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Differences in population density between species of varying size are frequently attributed to metabolic rates which are assumed to scale with body size with a slope of 0.75. This assumption is often criticised on the grounds that 0.75 scaling of metabolic rate with body size is not universal and can vary significantly depending on species and life-history. However, few studies have investigated how interspecific variation in metabolic scaling relationships affects population density in different sized species. Here we predict inter-specific differences in metabolism from niche requirements, thereby allowing metabolic predictions of species distribution and abundance at fine spatial scales. Due to the differences in energetic efficiency required along harsh-benign gradients, an extremophile fish (brown mudfish, Neochanna apoda) living in harsh environments had slower metabolism, and thus higher population densities, compared to a fish species (banded kōkopu, Galaxias fasciatus) in physiologically more benign habitats. Interspecific differences in the intercepts for the relationship between body and density disappeared when species mass-specific metabolic rates, rather than body sizes, were used to predict density, implying population energy use was equivalent between mudfish and kōkopu. Nevertheless, despite significant interspecific differences in the slope of the metabolic scaling relationships, mudfish and kōkopu had a common slope for the relationship between body size and population density. These results support underlying logic of energetic equivalence between different size species implicit in metabolic theory. However, the precise slope of metabolic scaling relationships, which is the subject of much debate, may not be a reliable indicator of population density as expected under metabolic theory.

Background: Despite intensive research and novel adjuvant therapies, there is currently no cure for metastatic melanoma. The chemokine receptor CXCR4 controls metastasis to sites such as the liver; however, the therapeutic blockade with the existing agents has proven difficult. Methods: AMD11070, a novel orally bioavailable inhibitor of CXCR4, was tested for its ability to inhibit the migration of melanoma cells compared with the commonly described antagonist AMD3100. Results: AMD11070 abrogated melanoma cell migration and was significantly more effective than AMD3100. Importantly for the clinical context, the expression of B-RAF-V600E did not the affect the sensitivity of AMD11070. Conclusion: Liver-resident myofibroblasts excrete CXCL12, which is able to promote the migration of CXCR4-expressing tumour cells from the blood into the liver. Blockade of this axis by AMD11070 thus represents a novel therapeutic strategy for both B-RAF wild-type and mutated melanomas.

Background Laparoscopic distal pancreatectomy (LDP) is performed increasingly for pancreatic pathology in the body and tail of the pancreas. However, only few reports have compared its oncological efficacy with open distal pancreatectomy (ODP). We compared these two techniques in patients with pancreatic ductal adenocarcinoma. Methods From a prospectively maintained database, all patients who underwent either LDP or ODP for adenocarcinoma in the body and tail of the pancreas between January 2008 and December 2011 were compared. Data were analysed using SPSS ® v19 utilising standard tests. A p value <0.05 was considered significant. Results Of 101 patients who underwent distal pancreatectomy, 22 had histologically confirmed adenocarcinoma (LDP n  = 8, ODP n  = 14). Both groups were well matched for age and the size of tumour (22 vs. 32 mm, p  = 0.22). Intraoperative blood loss was 306 ml compared with 650 ml for ODP ( p  = 0.152). A longer operative time was noted for LDP (376 vs. 274 min, p  < 0.05). Total length of stay was shorter for LDP compared with ODP (8 vs. 12 days, p  = 0.05). The number of postoperative pancreatic fistulas were similar (LDP n  = 2 vs. ODP n  = 3, p  = 0.5). Complete resection (R0) was achieved in 88 % of LDP ( n  = 7) compared with 86 % of ODP ( n  = 12). The median number of lymph nodes harvested was 16 for LDP versus 14 for ODP. Overall 3-year survival also was similar: LDP = 82 %, ODP = 74 % ( p  = 0.89). Conclusions From an oncological perspective, LDP is a viable procedure and its results are comparable to ODP for ductal adenocarcinomas arising in the body and tail of the pancreas.

