR 2.47; P = 0.036), and with use of the 2.4-GHz ablation system (HR 3.79; P = 0.001). Tumour size (P < 0.001) and perivascular position (P = 0.045) remained significant independent predictors on multivariable analysis. Regional chemotherapy was associated with decreased local recurrence (HR 0.49; P = 0.049). Overall survival at 4 years was 58.3 per cent for CRLM and 79.4 per cent for other pathology (P = 0.360). CONCLUSION: Microwave ablation of liver malignancies, either combined or not combined with liver resection, and selective regional and systemic therapy resulted in good long-term survival. Local recurrence rates were low after treatment of tumours smaller than 3 cm in diameter, and those remote from vessels.

Perioperative complications influence recurrence and survival after resection of hepatic colorectal metastases.

BACKGROUND: Perioperative outcomes, such as blood loss, transfusions, and morbidity, have been linked to cancer-specific survival, but this is largely unsupported by prospective data. METHODS: Patients from a previous, randomized trial that evaluated acute normovolemic hemodilution during major hepatectomy (≥3 segments) were reevaluated and those with metastatic colorectal cancer (n = 90) were selected for analysis. Survival data were obtained from the medical record. Disease extent was measured using a clinical-risk score (CRS). Log-rank test and Cox proportional hazard model were used to evaluate recurrence-free survival (RFS) and overall survival (OS). RESULTS: Median follow-up was 71 months. The CRS was ≥3 in 45 % of patients; 59 % had extrahepatic procedures. Morbidity and mortality were 33 and 2 %, respectively. Postoperative chemotherapy was given to 87 % of patients (78/90) starting at a median of 6 weeks. RFS and OS were 29 and 60 months, respectively. Postoperative morbidity significantly reduced RFS (23 vs. 69 months; P < 0.001) and OS (28 vs. 74 months; P < 0.001) on uni- and multi-variate analysis; positive resection margins and high CRS also were significant factors. Delayed initiation of postoperative chemotherapy (≥8 weeks) was common in patients with complications (37 vs. 12 %; P = 0.01). CONCLUSIONS: In this selected cohort of patients from a previous RCT, perioperative morbidity was strongly (and independently) associated with cancer-specific outcome. It also was associated with delayed initiation of postoperative chemotherapy, the impact of which on survival is unclear.

Hepatic arterial nodal metastases in pancreatic cancer: is this the node of importance?

BACKGROUND: The hepatic artery lymph node (HALN) is frequently sampled during pancreaticoduodenectomy (PD). Data suggest that survival in the setting of HALN metastases is similar to that of stage IV pancreatic ductal adenocarcinoma (PDAC). The objectives of this study were to describe the prognostic significance of HALN metastases and to assess the predictive performance of HALN compared to peripancreatic lymph node status. METHODS: Patients undergoing PD for PDAC from January 2000-October 2010 were identified from a prospectively maintained database. Patients were included if during PD the HALN was submitted for pathologic evaluation. Patients were excluded if margins were macroscopically positive, if pathology was found to be consistent with a diagnosis other than PDAC. Overall (OS) and disease-free survival (DFS) were estimated by Kaplan-Meier methods. RESULTS: Of the 671 patients who underwent PD for PDAC, HALN status was analyzed for 147 patients. HALN was positive in 23 patients (16 %), 38 were peripancreatic lymph node (PPLN) and HALN negative, and 86 were PPLN+/HALN-. Median follow-up for survivors was 10 months. In a multivariable model, lymph node status and tumor differentiation predicted OS and DFS. Hazard of death and relapse/death were highest among the HALN+ patients (hazard ratio [HR] 2.94; p = 0.017 and HR 2.66; p = 0.011, respectively). Kaplan-Meier analysis revealed significant differences in OS (p = 0.017) and DFS (p = 0.013) based on lymph node status. CONCLUSIONS: OS and DFS are significantly reduced in patients with a positive HALN. Differentiation and lymph node status were predictors of OS and DFS. In the multivariate models, differentiation and lymph node status remain independent predictors of OS and DFS.

Downstaging in pancreatic cancer: a matched analysis of patients resected following systemic treatment of initially locally unresectable disease.

BACKGROUND: Patients with locally unresectable pancreatic cancer (AJCC stage III) have a median survival of 10-14 months. The objective of this study was to evaluate outcome of initially unresectable patients who respond to multimodality therapy and undergo resection. METHODS: Using a prospectively collected database, patients were identified who were initially unresectable because of vascular invasion and had sufficient response to nonoperative treatment to undergo resection. Overall survival (OS) was compared with a matched group of patients who were initially resectable. Case matching was performed using a previously validated pancreatic cancer nomogram. RESULTS: A total of 36 patients with initial stage III disease were identified who underwent resection after treatment with either systemic therapy or chemoradiation. Initial unresectability was determined by operative exploration (n = 15, 42%) or by cross-sectional imaging (n = 21, 58%). Resection consisted of pancreaticoduodenectomy (n = 31, 86%), distal pancreatectomy (n = 4, 11%), and total pancreatectomy (n = 1, 3%). Pathology revealed T3 lesions in 26 patients (73%), node positivity in 6 patients (16%), and a negative margin in 30 patients (83%). The median OS in this series was 25 months from resection and 30 months since treatment initiation. There was no difference in OS from time of resection between the initial stage III patients and those who presented with resectable disease (P = .35). CONCLUSIONS: In this study, patients who were able to undergo resection following treatment of initial stage III pancreatic cancer experienced survival similar to those who were initially resectable. Resection is indicated in this highly select group of patients.

An alternative approach for the measurement of trimethylamine oxide in body fluid samples of elasmobranchs.

The present study examined an alternative approach to the measurement of trimethylamine oxide (TMAO) in body fluids of an elasmobranch, the little skate Leucoraja erinacea. Using ion exchange chromatography, the values measured compared favourably with values from the same samples measured using a recognized and frequently published spectrophotometric technique.

Cohesive social behaviour shortens the stress response: the effects of conspecifics on the stress response in lake sturgeon Acipenser fulvescens.

An examination was made of whether social interactions can have a beneficial effect through the attenuation of the stress response in a social species. In the first experiment, one larger (mean +/-s.e. 194.0 +/- 12.5 g) and seven smaller (32.0 +/- 2.6 g) juvenile lake sturgeon Acipenser fulvescens were placed in tanks to determine whether a classic dominance effect would be established based on body size (n = 6). Large fish did not establish a territory or aggressively interact with smaller fish, as there were no significant differences in nearest-neighbour distances and an absence of aggressive behaviour (biting, chasing and pushing). In the second experiment, it was hypothesized that the presence of conspecifics would have a beneficial effect through an attenuation of the stress response. Fish in groups or isolation were stressed by a brief aerial exposure (30 s), and blood plasma was measured at regular time intervals (0, 20, 40, 60, 120 and 240 min) following the stressor via an implanted cannula (n = 9-11). The presence of conspecifics did not affect the peak cortisol response, however, the overall cortisol response was shorter in duration compared to fish in isolation. Furthermore, secondary stress variables (plasma ions and glucose) showed differences between fish in groups and isolation. The results of these experiments suggest that social interaction plays an important and beneficial role in regulating the stress response in cohesive social species such as A. fulvescens.

Current management of cystic neoplasms of the pancreas.

Over the last decade there has been a dramatic increase in the number of patients identified with pancreatic cysts. This increase has been largely attributed to advances in imaging. The majority of these cysts represent benign neoplasms; however, a significant fraction of these are pre-malignant or malignant. Because the majority of these neoplasms are benign, many reports have advocated a selective approach to surgical resection. Here we review the literature that has contributed to the development of our approach to the management of these cystic neoplasms. We provide an overview of the key features in diagnosis and in predicting malignancy. Particular attention is given to the natural history and management of intraductal papillary mucinous neoplasms (IPMN).

Efficacy of supra-choroidal, bipolar, electrical stimulation in a vision prosthesis.

The key to successful, clinical application of therapeutic neurostimulators lies primarily with the safety and efficacy of their electrode-tissue interfaces. The authors posit that for electrical stimulation of the visual system, supra-choroidal electrode placement provides a safe, stable and readily-accessible site for implantation and the provision of electrical stimulation. The present paper explores the efficacy of supra-choroidal electrical stimulation of retinal neurons. Based upon recordings made with surface electrodes placed on the primary visual cortex, areas of activation in the cortex were shown to change when different areas on the supra-choroidal space were stimulated. Finally, the threshold to elicit a response from neurons in the visual cortex, was found to be 77.55 +/- 29.85 nC.

Immunohistochemical analysis of sentinel lymph nodes from patients with Merkel cell carcinoma.

BACKGROUND: Immunohistochemical analysis of sentinel lymph nodes from patients with breast carcinoma and melanoma has been shown to increase the sensitivity for detecting lymph node metastases. To the authors' knowledge, this technique has not been described in patients with Merkel cell carcinoma. METHODS: Lymphatic mapping and sentinel lymph node biopsy was performed on 26 patients with Merkel cell carcinoma between 1997 and 1999. All sentinel lymph nodes were analyzed with conventional hematoxylin and eosin (H&E) staining and then analyzed with immunohistochemical staining to evaluate whether this additional technique would increase the number of patients found to have lymph node metastasis. RESULTS: The median age of the patients in the current study was 67 years and the median tumor size at the time of presentation was 2 cm. Lymph node metastases were identified in 5 of the 26 patients (19%). Three of these five lymph node positive patients were identified with H&E staining. The remaining two patients were identified only after immunohistochemical analysis. The median follow-up in this group of lymph node positive patients was 14 months, with 2 of the 5 lymph node positive patients developing a recurrence. The median follow-up in the 21 patients who were lymph node negative was 19 months, with only 1 patient having developed a recurrence at the time of last follow-up. CONCLUSIONS: Immunohistochemical analysis of sentinel lymph nodes from patients with Merkel cell carcinoma appears to increase the sensitivity of detecting clinically occult lymph node metastases.

Polymyography combined with time-locked video recording (video EMG) for presurgical assessment of patients with cervical dystonia.

We assessed 26 patients with cervical dystonia, in whom botulinum toxin (BT) injections had failed, before selective peripheral denervation. We decided to base the decision which muscle should be denervated on both clinical information and EMG data and focussed on the following features: activity at onset or during 'dystonic spasms' (according to the concept of the 'leading' dystonic muscle), paradoxical activity during voluntary head movements causing restriction of head movements opposite the side of head turn or tilt and activity when symptoms deteriorated during walking. To identify these muscles we developed a new recording system that integrates simultaneous video-taping and polymyography (video EMG) by means of a digital counter, driven by the recording software (resolution 0.1 s), that was fixed in view of the video camera. This system time-locked clinical signs with relevant EMG activity thus allowing demonstration of the above features. These were found in 68% of dystonic muscles with each of them being present in approximately 40%. Video EMG allows an integrated approach to identify overactive neck muscles in patients with cervical dystonia taking into account both relevant clinical findings and EMG data.