Ecological indicators may provide information about multi‐stressor impacts, but they are often applied under hidden and untested assumptions, such as the number of stressors the indicator is sensitive to, the identity of those stressors, and the sensitivity of the indicator to individual stressors. Indicators used under false assumptions lead to perverse outcomes like failure to identify and regulate polluters. We analyzed the sensitivity of New Zealand macroinvertebrate community indicators (macroinvertebrate community index and its quantitative variant and average score per metric, hereafter, collectively, NZMCIs) to multiple stressors. We tested three assumptions: (1) NZMCIs exhibit a negative relationship with dissolved nutrients and suspended fine sediment (SFS). (2) Taxon‐specific “tolerance values” (TVs), upon which NZMCIs are based, accurately characterize invertebrates' tolerances of nutrients and SFS. NZMCI TVs have been derived using professional opinion and studies with narrow spatial and temporal domains. We determined whether these TVs are positively correlated with alternative measures of tolerance—“critical tolerances” (TTcrits)—developed using national, long‐term datasets and rigorous statistical models. (3) Macroinvertebrate taxa are positively co‐tolerant to nutrients and SFS, such that the order of taxon‐specific TTcrits for nutrients is positively correlated with that of SFS. We found little support for these assumptions. Although NZMCIs declined with increasing nutrients and SFS, the magnitude of decline was negligible, spanning only 7% of the NZMCI range observed in the data. NZMCI TVs were poorly correlated with TTcrits, so a factor contributing to the low sensitivity of NZMCIs to nutrients and SFS may be TVs that poorly reflect taxon‐specific tolerances. Taxa tolerant of nutrients were not necessarily tolerant of SFS; hence, the assumption of positive co‐tolerance was unsupported. Given our data and models, NZMCIs appear to be poor indicators of nutrient and SFS effects. Decision‐makers concerned with nutrients and SFS impacts should interpret NZMCI data cautiously. Macroinvertebrate communities can tell us a lot about ecosystem health, but how we use them for that purpose should be more critically assessed and matched to the specific water resource problems we are trying to solve. We present suggestions for improving the means by which we use macroinvertebrate communities as ecological indicators.

Background: Chemotherapy-associated liver injury (CALI) has been linked to increased morbidity and poorer disease-specific outcomes in patients undergoing resection of colorectal liver metastases (CRLM). The aim of this study was to assess the contribution of tumour-related factors to the development of FOLFOX-induced liver injury. Methods: We assessed the effect of FOLFOX treatment on the murine liver either in the presence or absence of CRLM to evaluate the contribution of both chemotherapy and tumour death to the development of CALI. Results: In the presence of liver metastases, there was increased hepatic expression of plasminogen activator inhibitor-1 (146-fold; P <0.01) and vWF (2.4-fold; P <0.01) transcript as compared with sham-operated controls. In addition, we detected large clusters of megakaryocytes in the spleen of FOLFOX-treated tumour-bearing animals. The livers of FOLFOX-treated animals also showed changes in matrix remodelling genes such as TGFβ ( P <0.01), MMP2 ( P <0.001), TIMP1 ( P <0.001) and Pro-Collagen I ( P <0.05) which was exacerbated in the presence of tumour. These genes have previously been demonstrated to have a key role in FOLFOX-induced liver injury. Conclusion: It appears that the toxicity of FOLFOX chemotherapy is enhanced by tumour-related factors.

AbstractThe purpose of this study was to characterize Cognitive Motor Dual Task (CMDT) costs for a community-based sample of older adults with Motoric Cognitive Risk Syndrome (MCR), as well as investigate associations between CMDT costs and cognitive performance. Twenty-five community-dwelling older adults (ages 60–89 years) with MCR performed single and dual task complex walking scenarios, as well as a computerized cognitive testing battery. Participants with lower CMDT costs had higher scores on composite measures of Working Memory, Processing Speed, and Shifting, as well as an overall cognitive composite measure. In addition, participants with faster single task gait velocity had higher scores on composite measures of Working Memory, Processing Speed, and overall cognition. Taken together, these results suggest that CMDT paradigms can help to elucidate the interplay between cognitive and motor abilities for older adults with MCR.

A laparoscopic approach is being used increasingly in specialist centres for the resection of hepatocellular carcinomas and compares favourably with the traditional open approach, in terms of perioperative morbidity and mortality as well as long-term survival. We present a case of port site recurrence in a patient who underwent a laparoscopic left lateral segmentectomy for a hepatocellular carcinoma diagnosed during investigation of symptomatic gallstones. Nearly three years following surgery, surveillance computed tomography demonstrated a suspicious lesion at the site of one of the laparoscopic ports. Further resection was carried out and the lesion was confirmed histologically to be an isolated recurrence of the primary hepatocellular carcinoma, involving peritoneum and adominal wall. This case demonstrates that it is possible to encounter port site metastasis following laparoscopic resection of primary liver tumours although the incidence is very rare.

Advanced (pT2/T3) incidental gallbladder cancer is often deemed unresectable after restaging. This study assesses the impact of the primary operation, tumour characteristics and timing of management on re-resection. The records of 60 consecutive referrals for incidental gallbladder cancer in a single tertiary centre from 2003 to 2011 were reviewed retrospectively. Decision on re-resection of incidental gallbladder cancer was based on delayed interval restaging at three months following cholecystectomy. Demographics, index cholecystectomy data, primary pathology, CA19-9 tumour marker levels at referral and time from cholecystectomy to referral as well as from referral to restaging were analysed. Thirty-seven patients with pT2 and twelve patients with pT3 incidental gallbladder cancer were candidates for radical re-resection. Following interval restaging, 24 patients (49%) underwent radical resection and 25 (51%) were deemed inoperable. The inoperable group had significantly more patients with positive resection margins at cholecystectomy (p=0.002), significantly higher median CA19-9 levels at referral (p=0.018) and were referred significantly earlier (p=0.004) than the patients who had resectable tumours. On multivariate analysis, urgent referral (p=0.036) and incomplete cholecystectomy (p=0.048) were associated significantly with inoperable disease following restaging. In patients with incidental, potentially resectable, pT2/T3 gallbladder cancer, inappropriate index cholecystectomy may have a significant impact on tumour dissemination. Early referral of breached tumours is not associated with resectability.

Understanding the determinants of species' niche breadth is important due to the negative relationship between niche breadth and extinction probability. Species tolerant to extremely harsh abiotic conditions (e.g. low pH or hypoxia) often have relatively small realised niches due to a trade-off between abiotic and biotic stress tolerance, and are therefore particularly vulnerable to extinction. We hypothesised that tolerance to multiple extreme conditions (e.g. low pH, hypoxia and drought) in brown mudfish Neochanna apoda, would increase their realised niche breadth because each extreme would provide additive refuge against a dominant species, the banded kokopu Galaxias fasciatus. Fish distributions were surveyed in 65 peat-swamp-forest streams and pools in New Zealand, which varied in dissolved oxygen, acidity and hydroperiod. Mudfish distribution was extremely patchy, and almost completely allopatric with kokopu. Allopatry was driven mainly by pool hydroperiod; mudfish occupied 88 percent of temporary pools due to their tolerance of habitat drying, whereas kokopu were absent from temporary pools. Within permanent pools, mudfish occurrence was negatively related to pool oxygen and pH, whereas kokopu occurrence was positively related to these conditions. Pool conditions were independently distributed in the landscape, suggesting that each abiotic stressor offered additive refuge for mudfish from kokopu predation/competition. Consequently, the mudfish realised niche breadth depended on the number of abiotic factors driving their allopatry with kokopu. Given the widespread negative relationships between niche breadth and species extinction probabilities, our results indicate that tolerance to multiple stressors may play an important role in insuring species persistence against the multiple drivers of global environmental change.

This paper compares established Systems Dynamics (SD) models of software projects with models of agile development. A new minimal SIMULINK™ agile project model was created and compared to a Waterfall model of a NASA project. Results are presented to enable project managers to predict the performance of future agile project processes. The model includes the time to generate the requirements and a function to provide requirements volatility. These models show that for the same productivity and fraction of errors that are satisfactory, the overall development staff costs are similar for agile and waterfall projects and the undiscovered rework is less for the agile project. This model generally supports empirical observations that shorter time-box iterations yield a shorter overall project completion.